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1.
J Cardiovasc Med (Hagerstown) ; 24(1): 52-58, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36473121

RESUMO

AIMS: The aim of the colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study is to evaluate the effects of the addition of short-term, low-dose colchicine to high-dose atorvastatin in limiting levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: The COLOR-ACS study is a multicenter, randomized, open-label, two-arm trial. Statin-naive patients with NSTE-ACS, scheduled for an early invasive strategy, are randomized on admission to receive standard treatment of atorvastatin 80 mg or standard treatment plus colchicine (1 mg loading dose followed by 0.5 mg/day until discharge). The main exclusion criteria are prior statin and/or colchicine treatment, current treatment with potent inhibitors of CYP3A4, P-glycoprotein or immunosuppressive drugs, known active malignancy, severe kidney, cardiac, liver disease. There is clinical and biochemical follow-up at 30 days after discharge and telephone interview at 6 months. The primary end point is the change in hs-CRP from admission to discharge. Secondary end points include: incidence of acute kidney injury; MB fraction of creatine kinase peak value; glomerular filtration rate change from baseline to 30 days; persistence of hs-CRP ≥2 mg/dl at 30 days; adverse clinical events within 30 days; tolerance to colchicine. CONCLUSION: The COLOR-ACS study will provide evidence on the efficacy of early short-term treatment with colchicine in addition to high-dose atorvastatin compared to atorvastatin alone in ACS patients. The potential anti-inflammatory action of colchicine plus atorvastatin is expected to limit hs-CRP increase with resultant clinical benefits. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05250596.


Assuntos
Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Atorvastatina/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Coronariana Aguda/terapia , Proteína C-Reativa/metabolismo , Colchicina/efeitos adversos , Resultado do Tratamento , Inflamação/tratamento farmacológico
2.
J Thorac Cardiovasc Surg ; 164(4): 1092-1101.e1, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33168168

RESUMO

OBJECTIVE: Both increased natriuretic peptide levels and restrictive filling pattern (RFP) are important risk predictors in patients with heart failure. The aim of this study was to examine the role of the combined use of natriuretic peptide and RFP for the prognostic stratification of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration in the Biomarker Plus study. METHODS: A total of 186 patients (aged 64 ± 10 years) underwent echocardiographic study and N-terminal pro-B-type natriuretic peptide assay at baseline (before surgical ventricular restoration). Patients were divided into 4 groups depending on baseline diastolic filling pattern (RFP/no RFP) and N-terminal pro-B-type natriuretic peptide level (less than or greater than or equal to the upper tertile value of 2003 ŋg/L). RFP was defined as E/A ratio ≥2. All-cause death or heart failure hospitalizations within 36-month follow-up were analyzed. RESULTS: Despite similar ejection fraction, volumes, and mass, the 4 groups presented distinct clinical and structural pattern of presurgical ventricular restoration ventricular remodeling and significantly different clinical outcome after surgical unloading. During follow-up, 67 patients died or were hospitalized for heart failure (36%). High N-terminal pro-B-type natriuretic peptide levels and RFP, considered individually, were significantly associated with outcome (P < .0001). The combination of both was associated with the highest adjusted hazard of adverse events (hazard ratio, 3.63; 95% CI, 1.73-7.6; P < .0001). CONCLUSIONS: The simultaneous use of 2 markers, 1 biological and 1 echocardiographic, may allow better prognostic stratification and characterization of the distinct structural and clinical phenotypes in a population of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration. This approach could be useful in the decision-making process to guide treatment choices in patients with ischemic cardiomyopathy.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Biomarcadores , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Remodelação Ventricular
3.
Artigo em Inglês | MEDLINE | ID: mdl-36612336

RESUMO

The relationship between endocrine disrupting chemical (EDC) exposure and Precocious Puberty (PP) was investigated in this pilot study, involving girls with signs of PP (P) and pre-pubertal girls (C). Risk factors for PP were assessed through questionnaires, while 17ß-oestradiol (E2) levels and oestrogenic activity were quantified on sera. The oestrogenic activity, expressed as E2 equivalent concentration (EEQ), was applied as EDC exposure biomarker. Questionnaires showed a low EDC knowledge, a high EDC exposure, and a potential relationship between some habits at risk for EDC exposure and PP. EEQs were similar between C and P; however, they were significantly higher in girls living in an urban environment than in girls living in a rural environment, suggesting a potential higher EDC exposure in cities. The results of this pilot study highlighted the need to raise awareness on EDCs and can be considered a starting point to clarify the relationship between EDC exposure and PP.


Assuntos
Disruptores Endócrinos , Puberdade Precoce , Feminino , Humanos , Disruptores Endócrinos/toxicidade , Projetos Piloto , Puberdade Precoce/induzido quimicamente , Estradiol , Estrona , Biomarcadores
4.
J Thorac Cardiovasc Surg ; 161(2): 651-660, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31767363

RESUMO

OBJECTIVE: To examine factors possibly involved in the resolution or persistence of restrictive filling pattern (RFP) after surgical ventricular restoration (SVR) in a series of patients with ischemic cardiomyopathy (ICM) and RFP. METHODS: Echocardiography was performed at baseline (pre-SVR), discharge, and follow-up in 43 patients with ICM and RFP (E/A ratio ≥2). Patients were divided into 2 groups based on E/A ratio at discharge: improved (E/A ratio <2; 22 patients) and unchanged (E/A ratio ≥2; 21 patients). RESULTS: The improved group had a significantly increased mean deceleration time (from 137 ± 22 ms to 194 ± 68 ms; P = .002) and mean A wave velocity (from 43 ± 10 cm/s to 92 ± 37 cm/s; P = .001), and decreased E/e' ratio (from 27.7 ± 9.5 to 19.2 ± 7.8; P = .01) after SVR. The unchanged group did not show any significant variations in diastolic parameters. The only significant differences at baseline between the two groups were thinner left ventricle posterior wall and lower relative wall thickness (RWT) in the unchanged group. RWT was the sole baseline parameter independently associated with persistent RFP. CONCLUSIONS: RFP was reversed after SVR in 22 of our 43 patients with ICM with a response that remained stable over time, associated with improved New York Heart Association class. RWT was the sole baseline echocardiographic parameter significantly associated with the evolution of RFP after SVR.


Assuntos
Isquemia Miocárdica/cirurgia , Disfunção Ventricular Esquerda/cirurgia , Idoso , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia
5.
Sci Total Environ ; 740: 140050, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32927569

RESUMO

Biological assays can evaluate the cumulative effect of a mixture, considering synergistic/antagonistic interactions and effects of unknown/unconsidered compounds. Therefore, their application could increase in the next years also to analyse biological samples. The aim of this review is to discuss the methodological approach and the application of estrogenic activity assays in human biological samples. 75 research articles were analysed and divided according to whether they used these assays: i) to quantify the level of estrogens and/or as a biomarker of estrogenic status ii) as a biomarker of exposure to endocrine disrupting chemicals (EDCs). For the first purpose, some authors extracted biological samples while others tested them directly without any treatment. The study of these methodologies outlined that the methodology applied influenced the specificity of analysis. The estrogenic activity biomarker was used to analyse physiological variations of estrogens, pediatric diseases, hormone-dependent diseases and estrogen suppression/enhancement after pharmaceutical treatments. For the second purpose, some authors extracted samples while others tested them directly, some authors divided endogenous estrogens from xenoestrogens while others tested samples without separation. The analysis of these methodologies outlined some limitations related to the efficiency of extraction and the incorrect separation of some compounds. The studies which applied this EDC biomarker showed that it was correlated with some EDCs, it varied according to the exposure of the population and it allowed the identification of some relationships between EDC exposure and breast cancer, type 1 diabetes and adverse health effects on children. In conclusion, the estrogenic activity of biological samples can be a useful tool: to quantify low levels of 17ß-estradiol, to assess the combined effect of endogenous estrogens and xenoestrogens, to estimate the estrogenic status providing considerable insight into physiological or pathological conditions, to evaluate EDC presence implementing the existing knowledge about EDC exposure and adverse health effects.


Assuntos
Disruptores Endócrinos , Biomarcadores , Criança , Estradiol , Estrogênios , Estrona , Humanos
6.
CJC Open ; 2(4): 236-243, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32695974

RESUMO

BACKGROUND: The residual burden of coronary artery disease after percutaneous coronary intervention (PCI) has been associated with worse ischemic outcome. However, data are conflicting in elderly patients. The aim of our study was to verify the incremental value of the residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (rSS) over clinical variables and baseline SYNTAX score (bSS) in predicting 1-year mortality or cardiovascular events. METHODS: A post hoc analysis of data collected in the Elderly-ACS 2 multicenter randomized trial was performed. We included 630 patients aged > 75 years with multivessel coronary disease undergoing PCI for acute coronary syndrome (ACS). The primary outcome was a composite of death, recurrent myocardial infarction, and stroke at 1-year follow up. Change in c-statistic and standardized net benefit were used to evaluate the incremental value of the rSS. RESULTS: Event rates were significantly higher in patients with incomplete revascularization (rSS > 8). When the rSS was included in a core Cox regression model containing age, previous myocardial infarction, and ACS type, the hazard ratio for patients with score values > 8 was 2.47 (95% confidence interval, 1.51-4.06). However, the core model with rSS did not increase the c-statistic compared with the core model with the bSS (from 0.69 to 0.70) and gave little incremental value in the standardized net benefit. CONCLUSIONS: In elderly patients with ACS with multivessel disease undergoing PCI, incomplete revascularization was associated with worse outcome at 1-year follow-up. However, there was no clear incremental value of the rSS in the prediction of 1-year adverse outcome compared with a model including clinical variables and bSS.


CONTEXTE: Le fardeau résiduel de la coronaropathie après une intervention coronarienne percutanée (ICP) a été associé à de moins bons résultats sur le plan ischémique. Les données recueillies chez les patients âgés sont toutefois contradictoires. Cette étude avait donc pour objectif de valider la valeur ajoutée du score SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) résiduel (SSr) par rapport aux paramètres cliniques et au score SYNTAX initial (SSi) pour prédire la mortalité à 1 an et les manifestations cardiovasculaires. MÉTHODOLOGIE: Une analyse a posteriori des données de l'étude multicentrique avec répartition aléatoire Elderly-ACS 2 a été effectuée. Pour ce faire, 630 patients âgés de plus de 75 ans, atteints d'une coronaropathie multitronculaire et ayant subi une ICP pour traiter un syndrome coronarien aigu (SCA) ont été retenus. Le critère d'évaluation principal était composé du décès, de l'infarctus du myocarde récurrent et de l'accident vasculaire cérébral (AVC) au moment du suivi à 1 an. La variation de la statistique C et le bénéfice net normalisé ont servi à évaluer la valeur ajoutée du SSr. RÉSULTATS: Les manifestations étaient significativement plus fréquentes chez les patients dont la revascularisation était incomplète (SSr > 8). Lorsque le SSr a été pris en compte dans un modèle de régression de Cox de base ayant pour facteurs l'âge, les antécédents d'infarctus du myocarde et le type de SCA, le rapport des risques instantanés pour les patients ayant un score > 8 était de 2,47 (intervalle de confiance à 95 % : 1,51-4,06). L'intégration du SSr dans le modèle de base n'a toutefois pas donné lieu à une statistique C plus élevée que celle du SSi (0,70 vs 0,69) et conférait peu de valeur ajoutée sur le plan du bénéfice net normalisé. CONCLUSIONS: Chez les patients âgés présentant un SCA et une atteinte multitronculaire, et subissant une ICP, la revascularisation incomplète a été associée à de moins bons résultats au moment du suivi à 1 an. Le SSr n'a toutefois pas été clairement associé à une valeur ajoutée pour prédire une issue défavorable à 1 an comparativement à un modèle reposant sur des paramètres cliniques et le SSi.

7.
J Am Heart Assoc ; 8(2): e010956, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30636561

RESUMO

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( Padj<0.001) without a difference in ADBRs ( Padj=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( Padj<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( Padj<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Infarto do Miocárdio/etiologia , Cloridrato de Prasugrel/efeitos adversos , Síndrome Coronariana Aguda/cirurgia , Idoso , Clopidogrel/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Hemorragia/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/administração & dosagem , Prognóstico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Método Simples-Cego , Taxa de Sobrevida/tendências , Fatores de Tempo
8.
J Am Coll Cardiol ; 71(25): 2880-2889, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29929610

RESUMO

BACKGROUND: Intravascular volume expansion plays a major role in the prevention of contrast-induced acute kidney injury (CI-AKI). Recommended standard amounts of fluid infusion before procedures do not produce homogeneous responses in subjects with different initial hydration status. OBJECTIVES: The goal of this study was to compare the effect of standard and double intravenous (IV) infusion volumes in patients with low body fluid level, assessed by using bioimpedance vector analysis (BIVA), on the incidence of CI-AKI after elective coronary angiographic procedures. METHODS: A total of 303 patients with low BIVA level on admission were randomized to receive standard volume saline (1 ml/kg/h for 12 h before and after the procedure) or double volume saline (2 ml/kg/h). Patients (n = 715) with an optimal BIVA level received standard volume saline and were included in a prospective registry. The saline infusion was halved in all patients with an ejection fraction <40%. BIVA was repeated immediately before the angiographic procedure in all patients. CI-AKI was defined as an increase in levels of cystatin C ≥10% above baseline at 24 h after contrast administration. RESULTS: The incidence of CI-AKI was significantly lower (11.5% vs. 22.3%; p = 0.015) in patients receiving double volume saline than in those receiving standard volume saline, respectively. Before the angiographic procedure, 50% of the double volume patients achieved the optimal BIVA level compared with only 27.7% in the standard group (p = 0.0001). The findings were consistent in all the pre-specified subgroups excluding patients with a left ventricular ejection fraction <40% (p for interaction = 0.01). CONCLUSIONS: Evaluation of BIVA levels on admission in patients with stable coronary artery disease allows adjustment of intravascular volume expansion, resulting in lower CI-AKI occurrence after angiographic procedures. (Personalized Versus Standard Hydration for Prevention of CI-AKI: A Randomized Trial With Bioimpedance Analysis; NCT02225431).


Assuntos
Injúria Renal Aguda/prevenção & controle , Composição Corporal , Meios de Contraste/efeitos adversos , Impedância Elétrica , Solução Salina/administração & dosagem , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Feminino , Humanos , Incidência , Infusões Intravenosas , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade
9.
Am Heart J ; 181: 101-106, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27823681

RESUMO

BACKGROUND: Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding. STUDY DESIGN: The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score). CONCLUSION: The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503).


Assuntos
Síndrome Coronariana Aguda/terapia , Aspirina/uso terapêutico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Clopidogrel , Quimioterapia Combinada , Intervenção Médica Precoce , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Mortalidade , Infarto do Miocárdio/epidemiologia , Readmissão do Paciente , Recidiva , Acidente Vascular Cerebral/epidemiologia , Ticlopidina/uso terapêutico , Resultado do Tratamento
10.
JACC Cardiovasc Interv ; 7(10): 1117-27, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25240538

RESUMO

OBJECTIVES: The aim of this study was to investigate the association between high on-treatment platelet reactivity (HPR) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) for risk prediction of major adverse cardiovascular events (MACE) in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Platelet function testing may be used to optimize antiplatelet therapy in high-risk patients, but identification of this category of patients remains challenging. METHODS: The GEPRESS (Gene Polymorphism, Platelet Reactivity, and the Syntax Score) study was a prospective, multicenter, observational study enrolling 1,053 patients with NSTEACS undergoing PCI and treated with clopidogrel. The platelet reactivity index (PRI) was measured at 3 time points: before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertile ≥15). The primary objective of this study was the risk of MACE in the period between 1 month and 1 year. RESULTS: Between 1 month and 1 year, 1-month HPR was an independent predictor of MACE in patients with an SS ≥15, but not in those with an SS <15, displaying a 5-fold increase in event rates (10.4% vs. 2.5%; p < 0.0001). CYP2C19*2 was the only single nucleotide polymorphism associated with HPR, but it was not associated with MACE. Although there was a significant variability in the PRI across the 1-month period, predischarge HPR and SS effectively stratified the risk of subsequent MACE up to 1-year follow-up. CONCLUSIONS: In clopidogrel-treated patients with NSTEACS undergoing PCI, HPR was independently associated with an increased risk of MACE only in the presence of a high SS.


Assuntos
Síndrome Coronariana Aguda/terapia , Plaquetas/efeitos dos fármacos , Angiografia Coronária , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária , Polimorfismo Genético , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Biotransformação/genética , Plaquetas/metabolismo , Clopidogrel , Trombose Coronária/sangue , Trombose Coronária/etiologia , Citocromo P-450 CYP2C19/metabolismo , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Razão de Chances , Intervenção Coronária Percutânea/mortalidade , Fenótipo , Inibidores da Agregação Plaquetária/farmacocinética , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Ticlopidina/farmacocinética , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
11.
G Ital Cardiol (Rome) ; 14(9): 574-84, 2013 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-23903277

RESUMO

Antiplatelet therapy with clopidogrel should be administered to patients with acute coronary syndromes and those submitted to percutaneous coronary intervention (PCI) (secondary prevention). Clopidogrel is a pro-drug which requires hepatic cytochrome P450 (CYP) metabolic activation to produce the active metabolite that inhibits platelet aggregation. CYP2C19 and CYP3A4/5 are the principal contributors in the two-step hepatic oxidation of clopidgrel. However, the response to clopidogrel is not uniform; it varies from patients platelet reactivity on standard-dose clopidogrel are at increased risk of recurrence of adverse cardiovascular events. Also drug-drug interactions that influence the function of CYP isoenzymes may affect the response to clopidogrel. Lipophilic statins, such as atorvastatin, are predominantly metabolized by CYP3A4 and may interfere with CYP activation of clopidogrel, contrary to what happens with hydrophilic statins, such as rosuvastin or pravastatin. Recently, it has been shown that in patients who presented post-PCI high on-treatment platelet reactivity on standard-dose clopidogrel during chronic treatment with clopidogrel and low-dose atorvastatin (10 mg), switching to a non-CYP3A4-metabolized statin, such as rosuvastatin or pravastatin, resulted in a significant decrease in platelet reactivity. The clinical benefit of statins is attributed to mulitple mechanisms which go beyond their lipid-lowering effects and include also antithrombotic properties. In particular, atorvastatin inhibits adenosine diphospate and thrombin-induced platelet aggregation. Moreover, pharmacodynamic studies appear to show some synergy between clopidogrel and atorvastatin: the enhancement of clopidogrel effects due to atorvastatin seems to be dose-related and independent of LDL cholesterol reduction. A recent study shows that the addition of high-dose atorvastatin (80mg) for 30 days significantly improves the pharmacodynamic effects of double-dose clopidogrel, reducing platelet reactivity and improving optimal clopidogrel response in statin naïve patients with high-on treatment platelet reactivity on standard-dose clopidogrel. These pharmacodynamic studies suggest that switching to a no CYP3A4-metabolized statin in patients with high on-treatment platelet reactivity on standard-dose clopidogre on chronic treatment with low-dose atorvastatin or administration of high-dose atorvastatin maybe two alternative strategies to avoid possible negative drug-drug interactions and to improve individual patient response to clopidogrel.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Ensaios Clínicos como Assunto , Clopidogrel , Interações Medicamentosas , Humanos , Ticlopidina/farmacologia
12.
JACC Cardiovasc Interv ; 6(2): 169-79, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23428009

RESUMO

OBJECTIVES: The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic (PD) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease (CAD) and high-on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel before percutaneous coronary intervention (PCI). BACKGROUND: Patients with HTPR are at increased risk of adverse cardiovascular events after PCI. High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms, including antithrombotic effects. METHODS: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study was a randomized PD study of high-dose (80 mg) atorvastatin in addition to double-dose (150 mg) clopidogrel (atorvastatin group, n = 38) versus double-dose clopidogrel alone (control group, n = 38) in patients with HTPR. HTPR was defined as P2Y(12) reaction units (PRU) ≥235 by the VerifyNow P2Y12 assay. Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days. RESULTS: Patients randomized to atorvastatin had lower PRU values (188 ± 48 vs. 223 ± 53 PRU, p < 0.01; primary endpoint) and HTPR rates (16% vs. 42%, p < 0.01) at 30 days than patients in the control group. Statin treatment (odds ratio [OR]: 3.8, p = 0.011), baseline PRU <298 (OR: 10.7, p = 0.0001), noncarrier status of CYP2C19*2 loss-of-function allele (OR: 2.9, p = 0.043), and age (OR: 0.94, p = 0.032) were variables significantly associated with optimal PD response (PRU <235) at 30 days. No correlations were found between PRU and lipid fractions. CONCLUSIONS: High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ACHIDO]; NCT01335048).


Assuntos
Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/terapia , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Pirróis/administração & dosagem , Ticlopidina/análogos & derivados , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Hidrocarboneto de Aril Hidroxilases/genética , Atorvastatina , Plaquetas/metabolismo , Distribuição de Qui-Quadrado , Clopidogrel , Doença da Artéria Coronariana/sangue , Citocromo P-450 CYP2C19 , Interações Medicamentosas , Resistência a Medicamentos , Feminino , Ácidos Heptanoicos/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Itália , Masculino , Pessoa de Meia-Idade , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Farmacogenética , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Pirróis/efeitos adversos , Receptores Purinérgicos P2Y12/sangue , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Medição de Risco , Fatores de Risco , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
13.
JACC Cardiovasc Interv ; 5(9): 906-16, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22995877

RESUMO

OBJECTIVES: This study sought to determine the risk versus benefit ratio of an early aggressive (EA) approach in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS). BACKGROUND: Elderly patients have been scarcely represented in trials comparing treatment strategies in NSTEACS. METHODS: A total of 313 patients ≥ 75 years of age (mean 82 years) with NSTEACS within 48 h from qualifying symptoms were randomly allocated to an EA strategy (coronary angiography and, when indicated, revascularization within 72 h) or an initially conservative (IC) strategy (angiography and revascularization only for recurrent ischemia). The primary endpoint was the composite of death, myocardial infarction, disabling stroke, and repeat hospital stay for cardiovascular causes or severe bleeding within 1 year. RESULTS: During admission, 88% of the patients in the EA group underwent angiography (55% revascularization), compared with 29% (23% revascularization) in the IC group. The primary outcome occurred in 43 patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not differ between groups. The primary endpoint was significantly reduced in patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for interaction = 0.03). CONCLUSIONS: The present study does not allow a definite conclusion about the benefit of an EA approach when applied systematically among elderly patients with NSTEACS. The finding of a significant interaction for the treatment effect according to troponin status at baseline should be confirmed in a larger size trial. (Italian Elderly ACS Study; NCT00510185).


Assuntos
Síndrome Coronariana Aguda/terapia , Ponte de Artéria Coronária , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Fármacos Cardiovasculares/uso terapêutico , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio/etiologia , Readmissão do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Hemorragia Pós-Operatória/etiologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Troponina/sangue , Regulação para Cima
14.
J Cardiovasc Med (Hagerstown) ; 12(5): 318-21, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21045713

RESUMO

OBJECTIVES: Short-term high-dose atorvastatin administered before percutaneous coronary intervention (PCI) reduces the rate of periprocedural myocardial infarction (pMI) in high-risk patients, such as those with acute coronary syndromes and those with elevated high-sensitivity C-reactive protein. It is unknown whether short-term high-dose administration reduces the rate of pMI in patients with chronic kidney disease. Recently, we observed that in 304 patients with estimated creatinine clearance less than 60 ml/min randomized to receive 80 mg/day of atorvastatin or placebo for 48 h before elective coronary angiography and/or angioplasty, statin administration did not reduce contrast-induced nephropathy (CIN). In this post-hoc analysis, we evaluate the pMI in the subgroup of 161 patients who underwent PCI. METHODS: In all patients, creatine kinase myocardial isoenzyme (CK-MB) [upper reference limit (URL) 5 ng/ml] was assessed before and at 12 and 24 h after PCI. The pMI, defined as CK-MB elevation more than three times the URL, occurred in 27 (17%) patients. RESULTS: The incidence of pMI was 10.4% (of 77 patients) in the atorvastatin and 23% (of 84 patients) in the placebo group (P < 0.05). Multivariate analysis identified the pretreatment with high-dose atorvastatin as an independent predictor of reduced risk of pMI [odds ratio 0.39, 95% confidence interval 0.16-0.96, P < 0.05]. CONCLUSION: This post-hoc analysis shows that short-term high-dose atorvastatin administration reduced pMI in patients with renal dysfunction submitted to elective PCI, but without benefit regarding CIN prevention.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Doença da Artéria Coronariana/terapia , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Nefropatias/complicações , Infarto do Miocárdio/prevenção & controle , Pirróis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Atorvastatina , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Creatina Quinase Forma MB/sangue , Creatinina/sangue , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular , Humanos , Itália , Nefropatias/sangue , Nefropatias/fisiopatologia , Modelos Logísticos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
15.
J Thorac Cardiovasc Surg ; 140(6): 1325-31.e1-2, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20381078

RESUMO

OBJECTIVE: Left ventricular end-diastolic volume is decreased and ejection fraction is increased after surgical ventricular reconstruction; however, the impact on left ventricular stroke volume is not well established. METHODS: We analyzed 248 consecutive patients who underwent surgical ventricular reconstruction at a single center. There were 14 perioperative deaths (5.6%). The 234 surviving patients had pre- and postsurgical ventricular reconstruction echocardiographic measurement of end-diastolic volume, end-systolic volume, and stroke volume, each indexed to body size and ejection fraction. A total of 120 patients had echocardiography data at follow-up (median 8 months). RESULTS: Overall, surgical ventricular reconstruction resulted in reductions in end-diastolic volume index (-30% ± 18%) and end-systolic volume index (-37% ± 20%), and increases in ejection fraction (21% ± 18% relative increase). However, stroke volume index decreased from 35 ± 8 mL/m(2) preoperatively to 28 ± 7 mL/m(2) early postoperatively (a 17% ± 24% relative reduction, P < .0001); 165 patients (71%) exhibited a decrease and 69 patients (29%) exhibited an increase or no change in stroke volume index after surgical ventricular reconstruction. Stroke volume index reduction was strictly related to end-diastolic volume reduction. Patients who initially had a stroke volume index decrease showed recovery, so that at the time of chronic follow-up there was no significant difference between the groups. Notably, 4-year survival was approximately 85% and did not differ between patients with an increase or decrease in stroke volume index (P = .383). CONCLUSIONS: Although surgical ventricular reconstruction uniformly results in an impressive decrease in end-diastolic volume index and increase in ejection fraction, seemingly indicating beneficial remodeling and improved pump function, systolic volume index, which more directly indexes cardiac pump function, frequently decreases after surgical ventricular reconstruction. Further study is needed to identify baseline characteristics that predict those patients in whom cardiac performance is enhanced by surgical ventricular reconstruction and to clarify whether there is a beneficial impact on exercise tolerance and cardiac output at peak exercise.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiomiopatias/cirurgia , Ventrículos do Coração/cirurgia , Isquemia Miocárdica/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Volume Sistólico , Análise de Variância , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
16.
J Cardiovasc Med (Hagerstown) ; 11(6): 444-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20164783

RESUMO

OBJECTIVES: To develop a simplified scoring system based on preprocedure clinical characteristics to predict contrast-induced nephropathy (CIN) before elective coronary angiography and percutaneous coronary intervention (PCI). BACKGROUND: CIN is associated with increased mortality and morbidity following coronary angiography and PCI and accounts for increased hospital costs. METHODS: Several baseline clinical characteristics of 1218 patients were considered as candidate univariate predictors of CIN (increase > or =0.5 mg/dl in serum creatinine within 5 days after contrast exposure). On the basis of the odds ratio at multivariate logistic regression, seven markers (with weighted scores) were identified as independent correlates of CIN: age at least 73 years (1), diabetes mellitus (2), left ventricular ejection fraction 45% or less (2), baseline serum creatinine value at least 1.5 mg/dl (2), baseline creatinine clearance 44 ml/min or less (2), posthydration creatinine > or = prehydration creatinine value (2) and one procedure effected within the past 72 h (3). RESULTS: CIN occurred in 114 (9.4%) patients [range 1.1-52.1% for a low (< or =3) and very high (> or =9) risk score, respectively]; the odds of CIN increased significantly with each class (Cochran-Armitage chi-square, P < 0.0001) and the risk score allowed us to determine patients with low and high risk for postprocedure CIN (c-statistic = 0.86). These results were reproduced in a validation set. CONCLUSION: Preprocedural clinical risk factors have different influences on the likelihood of CIN. Risk classification based on the most significant parameters can be used to predict CIN before contrast exposure. The simple scoring system proposed here provides a good estimate of the risk of CIN, allowing the interventional team to make adequate adjustment to the procedures.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Ácidos Tri-Iodobenzoicos/efeitos adversos , Idoso , Angioplastia Coronária com Balão , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Medição de Risco
17.
Am J Cardiol ; 105(3): 288-92, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20102936

RESUMO

We investigated the efficacy of short-term high-dose atorvastatin in decreasing the risk of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) subjected to coronary angiography and/or angioplasty. CIN occurs in up to 15% of patients with pre-existing CKD and affects clinical outcome. The protective effect of statin therapy against CIN is still controversial. A prospective, single-center study of 304 patients with baseline estimated creatinine clearance <60 ml/min were randomized to receive atorvastatin 80 mg/day or placebo for 48 hours before and 48 hours after contrast medium administration. All patients received intravenous saline hydration and oral N-acetylcysteine 1,200 mg 2 times/day. Iso-osmolar contrast medium was used. CIN was defined as an absolute increase of serum creatinine > or = 0.5 mg/dl within 5 days after the procedure. CIN occurred in 31 patients (10%), 16 (11%) in the placebo group and 15 (10%) in the atorvastatin group (p = 0.86). Mean increase in creatinine was not significantly different in the 2 groups (0.59 + or - 0.17 in placebo group vs 0.72 + or - 0.26 mg/dl in atorvastatin group, p = 0.31). Persistent kidney injury, defined as 1-month increase from baseline creatinine value > or = 25%, was observed in 30% in the placebo group and in 31% in the atorvastatin group (p = 0.58). In conclusion, a short-term administration of high doses of atorvastatin before and after contrast exposure, in addition to standard intravenous hydration and oral N-acetylcysteine, does not decrease CIN occurrence in patients with pre-existing CKD.


Assuntos
Injúria Renal Aguda/prevenção & controle , Anticolesterolemiantes/uso terapêutico , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Ácidos Heptanoicos/uso terapêutico , Pirróis/uso terapêutico , Insuficiência Renal Crônica/induzido quimicamente , Acetilcisteína/uso terapêutico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Atorvastatina , Biomarcadores/sangue , Meios de Contraste/administração & dosagem , Creatinina/sangue , Feminino , Hidratação , Humanos , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Fatores de Risco
18.
J Am Coll Cardiol ; 52(8): 599-604, 2008 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-18702961

RESUMO

OBJECTIVES: The purpose of this study was to compare the efficacy of sodium bicarbonate versus isotonic saline in addition to N-acetylcysteine (NAC) to prevent contrast-induced nephropathy (CIN) in a larger population of patients with renal dysfunction undergoing coronary angiography or intervention. BACKGROUND: Contrast-induced nephropathy accounts for more than 10% of hospital-acquired renal failure. Recent studies suggest that hydration with sodium bicarbonate is more protective than isotonic saline in the prevention of CIN. METHODS: The prospective, single center study included 502 patients with estimated creatinine clearance <60 ml/min, randomized to receive infusion of either saline or sodium bicarbonate before and after iso-osmolar contrast medium administration. All patients received oral NAC 600 mg twice a day. Contrast-induced nephropathy was defined as an absolute increase of serum creatinine > or =0.5 mg/dl measured within 5 days. RESULTS: Contrast-induced nephropathy occurred in 54 patients (10.8%); 25 (10%) were treated with sodium bicarbonate and 29 (11.5%) with saline (p = 0.60). In patients with CIN, the mean increase in creatinine was not significantly different in the 2 study groups (0.9 +/- 0.6 mg/dl vs. 0.7 +/- 0.2 mg/dl, respectively; p = 0.15). Only 2 patients needed temporary hemofiltration. CONCLUSIONS: Hydration with sodium bicarbonate plus NAC before contrast medium exposure is not more effective than hydration with isotonic saline plus NAC for prophylaxis of CIN in patients with moderate-to-severe renal dysfunction. (Sodium Bicarbonate Versus Saline for the Prevention of Contrast-Induced Nephropathy; NCT00606827).


Assuntos
Angiografia Coronária , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Bicarbonato de Sódio/administração & dosagem , Cloreto de Sódio/administração & dosagem , Idoso , Angioplastia Coronária com Balão , Doença das Coronárias/epidemiologia , Doença das Coronárias/terapia , Creatinina/sangue , Feminino , Humanos , Masculino , Estudos Prospectivos , Insuficiência Renal/epidemiologia , Fatores de Risco
19.
Ann Thorac Surg ; 82(6): 2102-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17126118

RESUMO

BACKGROUND: We sought to analyze the characteristics of local left ventricular deformation related to functional mitral regurgitation (MR) in post-anterior myocardial infarction scar, and to evaluate how local remodeling contributes to late development of MR after surgical ventricular reconstruction by endoventricular circular patch plasty repair. METHODS: Two hundred twenty-one consecutive patients (aged 60 +/- 9 years; 193 males) with previous transmural anterior infarction underwent heart catheterization both before and 1 year after endoventricular circular patch plasty repair. Preoperative global left ventricular shape determinants (eccentricity and circularity indexes), regional curvature and wall motion (centerline), and both preoperative and 1-year postoperative hemodynamic parameters (volumes, ejection fraction, capillary wedge and pulmonary artery pressures) were calculated. RESULTS: Forty-eight patients had (MR patients), and 173 did not have (NoMR patients) angiographic MR grade 2 or more preoperatively; at follow-up, 30 NoMR patients had MR (late MR [LMR]). Before surgery, MR patients had larger left ventricular volumes, higher capillary wedge and mean pulmonary artery pressures, and lower ejection fraction and cardiac index. The LMR patients had similarly high capillary wedge and pulmonary artery pressures as MR patients; otherwise, they did not differ from NoMR patients. Mitral regurgitation patients had wider lateral wall akinesia and greater inferior wall asynergy; the inferobasal region was hypokinetic in LMR patients. In MR patients, inferior wall systolic curvature was less negative; the inferobasal region had a more positive curvature in LMR patients. CONCLUSIONS: Local deformation of the inferior wall with loss of systolic inward bending is associated with functional MR, while asynergy and systolic deformation of the inferobasal region and high capillary wedge pressure are prognostic signs of MR development late after endoventricular circular patch plasty repair.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ventrículos do Coração/cirurgia , Insuficiência da Valva Mitral/fisiopatologia , Remodelação Ventricular/fisiologia , Idoso , Cateterismo Cardíaco , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Infarto do Miocárdio/complicações , Estudos Retrospectivos
20.
Circulation ; 109(21): 2536-43, 2004 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-15159292

RESUMO

BACKGROUND: In ischemic cardiomyopathy, dyssynchrony of left ventricular (LV) mechanical contraction produces adverse hemodynamic consequences. This study tests the capacity of geometric rebuilding by surgical ventricular restoration (SVR) to restore a more synchronous contractile pattern after a mechanical, rather than electrical, intervention. METHODS AND RESULTS: A prospective study of the global and regional components of dyssynchrony was conducted in 30 patients (58+/-8 years of age) undergoing SVR at the Cardiothoracic Center of Monaco. The protocol used simultaneous measurements of ventricular volumes and pressure to construct pressure/volume (P/V) and pressure/length (P/L) loops. Angiograms were done before and after SVR to study a 600-ms cycle during atrial pacing at 100 bpm. Mean QRS duration was similar, at 100+/-17 ms preoperatively and 114+/-28 ms postoperatively (NS). Preoperative LV contraction was highly asynchronous, because P/V loops showed abnormal isometric phases with a right shifting. Endocardial time motion was either early or delayed at the end-systolic phase so that P/L loops were markedly abnormal in size, shape, and orientation. Postoperatively, SVR resulted in leftward shifting of P/V loops and increased area; endocardial time motion and P/L loops almost normalized to allow a better contribution of single regions to global ejection. The hemodynamic consequences of SVR were improved ejection fraction (30+/-13% to 45+/-12%; P=0.001); reduced end-diastolic and end-systolic volume index (202+/-76 to 122+/-48 and 144+/-69 to 69+/-40 mL/m(2); P=0.001); more rapid peak filling rate (1.75+/-0.7 to 2.32+/-0.7 EDV/s; P=0.0001); peak ejection rate (1.7+/-0.7 to 2.6+/-0.9 Sv/s; P=0.0002), and mechanical efficiency (0.56+/-0.15 to 0.65+/-0.18; P=0.04). CONCLUSIONS: SVR produces a mechanical intraventricular resynchronization that improves LV performance.


Assuntos
Ventrículos do Coração/cirurgia , Anastomose de Artéria Torácica Interna-Coronária , Isquemia Miocárdica/cirurgia , Disfunção Ventricular Esquerda/cirurgia , Idoso , Cateterismo Cardíaco , Diástole , Endocárdio/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Contração Miocárdica , Isquemia Miocárdica/complicações , Estudos Prospectivos , Volume Sistólico , Sístole , Ultrassonografia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda
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