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1.
J Nucl Cardiol ; 28(2): 536-542, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30877551

RESUMO

BACKGROUND: Assessing for coronary artery disease (CAD) in patients with left bundle branch block (LBBB) is difficult with noninvasive cardiac imaging. Few studies report the prevalence of LBBB associated septal-apical perfusion defects using regadenoson stress on Positron Electron Tomography (PET) imaging. METHODS AND RESULTS: We identified 101 consecutive patients with baseline LBBB, and without known CAD, who underwent rest-stress regadenoson PET. Investigators have the ability to prospectively identify studies, whose quality is limited by LBBB artifact. With the infusion of regadenoson, resting to peak stress heart rate rose from a median of 78 to 93 BPM. Despite this, LBBB perfusion artifacts were not identified in any studies. 10 individuals had both regadenoson SPECT and PET within 1 year. 3 of the 10 SPECT studies had LBBB artifacts, all of which were not seen on subsequent PET. 21 patients with PET had subsequent coronary angiography. Of these, 9 PETs were without significant inducible ischemia, and angiogram was without flow-limiting disease. 3 PETs identified inducible ischemia, but did not have flow-limiting disease on angiogram. 9 PETs identified inducible ischemia and had flow-limiting disease on angiogram. CONCLUSIONS: In patients with LBBB undergoing regadenoson PET stress imaging, artifactual septal perfusion defects are rare.


Assuntos
Bloqueio de Ramo/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Septos Cardíacos/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Tomografia por Emissão de Pósitrons/métodos , Purinas/farmacologia , Pirazóis/farmacologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único
2.
Arterioscler Thromb Vasc Biol ; 29(4): 465-71, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19179641

RESUMO

OBJECTIVE: The peroxisome proliferator activated receptor-gamma (PPARgamma) protein is a nuclear transcriptional activator with importance in diabetes management as the molecular target for the thiazolidinedione (TZD) family of drugs. Substantial evidence indicates that the TZD family of PPARgamma agonists may retard the development of atherosclerosis. However, recent clinical data have suggested that at least one TZD may increase the risk of myocardial infarction and death from cardiovascular disease. In this study, we used a genetic approach to disrupt PPARgamma signaling to probe the protein's role in smooth muscle cell (SMC) responses that are important for atherosclerosis. METHODS AND RESULTS: SMC isolated from transgenic mice harboring the dominate-negative P465L mutation in PPARgamma (PPARgamma(L/+)) exhibited greater proliferation and migration then did wild-type cells. Upregulation of ETS-1, but not ERK activation, correlated with enhanced proliferative and migratory responses PPARgamma(L/+) SMCs. After arterial injury, PPARgamma(L/+) mice had a approximately 4.3-fold increase in the development of intimal hyperplasia. CONCLUSIONS: These findings are consistent with a normal role for PPARgamma in inhibiting SMC migration and proliferation in the context of restenosis or atherosclerosis.


Assuntos
Movimento Celular , Proliferação de Células , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , PPAR gama/metabolismo , Animais , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Células Cultivadas , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hiperplasia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Mutação , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , PPAR gama/genética , Fosforilação , Proteína Proto-Oncogênica c-ets-1/metabolismo , Fatores de Tempo , Cicatrização
3.
J Mol Cell Cardiol ; 46(2): 241-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19028502

RESUMO

Myocyte apoptosis is central to myocardial dysfunction following ischemia/reperfusion (I/R) and during the transition from hypertrophy to heart failure. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase regulates adhesion-dependent survival signals and unopposed FAK activation has been linked to tumor development. We previously showed that conditional myocyte-specific deletion of FAK (MFKO) in the adult heart did not affect basal cardiomyocyte survival or cardiac function but led to dilated cardiomyopathy and heart failure following pressure overload. In the present study, we sought to determine if FAK functions to limit stress-induced cardiomyocyte apoptosis. We reasoned that (I/R), which stimulates robust apoptotic cell death, might uncover an important cardioprotective function for FAK. We found that depletion of FAK markedly exacerbates hypoxia/re-oxygenation-induced cardiomyocyte cell death in vitro. Moreover, deletion of FAK in the adult myocardium resulted in significant increases in I/R-induced infarct size and cardiomyocyte apoptosis with a concomitant reduction in left ventricular function. Finally, our results suggest that NF-kappaB signaling may play a key role in modulating FAK-dependent cardioprotection, since FAK inactivation blunted activation of the NF-kappaB survival signaling pathway and reduced levels of the NF-kappaB target genes, Bcl2 and Bcl-xl. Since the toggling between pro-survival and pro-apoptotic signals remains central to preventing irreversible damage to the heart, we conclude that targeted FAK activation may be beneficial for protecting stress-dependent cardiac remodeling.


Assuntos
Quinase 1 de Adesão Focal/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/fisiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Quinase 1 de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/genética , Camundongos , Camundongos Mutantes , Traumatismo por Reperfusão Miocárdica/genética , NF-kappa B/genética , NF-kappa B/fisiologia , Traumatismo por Reperfusão/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
4.
Curr Treat Options Cardiovasc Med ; 21(10): 50, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473859

RESUMO

PURPOSE OF REVIEW: This article reviews recent advances in echocardiographic strain imaging, particularly in its ability to prognosticate in cardiovascular outcomes and impact clinical decision making. RECENT FINDINGS: Strain has been proposed as a sensitive tool in detecting early ventricular dysfunction. Left ventricular global longitudinal strain (LV-GLS) detects subtle changes in myocardial function, often not quantifiable by ejection fraction alone. Thus, LV-GLS provides the opportunity for early decision-making, and the implementation of more effective treatments, improving outcomes in a variety of diseases such as valvular heart diseases, cardio-oncology, ischemic heart disease, cardiomyopathies, heart transplantation, and pericardial diseases and cardiomyopathies. Strain is a promising tool for the early detection of myocardial dysfunction in patients with preserved left ventricular ejection fraction and can prognosticate long-term outcomes.

5.
Am J Cardiol ; 119(4): 664-668, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-27939225

RESUMO

Atherosclerotic renal artery stenosis (RAS) is associated with high mortality rates, but large randomized trials have not shown improvement in survival with renal artery stenting. These results suggest that factors other than ongoing renal hypoperfusion are important in determining survival in patients with RAS. Using logistic regression models, we performed a single-center, case-control study that included 188 patients with ≥70% RAS with an average age of 67 ± 10 years, 54% women, 20% black, and 70% smokers; 118 patients (63%) underwent renal artery stenting. A total of 89 patients (47%) died during an average follow-up of 5.1 years. Previous myocardial infarction (MI) (odds ratio 2.6 95% confidence interval [1.4 to 4.7]), left ventricular ejection fraction (LVEF) ≤35% (odds ratio 4.1 95% confidence interval [1.6 to 10.6]), and renal insufficiency were predictors of mortality in this study. The risk associated with LVEF ≤35% and previous MI were additive with mortality of 40%, 54%, and 85%, respectively, with 0, 1, or both these factors. Renal artery stenting was associated with a 43% reduction in mortality in patients with 0 or 1 mortality risk factors (defined as LVEF ≤35%, previous MI, and glomerular filtration rate ≤45 ml/min/1.73 m2) but had no effect on mortality in patients with 2 or 3 mortality risk factors. Systolic blood pressure, diastolic blood pressure, or severity of RAS did not correlate with survival. In conclusion, this retrospective analysis suggests that clinical, in addition to anatomic and physiological, factors should be considered in future studies examining effects of renal artery stenting on survival.


Assuntos
Aterosclerose/cirurgia , Mortalidade , Infarto do Miocárdio/epidemiologia , Obstrução da Artéria Renal/cirurgia , Artéria Renal/cirurgia , Insuficiência Renal/epidemiologia , Stents , Disfunção Ventricular Esquerda/epidemiologia , Idoso , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Índice de Gravidade de Doença , Volume Sistólico , Taxa de Sobrevida
7.
J Am Heart Assoc ; 2(2): e000004, 2013 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-23557748

RESUMO

BACKGROUND: Major advances have been made in the treatment of ST-elevation myocardial infarction (STEMI) in outpatients. In contrast, little is known about outcomes in STEMI that occur in patients hospitalized for a noncardiac condition. METHODS AND RESULTS: This was a retrospective, single-center study of inpatient STEMIs from January 1, 2007, to July 31, 2011. Forty-eight cases were confirmed to be inpatient STEMIs of a total of 139 410 adult discharges. These patients were older and more often female and had higher rates of chronic kidney disease and prior cerebrovascular events compared with 227 patients with outpatient STEMIs treated during the same period. Onset of inpatient STEMI was heralded most frequently by a change in clinical status (60%) and less commonly by patient complaints (33%) or changes on telemetry. Coronary angiography and percutaneous coronary intervention were performed in 71% and 56% of patients, respectively. The median time to obtain ECG (41 [10, 600] versus 5 [2, 10] minutes; P<0.001), ECG to angiography time (91 [26, 209] versus 35 [25, 46] minutes; P<0.001) and ECG to first device activation (FDA) (129 [65, 25] versus 60 [47, 76] minutes; P<0.001) were longer for inpatient versus outpatient STEMI. Survival to discharge was lower for inpatient STEMI (60% versus 96%; P<0.001), and this difference persisted after adjusting for potential confounders. CONCLUSIONS: Patients who develop a STEMI while hospitalized for a noncardiac condition are older and more often female, have more comorbidities, have longer ECG-to-FDA times, and are less likely to survive than patients with an outpatient STEMI.


Assuntos
Infarto do Miocárdio/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Centros Médicos Acadêmicos , Distribuição por Idade , Idoso , Comorbidade , Angiografia Coronária , Eletrocardiografia , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Estudos Retrospectivos , Distribuição por Sexo , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
Am J Cardiol ; 111(11): 1547-51, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23523062

RESUMO

Abrupt onset of renal ischemia is associated with increased blood pressure (BP), but it is unknown whether BP remains elevated in patients with chronic severe atherosclerotic renal artery stenosis (RAS). Patients undergoing coronary angiography who had concurrent renal angiography were divided into 3 groups: severe (stenosis ≥70% diameter reduction), moderate (10%-69%), and minimal RAS. Aortic BP was measured at the time of angiography. Renal angiography was performed in 762 (5.4%) of 14,181 patients undergoing coronary angiography. The mean age was 62 ± 12 years, 52% were women, 93% had hypertension, and 42% had diabetes mellitus. Minimal, moderate, or severe RAS was found in 62%, 30%, and 9% of patients. Patients with minimal RAS were younger, less likely to have hypercholesterolemia or coronary artery disease, and had a lower creatinine than patients with severe RAS. Severe RAS was associated with a lower diastolic BP and mean BP and a higher pulse pressure (PP), but there was no difference in systolic BP or the number of antihypertensive medications between the 3 groups. The degree of RAS had a weak positive correlation with PP, a weak negative correlation with diastolic BP, and almost no correlation with systolic BP or mean BP. In multivariate linear regression analysis, there was an association between severity of RAS and PP but not with mean BP or systolic BP. In conclusion, PP, but not systolic BP, diastolic BP, mean BP, or number of antihypertensive medications, was elevated in patients with severe RAS.


Assuntos
Angiografia/métodos , Pressão Sanguínea/fisiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Obstrução da Artéria Renal/fisiopatologia , Idoso , Pressão Arterial/fisiologia , Angiografia Coronária , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Sístole
10.
PLoS One ; 4(12): e8183, 2009 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-20016837

RESUMO

BACKGROUND: Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease). METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations. CONCLUSIONS/SIGNIFICANCE: These data support the concept of stable patterns of gene transcription unique to a geographic ancestral lineage. Differences in expression of several carbohydrate metabolism genes suggest both genetic and transcriptional mechanisms contribute to these patterns and may play a role in exacerbating the disproportionate levels of obesity, diabetes, and cardiovascular disease observed in Americans with African ancestry.


Assuntos
Metabolismo dos Carboidratos/genética , Regulação da Expressão Gênica , Genealogia e Heráldica , Geografia , Adolescente , Adulto , Demografia , Doença/genética , Frequência do Gene/genética , Glucose/metabolismo , Haplótipos/genética , Homeostase/genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Grupos Populacionais/genética , Sequências Reguladoras de Ácido Nucleico/genética , Reprodutibilidade dos Testes , Proteína de Ligação a Elemento Regulador de Esterol 1 , Fatores de Transcrição/metabolismo , Transcrição Gênica , Adulto Jovem
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