RESUMO
This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m2; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Ácido ÚricoRESUMO
Subclinical peripheral artery disease (PAD) might be associated with pathophysiology of contrast-induced acute kidney injury (CI-AKI). We hypothesized that concomitant PAD in patients with the acute coronary syndrome (ACS) would represent a high-risk subgroup with a greater incidence of CI-AKI, both of which lead to higher mortality after percutaneous coronary intervention (PCI). Six hundred and seventy-five consecutive patients with ACS who underwent PCI and examination of ankle-brachial index (ABI) were analyzed retrospectively. The presence of PAD was defined as an ABI < 0.9. We investigated whether (1) PAD was an independent predictor of CI-AKI (≥ 0.3 mg/dL or ≥ 50% relative increase in serum creatinine within 48 h after PCI) and (2) PAD and CI-AKI were independently associated with long-term mortality. Of the 675 patients with ACS, 114 (17%) exhibited PAD. The incidence of CI-AKI was significantly higher in PAD patients, compared with the remaining patients (12% vs. 4%, p < 0.001). Multivariate logistic regression analysis revealed that the presence of PAD was an independent predictor for the development of CI-AKI [odds ratio 2.50, 95% confidence interval (CI) 1.07-5.73, p < 0.05]. During the median 4-year follow-up, there were 65 incidents of all-cause death. In the multivariate Cox proportional hazard regression analysis, the presence of PAD [hazard ratio (HR) 2.08, 95% CI 1.17-3.65, p < 0.05] and CI-AKI (HR 2.23, 95% CI 1.08-4.26, p < 0.05) were associated with an increased risk of all-cause mortality. Assessment of ABI provides useful information for predicting CI-AKI and long-term mortality in patients with ACS after PCI.
Assuntos
Síndrome Coronariana Aguda/terapia , Injúria Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Doença Arterial Periférica/complicações , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/administração & dosagem , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the impact of stent deformity induced by final kissing balloon technique (KBT) for coronary bifurcation lesions on in-stent restenosis (ISR). BACKGROUND: In experimental models, the detrimental effects of KBT have been clearly demonstrated, but few data exists regarding the impact of proximal stent deformity induced by KBT on clinical outcomes. METHODS: We examined 370 coronary lesions where intravascular ultrasound (IVUS)-guided second-generation drug-eluting stent (DES) implantation for coronary bifurcation lesions was performed. Based on IVUS analysis, the stent symmetry index (minimum/maximum stent diameter) and stent overstretch index (the mean of stent diameter/the mean of reference diameter) were calculated in the proximal main vessel. RESULTS: The stent symmetry index was significantly lower (0.75 ± 0.07 vs 0.88 ± 0.06, P < 0.0001) and the stent overstretch index was significantly higher (1.04 ± 0.08 vs 1.01 ± 0.06, P = 0.0007) in lesions with KBT (n = 174) compared to those without KBT (n = 196). The number of two-stent technique in lesions with KBT was 31 (18%). In multivariate analysis, the degree of stent deformity indices was not associated with ISR in lesions with KBT; however, two-stent technique use was the only independent predictor of ISR at 8 months (hazard ratio: 3.96, 95% confidence interval: 1.25-12.5, P = 0.01). CONCLUSIONS: Second-generation DES deformity induced by KBT was not associated with mid-term ISR.
Assuntos
Angioplastia Coronária com Balão , Reestenose Coronária , Stents Farmacológicos/efeitos adversos , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/diagnóstico , Reestenose Coronária/etiologia , Reestenose Coronária/cirurgia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Falha de Prótese , Fatores de Tempo , Resultado do TratamentoRESUMO
Although statin therapy is beneficial in the setting of acute coronary syndrome (ACS), a substantial proportion of patients with ACS still do not receive the guideline-recommended lipid management in contemporary practice. We hypothesize that the low-density lipoprotein cholesterol (LDL-C) level at the time of admission might affect patient management and the subsequent outcome. Nine-hundred and forty-two consecutive patients with ACS who underwent percutaneous coronary intervention were analyzed retrospectively. The study patients were first divided into two groups based on the LDL-C level on admission: group A (n = 267), with LDL-C < 100 mg/dL; and group B (n = 675), with LDL-C ≥ 100 mg/dL. Each group was then further divided into those who were prescribed statins or not at the time of discharge from the hospital. The primary endpoint was all-cause death. In addition, we analyzed the serial changes of LDL-C within 1 year. Patients in group A were significantly older and more likely to have multiple comorbidities compared with group B. The proportion of patients who were prescribed statin at discharge was significantly smaller in group A compared with group B (57.7 vs. 77.3%, p < 0.001). During the median 4-year follow-up, there were 122 incidents of all-cause death. Multivariate Cox proportional hazard analysis revealed that LDL-C < 100 mg/dL on admission [hazard ratio (HR), 1.61; 95% confidence interval (CI), 1.09-2.39; p < 0.05] and prescription of statins at discharge (HR, 0.52; 95% CI, 0.36-0.76; p < 0.001) were associated significantly with all-cause death. Under these conditions, increasing LDL-C levels were documented during follow-up in those patients in group A when no statins were prescribed at discharge (79 ± 15-96 ± 29 mg/dL, p < 0.001), whereas these remained unchanged when statins were prescribed at discharge (79 ± 15-77 ± 22 mg/dL, p = 0.30). These results demonstrate that decreased LDL-C on admission in ACS led to less prescription for statins, which could result in increased death, probably due to underestimation of the baseline LDL-C.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/cirurgia , Idoso , LDL-Colesterol/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of the present study was to evaluate the long-term outcomes at 2 years in patients in whom everolimus-eluting stents (EESs) were implanted in small and non-small vessels. A small vessel is an important risk factor for restenosis with BMSs, even in the first generation DESs. The 690 patients with 690 lesions implanted with an EES were enrolled and divided into two groups by vessel reference diameter (RD): >2.5 mm for non-small vessels (Non-S-group) and ≤2.5 mm for small vessels (S-group). Two years later, the 365 patients with no restenosis at 8 months who underwent angiography were enrolled into the late catch-up study. At the initial 8-month follow-up, the rates of restenosis and target lesion revascularization (TLR) of both groups were not significantly different (restenosis 3.9 vs 6.5%, p = 0.17; TLR 3.9 vs 6.5%, p = 0.17). At the late 2-year follow-up, there were no significant differences in the late loss (0.36 ± 0.66 vs 0.34 ± 0.50 mm, p = 0.14), net gain (1.50 ± 0.75 vs 1.26 ± 0.60 mm, p = 0.39), late catch-up restenosis rate (5.1 vs 3.4%, p = 0.38), TLR (4.9 vs 2.7%, p = 0.40), and delayed late loss (0.14 ± 0.58 vs 0.15 ± 0.49 mm, p = 0.10) between both groups. There is no correlation between delayed late loss and RD in all patients(r = -0.009) and in AMI patients (r = -0.004). These results demonstrate that the initial and late catch-up restenosis rates of small coronary vessels with EES placement were excellent, the same as for non-small coronary vessels. We suggest that involvement of small coronary arteries may not be a risk factor for restenosis and results of stenting for small coronary arteries with EES placement were excellent.
Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/prevenção & controle , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Everolimo/farmacologia , Intervenção Coronária Percutânea/métodos , Idoso , Doença da Artéria Coronariana/diagnóstico , Reestenose Coronária/diagnóstico , Reestenose Coronária/epidemiologia , Vasos Coronários/cirurgia , Feminino , Seguimentos , Humanos , Imunossupressores/farmacologia , Incidência , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of the study was to elucidate the aggressive reduction of both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) reduced coronary atherosclerotic plaque volume compared with a standard treatment of LDL-C and BP in Japanese patients with coronary artery disease (CAD). This study is a prospective, randomized, and open-labelled with a blind-endpoint evaluation study. A total of 97 patients (81 men, mean age 62.0 ± 9.6) with CAD undergoing intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) were randomized, and 68 patients had IVUS examinations at baseline and at 18-24 months follow-up. Patients were randomly assigned to standard or aggressive strategies targeting LDL-C and a BP of 100 mg/dL and 140/90 mmHg vs. 70 mg/dL and 120/70 mmHg, respectively. The primary endpoint was the percent change in coronary plaque volume. Both standard and aggressive strategies succeeded to achieve target levels of LDL-C and BP; 74.9 ± 14.7 vs. 63.7 ± 11.9 mg/dL (NS) and 124.1 ± 9.4/75.8 ± 7.7 vs. 113.6 ± 9.6/65.8 ± 9.4 mmHg (systolic BP; NS, diastolic BP; p < 0.05), respectively. Both groups showed a significant reduction in the coronary plaque volume of -9.4 ± 10.7% and -8.7 ± 8.6% (NS) in standard and aggressive therapies, respectively. Both standard and aggressive intervention significantly regressed coronary plaque volume by the same degree, suggesting the importance of simultaneous reductions of LDL-C and BP for prevention of CAD.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doença da Artéria Coronariana/terapia , Hipolipemiantes/uso terapêutico , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea , Placa Aterosclerótica/terapia , Ultrassonografia de Intervenção/métodos , Idoso , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico , Estudos Prospectivos , Fatores de TempoRESUMO
A 78-year-old man with unstable angina showed 90% stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitroprusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Importantly, there occurred slow flow again after balloon angioplasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neoatherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.
Assuntos
Angioplastia Coronária com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Reestenose Coronária/terapia , Estenose Coronária/terapia , Stents Farmacológicos , Fenômeno de não Refluxo/etiologia , Sirolimo/administração & dosagem , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angiografia Coronária , Circulação Coronária , Reestenose Coronária/diagnóstico , Reestenose Coronária/etiologia , Reestenose Coronária/fisiopatologia , Estenose Coronária/diagnóstico , Estenose Coronária/fisiopatologia , Prótese Parcial Temporária , Humanos , Masculino , Fenômeno de não Refluxo/diagnóstico , Fenômeno de não Refluxo/fisiopatologia , Recidiva , Retratamento , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
A line of epidemiological studies suggests that the accumulation of coronary risk factors promotes the progression of coronary atherosclerosis. Recent clinical studies showed that aggressive low-density lipoprotein (LDL) cholesterol-lowering therapy using statins could regress coronary atheroma and reduce major cardiovascular events. Additionally, therapy that controlled amlodipine-based blood pressure reduced major cardiovascular events in patients with hypertension compared with an atenolol-based regimen. An open-label randomized multicenter study is primarily planned to evaluate the changes in coronary atheroma volume using intravascular ultrasonography 18-24 months after intensive lowering of LDL-cholesterol and blood pressure compared with a standard therapy indicated by current guidelines in Japanese patients with coronary artery disease (CAD). The secondary endpoints include changes in serum lipid levels, inflammatory markers, glucose markers and blood pressure. In total, 100 subjects with CAD who are undergoing percutaneous coronary intervention will be tested. The MILLION study will provide new evidence and therapeutic standards for the prevention of CAD in Japanese patients by controlling both LDL-C levels and blood pressure.
Assuntos
Anlodipino/uso terapêutico , Pressão Sanguínea/fisiologia , Doença da Artéria Coronariana/tratamento farmacológico , Ácidos Heptanoicos/uso terapêutico , Lipídeos/sangue , Placa Aterosclerótica/tratamento farmacológico , Pirróis/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Progressão da Doença , Combinação de Medicamentos , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST). METHODS AND RESULTS: Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization. CONCLUSION: Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.
Assuntos
Angioplastia com Balão/mortalidade , Reestenose Coronária/mortalidade , Trombose Coronária/mortalidade , Stents Farmacológicos/efeitos adversos , Sistema de Registros/estatística & dados numéricos , Sirolimo/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/métodos , Morte Súbita Cardíaca/epidemiologia , Stents Farmacológicos/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: (18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is assumed to be the most useful method for evaluating the viability of the myocardium. However, there are few reports regarding serial changes in (18)F-FDG-PET images of acute myocardial infarction (AMI). We evaluated serial changes in glucose-loaded (18)F-FDG-PET, (123)I-ß-methyl-p-iodophenyl-penta-decanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and (99m)Tc-Tetrofosmin (TF) gated SPECT images in patients with AMI. METHODS AND RESULTS: We enrolled 7 consecutive patients with first anterior AMI who successfully underwent percutaneous coronary intervention (PCI). (18)F-FDG-PET images were obtained in the acute, subacute, chronic, mid-term and long-term phases. (123)I-BMIPP and (99m)Tc-TF SPECT images were obtained in the subacute, chronic, mid-term and long-term phases. We determined the total defect score (TDS) for each image. The TDS of the glucose-loaded (18)F-FDG-PET, (123)I-BMIPP and( 99m)Tc-TF SPECT images indicated significant serial decrease (P<0.001). Comparing these images, the TDS of the glucose-loaded (18)F-FDG-PET images was larger than that of the (123)I-BMIPP and (99m)Tc-TF SPECT images, and the TDS indicated (18)F-FDG-PET>(123)I-BMIPP>(99m)Tc-TF in all phases. CONCLUSIONS: The defect areas of glucose-loaded (18)F-FDG-PET images were significantly larger than those of (123)I-BMIPP and( 99m)Tc-TF SPECT images during 9 months follow-up of patients with successful PCI for anterior AMI. Additionally, the impairment of glucose metabolism was prolonged.
Assuntos
Ácidos Graxos/administração & dosagem , Fluordesoxiglucose F18/administração & dosagem , Iodobenzenos/administração & dosagem , Infarto do Miocárdio/diagnóstico por imagem , Intervenção Coronária Percutânea , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Compostos Organofosforados , Compostos de Organotecnécio , RadiografiaRESUMO
BACKGROUND: The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately. METHODS AND RESULTS: In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P<0.001; 0.72% versus 0.07%, P=0.02; and 2.1% versus 0.14%, P=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (P=0.99) in the 6-month landmark analysis. CONCLUSIONS: Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.
Assuntos
Stents Farmacológicos/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Sirolimo/administração & dosagem , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/uso terapêuticoRESUMO
AIMS: The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. METHODS AND RESULTS: We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analysed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as 'pathogenic' by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that two variants in KCNH2 and SCN5A, four variants in SCN10A, and one variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from 'Uncertain significance' to 'Likely pathogenic' in six probands. CONCLUSION: Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD.
Assuntos
Doença do Sistema de Condução Cardíaco/genética , Sequenciamento do Exoma , Variação Genética , Frequência Cardíaca/genética , Potenciais de Ação/genética , Adulto , Idade de Início , Idoso , Animais , Doença do Sistema de Condução Cardíaco/epidemiologia , Doença do Sistema de Condução Cardíaco/metabolismo , Doença do Sistema de Condução Cardíaco/fisiopatologia , Estudos de Casos e Controles , Simulação por Computador , Canal de Potássio ERG1/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Japão/epidemiologia , Lamina Tipo A/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Proteínas Nucleares/genética , Fenótipo , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Adulto Jovem , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data-and in particular multicentre data-exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds. METHODS AND ANALYSIS: The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies. ETHICS AND DISSEMINATION: This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000038210.
Assuntos
Hiperlipoproteinemia Tipo II , Estudos de Coortes , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Japão/epidemiologia , Estudos Prospectivos , Sistema de RegistrosRESUMO
BACKGROUND: Although concomitant peripheral artery disease in patients with acute coronary syndrome (ACS) has been considered as a high-risk subgroup with a greater incidence of bleeding after percutaneous coronary intervention (PCI), few data exist regarding the clinical utility of the ankle-brachial index (ABI) for predicting bleeding complications, which affects the subsequent outcome. METHODS: Eight hundred and twenty-four consecutive patients with ACS who underwent PCI and ABI examination were analyzed retrospectively. Decreased-ABI was defined as ABI <0.9. The primary outcome was bleeding complications within 30 days, which was defined according to the Bleeding Academic Research Consortium classification grade ≥3. The secondary endpoint was all-cause death during follow-up. RESULTS: Of the 824 patients with ACS, 137 (16.6%) exhibited decreased-ABI. The incidence of bleeding complications was significantly higher in patients with decreased-ABI, compared with the remaining patients (21.9% vs. 6.0%, p<0.001). In multivariate analysis, anemia [odds ratio (OR) 2.14], estimated glomerular filtration rate<60mL/min/1.73m2 (OR 2.14), femoral access (OR 3.31), use of an intra-aortic balloon pump (OR 3.16), and decreased-ABI (OR 2.58) were independent predictors of 30-day bleeding complications. Assigning 1 point for each variable, we developed a new bleeding risk score (range, 0-5). The area under the receiver-operating characteristic curve for the probability of 30-day bleeding for the new risk score was significantly superior than that of the traditional one (0.82 vs. 0.76, p<0.05). During the median 4-year follow-up, there were 98 incidents of all-cause death. Multivariate Cox-proportional hazard analysis revealed that decreased-ABI [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.15-3.13, p<0.05] and 30-day bleeding (HR 3.00, 95% CI 1.76-4.97, p<0.001) were associated with an increased risk of all-cause mortality. CONCLUSIONS: Assessment of ABI provides useful information for predicting 30-day bleeding complications and long-term mortality in patients with ACS after PCI.
Assuntos
Síndrome Coronariana Aguda/mortalidade , Índice Tornozelo-Braço , Intervenção Coronária Percutânea/mortalidade , Doença Arterial Periférica/diagnóstico , Hemorragia Pós-Operatória/mortalidade , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/cirurgia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/mortalidade , Hemorragia Pós-Operatória/etiologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
Mutations in the betaMHC (beta-myosin heavy chain), a sarcomeric protein are responsible for hypertrophic and dilated cardiomyopathy. However, the mechanisms whereby distinct mutations in the betaMHC gene cause two kinds of cardiomyopathy are still unclear. In the present study we report a novel betaMHC mutation found in a patient with isolated LVNC [LV (left ventricular) non-compaction] and the phenotype of a mouse mutant model carrying the same mutation. To find the mutation responsible, we searched for genomic mutations in 99 unrelated probands with dilated cardiomyopathy and five probands with isolated LVNC, and identified a p.Met531Arg mutation in betaMHC in a 13-year-old girl with isolated LVNC. Next, we generated six lines of transgenic mice carrying a p.Met532Arg mutant alphaMHC gene, which was identical with the p.Met531Arg mutation in the human betaMHC. Among these, two lines with strong expression of the mutant alphaMHC gene were chosen for further studies. Although they did not exhibit the features characteristic of LVNC, approx. 50% and 70% of transgenic mice in each line displayed LVH (LV hypertrophy) by 2-3 months of age. Furthermore, LVD (LV dilation) developed in approx. 25% of transgenic mice by 18 months of age, demonstrating biphasic changes in LV wall thickness. The present study supports the idea that common mechanisms may be involved in LVH and LVD. The novel mouse model generated can provide important information for the understanding of the pathological processes and aetiology of cardiac dilation in humans.
Assuntos
Cardiomiopatia Dilatada/genética , Hipertrofia Ventricular Esquerda/genética , Cadeias Pesadas de Miosina/genética , Mutação Puntual , Miosinas Ventriculares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Cardiomiopatia Dilatada/patologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Ventrículos do Coração/ultraestrutura , Humanos , Hipertrofia Ventricular Esquerda/patologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Miócitos Cardíacos/ultraestrutura , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Although Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score based on angiographic scoring system was developed in patients with previous coronary artery bypass grafting (CABG), few data exist regarding its prognostic utility in patients undergoing percutaneous coronary intervention (PCI). We examined 272 patients with previous CABG (217 men; mean age, 70.4 ± 9.7 years) undergoing PCI. Severity of the coronary anatomy was evaluated using CABG-SYNTAX score. The primary end point of this study was cardiovascular death. The baseline CABG-SYNTAX score ranged from 2 to 53.5, with an average of 26.0 ± 10.2. In the index procedures, PCI for the native coronary accounted for nearly all patients (88%). During follow-up (median 4.1 years), 40 cardiovascular deaths had occurred. In multivariate analysis, age >75 years (hazard ratio [HR] 2.82, 95% CI 1.45 to 5.52), left ventricular ejection fraction <40% (HR 2.99, 95% CI 1.39 to 6.07), end-stage renal disease (HR 2.90, 95% CI 1.15 to 6.75), peripheral artery disease (HR 2.20, 95% CI 1.10 to 4.64), and CABG-SYNTAX score >25 (HR 2.37, 95% CI 1.19 to 5.05) were independent predictors of cardiovascular death. After creating a composite risk score in consideration of identified predictors, the freedom from cardiovascular death at 5 years was 98%, 86%, and 58% in the low (0 to 1), medium (2), and high (3 to 5) scores, respectively (p <0.001). The area under the receiver-operating characteristic curve for cardiovascular death for the CABG-SYNTAX and composite risk scores were 0.66 and 0.77, respectively (p <0.05). In conclusion, the combination of angiographic and clinical characteristics is useful for risk stratification in patients with previous CABG undergoing PCI.
Assuntos
Doença da Artéria Coronariana/cirurgia , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Comorbidade , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Teste de Esforço , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/epidemiologia , Doença Arterial Periférica/epidemiologia , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
UNLABELLED: Serial changes in fatty acid metabolism or use associated with acute ischemia and reperfusion were examined in rat hearts. METHODS: Male Wistar rats were subjected to occlusion of the left coronary artery for 20 min followed by reperfusion. After release of the occlusion, groups of animals were allowed to recover for intervals of 20 min (n = 9), 1 d (n = 9), 3 d (n = 6), 7 d (n = 6), or 30 d (n = 6). Hearts were excised 15-20 min after injection of 0.74 MBq of (125)I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 14.8 MBq of (201)Tl. One minute before resection, the left coronary artery was reoccluded and 185 MBq of (99m)Tc-sestamibi were injected to document the area at risk. Triple-tracer autoradiography was performed to assess tracer uptake. Uptake ratios of BMIPP and (201)Tl in the area at risk were calculated on the basis of the count density in the lesion divided by that in the normally perfused area. RESULTS: (201)Tl uptake did not change throughout the observation period (P = 0.25). In contrast, BMIPP uptake increased early in the acute phase (20 min and 1 d), decreased during the subacute phase (7 d), and subsequently recovered in the chronic phase (30 d). CONCLUSION: The present investigation clearly illustrated that BMIPP uptake is higher than (201)Tl uptake in the acute phase, that BMIPP uptake is lower than (201)Tl uptake in the subacute phase, and that BMIPP uptake and (201)Tl uptake are similar in the chronic phase. These results yield data essential to the precise interpretation of BMIPP images.
Assuntos
Ácidos Graxos/farmacocinética , Coração/diagnóstico por imagem , Iodobenzenos/farmacocinética , Miocárdio/metabolismo , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/metabolismo , Tálio/farmacocinética , Animais , Modelos Animais de Doenças , Radioisótopos do Iodo/farmacocinética , Masculino , Taxa de Depuração Metabólica , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
UNLABELLED: Histological diagnosis and grading of cartilaginous tumors are closely correlated with patient prognosis; consequently, they are essential elements. We attempted to clarify the characteristics of 201Tl uptake in various histological types of cartilaginous tumors and to assess its clinical value. METHODS: Twenty-two cases with histologically proven cartilaginous tumors (3 enchondromas, 15 conventional chondrosarcomas (grade I = 9, II = 5, III = 1), 3 mesenchymal chondrosarcomas, and 1 de-differentiated chondrosarcoma) were examined retrospectively. Planar 201Tl images were recorded 15 min following intravenous injection of 201Tl (111 MBq). 201Tl uptake in the tumor was evaluated visually employing a five-grade scoring system: 0 = no appreciable uptake, 1 = faint uptake above the background level, 2 = moderate uptake, 3 = intense uptake but lower than heart uptake and 4 = uptake higher than heart uptake. RESULTS: 201Tl uptake scores were 0 in 3 of 3 enchondromas, 9 of 9 grade I, and 4 of 5 grade II conventional chondrosarcomas. 201Tl uptake scores were 1 among 1 of 5 grades II and a grade III conventional chondrosarcoma. Mesenchymal chondrosarcoma and de-differentiated chondrosarcoma displayed 201Tl uptake scores of 2 or 3. CONCLUSIONS: Absence of elevated 201Tl uptake in cartilaginous tumors was indicative of enchondroma or low-grade conventional chondrosarcoma. However, in instances in which 201Tl uptake is obvious, high-grade chondrosarcoma or variant types should be considered.
Assuntos
Cartilagem/diagnóstico por imagem , Neoplasias de Tecido Conjuntivo/diagnóstico por imagem , Tálio/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cartilagem/metabolismo , Condroma/diagnóstico por imagem , Condroma/metabolismo , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neoplasias de Tecido Conjuntivo/metabolismo , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
BACKGROUND: The influence of antiplatelet therapy discontinuation on the incidence of stent thrombosis, especially very late stent thrombosis, after drug-eluting stent implantation has not been yet fully addressed. METHODS: Relationship between antiplatelet therapy discontinuation and stent thrombosis up to 5years was evaluated in 12,812 consecutive patients undergoing sirolimus-eluting stents (SES) implantation in the j-Cypher registry. Data on status of antiplatelet therapy during follow-up were collected prospectively. RESULTS: Median follow-up interval was 1699days (interquartile range, 1184-1928days). Incidences of definite stent thrombosis were 0.34% at 30days, 0.55% at 1year, and 1.6% at 5years. Dual antiplatelet therapy was maintained in 97.4%, 63%, and 43.9% of patients at 30days, 1year, and 5years, respectively. The rates of stent thrombosis in patients who discontinued both thienopyridine and aspirin were significantly higher in the time intervals of 31-365days, 2-3years and 3-4years, and tended to be higher in the time intervals of 1-2years and 4-5years than those in patients who continued both (31-365days: 1.26% versus 0.2%, P<0.001; 1-2years: 0.59% versus 0.15%, P=0.06; 2-3years: 1.35% versus 0.2%, P=0.004; 3-4years: 1.09% versus 0.25%, P=0.0496; 4-5years: 1.35% versus 0.43%, P=0.17). Patients who discontinued either thienopyridine or aspirin only did not have an excess of stent thrombosis in any time intervals. CONCLUSIONS: In conclusion, discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine or aspirin only, was associated with an increased incidence of late and very late stent thrombosis up to 5years after SES implantation.
Assuntos
Trombose Coronária/etiologia , Stents Farmacológicos , Oclusão de Enxerto Vascular/etiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Sistema de Registros , Sirolimo/farmacologia , Suspensão de Tratamento , Idoso , Trombose Coronária/epidemiologia , Feminino , Seguimentos , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Imunossupressores/farmacologia , Incidência , Japão/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
A 70-year-old woman with dilated cardiomyopathy and recurrent severe heart failure was admitted for biventricular pacing (BVP), which was recently reported to have clinical efficacy for severe heart failure with intraventricular conduction delay. An electrocardiogram showed complete left bundle branch block, and the QRS interval was markedly prolonged at 195 msec. Echocardiogram showed marked dilatation, diffuse hypokinesis and dyssynchrony of the left ventricle, and grade III mitral valve regurgitation. The patient underwent implantation of an atriobiventricular pacemaker and three pacing leads transvenously. The QRS interval shortened to 165 msec immediately after the BVP therapy, and improvements in echocardiographic parameters were seen at 5 months after BVP therapy. Myocardial oxidative metabolism was assessed by the monoexponential clearance rate of [11C]acetate (Kmono) as measured by positron emission tomography (PET), and myocardial efficiency was assessed by the work metabolic index (WMI) at 1 and 5 months after the BVP therapy. The PET images obtained 5 months after BVP therapy showed a decrease in the clearance of [11C]acetate compared with that obtained 1 month after BVP therapy. The Kmono of the whole left ventricle decreased from 0.051 at 1 month to 0.038 min-1 at 5 months after BVP therapy, and that of the septum, anterior wall, lateral wall and posterior wall also decreased. The WMI increased from 4.2 x 10(6) to 6.8 x 10(6) mmHg. ml/m2. These results suggest that BVP improved left ventricular function without increasing myocardial oxidative metabolism, resulting in improved myocardial efficiency, and that BVP may improve the long-term prognosis of heart failure patients with ventricular dyssynchrony. [11C]acetate PET is a useful method of evaluating global and regional myocardial oxidative metabolism in patients who have undergone BVP therapy.