RESUMO
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
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.
Assuntos
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
AIMS: To assess whether platelet reactivity is increased in offspring of patients with early acute myocardial infarction (AMI) and its possible relation with endothelial dysfunction. METHODS AND RESULTS: We studied 23 healthy children (15±3 years, 13 males) of patients with early AMI (≤50 years old; Group 1) and 21 healthy children of healthy subjects without any history of cardiovascular disease (14±3 years, 10 males; Group 2). Platelet reactivity was assessed by flow cytometry as the increase in monocyte-platelet aggregates (MPA) and CD41 and PAC-1 platelet expression in response to exercise stress test (EST), adenosine diphosphate (ADP) stimulation (10(-7) M), or both. Endothelial function was assessed by measuring brachial artery dilation during post-ischaemic forearm hyperaemia [flow-mediated dilation (FMD)]. Both EST and ADP induced a higher percentage increase in platelet receptor expression in Group 1, compared with Group 2, with the most significant difference being shown for the response to the combined stimuli (e.g. MPA, 23.1±12 vs. 5.63±8%, P<0.001; platelet PAC-1, 57.7±47 vs. 13.2±7%, P<0.001). Compared with Group 2, Group 1 children showed lower FMD (10.7±3.1 vs. 8.0±2.9%, respectively; P=0.007). However, no significant association was found between FMD and platelet reactivity. CONCLUSION: Our results show increased platelet reactivity in children of patients with early AMI; the finding was not significantly correlated with endothelial dysfunction, suggesting that other mechanisms are mainly involved in the enhanced platelet response to agonistic stimuli.
Assuntos
Endotélio Vascular/fisiologia , Infarto do Miocárdio/sangue , Agregação Plaquetária/fisiologia , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Difosfato de Adenosina/farmacologia , Adolescente , Adulto , Análise de Variância , Anticorpos Monoclonais Murinos/metabolismo , Criança , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/fisiologia , Infarto do Miocárdio/genética , Linhagem , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/genética , Inibidores da Agregação Plaquetária/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Vasodilatação/fisiologiaRESUMO
Flow-mediated dilation (FMD) is a widely used tool to investigate endothelial function. However, FMD assessment may cause mechanical damage to the arterial endothelium. In this study we investigated the effect of FMD assessment on endothelial function. We studied 20 healthy subjects (26 ± 6 years; 12 males). FMD was assessed by measuring brachial artery dilation in response to hyperemia after 5 min of forearm cuff inflation. Subjects were studied on 2 subsequent days. On day 1 they underwent two consecutive FMD measures, with the second test (FMD2) performed 15 min after the first test (FMD1). On day 2, the subjects were randomized to receive either placebo (saline) or intravenous L: -arginine (10 g in 20 min). At the end of the infusion, patients underwent two consecutive FMD measures following the same protocol as on day 1. Asymmetric dimethyl-arginine (ADMA) serum levels were assessed on day 2 before FMD1 and FMD2. On day 1, FMD2 was lower than FMD1 in both groups (placebo 6.47 ± 2.1 vs. 7.86 ± 1.8%, P < 0.01; arginine 6.13 ± 2.6 vs. 7.76 ± 2.7%, P < 0.01). On day 2, a significant reduction of FMD was observed during FMD2 compared to FMD1 in the placebo group (5.82 ± 1.7 vs. 7.44 ± 2.2%, P < 0.001), but not in the arginine group (7.19 ± 1.5 vs. 7.27 ± 1.5, P = 0.67). ADMA levels significantly increased compared to baseline after FMD1 (0.59 ± 0.12-0.91 ± 0.64 µmol/l, P = 0.036), with similar changes in the two groups. FMD assessment induces a significant impairment of endothelial function. An increase of endogenous NO synthesis inhibitors seems responsible for the phenomenon that is reversed by L: -arginine administration.
Assuntos
Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Hiperemia/fisiopatologia , Vasodilatação , Adulto , Arginina/administração & dosagem , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/efeitos dos fármacos , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Hiperemia/diagnóstico por imagem , Infusões Intravenosas , Itália , Masculino , Fatores de Tempo , Ultrassonografia Doppler , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: In patients with cardiac syndrome X (CSX) who present with refractory angina episodes, spinal cord stimulation (SCS) has beneficial effects. The mechanisms of SCS, however, remain speculative. We assessed the effects of SCS on cardiac sympathetic function in these patients. METHODS AND RESULTS: We studied 11 CSX patients treated by SCS for refractory angina (mean age, 60 +/- 9 years; 5 men and 6 women), both during SCS therapy (SCS-ON) and after withdrawal of SCS therapy (SCS-OFF), using a randomized crossover design. Planar and single photon emission computed tomography iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and technetium 99m sestamibi (MIBI) bicycle exercise stress testing were performed at the end of each period. Compared with 10 healthy control subjects, CSX patients showed a lower heart-mediastinum ratio for MIBG uptake (2.19 +/- 0.3 vs 1.69 +/- 0.3, P = .001) and a higher cardiac MIBG uptake score (4.0 +/- 2.5 vs 19.7 +/- 27, P = .08). There were no differences in CSX patients during the SCS-ON and SCS-OFF phases of the study in heart-mediastinum ratio (1.74 +/- 0.3 vs 1.69 +/- 0.3, P = .13), cardiac washout rate of MIBG (42.9% +/- 14% vs 43.3% +/- 14%, P = .08), or MIBG defect score (18.7 +/- 25 vs 19.7 +/- 27, P = .22). Reversible perfusion defects during the SCS-OFF phase were detected in 8 patients; an improvement in perfusion defects was observed in 2 patients (25%) during the SCS-ON phase. CONCLUSIONS: Our data confirm the presence of abnormal cardiac adrenergic nerve function in CSX patients. SCS was unable to result in significant improvement of cardiac MIBG uptake abnormalities, suggesting that its therapeutic effects are unlikely to be mediated by modulation of cardiac adrenergic nerve activity.
Assuntos
Angina Microvascular/patologia , Neurônios/metabolismo , Receptores Adrenérgicos/metabolismo , Medula Espinal/patologia , 3-Iodobenzilguanidina/farmacologia , Idoso , Angiografia Coronária/métodos , Feminino , Humanos , Radioisótopos do Iodo/farmacologia , Masculino , Angina Microvascular/diagnóstico , Pessoa de Meia-Idade , Radioisótopos/farmacologia , Tecnécio Tc 99m Sestamibi/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
BACKGROUND: More than 450 000 Americans die suddenly each year from sustained ventricular tachycardia (VT) or fibrillation. Overall, event rates in Europe are similar to those in the United States. A correct risk stratification is essential to reduce the incidence of sudden cardiac death. Ventricular late potentials (VLPs) represent delayed conduction through a diseased myocardium and consist of the presence of electrical activity after the end of the standard QRS. The VLPs are potential substrates for reentry VT. CLINICAL APPLICATIONS: The VLPs were found highly predictive of cardiac events, in particular, arrhythmic events, in patients with acute myocardial infarction. The weakness of VLPs is the low positive predictive value, especially as a single technique. However, their negative predictive value for arrhythmic events is very high. The VLPs are observed in more than 50% of patients with arrhythmogenic right ventricular cardiomyopathy, and are actually considered a helpful diagnostic tool in this setting. In patients with syncope of unknown cause, VLP analysis, combined with patient history and other diagnostic tests, can help identify or exclude a mechanism of VT as a cause of the syncope. CONCLUSIONS: The VLP assessment offers a practical and low-cost tool to the clinical cardiologist to recognize the possible electrophysiologic substrate underlying life-threatening ventricular arrhythmias. The strength of VLPs is their high negative predictive value. When positive, VLPs still help better stratify the arrhythmic risk of patients in several clinical settings.
Assuntos
Eletrocardiografia/métodos , Taquicardia Ventricular/diagnóstico , Fibrilação Ventricular/diagnóstico , Diagnóstico Diferencial , HumanosRESUMO
A 47-year-old woman presented to our clinic 1 day after an intervention for a tibial shaft fracture because of sudden onset of chest pain and palpitations. Hospital drug therapy included enoxaparin. The ECG showed atrial fibrillation with a rapid ventricular rate. Transthoracic echocardiography showed a mass in the LA. Transoesophageal echocardiography (TEE) was performed which showed a multilobulated liquid-filled mass (3.6 x 3.7 cm), adherent to the septal, anterior and posterolateral LA most consistent with thrombosis. Tests for hypercoagulable disorders revealed antithrombin deficiency (antithrombin-heparin co-factor level = 30% [normal pooled plasma activity 70%-140%]), suggesting that it played an outstanding role in the LA thrombosis. After initial stabilization, the patient was discharged with warfarin (target INR = 2.5-3.5) together with beta-blockers, statins and metformin. After 1 month of follow-up the patient underwent TEE which showed a dramatic reduction of the left atrial thrombosis. Our patient is doing well and is continuing life-long anticoagulant therapy.
Assuntos
Anticoagulantes/efeitos adversos , Deficiência de Antitrombina III/tratamento farmacológico , Fibrilação Atrial/etiologia , Átrios do Coração/patologia , Tromboembolia/induzido quimicamente , Doença Aguda , Anticoagulantes/administração & dosagem , Ecocardiografia Transesofagiana , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Tromboembolia/complicações , Tromboembolia/diagnóstico por imagem , Tromboembolia/etiologiaRESUMO
Data on coronary flow reserve (CFR) in patients with syndrome X are still controversial. Further, noninvasive evaluation of epicardial and microvascular flow reserves in these patients has never been performed. In 17 patients with syndrome X and in 17 age- and gender-matched control subjects, CFR in the mid left anterior descending coronary artery (LAD) was evaluated by transthoracic color and pulse-wave Doppler using a 7-mHz probe (Sequoia, Siemens). Peak diastolic LAD flow was calculated at rest and at peak adenosine (140 microg/kg/min intravenously in 90 seconds). Myocardial contrast echocardiography (MCE) was performed at rest and during adenosine use by real-time cadence pulse sequencing and intravenous SonoVue (Bracco; 5 ml at 1 ml/min) and microvascular blood volume (A), velocity (beta), and flow (Axbeta) by replenishing curves (y = A[1 - e(betat)]). CFR was measured by Doppler echocardiography as an adenosine/rest velocity ratio and by MCE as a microvascular volume, velocity, and flow adenosine/rest ratio. Compared with controls, patients with syndrome X demonstrated lower LAD CFR and velocity and flow microvascular flow reserves (p <0.01, <0.005, and <0.005, respectively). In patients with syndrome X, those with angina and ST-segment depression during adenosine testing had even lower LAD CFR and velocity and flow microvascular flow reserves compared with those with no symptoms (p <0.0001, <0.0001, and <0.005, respectively). LAD CFR demonstrated a significant linear correlation with velocity microvascular flow reserve (r = 0.92, p <0.0001) and flow microvascular flow reserve (r = 0.77, p <0.0001). In conclusion, CFR in the LAD, successfully evaluated by transthoracic Doppler echocardiography and MCE, is significantly decreased in patients with syndrome X and even more in those with angina pectoris and ST-segment depression during adenosine testing. Thus, noninvasive evaluation of CFR by echocardiography is feasible and provides information on the severity of microvascular impairment.
Assuntos
Circulação Coronária , Vasos Coronários/fisiopatologia , Angina Microvascular/fisiopatologia , Adenosina , Adulto , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Volume Sanguíneo/efeitos dos fármacos , Estudos de Casos e Controles , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/diagnóstico por imagem , Ecocardiografia , Ecocardiografia Doppler em Cores , Eletrocardiografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Microcirculação/efeitos dos fármacos , Angina Microvascular/diagnóstico por imagem , Pessoa de Meia-Idade , Descanso , VasodilatadoresRESUMO
INTRODUCTION: In previous studies we have consistently shown a significant increase of platelet reactivity after exercise in patients with obstructive coronary artery disease (CAD). We also observed a significant individual variability in the response to exercise of platelet reactivity in these patients. Whether exercise-induced changes in platelet reactivity correlate with changes in platelet membrane receptors in patients with CAD is unknown. METHODS: We studied 26 patients with stable CAD and 10 matched healthy controls who underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected at rest and within 5 min of peak exercise. Platelet reactivity was measured by the PFA-100 method as time to occlude (closure time, CT) a ring coated with collagen/adenosine diphosphate (C/ADP). Platelet expression of glycoprotein (GP) IIb/IIIa, in both global (CD41) and active form (PAC-1), and P-selectin (CD62P) and formation of leukocyte-platelet aggregates were assessed by flow cytometry. RESULTS: After exercise CT did not change in controls (85.4+/-12 to 84.0+/-9 s, p=0.37), whereas it decreased in CAD patients (98.8+/-24 to 91.4+/-25 s, p<0.001). After exercise, CD41 and PAC-1 platelet expression increased significantly in CAD patients (p=0.04 for both), but not in controls (p=0.39 and p=0.98, respectively). To evaluate the relationship between the response to exercise of platelet reactivity and of platelet receptor expression, CAD patients were divided into two groups: CAD group 1 (16 patients, decrease in CT >5 s after exercise) and CAD group 2 (10 patients no increase in platelet reactivity after exercise). CD41 and PAC-1 expression increased in CAD group 1 (p=0.008 and p=0.026, respectively) but not in CAD group 2 (p=0.39 and p=0.50, respectively). No significant differences were observed between the 2 groups for changes in CD62P and leukocyte-platelet aggregates. CONCLUSIONS: Our data show that, in patients with stable CAD, an increased platelet reactivity to C/ADP stimulation after exercise, as assessed by the PFA-100 method, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor.
Assuntos
Plaquetas/fisiologia , Doença da Artéria Coronariana/sangue , Atividade Motora/fisiologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Idoso , Doença da Artéria Coronariana/fisiopatologia , Teste de Esforço , Feminino , Citometria de Fluxo , Humanos , Integrina beta3/metabolismo , Leucócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Selectina-P/metabolismo , Ativação Plaquetária/fisiologia , Glicoproteína IIb da Membrana de Plaquetas/metabolismoRESUMO
BACKGROUND: We previously demonstrated that bariatric surgery (BS) leads to a short-term significant improvement of endothelial function and coronary microvascular function. In this study we assessed whether BS maintains its beneficial effect at long-term follow up. DESIGN: We studied 19 morbidly obese patients (age 43±9years, 12 women) without any evidence of cardiovascular disease who underwent BS. Patients were studied before BS, at 3 months and at 4.0±1.5years follow up. METHODS: Peripheral vascular function was assessed by flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), i.e., brachial artery diameter changes in response to post-ischemic forearm hyperhaemia and to nitroglycerin administration, respectively. Coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to intravenous adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery. RESULTS: Together with improvement of anthropometric and metabolic profile, at long-term follow-up patients showed a significant improvement of FMD (6.43±2.88 vs. 8.21±1.73%, p=0.018), and CBF response to both adenosine (1.73±0.48 vs. 2.58±0.54; p<0.01) and CPT (1.43±0.30 vs. 2.23±0.48; p<0.01), compared to basal values. No differences in vascular end-points were shown at 3-month and 4-year follow-up after BS. CONCLUSIONS: Our data show that, in morbidly obese patients, BS exerts beneficial and long lasting effects on peripheral endothelial function and on coronary microvascular dilator function.
Assuntos
Cirurgia Bariátrica , Vasos Coronários , Endotélio Vascular , Microvasos , Obesidade Mórbida/cirurgia , Adulto , Artéria Braquial , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Vasos Coronários/fisiologia , Vasos Coronários/fisiopatologia , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Microvasos/fisiologia , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Fatores de Tempo , Adulto JovemRESUMO
Heart rate variability (HRV) and systemic markers of inflammation have prognostic value in patients with unstable angina pectoris (UAP). However, it is unknown whether any relation exists between HRV parameters and indexes of inflammation in this clinical context. We assessed HRV on 24-hour electrocardiographic Holter recordings, performed within 24 hours of admission, and measured C-reactive protein (CRP) serum levels by a high-sensitivity assay on admission, in 531 patients with UAP (65+/-10 years of age; 347 men) who were enrolled in the prospective multicenter study Stratificazione Prognostica dell'Angina Instabile (SPAI). A significant inverse correlation was found between CRP levels and all HRV parameters, with the highest r coefficient shown with SD of all RR intervals (r= -0.23; p<0.001) in the time domain and with very low-frequency amplitude (r= -0.22; p<0.001) in the frequency domain. When patients were categorized into 4 groups according to CRP quartile levels, statistically significant lower HRV values were observed in the upper CRP quartile. On separate multiple regression analyses, including the most important clinical and laboratory variables, SD of all RR intervals and very low-frequency amplitude were the most significant predictors of increasing CRP levels (p<0.001 for the 2 comparisons). In contrast, in models with SD of all RR intervals and very low-frequency amplitude as dependent variables, CRP was a strong predictor of impaired cardiac autonomic function (p<0.001 for the 2 comparisons). Thus, our data show that, in patients with UAP, high levels of serum CRP levels are significantly associated with decreased HRV, suggesting a possible pathophysiologic link between cardiac autonomic dysfunction and inflammatory activity.
Assuntos
Angina Instável/sangue , Angina Instável/fisiopatologia , Proteína C-Reativa/metabolismo , Frequência Cardíaca , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Troponina I/sangueRESUMO
BACKGROUND: Several patients with successful percutaneous coronary interventions (PCIs) show evidence of coronary microvascular dysfunction (CMVD), which can be responsible for persistent positivity of electrocardiographic exercise stress test (EST). In this study, we assessed whether post-PCI CMVD may predict clinical outcome in patients undergoing successful elective PCI of an isolated stenosis of the left anterior descending (LAD) coronary artery. METHODS: We studied 29 patients (age 64±6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the LAD coronary artery who underwent successful PCI with stent implantation. Coronary blood flow (CBF) velocity response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography 24h and 3months after PCI. The primary end-point was a combination of death, admission for acute coronary syndromes (ACS) or target vessel revascularization (TVR). RESULTS: No death or ACS occurred during 36months of follow-up, but TVR was performed in 5 patients (17.2%). CBF response to CPT at 3months after PCI was 1.31±0.2 vs. 1.71±0.4 in patients with or without TVR, respectively (p=0.03), whereas CBF response to adenosine at 3months in these two groups was 1.70±0.3 vs. 2.05±0.4 (p=0.059). CONCLUSIONS: Our data suggest that, in patients with successful PCI of LAD coronary artery stenosis, lower CBF response to the endothelium-dependent vasodilator stimulus CPT is associated with long-term recurrence of restenosis.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Microvasos/fisiopatologia , Intervenção Coronária Percutânea/tendências , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária/fisiologia , Reestenose Coronária/diagnóstico por imagem , Vasos Coronários/cirurgia , Ecocardiografia/tendências , Teste de Esforço/métodos , Feminino , Seguimentos , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Platelet reactivity is increased by exercise in patients with obstructive coronary artery disease (CAD) but not in patients with syndrome X. In this study, we prospectively investigated whether the platelet response to exercise might help distinguish, among patients with angina, those with obstructive CAD from those with normal coronary arteries (NCAs). METHODS AND RESULTS: Venous blood samples were collected before and 5 minutes after exercise from 194 consecutive patients with stable angina. Platelet reactivity was measured by the platelet function analyzer (PFA)-100 system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time). Coronary angiography showed CAD in 163 patients (84%) and NCA in 31 patients (16%). Baseline closure time was shorter in NCA patients (78.0+/-16 versus 95.5+/-23 seconds, P<0.0001). With exercise, closure time decreased in CAD patients (-15.5 seconds; 95% confidence limits [CL], -13.0 to -18.0 seconds; P<0.0001), but increased in NCA patients (12.5 seconds; 95% CL, 7.4 to 17.7 seconds; P=0.0004). An increase in closure time with exercise > or =10 seconds had 100% specificity and positive predictive value for NCAs. Similarly, a decrease > or =10 seconds had 100% specificity and positive predictive value for CAD. A closure time change (increase or decrease) > or =10 seconds allowed a correct classification of 55% of all patients. CONCLUSIONS: Among patients with stable angina, the response of platelet reactivity to exercise was predictive of normal or stenosed coronary arteries at angiography. Specifically, an increase in closure time with exercise > or =10 seconds was invariably associated with the presence of NCA.
Assuntos
Angina Pectoris/diagnóstico por imagem , Angina Pectoris/diagnóstico , Angiografia Coronária , Teste de Esforço , Ativação Plaquetária , Estenose Coronária/diagnóstico , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SíndromeRESUMO
In this study we assessed whether serum endothelin-1 levels were associated with indexes of disease severity in unstable angina, including troponin I, C-reactive protein, and transient myocardial ischemia. Endothelin-1 levels were higher in patients who had transient myocardial ischemia and in those who had 3-vessel disease on angiography but were not significantly correlated with levels of C-reactive protein and troponin I.
Assuntos
Angina Instável/sangue , Endotelina-1/sangue , Isquemia Miocárdica/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Troponina/sangueRESUMO
INTRODUCTION: Previous studies showed differences in platelet reactivity in response to exercise in patients with syndrome X (SX) and those with obstructive coronary artery disease (CAD). In this study, we investigated whether similar differences could be detectable in response to a mental stressful stimulus. MATERIALS AND METHODS: We studied 30 SX patients (60+/-8 years, 8 men), 20 patients with stable angina and angiographically documented CAD (SA, 66+/-8 years, 14 men), and 11 patients with unstable angina (UA, 67+/-8 years, 6 men). A control group of 22 healthy controls (50+/-7 years, 5 men) was also studied. All subjects underwent a mathematical mental stress test (MST) consisting of rapid consecutive subtractions of number 7 for a period of 5 min. A venous blood sample was collected at baseline and immediately after MST. Platelet reactivity was measured on flowing blood as time necessary to occlude a ring coated with collagen-adenosine diphosphate (ADP; closure time, CT), using the platelet function analyzer (PFA-100) system. RESULTS: At rest, CT was lower in UA patients (87+/-19 s) compared to controls (109+/-24 s, p=0.02) and SA patients (105+/-37 s, p=0.055), and also tended to be lower in SX patients (96+/-18 s) compared to controls (p=0.07). The CT response to MST differed significantly among groups (p=0.0009). At peak MST, CT did not change in controls (110+/-27 s, p=0.88), whereas it decreased in SA patients (96+/-29 s, p=0.003) and tended to decrease in UA patients (82+/-15 s, p=0.25). In contrast, a significant increase in CT with MST was shown in SX patients (103+/-21 s, p=0.007). CONCLUSIONS: Platelet reactivity is increased by MST in patients with CAD, whereas it paradoxically decreases in SX patients, which may constitute a protective effect against stress-induced events in these patients.
Assuntos
Doença da Artéria Coronariana/psicologia , Angina Microvascular/psicologia , Ativação Plaquetária , Estresse Psicológico/sangue , Idoso , Angina Pectoris/sangue , Angina Pectoris/psicologia , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Masculino , Angina Microvascular/sangue , Pessoa de Meia-Idade , Testes de Função PlaquetáriaRESUMO
An enhanced activity of Na(+)/Li(+) countertransport, studied as a surrogate of Na(+)/H(+) exchanger, has been described in red blood cells of patients with cardiac syndrome X. In this study we investigated whether abnormalities in the activity of platelet Na(+)/H(+) exchanger (NHE) also existed in syndrome X patients and whether such abnormality was associated with platelet activation. Platelet NHE activity was evaluated in 21 syndrome X patients and 18 controls by measuring the pH recovery in platelets after acid loading and/or thrombin stimulation. The linear correlation existing between the initial intracytoplasmic pH (pH(i)) values and the maximal velocity of pH recovery allowed to calculate the values of slope and intercept at pH(i)=6.6 (I(pH6.6)) for each individual. Urinary excretion of the major TXB(2) metabolite, 11-dehydro-TXB(2) was measured in 15 syndrome X patients and 15 controls. The acidification-induced NHE activity resulted significantly higher in syndrome X patients compared to controls. Indeed, slope values were 0.75+/-0.29 and 0.5+/-0.23 min(-1) in patients and controls, respectively (P=0.01), while I(pH6.6) values were 0.24+/-0.1 and 0.17+/-0.1 DeltapH/min (P=0.04). The thrombin-stimulated NHE activity, however, was not different in the two groups and no significant difference in the urinary excretion of 11-dehydro-TXB(2) between patients and controls (median 920 vs. 765 pg/mg creatinine, respectively) (P=0.32) was also found. Thus our data demonstrate an alkaline shift in pH-dependence of platelet NHE of syndrome X patients. This abnormality does not seem to be associated with increased platelet activation.
Assuntos
Angina Microvascular/fisiopatologia , Ativação Plaquetária/fisiologia , Trocadores de Sódio-Hidrogênio/fisiologia , Tromboxano B2/análogos & derivados , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Trombina/fisiologia , Tromboxano B2/urinaRESUMO
BACKGROUND: Several studies showed that thrombolysis reduces ventricular arrhythmias and improves heart rate variability (HRV) in patients with acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI) has recently become the treatment of choice for AMI, but it is still unknown whether it has favorable effects on these prognostic variables. METHODS: We studied a group of 44 consecutive AMI patients (39 males, 5 females, mean age 59 +/- 9 years) submitted to primary PCI and 93 consecutive AMI patients (80 males, 13 females, mean age 61.0 +/- 11 years) treated with thrombolytic therapy within 6 hours of symptom onset. All patients underwent 24-hour Holter recording before discharge. RESULTS: The number of premature ventricular beats and the prevalence of non-sustained ventricular tachycardia in the 24 hours were lower in the PCI group (162 +/- 474 and 9%, respectively) than in the thrombolysed group (334 +/- 1730 and 14%, respectively), but the difference did not achieve statistical significance (p = 0.62 and p = 0.58, respectively). There were also no significant differences in HRV variables between the two groups, although a lower proportion of PCI patients tended to have bottom quartile values of HRV variables. The favorable trend for arrhythmias and HRV in PCI patients, however, seemed to be related to a worse basal clinical profile of thrombolysed patients, including a higher prevalence of previous AMI (14 vs 2%, p = 0.065), diabetes (27 vs 18%, p = 0.14) and, in particular, a lower use of beta-blockers (35 vs 93%, p < 0.001). CONCLUSIONS: In this study, we failed to show any significant benefit of primary PCI compared to thrombolysis on ventricular arrhythmias and HRV in patients with ST-segment elevation AMI. The clinical implications of these findings deserve investigation in future studies.