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Objective: Smoking is a modifiable cardiovascular risk factor closely related to arterial stiffness (AS). However, data are lacking regarding the chronic effects of smoking on AS, especially in ex-smoker (ES) who faces remnant cardiovascular risk when compared to never-smokers (NS).Methods: Among 1722 health screening participants, we retrospectively evaluated 652 healthy men with different smoking history [240 current smoker (CS) vs. 228 ES vs. 184 NS]. To assess AS, augmentation index (AIx), pulse pressure amplification (PPamp), and carotid-femoral pulse wave velocity (cfPWV) were measured and compared.Results: Baseline characteristics were similar except age and triglyceride level. AIx was lowest in NS, followed by ES, and was highest in CS. PPamp was highest in NS, lowest in CS, and ES was of intermediate level. The differences were more robust after adjustment for baseline covariates (AIx, p = 0.005; PPamp: p = 0.001). On the other hand, no significant intergroup difference was observed for cfPWV in our middle-aged population. With the regression analyses revealing an independent association between smoking duration and AS in ES, subgroup analysis demonstrated that long-term ES (smoking duration ≥20 years) had significantly higher AS than short-term ES (<20 years) and NS, approaching levels comparable to CS (AIx and PPamp: p < 0.0001).Conclusions: Our study demonstrated impaired arterial elastic properties in long-term ES, suggesting that AS caused by chronic smoking might be irreversible even after smoking cessation. Further longitudinal studies are warranted to determine the impacts of past smoking on AS and its clinical relevance.
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Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Ex-Fumantes/estatística & dados numéricos , Fumar/efeitos adversos , Rigidez Vascular/fisiologia , Adulto , Doenças Cardiovasculares/etiologia , Doença Crônica , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Estudos Retrospectivos , Fumar/fisiopatologia , Fatores de TempoRESUMO
AIMS: The clinical implication of the inferior vena cava collapsibility index (IVCCI) has not been well evaluated in patients with various cardiovascular diseases. METHOD AND RESULTS: The relationships between clinical characteristics and echocardiographic indicators of the systemic intravascular volume status [IVCCI; the ratio of the early transmitral and early myocardial diastolic velocities (E/Em)] were evaluated at baseline, and the clinical status during follow-up was compared across the IVCCI levels. Among 1166 patients (mean age=63.8±13.4 years), 934, 171, and 61 had high (≥50%), intermediate (25%-50%), and low (<25%) IVCCIs, respectively. Age-, sex-, and body mass index-adjusted serum creatinine (sCr) levels were highest in patients with low IVCCI (P=.002) and E/Em >15 (P<.001). During follow-up (1108±463 days), 67 patients died, and 38 of these deaths were cardiovascular related. Age, body mass index, heart failure (HF), sCr levels, and a low IVCCI (vs high IVCCI: hazard ratio [HR]=3.193, 95% confidence interval [CI]=1.297-7.857, P=.012) were associated with all-cause mortality in multivariable analysis. HF, diuretic use, and a low IVCCI (vs high IVCCI: HR=4.428, 95% CI=1.406-13.104, P=.007) were significantly associated with cardiovascular mortality. CONCLUSION: A low IVCCI was significantly associated with reduced renal function and was an independent risk factor for adverse outcomes, regardless of underlying cardiovascular disease and renal function.
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Doenças Cardiovasculares/diagnóstico , Pressão Venosa Central/fisiologia , Ecocardiografia/métodos , Insuficiência Renal/fisiopatologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/fisiopatologia , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
Primary cardiac lymphoma (PCL) is a very rare malignancy although cardiac involvement with the disseminated disease is not uncommon. We present a case of a 43-year-old man with PCL that initially presented as marked thickening of all cardiac walls and was mistakenly diagnosed as an atypical type of hypertrophic cardiomyopathy. The diagnosis of PCL was made with a delay of 9 months after the initial presentation, when atypical lymphocytes staining positive for CD79a and CD20 were demonstrated in the rapidly growing mediastinal and neck mass. Anthracycline-based chemotherapy and anti-CD20 immunotherapy resulted in a remarkable reduction in cardiac wall thickness and mediastinal mass. The first lesson to be learnt from this case is that PCL can present as a diffuse infiltrative disease without a mass. The second lesson is that prompt exploratory thoracotomy should not be delayed when the diagnosis is elusive.
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Cardiomiopatia Hipertrófica/diagnóstico , Neoplasias Cardíacas/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Intensificação de Imagem Radiográfica , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Diagnóstico Tardio , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/etiologia , Ecocardiografia , Serviço Hospitalar de Emergência , Neoplasias Cardíacas/tratamento farmacológico , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Doenças Raras , Medição de Risco , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Few studies have examined the variations in longitudinal/circumferential/radial strain (LS/CS/RS) and strain rate (LSr/CSr/RSr) in individual hearts when the left ventricular ejection fraction (LVEF) has changed. We hypothesized the relationships of strain/strain rate and LVEF are not linear, but vary with multiple inflection points (IPs) in individual hearts.Twenty-five patients with fluctuating LVEF (ΔLVEF > 10%) who had 2-D speckle tracking echocardiography available for analysis were enrolled. After models of best fit were obtained from the 'collective' plots to determine inflection points, the decrements of slopes above inflection points (IP) were compared with those below IPs in the 'individual hearts' plots.In the 'collective' plots, both LS and LSr linearly decreased in proportion to LVEF when LVEF ≥ 40% but remained constant regardless of LVEF when LVEF < 40% (IPs when LVEF = 40%, P < 0.0001). The RS-LVEF relationship was sigmoid with two IPs when LVEF = 30% and 50% (P < 0.0001). However, in the 'individual hearts' plots, the decrements of slopes above and below IPs were not different for LS-LVEF and LSr-LVEF, and marginally different for RS-LVEF (P = 0.049, across IP when LVEF = 50%).Collectively, the relationship of LS/LSr/RS and LVEF seemed to be not linear, but inflective, however, we could not prove the inflective relationship in individual hearts with fluctuating LVEF. Further study with more patients is needed to prove our hypothesis.
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Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
Although wireless capsule endoscopy (WCE) detects small bowel diseases effectively, it has some limitations. For example, the reading process can be time consuming due to the numerous images generated per case and the lesion detection accuracy may rely on the operators' skills and experiences. Hence, many researchers have recently developed deep-learning-based methods to address these limitations. However, they tend to select only a portion of the images from a given WCE video and analyze each image individually. In this study, we note that more information can be extracted from the unused frames and the temporal relations of sequential frames. Specifically, to increase the accuracy of lesion detection without depending on experts' frame selection skills, we suggest using whole video frames as the input to the deep learning system. Thus, we propose a new Transformer-architecture-based neural encoder that takes the entire video as the input, exploiting the power of the Transformer architecture to extract long-term global correlation within and between the input frames. Subsequently, we can capture the temporal context of the input frames and the attentional features within a frame. Tests on benchmark datasets of four WCE videos showed 95.1% sensitivity and 83.4% specificity. These results may significantly advance automated lesion detection techniques for WCE images.
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Drug-eluting stent (DES) recipients require 6-12 months of dual antiplatelet treatment (DAPT) and long-term aspirin mono-antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated. We evaluated 15-year APT trends based on nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea. DAPT (80.7%) was the most preferred initial APT post-PCI. Many DES recipients received prolonged DAPT (post-PCI 3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid to late 2000s (after the late-stent thrombosis concerns of first-generation DESs raised); the conversion after that was similar during the 2010s, occurring most robustly at 12-18 months post-PCI. Clopidogrel had long and increasingly been used for MAPT, surpassing aspirin. The recent increase in newer P2Y12 inhibitor prescriptions was noted. The patients treated with newer P2Y12 inhibitors were more likely younger men and presented with acute myocardial infarction. Real-world APT is evolving, and guideline-practice gaps exist. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.
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BACKGROUND: In doxorubicin-induced cardiomyopathy (DIC), the sequence of decrease in multidirectional myocardial deformation has not been clearly elucidated. OBJECTIVES: We investigated the sequence of myocardial deformations in rat DIC, using two-dimensional speckle tracking echocardiography (2DSTE). METHODS: Twenty rats were treated with doxorubicin (1.25 mg/kg × 16 times, intraperitoneal) for 4 weeks and compared with nine control rats. Myocardial strain analysis with 2DSTE, as well as conventional echocardiography, was obtained. RESULTS: Compared with baseline, longitudinal strain/strain rate (LS/LSr) decreased at week 2 (-15.7 ± 1.5 to -14.1 ± 1.4%, P = 0.01 for LS; -4.4 ± 0.7 to -3.9 ± 0.5 per second, P = 0.009 for LSr). Left ventricular ejection fraction (LVEF) and circumferential strain (CS) decreased at week 4 (80.3 ± 3.2 to 78.1 ± 3.3%, P = 0.031 for LVEF; -18.6 ± 1.9 to -15.0 ± 3.4%, P = 0.019 for CS). Circumferential strain rate (CSr) decreased at week 6 (-5.5 ± 0.8 to -4.6 ± 1.0 per second, P = 0.008). Radial strain/strain rate (RS/RSr) decreased at week 8 (54.8 ± 9.4 to 43.7 ± 10.6%, P = 0.005 for RS; 8.0 ± 1.1 to 7.0 ± 1.1 per second, P = 0.005 for RSr), while there was no significant change in LS/LSr, LVEF, CS/CSr, or RS/RSr in the control group. LVEF had the highest correlation with LS (r =-0.607, P = 0.000) and the lowest correlation with RSr (r = 0.357, P = 0.000). CONCLUSIONS: In DIC of rat hearts, LS/LSr decreased first, and then LVEF, CS, CSr, RS/RSr subsequently decreased. LS/LSr is considered to be a more sensitive predictor than LVEF in progressive rat DIC, and RS/RSr was preserved until the last stage.
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Cardiomiopatias/induzido quimicamente , Cardiomiopatias/fisiopatologia , Doxorrubicina/efeitos adversos , Ecocardiografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Animais , Antineoplásicos/efeitos adversos , Cardiomiopatias/diagnóstico por imagem , Módulo de Elasticidade/efeitos dos fármacos , Ventrículos do Coração/diagnóstico por imagem , Masculino , Ratos , Ratos Sprague-Dawley , Resistência à Tração/efeitos dos fármacosRESUMO
CONTEXT: Doxorubicin is widely used anti-neoplastic drug but has serious cardiotoxicity. Long-term cardioprotective effects of statin and carvedilol against delayed cardiotoxicity of doxorubicin was not well elucidated. OBJECTIVE: To evaluate long-term cardioprotective effects of co-administered rosuvastatin and carvedilol against chronic doxorubicin-induced cardiomyopathy (DIC) in rats. METHODS: Sixty-one rats were assigned to six groups: group I, control; group II, doxorubicin only (1.25 mg/kg, bi-daily, I.P.); group III, doxorubicin + rosuvastatin (2 mg/kg/day, P.O.); group IV, doxorubicin + rosuvastatin(10 mg/kg/day, P.O.); group V, doxorubicin + carvedilol (5 mg/kg/day, P.O.); group VI, doxorubicin + carvedilol (10 mg/kg/day, P.O.). Drugs were administered for 4 weeks (by week 4) and rats were observed without drugs for 4 weeks (by week 8). RESULTS: After 4 weeks discontinuation of drugs (week 8), group III showed higher +dP/dt (p = 0.058), lower -dP/dt (p = 0.009), lower left ventricular (LV) tissue malondialdehyde (MDA; p = 0.022), and less LV fibrosis (p = 0.011) than group II. Group IV showed similar results to group III. However, in group V and VI, carvedilol failed to reduce LV dysfunction, elevation of troponin or myocardial fibrosis, although group V showed lower LV tissue MDA (p = 0.004) than group II. DISCUSSION AND CONCLUSIONS: Myocardial injury and LV systolic/diastolic dysfunction at week 8 was alleviated by co-administered rosuvastatin, but not by carvedilol. It is unclear whether the cardioprotective effect of rosuvastatin is attributed to a suppression of oxidative stress induced by doxorubicin, because carvedilol did not exhibit a cardioprotective effect despite its antioxidant effects.
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Antineoplásicos/toxicidade , Carbazóis/farmacologia , Cardiotônicos/farmacologia , Doxorrubicina/toxicidade , Fluorbenzenos/farmacologia , Coração/efeitos dos fármacos , Propanolaminas/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Animais , Carvedilol , Ecocardiografia , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Rosuvastatina CálcicaRESUMO
Balloon-injured coronary segments are known to harbor abnormal vasomotion. We evaluated whether de novo coronary lesions treated using drug-coated balloon (DCB) are prone to vasospasm and how they respond to ergonovine and nitrate. Among 132 DCB angioplasty recipients followed, 89 patients underwent ergonovine provocation test at 6-9 months follow-up. Within-subject ergonovine- and nitrate-induced diameter changes were compared among three different sites: DCB-treated vs. angiographically normal vs. segment showing prominent vasoreactivity (spastic). No patient experienced clinically refractory vasospastic angina or symptom-driven revascularization during follow-up. Ergonovine induced vasospasm in seven patients; all were multifocal spasm either involving (n = 2) or rather sparing DCB-treated segments (n = 5). None showed focal spasm that exclusively involved DCB-treated lesions. Among 27 patients with vasospastic features, DCB-treated segments showed less vasoconstriction than spastic counterparts (p < 0.001). A total of 110 DCB-treated lesions were analyzed to assess vasomotor function. Vasomotor function, defined as a combined constrictor and dilator response, was comparable between DCB-treated and angiographically normal segments (p = 0.173), while significant differences were observed against spastic counterparts (p < 0.001). In our study, DCB-treated lesions were not particularly vulnerable to vasospasm and were found to have vasomotor function similar to angiographically normal segments, supporting safety of DCB-only strategy in treating de novo native coronary lesions.
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Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial ischemia. Multivessel SCAD is much rarer than single vessel involvement and acute coronary syndrome is the most frequent clinical presentation of a patient with SCAD. The patient in this report had SCAD in both the left anterior descending and right coronary arteries at the same time. However, the clinical manifestation was not acute coronary syndrome but rather congestive heart failure. Successful angioplasty and stent placement was performed and the symptoms of congestive heart failure were successfully resolved with medical treatment.
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Dissecção Aórtica/complicações , Aneurisma Coronário/complicações , Insuficiência Cardíaca/etiologia , Adulto , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/terapia , Angioplastia Coronária com Balão/instrumentação , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/terapia , Angiografia Coronária , Feminino , Insuficiência Cardíaca/terapia , Humanos , Stents , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: We investigated the impact of obesity on the clinical outcomes following percutaneous coronary intervention (PCI). METHODS: We included South Koreans aged > 20 years who underwent the Korean National Health Screening assessment between 2009 and 2012. Obesity was defined using the body mass index (BMI), according to the World Health Organization's recommendations. Abdominal obesity was defined using the waist circumference (WC), as defined by the Korean Society for Obesity. The odds and hazard ratios in all-cause mortality were calculated after adjustment for multiple covariates. Patients were followed up to the end of 2017. RESULTS: Among 130,490 subjects who underwent PCI, the mean age negatively correlated with BMI. WC, hypertension, diabetes, dyslipidemia, fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels correlated with the increased BMI. The mortality rates were higher in the lower BMI and WC groups than the higher BMI and WC groups. The non-obese with abdominal obesity group showed a mortality rate of 2.11 per 1,000 person-years. Obese with no abdominal obesity group had the lowest mortality rate (0.88 per 1,000 person-years). The mortality showed U-shaped curve with a cut-off value of 29 in case of BMI and 78 cm of WC. CONCLUSION: The mortality showed U-shaped curve and the cut-off value of lowest mortality was 29 in case of BMI and 78 cm of WC. The abdominal obesity may be associated with poor prognosis in Korean patients who underwent PCI.
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Obesidade Abdominal , Intervenção Coronária Percutânea , Índice de Massa Corporal , Humanos , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade Abdominal/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Circunferência da CinturaRESUMO
BACKGROUND: Chronic diseases like hypertension need comprehensive lifetime management. This study assessed clinical and patient-reported outcomes and compared them by treatment patterns and adherence at 6 months among uncontrolled hypertensive patients in Korea. METHODS: This prospective, observational study was conducted at 16 major hospitals where uncontrolled hypertensive patients receiving anti-hypertension medications (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) were enrolled during 2015 to 2016 and studied for the following 6 months. A review of medical records was performed to collect data on treatment patterns to determine the presence of guideline-based practice (GBP). GBP was defined as: (1) maximize first medication before adding second or (2) add second medication before reaching maximum dose of first medication. Patient self-administered questionnaires were utilized to examine medication adherence, treatment satisfaction and quality of life (QoL). RESULTS: A total of 600 patients were included in the study. Overall, 23% of patients were treated based on GBP at 3 months, and the GBP rate increased to 61.4% at 6 months. At baseline and 6 months, 36.7 and 49.2% of patients, respectively, were medication adherent. The proportion of blood pressure-controlled patients reached 65.5% at 6 months. A higher blood pressure control rate was present in patients who were on GBP and also showed adherence than those on GBP, but not adherent, or non-GBP patients (76.8% vs. 70.9% vs. 54.2%, P < 0.001). The same outcomes were found for treatment satisfaction and QoL (P < 0.05). CONCLUSIONS: This study demonstrated the importance of physicians' compliance with GBP and patients' adherence to hypertensive medications. GBP compliance and medication adherence should be taken into account when setting therapeutic strategies for better outcomes in uncontrolled hypertensive patients.
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The central hemodynamic characteristics of young adults with isolated systolic hypertension (ISH) remain controversial, particularly regarding the extent of pulse pressure amplification (PPamp) compared with that of normotensives (NTs). Given the lack of ambulatory blood pressure monitoring (ABPM)-based data, this study evaluated 509 untreated young adults (18-35 years) who had undergone ABPM during the last decade, 109 who had undergone both ABPM and SphygmoCor analysis, and 26 newly recruited NTs. The agreement rate between office BP- and ABPM-based subtype classification was alarmingly low (50.7%). ISH was distinguishable from systolic-diastolic hypertension, the predominant subtype characterized by increased central BPs and stiffened arteries. The central hemodynamic parameters were all similar between patients with ISH and white-coat hypertension (WC). ISH patients had central BPs that were, albeit higher than those of NTs, at an upper-normal level that was comparable to those of WC patients. ISH patients had similar cfPWV but significantly higher PPamp than NTs (p = 0.032). The central hemodynamic parameters of the participants were further analyzed according to central pressure waveform types (A vs. B vs. C). Type C waves were associated with the highest PPamp and lowest cfPWV, whereas type A waves were associated with the lowest PPamp and highest cfPWV. Subjects with type B waves, an intermediate form, also had considerably high PPamps. Waveform composition differed significantly across hypertension subtypes (p < 0.001). ISH patients mostly had type B or C waves (96.7%), with only 3.3% having type A waves. This study based on a refined diagnosis showed that the ambulatory ISH of young adults arises from highly elastic arteries and related robustness of PPamp and shares similar central hemodynamic characteristics with WC patients.
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Pressão Sanguínea/fisiologia , Hemodinâmica/fisiologia , Hipertensão/fisiopatologia , Adolescente , Adulto , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sístole , Adulto JovemRESUMO
PURPOSE: Dyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD. METHODS: This multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150-500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non-HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment. FINDINGS: The difference in the mean percentage change in non-HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was -12.45% (95% CI, -17.18 to -7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non-HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. IMPLICATIONS: In these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non-HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.
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Dislipidemias/tratamento farmacológico , Fenofibrato/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Apolipoproteínas B/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , República da Coreia , Triglicerídeos/sangueRESUMO
OBJECTIVE: The aim of this study was to evaluate under target rates of low-density lipoprotein-cholesterol (LDL-C) in Korean patients with stable coronary artery disease (CAD) or an acute coronary syndrome (ACS) in real world practice. METHODS: Dyslipidemia International Study II was an international observational study of patients with stable CAD or an ACS. Lipid profiles and use of lipid-lowering therapy (LLT) were documented at enrollment, and for the ACS cohort, 4 months follow-up was recommended. Rates of under target LDL-C as per European guidelines, were evaluated, and multivariate regression was performed to identify predictive factors of patients presenting under the target. RESULTS: A total of 808 patients were enrolled in Korea, 500 with stable CAD and 308 with ACS. Of these, 90.6% and 52.6% were being treated with LLT, respectively. In the stable CAD group, 40.0% were under target LDL-C, while in ACS group, the rate was 23.7%. A higher statin dose was independently associated with under target LDL-C in both groups (OR, 1.03; p=0.046 [stable CAD] and OR, 1.05; p=0.01 [ACS]). The mean statin dosage (atorvastatin equivalent) was 17 mg/day. In the 79 ACS patients who underwent the follow-up examination, the LDL-C under target rate rose to 59.5%. CONCLUSION: Only a minority of patients with stable CAD or ACS were under their target LDL-C level at enrollment. The statin dose was not sufficient in the majority of patients. These results indicate a considerable LLT gap in Korean patients with established CAD.
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OBJECTIVES: We previously demonstrated that sphingosine kinase (SPK) increases the level of extracellular sphingosine-1-phosphate and promotes neovascularization in a mouse matrigel model. In this study, we tested the hypothesis that SPK gene transfer using a novel adenoviral 'gutless' vector (AGV) can enhance arteriogenesis in a rabbit hindlimb ischemia model. METHODS: Thirty-five male New Zealand white rabbits were randomized to the AGV-SPK group (n=13), AGV-null group (n=13), and control group (n=9). On day 10, after the induction of unilateral hindlimb ischemia, gene vectors or buffer were introduced and the effect examined on day 30, using calf blood pressure, quantitative angiographic analysis, and histology. RESULTS: Calf systolic blood pressure ratios of the ischemic limb to the normal limb on day 30 were 0.77+/-0.13 in control groups, including the AGV-null group, and 0.91+/-0.14 in the AGV-SPK group (P<0.05). Angiographic vessel counts were significantly increased (8.0+/-2.1 at baseline and 11.8+/-3.2 on day 30, P<0.001) in the AGV-SPK group. Histologic analysis showed that microscopic total vessel counts on day 30 were 3.5+/-1.8/field in the control and AGV-null group and 5.4+/-1.0/field in the AGV-SPK group. Arterioles (AGV-SPK; 3.0+/-0.8 versus control and AGV-null; 2.1+/-1.1, P<0.05) were significantly increased in the AGV-SPK group. CONCLUSIONS: This study shows that SPK promotes arteriogenesis, as evidenced by the maximal improvement in the blood pressure restoration and collateral vessel counts. SPK may be an important angiogenic target to improve perfusion in ischemic tissues.
Assuntos
Indutores da Angiogênese/metabolismo , Terapia Genética/métodos , Isquemia/tratamento farmacológico , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Adenoviridae/genética , Indutores da Angiogênese/uso terapêutico , Angiografia , Animais , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/crescimento & desenvolvimento , Técnicas de Transferência de Genes , Vetores Genéticos/biossíntese , Membro Posterior/irrigação sanguínea , Masculino , Modelos Animais , Neovascularização Fisiológica/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/uso terapêutico , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacosRESUMO
OBJECTIVE: Opioids have a cardioprotective effect during ischemia. Previously, we showed in an ex-vivo model of myocardial ischemia and reperfusion that 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2, a highly potent and long-acting opioid peptide analgesic with fewer side effects than morphine, provides improved cardioprotection compared with morphine. The purpose of this study was to confirm, in an in-vivo model, the cardioprotective effect of 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2. METHODS: Rats (n=6/group) were randomized to 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 therapy (intravenous 10 nmol bolus 30 min before ligation and 10 nmol/h continuous infusion), morphine (100 nmol bolus and 100 nmol/h infusion), or placebo, and underwent left anterior descending (LAD) ligation for 10 min followed by reperfusion for 30 min. Continuous transesophageal echocardiogram and electrocardiogram were monitored. Fractional shortening and systolic wall thickening of the ischemic area were calculated. Time to recovery of left ventricular function was the duration of time needed for fractional shortening to recover to 90% of baseline following reperfusion. Duration of reperfusion arrhythmia was the time to the cessation of salvo (at least three consecutive premature ventricular contractions (PVCs)) following reperfusion. RESULTS: Time to recovery of left ventricular function was significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (4.4+/-2.2 min) and morphine groups (6.0+/-2.5 min) than in the controls (10.5+/-2.2 min; p<0.01). The 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 group showed significantly higher fractional shortening and systolic wall thickening of the ischemic area than the control group. Duration of reperfusion arrhythmia was also significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (2.8+/-1.7 min) and morphine groups (5.8+/-3.9 min) than in the controls (11.8+/-2.0 min; p<0.05). CONCLUSION: 2',6'-Dimethyltyrosine-D-Arg-Phe-Lys-NH2 provides a cardioprotective effect against myocardial ischemia and reperfusion in vivo.
Assuntos
Traumatismo por Reperfusão Miocárdica/complicações , Miocárdio Atordoado/prevenção & controle , Oligopeptídeos/farmacologia , Animais , Modelos Animais de Doenças , Ecocardiografia , Miocárdio Atordoado/etiologia , Miocárdio Atordoado/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Opioides/agonistas , Volume Sistólico/efeitos dos fármacos , Sístole/efeitos dos fármacos , Sístole/fisiologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
OBJECTIVE: Mild systemic hypothermia has been shown to be feasible and safe in patients during acute myocardial infarction (AMI). Regional myocardial hypothermia of the ischemic myocardium only may be more effective in myocardial salvage with fewer side effects compared with systemic hypothermia. The purpose of this study was to evaluate the feasibility and safety of regional myocardial hypothermia in pigs. METHODS: Open-chest pigs with (n=5) or without (n=4) myocardial infarction underwent left anterior descending coronary artery (LAD) ligation followed by intracoronary infusion of lactated Ringer's solution (at room temperature and at 15 degrees C between 20-35 ml/min for 3 min) via the central lumen of a specially designed balloon catheter at the time of reperfusion. Intramyocardial temperatures via thermocouples at the ischemic zone (LAD territory) and non-ischemic zone (circumflex territory) as well as systemic temperature were constantly recorded, as were the hemodynamics. Each pig acted as its control regarding the myocardial temperature response to both solutions. In addition, intracoronary versus intramyocardial temperatures were compared with thermocouples in both territories during infusion. RESULTS: There was no hemodynamic compromise or arrhythmia seen during the intracoronary infusion of either temperature solution. There was a linear relationship between the infusion solution temperature and infusion rate versus intramyocardial temperature response, with the cooled solution providing 2 degrees C lower temperature and faster infusion resulting in lower intramyocardial temperature. There was no change in the non-ischemic zone or systemic temperature. On average, 6-8 degrees C reduction in tissue temperature, potential target temperature range for hypothermic therapy, was achieved in all animals. In addition, intracoronary temperature in distal LAD measured by intracoronary thermocouples correlated with the intramyocardial temperature (2 degrees C lower temperature in the coronary artery). CONCLUSION: It is feasible and safe to achieve regional myocardial hypothermia by intracoronary infusion of cooled solution in pigs.
Assuntos
Hipotermia Induzida , Isquemia Miocárdica/terapia , Animais , Temperatura Corporal/fisiologia , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Eletrocardiografia , Estudos de Viabilidade , Coração/fisiopatologia , Hipotermia Induzida/métodos , Hipotermia Induzida/normas , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/fisiopatologia , Segurança , Suínos , Resultado do TratamentoRESUMO
OBJECTIVE: Chronic total occlusion (CTO) of coronary arteries represents a challenge for percutaneous treatment. Although ameroid constrictors have been used to create CTOs from extrinsic compression of coronary arteries, this model is not suitable for evaluation of novel angioplasty equipment. Thus, the objective of this study was to create a new percutaneous animal model of CTO. METHODS: To create an animal model of CTO, we implanted copper-plated stents in the left circumflex coronary arteries of 18 pigs, and assigned the pigs to early group (n = 6; sacrifice at approximately 1 week), intermediate group (n = 6; sacrifice at approximately 4 weeks), and late group (n = 6; sacrifice at approximately 8 weeks). RESULTS: Follow-up angiography prior to sacrifice revealed complete occlusion in 14 of 17 animals, with the subtotal occlusive lesions (mean 60% stenosis) only in the early group. Most of the pigs with total occlusions (12 of 14) showed bridging collateral flow greater than or equal to grade 2 (grade 2: 4; grade 3: 8). Histology revealed organizing thrombus in the early group with persistent inflammation, and organized thrombus with fibrosis and calcification in the intermediate and late groups. Interestingly, there were fibrotic components in the proximal and distal edges of the occlusions with softer, organizing thrombus in the middle of the CTO in the late group, suggesting that the major areas of difficulty are at the entrance and exit segments of the CTO with percutaneous recanalization. CONCLUSION: This study shows the feasibility and reproducibility of a new porcine coronary percutaneous CTO model. This model may be useful in improving our percutaneous treatment of CTO.
Assuntos
Implante de Prótese Vascular/instrumentação , Doença das Coronárias/cirurgia , Modelos Animais de Doenças , Stents , Animais , Doença Crônica , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/patologia , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Estudos de Viabilidade , Seguimentos , Projetos Piloto , Reprodutibilidade dos Testes , Suínos , Resultado do TratamentoRESUMO
Renin-angiotensin system (RAS) blockers have shown clinical outcomes superior to those of the beta (ß)-blocker atenolol, despite similar reductions in the peripheral blood pressure (BP), perhaps because of different impacts on central hemodynamics. However, few comparative studies of RAS blockers and newer vasodilating ß-blockers have been performed. We compared the central hemodynamic effects of losartan and carvedilol in a prospective, randomized, open, blinded end point study. Of the 201 hypertensive patients enrolled, 182 (49.6±9.9 years, losartan group=88 and carvedilol group=94) were analyzed. Carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), AIx corrected for a heart rate (HR) of 75 beats per minute (AIx@HR75) and central BP were measured noninvasively at baseline and after a 24-week treatment regimen with losartan or carvedilol. After 24 weeks, there were no between-group differences in the brachial BP, cfPWV, AIx@HR75 or central BP changes, except for a more favorable AIx effect with losartan. The changes in all measured metabolic and inflammatory parameters were also not significantly different between the two groups, except for uric acid. Losartan and carvedilol showed generally comparable effects on central hemodynamic indices, metabolic profile, inflammatory parameters and peripheral arterial pressure with a 24-week treatment.