RESUMO
BACKGROUND: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data. METHODS AND RESULTS: Patients (n=294) were divided into three groups: those receiving only the assigned therapy (RFA and AAD groups) and those receiving both therapies (crossover group). The primary end points were AF burden in 7-day Holter recordings at 3, 6, 12, 18, and 24 months and cumulative AF burden in all recordings. At 24 months, AF burden was significantly lower in the RFA (n=110) than in the AAD (n=92) and the crossover (n=84) groups (90th percentile 1% vs. 10% vs. 16%, P=0.007), and more patients were free from any AF (89% vs. 73% vs. 74%, P=0.006). In the RFA, AAD and the crossover groups 63%, 59% and 21% (P<0.001) of the patients had no AF episodes in any Holter recording, respectively. Quality of life improved significantly in all groups. There were no differences in serious adverse events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P=0.10). CONCLUSIONS: In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s).
Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Idoso , Fibrilação Atrial/diagnóstico , Ablação por Cateter/normas , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large number of various mutations in the genes encoding sarcomeric proteins. However, two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in eastern Finland. OBJECTIVE: To assess the prevalence of these founder mutations in a large population of patients with HCM from all over Finland. Patients and methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in 306 unrelated Finnish patients with HCM from the regions covering a population of â¼4,000,000. RESULTS: The TPM1-D175N mutation was found in 20 patients (6.5%) and the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations showed regional clustering. TPM1-D175N was prevalent in central and western Finland, and MYBPC3-Q1061X in central and eastern Finland. CONCLUSION: The TPM1-D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases in the Finnish population, indicating that routine genetic screening of these mutations is warranted in Finnish patients with HCM.
Assuntos
Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Tropomiosina/genética , População Branca/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Finlândia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto JovemRESUMO
OBJECTIVE: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA) showed that an amlodipine-based regimen prevented more cardiovascular events than an atenolol-based regimen in patients at high risk of hypertension.The basis of this difference is partly unknown and may be due to their divergent effects on the remodelling process of hypertensive heart disease. METHODS AND RESULTS: We measured plasma levels of aminoterminal propeptide of atrial natriuretic peptide (NT-proANP) and aminoterminal propeptide of B-type natriuretic peptide and serum levels of the aminoterminal propeptide of type I procollagen (PINP), aminoterminal propeptide of type III procollagen and type I collagen telopeptide in 93 patients randomized in the ASCOT study at baseline and after two and four years and compared them with echocardiographic parameters and blood pressure. NT-proANP decreased at two years by 22 (-484 - 153) pmol/l in the amlodipine-based regimen and increased by 109 (-297 - 1545) pmol/l in the atenolol-based regimen (P < 0.001), whereas no significant difference in NT-proBNP between the arms was found. PINP levels increased by 1.8 (-29 -31) microg/l in the amlodipine-based regimen and decreased by 4.7 (-27- 31) microg/I in the atenolol-based regimen, whereas no differences were found in other collagen markers between the arms. Major echocardiographic changes were not found. CONCLUSIONS: Our results show that the two treatment regimens of ASCOT-BPLA had different effects on plasma natriuretic peptides and serological markers of collagen turnover, probably reflecting divergent effects in cardiac remodelling.
Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Colágeno/metabolismo , Hipertensão/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Fator Natriurético Atrial/efeitos dos fármacos , Colágeno Tipo I , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/efeitos dos fármacos , Peptídeos , Pró-Colágeno/sangue , Pró-Colágeno/efeitos dos fármacos , Remodelação Ventricular/fisiologiaRESUMO
AIMS: Current guidelines recommend discontinuation of oral anticoagulation treatment (OAT) and switch to heparin 2-5 days before catheter ablation of atrial fibrillation (AF). However, increasing evidence leans against the 'bridge therapy' and support continuation of OAT during the procedure. METHODS AND RESULTS: We evaluated the safety of AF ablation among patients with therapeutic OAT. The study population comprised 193 consecutive patients who underwent 228 AF ablation procedures guided by electroanatomical mapping. Periprocedural international normalized ratio was <2 (1.6 ± 0.3) in 103 cases (Group 1) and ≥2 (2.4 ± 0.4) in 125 cases (Group 2). Heparin (5000 IU bolus followed by continuous infusion through an open-irrigated ablation catheter) was used in both groups. No intracardiac echocardiographic guidance was used and activated clotting time (ACT) was not monitored. The incidence of major (intracranial bleeding, tamponade, bleeding that required surgical intervention, or blood transfusion) and minor bleeding complications and all thrombo-embolic events were registered during the 3-month follow-up. There was no statistical difference in major (P = 1.0) and minor complications (P = 0.74) between the groups. The bleeding complications included one surgically corrected groin haematoma in both groups (0.9%), 25 small haematomas at the puncture site (11 in Group 1 (10.7%) and 14 in Group 2 (11.2%), P = 0.90), and two minor pericardial effusions in Group 1. In Group 2, one patient had ischaemic stroke 16 days after the procedure. CONCLUSION: Transseptal puncture and AF ablation can be performed safely in patients with ongoing OAT without intracardiac echocardiographic guidance and ACT monitoring.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Complicações Pós-Operatórias/prevenção & controle , Trombose/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Anticoagulantes/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/induzido quimicamente , Resultado do Tratamento , Varfarina/efeitos adversosRESUMO
Kawasaki disease (KD) is an acute vasculitis involving all blood vessels with frequent cardiovascular complications. We describe a 28-year-old patient with childhood KD having coronary complications at the age of 17 now presenting with sustained atrial tachycardia. Electrophysiological study and catheter ablation were performed. Electrophysiological study revealed a left atrial (LA) tachycardia (230 ms cycle length) with 2:1 atrioventricular node conduction. The mechanism for the arrhythmia was re-entry around the mitral annulus associated with the low-voltage scar area anterolateral to the annulus and juxtaproximal to the coronary artery calcification seen in fluoroscopy. We describe a patient with childhood KD presenting with LA re-entrant tachycardia associated with the atrial scar. The arrhythmia was successfully treated using radiofrequency catheter ablation.
Assuntos
Calcinose/etiologia , Aneurisma Coronário/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Taquicardia por Reentrada no Nó Atrioventricular/etiologia , Adulto , Nó Atrioventricular/fisiopatologia , Nó Atrioventricular/cirurgia , Calcinose/fisiopatologia , Ablação por Cateter , Aneurisma Coronário/fisiopatologia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Eletrocardiografia , Átrios do Coração/fisiopatologia , Humanos , Masculino , Infarto do Miocárdio/cirurgia , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Resultado do TratamentoRESUMO
AIMS: To assess the association of electrocardiographic repolarization and depolarization patterns to vulnerability to ventricular tachyarrhythmias. METHODS: In the present case-control study, a 12-lead ECG, signal-averaged ECG (SAECG), T-wave and QRS morphology, and T-wave alternans (TWA) were analyzed in post-MI patients with and without documented sustained ventricular tachycardia (VT) or fibrillation (VF) (VT/VF group, n=40, Non-VT/VF group, n=37, respectively) and healthy subjects (n=41). RESULTS: The QRS complex duration, measured from standard ECG (128 +/- 32 ms vs. 102 +/- 21 ms, p<0.001) or SAECG (125 +/- 25 ms vs. 99 +/- 20 ms, p<0.001), was significantly longer in the VT/VF than Non-VT/VF group. Several T-wave morphology variables, e.g., the total cosine of the angle between the main vectors of T-wave and QRS loops (TCRT), were different in the VT/VF (-0.13 +/- 0.58) and Non-VT/VF group (-0.11 +/- 0.48) compared to the healthy controls (0.47 +/- 0.50, p<0.001). However, there were no significant differences in any of the T-wave morphology variables including TWA between the two post-MI groups. CONCLUSION: Abnormalities in ventricular depolarization are more common among post-MI patients with prior VT/VF than in those without documented ventricular tachyarrhythmias. Abnormal T-wave morphology and TWA seem to reflect the heart disease rather than specifically vulnerability to VT/VF.
Assuntos
Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Infarto do Miocárdio/complicações , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/etiologia , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Finlândia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Fibrilação Ventricular/fisiopatologiaRESUMO
The launch of Internet-based remote monitoring is an important milestone in the management of patients with cardiac rhythm management (CRM) devices. A remote monitoring system consists of a portable patient monitor, a central database in a secure server, and a password-protected website, where clinicians can view and analyse patient's device data. The latest CRM devices support automatic wireless data transmission from the device to the patient monitor, making the system even more user-friendly. In Finland the longest experience with remote monitoring of cardiac rhythm management devices is in the Oulu University Hospital. According to our experience remote monitoring provides a tremendous convenience for patients and clinicians and reduces the cost of follow-up.
Assuntos
Arritmias Cardíacas/prevenção & controle , Desfibriladores Implantáveis , Internet , Monitorização Ambulatorial/instrumentação , Telemetria/instrumentação , Finlândia , HumanosRESUMO
AIMS: The purpose of this prospective study was to investigate whether internet-based remote monitoring offers a safe, practical, and cost-effective alternative to the in-office follow-up visits of patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Forty-one patients (62 +/- 10 years, range 41-76, 83% male) with previously implanted ICD were followed for 9 months. One-hundred and nineteen scheduled and 18 unscheduled data transmissions were performed. There were no device-related adverse events. Over 90% of the patients found the system easy to use. Physicians reported the system as being 'very easy' or 'easy' to use and found the data comparable to traditional device interrogation in 99% of the cases. They were able to address all unscheduled data transmissions remotely. Compared with the in-office visits, remote monitoring required less time from patients (6.9 +/- 5.0 vs. 182 +/- 148 min, P < 0.001) and physicians (8.4 +/- 4.5 vs. 25.8 +/- 17.0 min, P < 0.001) to complete the follow-up. Substitution of two routine in-office visits during the study by remote monitoring reduced the overall cost of routine ICD follow-up by 524 euro per patient (41%). CONCLUSION: Remote monitoring offers a safe, feasible, time-saving, and cost-effective solution to ICD follow-up.
Assuntos
Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/economia , Desfibriladores Implantáveis/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Consulta Remota/economia , Consulta Remota/estatística & dados numéricos , Adulto , Idoso , Análise Custo-Benefício/economia , Morte Súbita Cardíaca/epidemiologia , Feminino , Humanos , Internet/economia , Internet/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Carga de Trabalho/estatística & dados numéricosRESUMO
BACKGROUND: Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide produced in the heart, but controversy persists regarding its cardiac effects. We explored the potential role of AM on cardiac function and remodeling by direct recombinant adenoviral AM gene delivery into the anterior wall of the left ventricle (LV). METHODS: AM was overexpressed in healthy rat hearts and in hearts during the remodeling process in response to pressure overload and myocardial infarction. The AM effects were analysed with echocardiography and in an isolated perfused rat heart preparation. The expression of AM and the activation of underlying signaling pathways were also investigated. RESULTS: AM mRNA increased by 20.9-fold (p < 0.001) in healthy rat heart and improved fractional shortening by 14% (p < 0.05) and ejection fraction by 8% (p < 0.05). In isolated perfused hearts, an increase (p < 0.05) in the first derivative of isovolumic LV pressure rise (dP/dt(max)) without alteration in diastolic properties was noted. The overexpression of AM activated protein kinase Cepsilon and Cdelta isoforms in the LV, whereas p38 mitogen-activated protein kinase activity decreased. Angiotensin II-induced LV hypertrophy was significantly attenuated by AM (p < 0.01) without compromising cardiac contractility. By contrast, AM enhanced LV dilatation (p < 0.01) and anterior wall thinning (p < 0.001) and augmented the deterioration of LV function (p < 0.05) post-infarction. CONCLUSIONS: The results obtained in the present study show that AM overexpression improves LV systolic function without altering cardiac diastolic properties in the normal heart. Moreover, AM is a potent context-dependent modulator of LV remodeling because it promotes an adaptive response in pressure overload-induced LV hypertrophy and triggers a maladaptive process in post-infarction remodeling.
Assuntos
Adrenomedulina/metabolismo , Técnicas de Transferência de Genes , Coração/fisiopatologia , Miocárdio/metabolismo , Adenoviridae/efeitos dos fármacos , Adrenomedulina/farmacologia , Animais , Coração/efeitos dos fármacos , Coração/fisiologia , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Infarto do Miocárdio/fisiopatologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Sístole/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
AIMS: Sarcoidosis is a multisystem, granulomatous disease with occasional cardiac manifestations. The clinical course of patients with ventricular tachyarrhythmias as a primary presentation of sarcoidosis is mostly unknown. METHODS AND RESULTS: We describe nine patients (four males and five females) in whom sarcoidosis manifested as ventricular tachycardia (VT). The age of the patients was 53 +/- 10 years (range 33-68). The disease was diagnosed by endomyocardial biopsy in eight patients and by lymph node biopsy in one patient. The presenting arrhythmia varied from non-sustained VT to incessant VT and ventricular fibrillation. All patients received implantable cardioverter defibrillator (ICD) and anti-arrhythmic medication. High-dose steroid treatment was used in eight cases. During the follow-up (50 +/- 34 months), five patients underwent appropriate ICD therapies and non-sustained VT episodes were detected in four patients. Two patients developed incessant VT, which was treated by catheter ablation. One patient was referred for heart transplantation. CONCLUSION: Our data indicate that sarcoidosis can manifest as VT without any detectable systemic findings. This makes sarcoidosis an important diagnostic consideration in patients with VT of unknown origin. Arrhythmia control in cardiac sarcoidosis is difficult, and all modern treatments including high-dose steroids, anti-arrhythmic drugs, ICD, and catheter ablation are needed to suppress the arrhythmias.
Assuntos
Eletrocardiografia , Sarcoidose/complicações , Sarcoidose/diagnóstico , Taquicardia Ventricular/complicações , Taquicardia Ventricular/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms. METHODS AND RESULTS: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum. CONCLUSION: These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.
Assuntos
Fibrose Endomiocárdica/diagnóstico , Fibrose Endomiocárdica/genética , Lamina Tipo A/genética , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/genética , Adolescente , Adulto , Família , Feminino , Finlândia , Predisposição Genética para Doença/genética , Heterozigoto , Humanos , Lipopolissacarídeos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Aortic valve lesions are often found in patients with rheumatic diseases, but their clinical significance has not been properly evaluated. In the present study, the echocardiographic files of the cardiology unit of the Oulu University Hospital were screened for a diagnosis of aortic insufficiency (AI). The aetiology of the valve disease and specific details of the rheumatic disease were evaluated in 160 patients. Twenty-eight patients (18%) had a history of rheumatic fever. Rheumatic disease was found in 14 patients (8.8%) with AI, which is significantly more than the prevalence of rheumatic diseases (1.8%) in the corresponding age group (35-100 years) in Finland. Rheumatoid arthritis or juvenile rheumatoid arthritis was found in seven patients (4.4%), whereas ankylosing spondylitis or seronegative spondylarthropathy were found in four patients (2.5%). Other rheumatic diseases included Takayasu's arteritis (two patients) and scleroderma (one patient). When 38 patients with pure AI without other possible aetiology were analysed, rheumatic disease was found in five patients (13%). Patients with rheumatic disease as a potential aetiology of AI often had symptomatic valve disease, which required surgical treatment, although great differences between different aetiologies were not found.
Assuntos
Insuficiência da Valva Aórtica/etiologia , Doenças Reumáticas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/fisiopatologia , Doença Crônica , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/fisiopatologiaRESUMO
BACKGROUND: Several studies reported excellent long-term results after mitral valve repair for regurgitation, however a number of patients still experience recurrent mitral valve regurgitation which requires reoperation. We have evaluated the long-term outcome of a consecutive series of patients who underwent mitral valve repair for regurgitation in an attempt to identify the risk factors associated with late failures. PATIENTS AND METHODS: One-hundred and sixty-four patients underwent mitral valve repair for ischemic and degenerative mitral valve regurgitation. Seventy-two patients underwent echocardiographic evaluation a median of 5.6 years after surgery. RESULTS: Ten-year survival freedom from any fatal cardiac event was 75.9% and survival freedom from redo mitral valve surgery was 93.8%. Multivariable analysis showed that residual mitral valve regurgitation grade>1 as assessed during the immediate postoperative period (at 10-year, 60.6% vs. 95.7%, p=0.001, RR 20.7, 95%C.I. 3.4-125.3) and chronic obstructive pulmonary disease/asthma (at 10-year 66.8% vs. 95.2%, p=0.013, RR 12.0, 95%C.I. 1.7-85.2) were predictors of redo mitral valve surgery. The same findings were observed also among patients with myxomatous degenerative disease. At echocardiographic follow-up, no significant improvement was detected in terms of left ventricular ejection fraction, whilst mitral valve regurgitation grade (median, 3 to 1), New York Heart Association class (median, 2 to 1) and left atrium diameter (median, 50 to 44 mm) decreased significantly. CONCLUSIONS: This study confirms the excellent clinical long-term results after mitral valve repair. An adequate repair technique is advocated in order to decrease the immediate postoperative rate of residual regurgitation>1 as this is a main determinant of late failures requiring redo mitral valve surgery. Further studies are required to better define the possible causative role of chronic obstructive pulmonary disease and any underlying connective tissue metabolic disorder in late failures after mitral valve repair.
Assuntos
Insuficiência da Valva Mitral/cirurgia , Idoso , Intervalo Livre de Doença , Ecocardiografia , Feminino , Finlândia , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/epidemiologia , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Valor Preditivo dos Testes , Reoperação , Fatores de Risco , Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Hypertension is associated with changes in concentrations of vasoactive peptides and procollagen propeptides, but their relationships with left ventricular hypertrophy and cardiac function are unclear. METHODS: We measured plasma levels of atrial natriuretic peptide (ANP), its amino terminal propeptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-1 (ET-1), and serum levels of the aminoterminal propeptide of type I procollagen (PINP) and the aminoterminal propeptide of type III procollagen (PIIINP) and echocardiographic parameters in 97 patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial. RESULTS: Median values (reference values) of the peptides were: ANP 11.2 (6.9-14.9) pmol/l, NT-proANP 351 (143-311) pmol/l, BNP 1.1 (0.4-7.2) pmol/l, ET-1 8.7 (1.2-5.0) pmol/l, PIIINP 2.8 (1.7-4.2) microg/l and PINP 29 (19-84) microg/l. Plasma BNP levels in patients with left ventricular hypertrophy (1.2 pmol/l) and patients with echocardiographic signs of diastolic dysfunction (1.5 pmol/l) were greater than those in patients without hypertrophy (0.7 pmol/l) and normal diastolic parameters (0.9 pmol/l) (p<0.05). BNP was the only biochemical parameter that independently predicted interventricular septal diastolic diameter (p<0.05), left ventricular mass index (p<0.01) and ratio of the velocity-time integrals of the E and A waves of the mitral inflow in a stepwise logistic regression analysis (p<0.05). CONCLUSIONS: The results show that BNP reflects the remodelling process in hypertension.
Assuntos
Hipertensão/sangue , Hipertrofia Ventricular Esquerda/sangue , Peptídeo Natriurético Encefálico/sangue , Disfunção Ventricular Esquerda/sangue , Adulto , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Diástole/fisiologia , Endotelina-1/sangue , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Precursores de Proteínas/sangue , Ultrassonografia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH(2)-terminal proANP (r = 0.45, P < 0.001), BNP (r = 0.55, P < 0.001) and NH(2)-terminal proBNP (r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% (P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% (P < 0.001). ICTP levels correlated with NH(2)-terminal proBNP (r = 0.25, P < 0.05) and BNP (r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.
Assuntos
Fator Natriurético Atrial/sangue , Colágeno/sangue , Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/sangue , Biomarcadores/sangue , Cicatriz/etiologia , Colágeno Tipo I , Ecocardiografia , Eletrocardiografia , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Fragmentos de Peptídeos/sangue , Peptídeos , Pró-Colágeno/sangue , Radiografia Torácica , Fatores de Tempo , Disfunção Ventricular Esquerda/sangue , Remodelação VentricularRESUMO
BACKGROUND: Coronary patency is important for short- and long-term outcome after myocardial infarction. Serum myoglobin concentration is a sensitive marker of myocardial damage and its specificity can be improved by simultaneous measurement of carbonic anhydrase III, a skeletal muscle marker. In the present study we evaluated the role of myoglobin/carbonic anhydrase III ratio as a non-invasive marker of reperfusion. METHODS: We measured myoglobin, carbonic anhydrase III and creatine kinase MB-fraction release serially in 29 patients with acute myocardial infarction treated with thrombolysis and in 28 patients treated with primary coronary angioplasty. RESULTS: Thrombolytic therapy was followed by a 9.1+/-2.2-fold increase in myoglobin and 10.8+/-3.3-fold increase in creatine kinase MB-fraction during the first hour of treatment, while carbonic anhydrase III remained unchanged. The peak value of myoglobin/carbonic anhydrase III ratio was found at 2 h and that of creatine kinase MB-fraction at 8 h after thrombolysis. Knowledge of the reperfusion time point during primary angioplasty and follow-up of cardiac markers revealed that cut-off points of 3 and 10 h for the peak values of myoglobin/carbonic anhydrase III ratio and creatine kinase MB-fraction can be used as indicators for reperfusion, respectively. Myoglobin/carbonic anhydrase III ratio measured before treatment and at 2 and 4 h after the onset of treatment screened 23 of those 25 patients with probable reperfusion after thrombolysis. CONCLUSIONS: We conclude that measuring myoglobin/carbonic anhydrase III ratio during the first hours after initiation of thrombolysis may be useful in evaluating the success of reperfusion after acute myocardial infarction.
Assuntos
Anidrase Carbônica III/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Mioglobina/sangue , Ativador de Plasminogênio Tecidual/uso terapêutico , Angioplastia Coronária com Balão , Biomarcadores/sangue , Anidrase Carbônica III/efeitos dos fármacos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/terapia , Creatina Quinase/sangue , Creatina Quinase/efeitos dos fármacos , Creatina Quinase Forma MB , Serviço Hospitalar de Emergência , Feminino , Fibrinolíticos/uso terapêutico , Finlândia , Seguimentos , Humanos , Isoenzimas/sangue , Isoenzimas/efeitos dos fármacos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mioglobina/efeitos dos fármacos , Admissão do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Valor Preditivo dos Testes , Reoperação , Estreptoquinase/uso terapêutico , Terapia Trombolítica , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels increase after acute myocardial infarction (AMI) in humans. Experimental data suggest that these cytokines regulate the initiation of scar formation after AMI. We investigated the interrelationships of IL-6 and TNF-alpha, tissue injury, infarct size, cardiac function, and collagen formation in humans. METHODS: Serum and plasma samples were taken on 93 patients receiving thrombolytic treatment for their first AMI. Collagen formation was evaluated by measuring concentrations of serum aminoterminal propeptide of type III procollagen (PIIINP). RESULTS: IL-6 levels increased by 44% (P<.001) and peaked at 24 hours. Peak IL-6 levels correlated positively with area under the curve of creatine kinase MB mass (r=.31, P<.01), peak troponin T level (r=.34, P<.005), and PIIINP measured at discharge (r=.46, P<.001). There were no changes in TNF-alpha levels, and patients with left ventricular dysfunction (EF<40%) had similar TNF-alpha levels as those with preserved left ventricular function. CONCLUSIONS: IL-6 may regulate collagen formation and thus remodeling of the left ventricle after AMI. In addition, TNF-alpha measurement is useless in the assessment of infarct size or left ventricular function during the immediate post-infarction period.
Assuntos
Colágeno/sangue , Interleucina-6/sangue , Infarto do Miocárdio/sangue , Fator de Necrose Tumoral alfa/metabolismo , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Área Sob a Curva , Arritmias Cardíacas/sangue , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Colágeno/efeitos dos fármacos , Creatina Quinase/efeitos dos fármacos , Creatina Quinase/metabolismo , Creatina Quinase Forma MB , Eletrocardiografia , Enalapril/uso terapêutico , Feminino , Finlândia , Humanos , Isoenzimas/efeitos dos fármacos , Isoenzimas/metabolismo , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/efeitos dos fármacos , Pró-Colágeno/sangue , Pró-Colágeno/efeitos dos fármacos , Quinapril , Índice de Gravidade de Doença , Estatística como Assunto , Volume Sistólico/efeitos dos fármacos , Tetra-Hidroisoquinolinas/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Trinitrotolueno/sangue , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVE: The purpose of the study was to carry out a candidate gene analysis in families with familial thoracic aortic aneurysms and dissections. METHODS: The study material consisted of 11 Finnish families (with 115 members genotyped) who underwent echocardiographic examination for measurement of the aortic root diameter. Selected candidate genes included the loci for Marfan and Ehlers-Danlos syndromes, the genes of matrix metalloproteinases 3 and 9 and tissue inhibitor of metalloproteinase 2 as well two loci on the chromosomes 5q13-14 and 11q23.2-q24, previously found to be linked to the disease. RESULTS: The chromosomal locus 5q13-14 was linked to the disease risk (nonparametric linkage score 3.0, P =.005) confirming the previous linkage. Other candidate genes and loci were excluded as major loci in these families. CONCLUSIONS: The identification of the gene at chromosomal location 5q13-14 causing the development of such diseases would give us important knowledge on the pathogenesis of the disease and enable the identification of subjects at risk. This in turn would lead to appropriate treatment before the occurrence of fatal complications and, likely, to the development of new treatment methods.
Assuntos
Aorta/patologia , Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 5/genética , Ligação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/genética , Saúde da Família , Feminino , Finlândia , Heterogeneidade Genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
B-type natriuretic peptide (BNP) plasma concentrations are raised in patients with heart failure. In several experimental models of cardiac overload, however, BNP mRNA and plasma BNP peptide levels are normal, despite the persistent increase in blood pressure and ventricular hypertrophy. In this study, the role of transcriptional mechanisms in the regulation of BNP gene expression were studied in angiotensin (Ang) II-induced hypertension by injecting DNA constructs containing the BNP promoter (-2200 to 75 bp of the transcriptional start site) linked to luciferase reporter into rat myocardium. Ang II was administered to conscious rats via intravenous infusion for 2 hours or by subcutaneous minipumps for 6 hours, 12 hours, 3 days, 1 week, and 2 weeks. Ang II increased blood pressure and cardiac mass and induced changes in diastolic function. The left ventricular BNP mRNA levels increased 2.2-fold (P<0.001) at 2 hours and peaked at 12 hours (5.2-fold, P<0.001). Thereafter, BNP mRNA levels decreased (1.8-fold induction at 3 days, P<0.05) and returned to control levels at 1 week, despite persistent hypertension and myocardial hypertrophy. Left ventricular BNP peptide concentrations followed the changes in BNP mRNA levels. The BNP promoter was activated 2.7-fold (P<0.05) at 2 hours and remained upregulated up to 2 weeks (2.8-fold, P<0.05) during Ang II infusion, except at 12 hours. These results indicate that posttranscriptional control plays a major role in the regulation of ventricular BNP gene expression in Ang II-induced hypertension.
Assuntos
Angiotensina II/farmacologia , Fator Natriurético Atrial/genética , Hipertensão/fisiopatologia , Animais , Fator Natriurético Atrial/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ecocardiografia , Regulação da Expressão Gênica/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertensão/induzido quimicamente , Hipertensão/genética , Masculino , Peptídeo Natriurético Encefálico , Tamanho do Órgão/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Processamento Pós-Transcricional do RNA , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição AP-1/metabolismoRESUMO
Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle that may accelerate atherogenesis and promote thrombosis. In the present study, relationships between serum Lp(a) levels and the severity of coronary artery disease and infarct artery patency were studied in 14 patients with acute myocardial infarction. Lp(a) was measured by enzyme-linked immunosorbent assay and the timing of reperfusion was evaluated using the creatine kinase myosin-brain fraction and myoglobin release curves. Thrombolysis in Myocardial Infarction (TIMI) flow grade and severity of coronary artery disease were assessed using a scoring system based on coronary angiography performed during hospitalization and 6 months thereafter. The median Lp(a) level on admission was 127 (range 11-2,513) mg/l. The overall coronary score was higher in patients with Lp(a) levels greater than 127mg/l than in those with Lp(a) less than 127mg/l (P < 0.01). Lp(a) level correlated with the coronary score measured during hospitalization (r = 0.80, P < 0.01) and 6 months later (r = 0.79, P < 0.01). The timing of reperfusion and infarct artery patency were not depen dent on the serum Lp(a) level. The results show that the serum Lp(a) level is associated with the angiographic severity of coronary artery disease postmyocardial infarction bu does not determine the patency of the infarct-related artery.