RESUMO
Cardiovascular complications, including heart failure, hypertension, ischemic syndromes and venous thromboembolism, have been identified in patients treated with anti-cancer drugs. Oxidative stress, mitochondrial dysfunction and DNA synthesis inhibition are considered to be responsible for the cardiotoxicity induced by these agents. Protein quality control (PQC) has 3 major components, including the endoplasmic reticulum (ER), the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, and participates in protein folding and degradation to maintain protein homeostasis. We have demonstrated that PQC dysfunction is a new causal mechanism for the development of cardiac hypertrophy and failure. Increasing evidence shows that anti-cancer drugs, such as tyrosine kinase inhibitors, proteasome inhibitors, anthracyclines and autophagy inhibitors, cause PQC dysfunction. Here, we provide an overview of the potential role of PQC dysfunction in the development of cardiovascular complications induced by anti-cancer drugs.
Assuntos
Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Proteínas/metabolismo , Animais , Autofagia/efeitos dos fármacos , Cardiotoxicidade , Doenças Cardiovasculares/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Dobramento de Proteína , Proteólise , UbiquitinaçãoRESUMO
AIM: The 9p21 region has been pointed out by the genome-wide association studies as a hot spot for disease-associated variants. Most of the diseases linked with the locus are aging-related conditions, such us cardiovascular disease, diabetes and cancer. Centenarians are known to present a reduced risk and delayed onset for these conditions. Here, we aimed to assess if the 9p21 variants contribute to this protection by possibly altering basic aging mechanisms. METHODS: We genotyped 15 tag single-nucleotide polymorphisms (SNP) along the CDKN2A/B/ANRIL locus in 1505 individuals. The participants were divided in three groups: centenarians, septuagenarians and young controls. Centenarians were 593 participants (age range 100-116 years, mean 105.9 years), septuagenarians were 434 volunteers aged between 69 and 71 years (mean 70.1 ± 0.9 years) and the 478 young controls were under the age of 50 years (range 14-50 years, mean 41.8 years). We genotyped the SNP rs1333049 in an additional sample of 231 coronary artery disease patients to confirm the 9p21 association. RESULTS: The leading coronary artery disease-associated SNP rs1333049 was associated with coronary artery disease; however, none of the 9p21 SNP evaluated in the present study were associated with extreme longevity. CONCLUSIONS: Our findings suggest that the 9p21 disease-associated polymorphisms do not contribute to the life-long protection from cardiovascular and other age-related diseases observed in centenarians. It is likely that this protection is mediated by mechanisms different from the ones underlying the 9p21 association.
Assuntos
Cromossomos Humanos Par 9/genética , Doença da Artéria Coronariana/genética , Longevidade/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Variação Genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
UNLABELLED: Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis. OBJECTIVE: We assessed the hypothesis that 9p21 locus polymorphisms influence the expression of the transcripts in the region (ANRIL, CDKN2A/B) and that these transcripts contribute to atherogenesis through the modulation of proliferation in VSMC. METHODS: We genotyped 18 SNPs (r(2)<0.8 and MAF>0.05) across the region of interest: CDKN2A/B and ANRIL, encompassing the CVD-associated region. RNA and DNA were extracted from the blood of 57 volunteers (69-72 years old). Carotid ultrasound was performed in 56 subjects. CDKN2A/B and ANRIL (exons 1-2 and 17-18) expression was measured employing RT-PCR. Gene expression and cell growth were evaluated in cultured VSMC after the siRNA-mediated knock-down of ANRIL. RESULTS: The risk alleles for atherosclerosis-related phenotypes were consistently associated with a lower expression of ANRIL when evaluating exons 1-2. Common carotid artery stenosis was associated with a significantly lower (P<0.01) expression of ANRIL (exons 1-2). ANRIL knock-down in VSMC caused significant variation in expression of CDKN2A/B (P<0.05) and reduction of cell growth (P<0.05) in vitro. CONCLUSION: Disease-associated SNPs at the 9p21 locus predominantly affect the expression of ANRIL. Overall, our results suggest that several CVD-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation.
Assuntos
Aterosclerose/genética , Estenose das Carótidas/genética , Cromossomos Humanos Par 9 , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Polimorfismo de Nucleotídeo Único , RNA não Traduzido/genética , Idoso , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/metabolismo , Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Proliferação de Células , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Éxons , Frequência do Gene , Predisposição Genética para Doença , Humanos , Japão , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fenótipo , Interferência de RNA , RNA Longo não Codificante , RNA não Traduzido/metabolismoRESUMO
A new understanding of the genetic basis of coronary artery disease (CAD) has recently emerged from genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs), thus far performed mostly in European-descent populations. To identify novel susceptibility gene variants for CAD and confirm those previously identified mostly in populations of European descent, a multistage GWA study was performed in the Japanese. In the discovery phase, we first genotyped 806 cases and 1337 controls with 451 382 SNP markers and subsequently assessed 34 selected SNPs with direct genotyping (541 additional cases) and in silico comparison (964 healthy controls). In the replication phase, involving 3052 cases and 6335 controls, 12 SNPs were tested; CAD association was replicated and/or verified for 4 (of 12) SNPs from 3 loci: near BRAP and ALDH2 on 12q24 (P=1.6 × 10(-34)), HLA-DQB1 on 6p21 (P=4.7 × 10(-7)), and CDKN2A/B on 9p21 (P=6.1 × 10(-16)). On 12q24, we identified the strongest association signal with the strength of association substantially pronounced for a subgroup of myocardial infarction cases (P=1.4 × 10(-40)). On 6p21, an HLA allele, DQB1(*)0604, could show one of the most prominent association signals in an â¼8-Mb interval that encompasses the LTA gene, where an association with myocardial infarction had been reported in another Japanese study. CAD association was also identified at CDKN2A/B, as previously reported in different populations of European descent and Asians. Thus, three loci confirmed in the Japanese GWA study highlight the likely presence of risk alleles with two types of genetic effects - population specific and common - on susceptibility to CAD.
Assuntos
Doença da Artéria Coronariana/genética , Estudo de Associação Genômica Ampla , Adulto , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Haplótipos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos TestesRESUMO
A growing body of evidence has shown that Fas-mediated apoptosis is involved in atherosclerosis progression. Recent studies have revealed that a single nucleotide polymorphism (SNP) in the Fas promoter region (-670G/A) influences Fas expression. Here, we investigated whether -670G/A SNP influences the incidence of myocardial infarction (MI) by examining a comparison between MI patients (n=154) and control subjects (n=462) in a Japanese population. The allele frequency in each group was A 53.6%/G 46.4% in the MI patients, and A 43.9%/G 56.1% in the non-MI subjects (chi(2)=8.6; P=0.003). The odds ratio was 2.62 (95% CI: 1.43-4.88). As subjects with the -670AA genotype had a signal transducer and activator of transcription 1 (STAT1)-binding site in the Fas promoter region, STAT-1 activation by interferon-gamma may upregulate Fas expression in human vascular smooth muscle cells (VSMCs) of -670AA genotype subjects as described earlier. The Fas upregulation induces excess apoptosis to VSMCs, which leads to unstable plaque formation in atherosclerotic lesions and then potentially to plaque rupture, which can cause MI. Further investigation of hypertensive subjects revealed that the -670AA genotype does not induce hypertension occurrence, supporting that this difference of MI occurrence between the -670AA genotype and the -670GG genotype may be because of plaque rupture followed by excess apoptosis of VSMCs in the atherosclerotic lesion. We conclude that the Fas promoter gene, SNP (-670G/A), may be a risk factor of MI occurrence.
Assuntos
Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Receptor fas/genética , Idoso , Feminino , Frequência do Gene , Genótipo , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Hipertensão/genética , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Risco , Fator de Transcrição STAT1/genéticaRESUMO
Adenosine is known as an endogenous cardioprotectant. We previously reported that plasma adenosine levels increase in patients with chronic heart failure (CHF), and that a treatment that further elevates plasma adenosine levels may improve the pathophysiology of CHF. Therefore, we performed a prospective, open-randomized clinical trial to determine whether or not exposure to dipyridamole for 1 year improves CHF pathophysiology compared with conventional treatments. The study enrolled 28 patients (mean+/-SEM: 66+/-4 years of age) attending specialized CHF outpatient clinics with New York Heart Association (NYHA) class II or III, no major complications, and stable CHF status during the most recent 6 months under fixed medications. They were randomized into three groups with or without dipyridamole (Control: n=9; 75 mg/day: n=9; 300 mg/day: n=10) in addition to their original medications and were followed up for 1 year. The other drugs were not altered. Among the enrolled patients, 100%, 4%, 100%, and 79% received angiotensin-converting enzyme inhibitors, aldosterone analogue, loop diuretics, and beta-adrenoceptor blocker, respectively. Fifteen patients suffered from dilated cardiomyopathy, and 7/3/3 patients suffered from ischemic/valvular/hypertensive heart diseases, respectively. Mean blood pressure was comparable among the groups. While the baseline conditions were comparable, we found that echocardiographic ejection fraction (p<0.01 vs. baseline, p<0.01 vs. Control), left ventricular systolic diameter (p<0.05, p<0.05), Specific Activity Scale (SAS) score (p<0.05, p<0.01), maximal oxygen consumption (p<0.05, p<0.05) and plasma B-type natriuretic peptide level (p<0.01, p<0.01) were significantly improved in patients with dipyridamole after 1 year, generally in a dose-dependent manner. Therefore, we suggest that an additional administration of dipyridamole further improves CHF pathophysiology.
Assuntos
Dipiridamol/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Vasodilatadores/administração & dosagem , Idoso , Relação Dose-Resposta a Droga , Ecocardiografia , Exercício Físico , Teste de Esforço , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Although the short-term safety of statins is well established, their potential carcinogenicity in the long term is still being debated. The aim of this study was to investigate the association between statin-therapy and the incidence of cancer in coronary heart disease patients. METHODS: The subjects were 263 patients with coronary heart disease who were from Osaka prefecture and who were admitted to the Osaka Medical Center for Cancer and Cardiovascular Diseases between September 28, 1991 and March 31, 1995. The five-year cancer incidence among the subjects was checked using the database of the institution-based cancer registry of the hospital as well as the population-based Osaka Cancer Registry. The Cox's proportional hazards ratios (HRs) of all cancer incidence and observed/expected (O/E) ratios by cancer site were calculated. RESULTS: Cancer incidence was observed in 17 patients during the follow-up period. Age (HR=1.16 per one year of age) and continuous smoking during the period (HR=5.82 compared to not smoking during the period) were significantly associated with cancer incidence using multivariable analysis. After being adjusted for sex, age, total serum cholesterol level and smoking habit, the HR of cancer incidence with pravastatin use was 0.78 (95% confidence interval: 0.18-3.46). In the O/E analysis, significantly elevated risks were found for bladder cancer in all the subjects (HR=8.93), as well as in the pravastatin use patients (HR=13.76). CONCLUSIONS: Pravastatin use for 5 years did not indicate an increase in over all cancer risk.
Assuntos
Anticolesterolemiantes/efeitos adversos , Doença das Coronárias/prevenção & controle , Neoplasias/induzido quimicamente , Pravastatina/efeitos adversos , Anticolesterolemiantes/uso terapêutico , Colesterol/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Masculino , Neoplasias/epidemiologia , Pravastatina/uso terapêutico , Modelos de Riscos Proporcionais , Risco , Fumar/efeitos adversosRESUMO
Hepatocellular carcinoma (HCC) is the most common primary cancer in the liver. Liver invasion of non-Hodgkin's lymphoma (NHL) is also often observed. But simultaneous existence of HCC and NHL in a liver is extremely rare. Such patients reported previously had cirrhotic livers. Herein is reported a patient who simultaneously had HCC and NHL in a liver without cirrhosis, but with nodular regenerative hyperplasia (NRH). NHL was of the diffuse large B-cell type. Lymphoma cells invaded the portal vein, and formed thrombi. These thrombi would contribute to the development of NRH by decreasing portal vein blood flow. HCC was of the well-differentiated type and there was a 2 cm-sized nodule at the lateral segment. There is the possibility that NRH was associated with the HCC because NRH is reported as a premalignant lesion. HCC and NHL were colocalized in the liver without hepatic virus infection or cirrhosis, although common cause(s) of development of these malignancies remain unclear in the present case.
Assuntos
Carcinoma Hepatocelular/patologia , Hiperplasia Nodular Focal do Fígado/patologia , Neoplasias Hepáticas/patologia , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Primárias Múltiplas/patologia , Carcinoma Hepatocelular/terapia , Evolução Fatal , Humanos , Neoplasias Hepáticas/terapia , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/terapia , Cuidados PaliativosRESUMO
BACKGROUND: The development of an efficient noninvasive examination to detect coronary atherosclerosis is needed as a strategy to prevent coronary heart disease. To evaluate the usefulness of calcium score measured by multi-detector row computed tomography (MDCT), we compared calcium score derived from MDCT with findings of coronary artery stenosis assessed by coronary angiography (CAG). METHODS: In 108 patients (94 men, 14 women; average age, 65.7 years), we performed unenhanced CT scans and calculated coronary artery calcium score in 259 vessels without previous intervention and severe motion artifact to determine the correlation with the degree of coronary stenosis by CAG. RESULTS: The sensitivity and the specificity of calcification (calcium score 0.1+) for severe stenosis (75+%) were 89% and 43%, respectively. All four vessels with calcium score 1000+ had a severe stenosis. The areas under the receiver operating characteristics curve of calcium score for severe stenosis were 0.80 +/- 0.04, indicating the efficacy of this technique. CONCLUSIONS: Coronary artery calcification and calcium score determined by MDCT were associated with coronary arteries with severe stenosis. This technique appears to be useful for the evaluation of coronary atherosclerosis.
Assuntos
Calcinose/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Angiografia Coronária , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The pharmacoeconomics of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (pravastatin) therapy were evaluated using data from an open-labeled, randomized, controlled trial (PCS: Prevention of Coronary Sclerosis study) with a two-year follow-up period. METHODS: Patients with a serum total cholesterol concentration of between 180 and 219 mg/dL at baseline were randomly assigned to two groups: the pravastatin group (n=54) and the group that did not receive cholesterol-lowering drugs (no-pravastatin group, n=66). A cost-minimization analysis and a cost-effectiveness analysis were then performed from the perspective of a health insurance company, using insurance information obtained from the subjects. In the cost-minimization analysis, the expected costs associated with percutaneous transluminal coronary angioplasty (PTCA) and the pravastatin prescription were compared; the total medication costs between the two groups were also compared. In the cost-effectiveness analysis, the estimated savings per event-free year were calculated. RESULTS: The median cost of a PTCA procedure was 1,323,492 yen. The expected insurance cost for two years was 182,532 yen per patient in the pravastatin group and 224,444 yen per patient in the no-pravastatin group. The cost-minimization analysis showed that the cost of healthcare for the no-pravastatin group was higher than that for the pravastatin group. The mean total cost of medication was 729,849 yen per patient in the pravastatin group and 989,606 yen per patient in the no-pravastatin group. The cost-effectiveness ratio for coronary heart disease was 2,766,994 yen. CONCLUSION: Pravastatin therapy in normocholesterolemic patients with coronary sclerosis seems to have an excellent pharmacoeconomic profile.
Assuntos
Anticolesterolemiantes/farmacologia , Doença das Coronárias/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Pravastatina/farmacologia , Adulto , Idoso , Anticolesterolemiantes/economia , Doença das Coronárias/economia , Análise Custo-Benefício , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Pessoa de Meia-Idade , Pravastatina/economiaRESUMO
Efficacy of primary stenting in small coronary artery disease is still controversial. Cilostazol has been reported to control restenosis after balloon angioplasty (BA). The aim was to compare primary stenting with BA plus cilostazol administration in small coronary artery disease. Of 106 lesions located in small coronary artery (reference < 3.0 mm), 50 lesions were randomly assigned to the stenting and 56 lesions to the BA-cilostazol group. Multilink stent was implanted in the stenting group. In the BA-cilostazol group, cilostazol (200 mg/day) without aspirin was administered for 6 months after BA. Ticlopidine was given for 1 month when bailout stent was implanted. Serial quantitative angiography was performed at the procedure and 6 months. The primary endpoint was 6-month angiographic restenosis. Clinical event rates at 1 year were also assessed. Baseline characteristics were similar. All procedures were successful. Bailout stenting was performed in three lesions in the BA-cilostazol group. No side effects of cilostazol were observed. Postprocedural lumen diameter was significantly larger (2.69 vs. 2.03 mm; P < 0.0001) in the stenting group. However, the follow-up lumen diameter was not different (1.76 vs. 1.85 mm, stenting vs. BA-cilostazol). Although the difference was not statistically significant, restenosis rate was lower in the BA-cilostazol group (13.2% vs. 24.5%; P = 0.11). Subacute thrombosis occurred in one patient and target revascularization rate was higher in the stenting group (22.0% vs. 10.7%; P = 0.10). BA plus cilostazol administration seems to be a favorable strategy for small coronary artery disease.
Assuntos
Angioplastia com Balão , Doença da Artéria Coronariana/terapia , Fibrinolíticos/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Stents , Tetrazóis/administração & dosagem , Idoso , Angioplastia com Balão/efeitos adversos , Implante de Prótese Vascular , Cilostazol , Terapia Combinada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The potential benefit of cholesterol-lowering therapy for normocholesterolemic patients with coronary artery disease (CAD) has not been clarified. The Prevention of Coronary Sclerosis (PCS) Study was designed to evaluate the effect of pravastatin on secondary prevention of progression of CAD in normocholesterolemic patients for a period of 5 years. METHODS: A total of 329 patients with CAD were enrolled. Normocholesterolemic patients were defined by a serum total cholesterol (TC) level of 180-219 mg/dl. Patients in this group were randomized into pravastatin and dietary control groups. Patients whose serum TC level fell outside the normal range were divided into a high-cholesterol reference group (TC > or = 220 mg/dl) and a low-cholesterol reference group (TC < 180 mg/dl). Patients in the pravastatin and high-cholesterol groups received pravastatin 10 mg/day. Coronary angiography was performed at baseline, 2 years, and 5 years and analyzed by quantitative coronary arteriography. Angiographic coronary progression was evaluated by minimum obstruction diameter (MOD) and mean segment diameter (MSD). RESULTS: At 5 years, change in MOD was significantly (change, P=0.033; change/years, P=0.032) less in the pravastatin group (-0.04 +/- 0.17 mm) than in the dietary control group (-0.16 +/- 0.27 mm). Although a similar trend was observed in the MSD results, the differences were not significant. CONCLUSION: Long-term angiographic data show that cholesterol-lowering therapy by pravastatin prevents progression of coronary atherosclerosis in normocholesterolemic patients with CAD.
Assuntos
Doença da Artéria Coronariana/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pravastatina/uso terapêutico , Adulto , Idoso , Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de TempoRESUMO
Aggressive and optimal directional coronary atherectomy (DCA) using intravascular ultrasound (IVUS) guidance provides favorable outcomes within 1 year. However, no previous data are available on the changes that occur in target lesions for the long term after stand-alone DCA. This study's aim evaluates, using quantitative angiography and intravascular ultrasonography, the natural history of changes that occur in target lesions between short- (about 6 months) and long-term (>5 years) follow-up angiography after stand-alone DCA. Of 186 patients (221 lesions) with successful stand-alone DCA, 48 patients (53 lesions) underwent revascularization within 6 months, and 14 patients subsequently died, leaving a study population of 124 patients (154 lesions). Complete quantitative coronary angiography (QCA) was obtained in 91 patients (101 lesions) and complete serial IVUS assessment was obtained for 38 lesions before and after intervention and during follow-up. From short- to long-term follow-up angiography, the minimal luminal diameter significantly increased (from 2.12 to 2.56 mm; p <0.0001); lesion subgroups with >30% diameter stenosis at short-term follow-up angiography showed significant late regression as assessed by QCA. Serial IVUS assessment revealed that the vessel cross-sectional area did not change (from 17.3 to 17.4 mm(2); p = NS); however the lumen cross-sectional area significantly increased (from 7.3 to 9.5 mm(2); p <0.0001) due to the reduction of plaque plus media cross-sectional area (from 10.0 to 7.9 mm(2); p <0.0001). The change in lumen cross-sectional area correlated with the change in plaque plus media cross-sectional area (r = -0.686, p <0.0001). Target lesions show late regression due to plaque reduction at >5 years after stand-alone DCA.
Assuntos
Aterectomia Coronária , Angiografia Coronária , Estenose Coronária/diagnóstico , Estenose Coronária/terapia , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose Coronária/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
To evaluate the influence of preintervention remodeling on subsequent vessel behavior after directional coronary atherectomy (DCA) under intravascular ultrasound (IVUS) guidance, serial (before and after DCA and at 6-month follow-up) IVUS data were analyzed for 246 lesions that were classified into 2 categories: positive remodeling (PR) in 77 lesions versus intermediate or negative remodeling in 169 lesions. Although the 2 groups had similar baseline characteristics, IVUS data showed that the PR group had a greater acute lumen area (LA) gain without an increased late LA loss, resulting in a greater net (acute plus late) LA gain and follow-up LA. This suggests that IVUS-guided DCA may neutralize the negative impact of preintervention PR on late vessel patency.
Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Remodelação Ventricular/fisiologia , Idoso , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Percutaneous transluminal septal myocardial ablation (PTSMA) is a new therapeutic option for patients with hypertrophic obstructive cardiomyopathy (HOCM). In the present study, the acute and follow-up results of PTSMA were evaluated. From August 1997 to March 2003 27 medically refractory patients (New York Heart Association (NYHA) functional class 2.9+/-0.6) with HOCM underwent PTSMA. The target septal branch was determined by probationary ballooning in 3 and by myocardial contrast echocardiography in 24 patients. The mean resting left ventricular outflow tract pressure gradient (PG) was reduced from 70+/-44 to 24+/-22 mmHg (p<0.0001); the peak concentration of creatine kinase was 1545+/-686 IU/L. Although transient trifascicular block was observed in 14 patients, permanent pacemaker implantation was not required. There were no major adverse cardiac events during the hospital stay; the mean clinical follow-up was 2.2+/-1.7 years. Repeated PTSMA was needed in 1 patient; however, symptomatic improvement had been well preserved in all patients (NYHA class 1.2+/-0.4). Follow-up echocardiographic examination showed sustained improvement in PG, septal and left ventricular posterior wall thicknesses, and the grade of systolic anterior movement and regurgitation of the mitral valve. In conclusion, PTSMA is a safe and effective therapeutic option for medically refractory patients with HOCM.
Assuntos
Cardiomiopatia Hipertrófica/terapia , Cateterismo , Etanol/uso terapêutico , Septos Cardíacos/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia , Feminino , Seguimentos , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Retratamento , Resultado do TratamentoRESUMO
BACKGROUND: Recent intravascular ultrasound (IVUS) studies have suggested that plaque burden has a role in promoting intimal hyperplasia after stenting. We report on volumetric assessments of in-stent neointimal formation with 3-dimensional IVUS analysis, comparing directional coronary atherectomy (DCA) plus stenting (DCA/stenting) to stenting without DCA. METHODS: Twenty-four patients (24 lesions) treated with DCA before stenting were matched to 24 patients (24 lesions) receiving stenting without DCA. All stents were a single Multilink stent. In both groups, serial IVUS was performed before and after intervention and during the 6-month follow-up period. The arterial segments that were analyzed with a computer-based contour detection program were the same as the stented segments analyzed on serial studies. These measurements were obtained: (1) lumen volume (LV), (2) stent volume (SV), (3) vessel volume (VV), (4) in-stent neointimal volume (ISV) calculated as SV-LV, and (5) percent in-stent neointimal volume (%ISV) calculated as ([SV-LV]/SV) x 100. RESULTS: Baseline characteristics of the 2 groups were similar. After intervention, both groups achieved similar LV (140.0 mm(3) DCA/stenting vs 135.2 mm(3) stenting alone). However, the follow-up ISV and %ISV were significantly smaller in the DCA/stenting group (19.6 +/- 12.2 mm(3) DCA/stenting vs 44.6 +/- 29.5 mm(3) stenting alone; P =.00040; 15.3% +/- 10.6% DCA/stenting vs 31.5% +/- 17.7% stenting alone; P =.00040). Consequently, the DCA/stenting group showed a significantly greater follow-up LV (121.0 +/- 51.5 mm(3) DCA/stenting vs 91.5 +/- 26.7 mm(3) stenting alone; P =.016). CONCLUSIONS: Plaque removal with DCA before stenting inhibits in-stent neointimal hyperplasia.
Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana/terapia , Endossonografia/métodos , Imageamento Tridimensional , Stents , Túnica Íntima/patologia , Idoso , Terapia Combinada , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/prevenção & controle , Feminino , Humanos , Hiperplasia/prevenção & controle , Masculino , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) have been used to treat congestive heart failure (CHF). According to a MEDLINE search, however, few studies are available on the clinical differences between ARBs and ACEIs in CHF. OBJECTIVE: To examine the clinical differences between an ARB (candesartan cilexetil) and an ACEI (lisinopril) in the treatment of CHF, we investigated exercise capacity, ventricular function, and neurohormonal levels in hypertensive patients with CHF before and after treatment with these agents. METHODS: Patients with symptoms of CHF (New York Heart Association functional class II-III and left ventricular ejection fraction [LVEF] ≤45%) complicated by hypertension (systolic blood pressure [BP] ≥140 mm Hg or diastolic BP ≥90 mm Hg) were eligible for this single-center, open-label, randomized, parallel-group study. They were given either the ARB or the ACEI for 24 weeks. A cardiopulmonary exercise test and echocardiography were performed. Clinical findings and cardiac events in addition to the CHF symptoms were investigated. Neurohormonal levels were measured before and after 24 weeks of treatment with the study drug. The primary end point of this study was exercise capacity, which was measured using peak oxygen consumption (VO2). RESULTS: Forty-two patients with CHF were enrolled and 38 (28 men, 10 women; mean [SD] age, 69.0 [8.2] years) completed the study. None of these patients had definite progression of the CHF symptoms. In the ARB-treated patients, mean (SD) peak VO2 (mL/min/kg) and LVEF (%) increased from 14.1 (2.9) to 15.3 (3.4) and from 34.4 (9.5) to 41.8 (9.5), respectively. In the ACEI group, the peak VO2 did not change, but the LVEF (%) increased from 34.2 (10.2) to 40.4 (13.0). However, the differences between ARB and ACEI were not clarified because of the possibility of a small sample size. CONCLUSIONS: Although this study was not powered to show differences in efficacy between the ARB and ACEI in this study, our findings suggest that both ARB and ACEI had beneficial effects in hypertensive patients with CHF. Some unidentified differences in hemodynamic characteristics were found between the ARB and the ACEI groups.
RESUMO
A 56-year-old man with Tangier disease suffering from angina pectoris due to triple-vessel coronary artery disease evidenced extremely low blood high-density lipoprotein of 1 mg/dl, a specific laboratory indicator of this rare genetic disorder of lipid metabolism, considered to accompany juvenile arteriosclerosis. Because of the calcified ascending aorta, we conducted combined minimally invasive coronary artery bypass (CAB) for the left anterior descending coronary artery and percutaneous transluminal coronary angioplasty for other coronary artery lesions initially instead of conventional coronary artery bypass grafting. Angina recurred, however, due to refractory restenosis of the left circumflex coronary artery lesion. Two years later, we redid the CAB, grafting the free right internal thoracic artery from the functional left internal thoracic artery sequentially onto obtuse marginal and posterolateral coronary arteries. The patient returned to work angina-free.
Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Doença de Tangier/complicações , Angina Pectoris/cirurgia , Procedimentos Cirúrgicos Cardíacos , Reestenose Coronária/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Stenting inhibits vascular constrictive remodeling after directional coronary atherectomy (DCA). Cilostazol has been reported to control neointimal proliferation after stenting. This study's aim was to examine the effect of debulking and stenting with antirestenotic medication on restenosis. After optimal DCA, 117 lesions were randomly assigned to either the DCA with stent (DCA-stent) (58 lesions) group or the DCA only (59 lesions) group. Multilink stents were implanted in the DCA-stent group. Cilostazol (200 mg/day) without aspirin was administered to both groups for 6 months. Ticlopidine (200 mg/day) was given to the DCA-stent group for 1 month. Serial quantitative angiography and intravascular ultrasound (IVUS) were performed at the time of the procedure and at 6-month follow-up. The primary end point was 6-month angiographic restenosis. Clinical event rates at 1 year were also assessed. Baseline characteristics were similar. All procedures were successful. No adverse effects to cilostazol were observed. Postprocedural lumen diameter was significantly larger (3.27 vs 2.92 mm; p <0.0001) in the DCA-stent group. However, the follow-up lumen diameter was not significantly different (2.53 vs 2.41 mm, DCA-stent vs DCA). IVUS revealed that intimal proliferation was significantly larger in the DCA-stent group (4.2 vs 1.5 mm(2); p <0.0001), which accounted for the similar follow-up lumen area (6.5 vs 7.1 mm(2)). The restenosis rate was low in both groups (5.4% vs 8.9%), and the difference was not significant. Clinical event rates at 1 year were also not significantly different. These results suggest that optimal lesion debulking by DCA does not always need adjunctive stenting if cilostazol is administered.
Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Stents , Tetrazóis/uso terapêutico , Idoso , Implante de Prótese Vascular , Cilostazol , Terapia Combinada , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Reestenose Coronária/diagnóstico , Reestenose Coronária/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Previous reports suggest that vessel remodeling is the most important factor in late lumen loss in non-stented lesions, but because results of directional coronary atherectomy (DCA) show that increased plaque area (PA) is also important, the aim of this study was to redefine the mechanism of late lumen loss after DCA. One hundred and twenty lesions that underwent DCA with intravascular ultrasound (IVUS) guidance and serial IVUS analysis were studied, and vessel area (VA), lumen area (LA), PA (VA-LA) and corrected values (each value divided by the value of VA pre procedure to correct the vessel size) were analyzed. During follow-up, corrected VA (cVA) decreased by 0.058 +/- 0.191, whereas corrected PA (cPA) increased by 0.087 +/- 0.159. Though the %PA (PA/VA) after the procedure showed significant negative correlation with the subsequent change in cPA, it did not correlate with the subsequent change in cVA. In conclusions, the mechanism of late lumen loss after DCA consists of both arterial remodeling and plaque proliferation, and the residual %PA after the procedure determines the subsequent lumen loss. With a lower %PA, a change in the PA contributes more to late lumen loss than do changes in VA. With a high %PA, a change in the VA contributes more to late lumen loss.