Browsing by Subject "Myocardial Infarction"

Filter results by typing the first few letters
Now showing 1 - 20 of 59
  • Thumbnail Image
    ItemOpen Access
    A time-series analysis of the relation between unemployment rate and hospital admission for acute myocardial infarction and stroke in Brazil over more than a decade.
    (International journal of cardiology, 2016-12) Katz, Marcelo; Bosworth, Hayden B; Lopes, Renato D; Dupre, Matthew E; Morita, Fernando; Pereira, Carolina; Franco, Fabio GM; Prado, Rogerio R; Pesaro, Antonio E; Wajngarten, Mauricio

    Background

    The effect of socioeconomic stressors on the incidence of cardiovascular disease (CVD) is currently open to debate. Using time-series analysis, our study aimed to evaluate the relationship between unemployment rate and hospital admission for acute myocardial infarction (AMI) and stroke in Brazil over a recent 11-year span.

    Methods and results

    Data on monthly hospital admissions for AMI and stroke from March 2002 to December 2013 were extracted from the Brazilian Public Health System Database. The monthly unemployment rate was obtained from the Brazilian Institute for Applied Economic Research, during the same period. The autoregressive integrated moving average (ARIMA) model was used to test the association of temporal series. Statistical significance was set at p<0.05. From March 2002 to December 2013, 778,263 admissions for AMI and 1,581,675 for stroke were recorded. During this time period, the unemployment rate decreased from 12.9% in 2002 to 4.3% in 2013, while admissions due to AMI and stroke increased. However, the adjusted ARIMA model showed a positive association between the unemployment rate and admissions for AMI but not for stroke (estimate coefficient=2.81±0.93; p=0.003 and estimate coefficient=2.40±4.34; p=0.58, respectively).

    Conclusions

    From 2002 to 2013, hospital admissions for AMI and stroke increased, whereas the unemployment rate decreased. However, the adjusted ARIMA model showed a positive association between unemployment rate and admissions due to AMI but not for stroke. Further studies are warranted to validate our findings and to better explore the mechanisms by which socioeconomic stressors, such as unemployment, might impact on the incidence of CVD.
  • Thumbnail Image
    ItemOpen Access
    Acute Coronary Syndrome: Diagnosis and Initial Management.
    (American family physician, 2024-01) Nohria, Raman; Viera, Anthony J
    Acute coronary syndrome (ACS) is defined as reduced blood flow to the coronary myocardium manifesting as ST-segment elevation myocardial infarction or non-ST-segment elevation ACS, which includes unstable angina and non-ST-segment elevation myocardial infarction. Common risk factors include being at least 65 years of age or a current smoker or having hypertension, diabetes mellitus, hyperlipidemia, a body mass index greater than 25 kg per m2, or a family history of premature coronary artery disease. Symptoms most predictive of ACS include chest discomfort that is substernal or spreading to the arms or jaw. However, chest pain that can be reproduced with palpation or varies with breathing or position is less likely to signify ACS. Having a prior abnormal cardiac stress test result indicates increased risk. Electrocardiography changes that predict ACS include ST depression, ST elevation, T-wave inversion, or presence of Q waves. No validated clinical decision tool is available to rule out ACS in the outpatient setting. Elevated troponin levels without ST-segment elevation on electrocardiography suggest non-ST-segment elevation ACS. Patients with ACS should receive coronary angiography with percutaneous or surgical revascularization. Other important management considerations include initiation of dual antiplatelet therapy and parenteral anticoagulation, statin therapy, beta-blocker therapy, and sodium-glucose cotransporter-2 inhibitor therapy. Additional interventions shown to reduce mortality in patients who have had a recent myocardial infarction include smoking cessation, annual influenza vaccination, and cardiac rehabilitation.
  • Thumbnail Image
    ItemOpen Access
    Acute myocardial infarction in sub-Saharan Africa: the need for data.
    (PloS one, 2014-01) Hertz, Julian T; Reardon, Joseph M; Rodrigues, Clarissa G; de Andrade, Luciano; Limkakeng, Alexander T; Bloomfield, Gerald S; Lynch, Catherine A
    BACKGROUND: Trends in the prevalence of acute myocardial infarction in sub-Saharan Africa have not been well described, despite growing recognition of the increasing burden of cardiovascular disease in low- and middle-income countries. The aim of this systematic review was to describe the prevalence of acute myocardial infarction in sub-Saharan Africa. METHODS: We searched PubMed, EMBASE, Global Health Archive, CINAHL, and Web of Science, and conducted reference and citation analyses. Inclusion criteria were: observational studies, studies that reported incidence or prevalence of acute myocardial infarction, studies conducted in sub-Saharan Africa, and studies that defined acute myocardial infarction by EKG changes or elevation of cardiac biomarkers. Studies conducted prior to 1992 were excluded. Two independent reviewers analyzed titles and abstracts, full-texts, and references and citations. These reviewers also performed quality assessment and data extraction. Quality assessment was conducted with a validated scale for observational studies. FINDINGS: Of 2292 records retrieved, seven studies met all inclusion criteria. These studies included a total of 92,378 participants from highly heterogeneous study populations in five different countries. Methodological quality assessment demonstrated scores ranging from 3 to 7 points (on an 8-point scale). Prevalence of acute myocardial infarction ranged from 0.1 to 10.4% among the included studies. INTERPRETATION: There is insufficient population-based data describing the prevalence of acute myocardial infarction in sub-Saharan Africa. Well-designed registries and surveillance studies that capture the broad and diverse population with acute myocardial infarction in sub-Saharan Africa using common diagnostic criteria are critical in order to guide prevention and treatment strategies. REGISTRATION: Registered in International Prospective Register of Systematic Reviews (PROSPERO) Database #CRD42012003161.
  • No Thumbnail Available
    ItemOpen Access
    Acute myocardial infarction under-diagnosis and mortality in a Tanzanian emergency department: A prospective observational study.
    (American heart journal, 2020-08) Hertz, Julian T; Sakita, Francis M; Kweka, Godfrey L; Limkakeng, Alexander T; Galson, Sophie W; Ye, Jinny J; Tarimo, Tumsifu G; Temu, Gloria; Thielman, Nathan M; Bettger, Janet P; Bartlett, John A; Mmbaga, Blandina T; Bloomfield, Gerald S
    BACKGROUND:Growing evidence suggests that under-diagnosis of acute myocardial infarction (AMI) may be common in sub-Saharan Africa. Prospective studies of routine AMI screening among patients presenting to emergency departments in sub-Saharan Africa are lacking. Our objective was to determine the prevalence of AMI among patients in a Tanzanian emergency department. METHODS:In a prospective observational study, consecutive adult patients presenting with chest pain or shortness of breath to a referral hospital emergency department in northern Tanzania were enrolled. Electrocardiogram (ECG) and troponin testing were performed for all participants to diagnose AMI types according to the Fourth Universal Definition. All ECGs were interpreted by two independent physician judges. ECGs suggesting ST-elevation myocardial infarction (STEMI) were further reviewed by additional judges. Mortality was assessed 30 days following enrollment. RESULTS:Of 681 enrolled participants, 152 (22.3%) had AMI, including 61 STEMIs and 91 non-STEMIS (NSTEMIs). Of AMI patients, 91 (59.9%) were male, mean (SD) age was 61.2 (18.5) years, and mean (SD) duration of symptoms prior to presentation was 6.6 (12.2) days. In the emergency department, 35 (23.0%) AMI patients received aspirin and none received thrombolytics. Of 150 (98.7%) AMI patients completing 30-day follow-up, 65 (43.3%) had died. CONCLUSIONS:In a northern Tanzanian emergency department, AMI is common, rarely treated with evidence-based therapies, and associated with high mortality. Interventions are needed to improve AMI diagnosis, care, and outcomes.
  • Thumbnail Image
    ItemOpen Access
    An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs.
    (Science translational medicine, 2020-04) Huang, Ke; Ozpinar, Emily W; Su, Teng; Tang, Junnan; Shen, Deliang; Qiao, Li; Hu, Shiqi; Li, Zhenhua; Liang, Hongxia; Mathews, Kyle; Scharf, Valery; Freytes, Donald O; Cheng, Ke
    Cell therapy has been a promising strategy for cardiac repair after injury or infarction; however, low retention and engraftment of transplanted cells limit potential therapeutic efficacy. Seeding scaffold material with cells to create cardiac patches that are transplanted onto the surface of the heart can overcome these limitations. However, because patches need to be freshly prepared to maintain cell viability, long-term storage is not feasible and limits clinical applicability. Here, we developed an off-the-shelf therapeutic cardiac patch composed of a decellularized porcine myocardial extracellular matrix scaffold and synthetic cardiac stromal cells (synCSCs) generated by encapsulating secreted factors from isolated human cardiac stromal cells. This fully acellular artificial cardiac patch (artCP) maintained its potency after long-term cryopreservation. In a rat model of acute myocardial infarction, transplantation of the artCP supported cardiac recovery by reducing scarring, promoting angiomyogenesis, and boosting cardiac function. The safety and efficacy of the artCP were further confirmed in a porcine model of myocardial infarction. The artCP is a clinically feasible, easy-to-store, and cell-free alternative to myocardial repair using cell-based cardiac patches.
  • Thumbnail Image
    ItemOpen Access
    Angina and Future Cardiovascular Events in Stable Patients With Coronary Artery Disease: Insights From the Reduction of Atherothrombosis for Continued Health (REACH) Registry.
    (Journal of the American Heart Association, 2016-09-28) Eisen, Alon; Bhatt, Deepak L; Steg, P Gabriel; Eagle, Kim A; Goto, Shinya; Guo, Jianping; Smith, Sidney C; Ohman, E Magnus; Scirica, Benjamin M; REACH Registry Investigators
    The extent to which angina is associated with future cardiovascular events in patients with coronary artery disease has long been debated.Included were outpatients with established coronary artery disease who were enrolled in the REACH registry and were followed for 4 years. Angina at baseline was defined as necessitating episodic or permanent antianginal treatment. The primary end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included heart failure, cardiovascular hospitalizations, and coronary revascularization. The independent association between angina and first/total events was examined using Cox and logistic regression models. Out of 26 159 patients with established coronary artery disease, 13 619 (52%) had angina at baseline. Compared with patients without angina, patients with angina were more likely to be older, female, and had more heart failure and polyvascular disease (P<0.001 for each). Compared with patients without angina, patients with angina had higher rates of first primary end-point event (14.2% versus 16.3%, unadjusted hazard ratio 1.19, CI 1.11-1.27, P<0.001; adjusted hazard ratio 1.06, CI 0.99-1.14, P=0.11), and total primary end-point events (adjusted risk ratio 1.08, CI 1.01-1.16, P=0.03). Patients with angina were at increased risk for heart failure (adjusted odds ratio 1.17, CI 1.06-1.28, P=0.002), cardiovascular hospitalizations (adjusted odds ratio 1.29, CI 1.21-1.38, P<0.001), and coronary revascularization (adjusted odds ratio 1.23, CI 1.13-1.34, P<0.001).Patients with stable coronary artery disease and angina have higher rates of future cardiovascular events compared with patients without angina. After adjustment, angina was only weakly associated with cardiovascular death, myocardial infarction, or stroke, but significantly associated with heart failure, cardiovascular hospitalization, and coronary revascularization.
  • Thumbnail Image
    ItemOpen Access
    Antibody-Armed Platelets for the Regenerative Targeting of Endogenous Stem Cells.
    (Nano letters, 2019-03) Shen, Deliang; Li, Zhenhua; Hu, Shiqi; Huang, Ke; Su, Teng; Liang, Hongxia; Liu, Feiran; Cheng, Ke
    Stem cell therapies have shown promise in treating acute and chronic ischemic heart disease. However, current therapies are limited by the low retention and poor integration of injected cells in the injured tissue. Taking advantage of the natural infarct-homing ability of platelets, we engineered CD34 antibody-linked platelets (P-CD34) to capture circulating CD34-positive endogenous stem cells and direct them to the injured heart. In vitro, P-CD34 could bind to damaged aortas and capture endogenous stem cells in whole blood. In a mouse model of acute myocardial infarction, P-CD34 accumulated in the injured heart after intravenous administration, leading to a concentration of endogenous CD34 stem cells in the injured heart for effective heart repair. This represents a new technology for endogenous stem cell therapy.
  • Thumbnail Image
    ItemOpen Access
    Association between perceived life chaos and medication adherence in a postmyocardial infarction population.
    (Circulation. Cardiovascular quality and outcomes, 2013-11) Zullig, Leah L; Shaw, Ryan J; Crowley, Matthew J; Lindquist, Jennifer; Grambow, Steven C; Peterson, Eric; Shah, Bimal R; Bosworth, Hayden B

    Background

    The benefits of medication adherence to control cardiovascular disease (CVD) are well defined, yet multiple studies have identified poor adherence. The influence of life chaos on medication adherence is unknown. Because this is a novel application of an instrument, our preliminary objective was to understand patient factors associated with chaos. The main objective was to evaluate the extent to which an instrument designed to measure life chaos is associated with CVD-medication nonadherence.

    Methods and results

    Using baseline data from an ongoing randomized trial to improve postmyocardial infarction (MI) management, multivariable logistic regression identified the association between life chaos and CVD-medication nonadherence. Patients had hypertension and a myocardial infarction in the past 3 years (n=406). Nearly 43% reported CVD-medication nonadherence in the past month. In simple linear regression, the following were associated with higher life chaos: medication nonadherence (β=1.86; 95% confidence interval [CI], 0.96-2.76), female sex (β=1.22; 95% CI [0.22-2.24]), minority race (β=1.72; 95% CI [0.78-2.66]), having less than high school education (β=2.05; 95% CI [0.71-3.39]), low health literacy (β=2.06; 95% CI [0.86-3.26]), and inadequate financial status (β=1.93; 95% CI [0.87-3.00]). Being married (β=-2.09, 95% CI [-3.03 to -1.15]) was associated with lower life chaos. As chaos quartile increased, patients exhibited more nonadherence. In logistic regression, adjusting for sex, race, marital status, employment, education, health literacy, and financial status, a 1-unit life chaos increase was associated with a 7% increase (odds ratio, 1.07; 95% CI [1.02-1.12]) in odds of reporting medication nonadherence.

    Conclusions

    Our results suggest that life chaos may be an important determinant of medication adherence. Life chaos screenings could identify those at risk for nonadherence.

    Clinical trial registration

    URL: http://www.clinicaltrials.gov. Unique identifier: NCT000901277.
  • Thumbnail Image
    ItemOpen Access
    Association between stroke center hospitalization for acute ischemic stroke and mortality.
    (JAMA, 2011-01) Xian, Ying; Holloway, Robert G; Chan, Paul S; Noyes, Katia; Shah, Manish N; Ting, Henry H; Chappel, Andre R; Peterson, Eric D; Friedman, Bruce
    Although stroke centers are widely accepted and supported, little is known about their effect on patient outcomes.To examine the association between admission to stroke centers for acute ischemic stroke and mortality.Observational study using data from the New York Statewide Planning and Research Cooperative System. We compared mortality for patients admitted with acute ischemic stroke (n = 30,947) between 2005 and 2006 at designated stroke centers and nondesignated hospitals using differential distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. Patients were followed up for mortality for 1 year after the index hospitalization through 2007. To assess whether our findings were specific to stroke, we also compared mortality for patients admitted with gastrointestinal hemorrhage (n = 39,409) or acute myocardial infarction (n = 40,024) at designated stroke centers and nondesignated hospitals.Thirty-day all-cause mortality.Among 30,947 patients with acute ischemic stroke, 15,297 (49.4%) were admitted to designated stroke centers. Using the instrumental variable analysis, admission to designated stroke centers was associated with lower 30-day all-cause mortality (10.1% vs 12.5%; adjusted mortality difference, -2.5%; 95% confidence interval [CI], -3.6% to -1.4%; P < .001) and greater use of thrombolytic therapy (4.8% vs 1.7%; adjusted difference, 2.2%; 95% CI, 1.6% to 2.8%; P < .001). Differences in mortality also were observed at 1-day, 7-day, and 1-year follow-up. The outcome differences were specific for stroke, as stroke centers and nondesignated hospitals had similar 30-day all-cause mortality rates among those with gastrointestinal hemorrhage (5.0% vs 5.8%; adjusted mortality difference, +0.3%; 95% CI, -0.5% to 1.0%; P = .50) or acute myocardial infarction (10.5% vs 12.7%; adjusted mortality difference, +0.1%; 95% CI, -0.9% to 1.1%; P = .83).Among patients with acute ischemic stroke, admission to a designated stroke center was associated with modestly lower mortality and more frequent use of thrombolytic therapy.
  • Thumbnail Image
    ItemOpen Access
    Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.
    (Circ Cardiovasc Genet, 2010-04) Shah, Svati H; Bain, James R; Muehlbauer, Michael J; Stevens, Robert D; Crosslin, David R; Haynes, Carol; Dungan, Jennifer; Newby, L Kristin; Hauser, Elizabeth R; Ginsburg, Geoffrey S; Newgard, Christopher B; Kraus, William E
    BACKGROUND: Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events. METHODS AND RESULTS: We performed mass-spectrometry-based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls ("initial"), and 140 CAD cases and 140 controls ("replication"). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined ("event" group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled ("event-replication" group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis-derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial P=0.002, replication P=0.01), and 1 comprising urea cycle metabolites (factor 9, initial P=0.0004, replication P=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74; P=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87; P=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91; P=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91; P=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84; P=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14; P=0.01). CONCLUSIONS: Metabolite profiles are associated with CAD and subsequent cardiovascular events.
  • Thumbnail Image
    ItemOpen Access
    C1q/Tumor Necrosis Factor-Related Protein-9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways.
    (Circulation, 2017-11) Yan, Wenjun; Guo, Yongzhen; Tao, Ling; Lau, Wayne Bond; Gan, Lu; Yan, Zheyi; Guo, Rui; Gao, Erhe; Wong, G William; Koch, Walter L; Wang, Yajing; Ma, Xin-Liang

    Background

    Cell therapy remains the most promising approach against ischemic heart injury. However, the poor survival of engrafted stem cells in the ischemic environment limits their therapeutic efficacy for cardiac repair after myocardial infarction. CTRP9 (C1q/tumor necrosis factor-related protein-9) is a novel prosurvival cardiokine with significantly downregulated expression after myocardial infarction. Here we tested a hypothesis that CTRP9 might be a cardiokine required for a healthy microenvironment promoting implanted stem cell survival and cardioprotection.

    Methods

    Mice were subjected to myocardial infarction and treated with adipose-derived mesenchymal stem cells (ADSCs, intramyocardial transplantation), CTRP9, or their combination. Survival, cardiac remodeling and function, cardiomyocytes apoptosis, and ADSCs engraftment were evaluated. Whether CTRP9 directly regulates ADSCs function was determined in vitro. Discovery-drive approaches followed by cause-effect analysis were used to uncover the molecular mechanisms of CTRP9.

    Results

    Administration of ADSCs alone failed to exert significant cardioprotection. However, administration of ADSCs in addition to CTRP9 further enhanced the cardioprotective effect of CTRP9 (P<0.05 or P<0.01 versus CTRP9 alone), suggesting a synergistic effect. Administration of CTRP9 at a dose recovering physiological CTRP9 levels significantly prolonged ADSCs retention/survival after implantation. Conversely, the number of engrafted ADSCs was significantly reduced in the CTRP9 knockout heart. In vitro study demonstrated that CTRP9 promoted ADSCs proliferation and migration, and it protected ADSCs against hydrogen peroxide-induced cellular death. CTRP9 enhances ADSCs proliferation/migration by extracellular regulated protein kinases (ERK)1/2-matrix metallopeptidase 9 signaling and promotes antiapoptotic/cell survival via ERK-nuclear factor erythroid-derived 2-like 2/antioxidative protein expression. N-cadherin was identified as a novel CTRP9 receptor mediating ADSCs signaling. Blockade of either N-cadherin or ERK1/2 completely abolished the previously noted CTRP9 effects. Although CTRP9 failed to promote ADSCs cardiogenic differentiation, CTRP9 promotes superoxide dismutase 3 expression and secretion from ADSCs, protecting cardiomyocytes against oxidative stress-induced cell death.

    Conclusions

    We provide the first evidence that CTRP9 promotes ADSCs proliferation/survival, stimulates ADSCs migration, and attenuates cardiomyocyte cell death by previously unrecognized signaling mechanisms. These include binding with N-cadherin, activation of ERK-matrix metallopeptidase 9 and ERK-nuclear factor erythroid-derived 2-like 2 signaling, and upregulation/secretion of antioxidative proteins. These results suggest that CTRP9 is a cardiokine critical in maintaining a healthy microenvironment facilitating stem cell engraftment in infarcted myocardial tissue, thereby enhancing stem cell therapeutic efficacy.
  • Thumbnail Image
    ItemOpen Access
    Cardiac cell-integrated microneedle patch for treating myocardial infarction.
    (Science advances, 2018-11) Tang, Junnan; Wang, Jinqiang; Huang, Ke; Ye, Yanqi; Su, Teng; Qiao, Li; Hensley, Michael Taylor; Caranasos, Thomas George; Zhang, Jinying; Gu, Zhen; Cheng, Ke
    We engineered a microneedle patch integrated with cardiac stromal cells (MN-CSCs) for therapeutic heart regeneration after acute myocardial infarction (MI). To perform cell-based heart regeneration, cells are currently delivered to the heart via direct muscle injection, intravascular infusion, or transplantation of epicardial patches. The first two approaches suffer from poor cell retention, while epicardial patches integrate slowly with host myocardium. Here, we used polymeric MNs to create "channels" between host myocardium and therapeutic CSCs. These channels allow regenerative factors secreted by CSCs to be released into the injured myocardium to promote heart repair. In the rat MI model study, the application of the MN-CSC patch effectively augmented cardiac functions and enhanced angiomyogenesis. In the porcine MI model study, MN-CSC patch application was nontoxic and resulted in cardiac function protection. The MN system represents an innovative approach delivering therapeutic cells for heart regeneration.
  • Thumbnail Image
    ItemOpen Access
    Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction.
    (ACS applied materials & interfaces, 2018-10) Su, Teng; Huang, Ke; Daniele, Michael A; Hensley, Michael Taylor; Young, Ashlyn T; Tang, Junnan; Allen, Tyler A; Vandergriff, Adam C; Erb, Patrick D; Ligler, Frances S; Cheng, Ke
    Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for ischemic heart repair but is limited by low cellular engraftment and survival after transplantation. Previous versions of the cardiac patch strategy improve stem cell engraftment and encourage repair of cardiac tissue. However, cardiac patches that can enhance cardiomyogenesis and angiogenesis at the injured site remain elusive. Therapies that target cardiomyocyte proliferation and new blood vessel formation hold great potential for the protection against acute myocardial infarction (MI). Here, we report a new strategy for creating a vascularized cardiac patch in a facile and modular fashion by leveraging microfluidic hydrodynamic focusing to construct the biomimetic microvessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining the luminal surface and then encapsulating the BMVs in a fibrin gel spiked with human CSCs. We show that the endothelialized BMVs mimicked the natural architecture and function of capillaries and that the resultant vascularized cardiac patch (BMV-CSC patch) exhibited equivalent release of paracrine factors compared to those of coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A significant increase in myocardial capillary density was noted in the infarcted hearts that received BMV-CSC patch treatment compared to the infarcted hearts treated with conventional CSC patches. The striking therapeutic benefits and the fast and facile fabrication of the BMV-CSC patch make it promising for practical applications. Our findings suggest that the BMV-CSC patch strategy may open up new possibilities for the treatment of ischemic heart injury.
  • Thumbnail Image
    ItemOpen Access
    Cardiac Stromal Cell Patch Integrated with Engineered Microvessels Improves Recovery from Myocardial Infarction in Rats and Pigs.
    (ACS biomaterials science & engineering, 2020-11) Su, Teng; Huang, Ke; Mathews, Kyle G; Scharf, Valery F; Hu, Shiqi; Li, Zhenhua; Frame, Brianna N; Cores, Jhon; Dinh, Phuong-Uyen; Daniele, Michael A; Ligler, Frances S; Cheng, Ke
    The vascularized cardiac patch strategy is promising for ischemic heart repair after myocardial infarction (MI), but current fabrication processes are quite complicated. Vascularized cardiac patches that can promote concurrent restoration of both the myocardium and vasculature at the injured site in a large animal model remain elusive. The safety and therapeutic benefits of a cardiac stromal cell patch integrated with engineered biomimetic microvessels (BMVs) were determined for treating MI. By leveraging a microfluidic method employing hydrodynamic focusing, we constructed the endothelialized microvessels and then encapsulated them together with therapeutic cardiosphere-derived stromal cells (CSCs) in a fibrin gel to generate a prevascularized cardiac stromal cell patch (BMV-CSC patch). We showed that BMV-CSC patch transplantation significantly promoted cardiac function, reduced scar size, increased viable myocardial tissue, promoted neovascularization, and suppressed inflammation in rat and porcine MI models, demonstrating enhanced therapeutic efficacy compared to conventional cardiac stromal cell patches. BMV-CSC patches did not increase renal and hepatic toxicity or exhibit immunogenicity. We noted a significant increase in endogenous progenitor cell recruitment to the peri-infarct region of the porcine hearts treated with BMV-CSC patch as compared to those that received control treatments. These findings establish the BMV-CSC patch as a novel engineered-tissue therapeutic for ischemic tissue repair.
  • Thumbnail Image
    ItemOpen Access
    Cardiovascular Outcomes After Lower Extremity Endovascular or Surgical Revascularization: The EUCLID Trial.
    (Journal of the American College of Cardiology, 2018-10) Baumgartner, Iris; Norgren, Lars; Fowkes, F Gerry R; Mulder, Hillary; Patel, Manesh R; Berger, Jeffrey S; Jones, W Schuyler; Rockhold, Frank W; Katona, Brian G; Mahaffey, Kenneth; Hiatt, William R; Executive Committee and Investigators of the EUCLID Trial
    BACKGROUND:Lower extremity revascularization (LER) is a common treatment in patients with peripheral artery disease (PAD), but long-term outcomes are poorly defined. OBJECTIVES:The aim was to analyze LER in the EUCLID (Examining Use of tiCagreLor In paD) trial to determine predictors and cardiovascular outcomes. METHODS:Patients were grouped according to whether they received a post-randomization LER (n = 1,738) or not (n = 12,147). All variables were assessed for significance in univariable and parsimonious multivariable models. The primary endpoint was myocardial infarction, ischemic stroke, or cardiovascular death; major adverse limb events (MALE) included acute limb ischemia or major amputation. RESULTS:A post-randomization LER occurred in 12.5% of patients and was an endovascular LER in 74.7%. Endovascular LERs were performed more often in North America, whereas surgical procedures occurred more frequently in Europe. Independent factors predicting LER were prior and type of prior LER, geographic region, limb symptoms, diabetes, and smoking. A post-randomization LER was associated with an increased risk for the primary endpoint (hazard ratio: 1.60; 95% confidence interval: 1.35 to 1.90; p < 0.0001) and MALE (hazard ratio: 12.0; 95% confidence interval: 9.47 to 15.30; p < 0.0001). Event rates for the primary endpoint after LER were numerically higher in the surgical subgroup, but MALE were similar between surgical and endovascular LER. CONCLUSIONS:In the EUCLID trial, LER was most often endovascular. Following LER, there was an increased hazard for the primary endpoint (with higher event rates in the surgical group) and a markedly increased risk for MALE events (with similar event rates between surgical and endovascular LER procedures). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).
  • Thumbnail Image
    ItemOpen Access
    Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial.
    (American heart journal, 2019-02) Held, Claes; White, Harvey D; Stewart, Ralph AH; Davies, Richard; Sampson, Shani; Chiswell, Karen; Silverstein, Adam; Lopes, Renato D; Heldestad, Ulrika; Budaj, Andrzej; Mahaffey, Kenneth W; Wallentin, Lars; STABILITY Investigators

    Background

    Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.

    Methods

    Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.

    Results

    In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).

    Conclusions

    The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.
  • Thumbnail Image
    ItemOpen Access
    Differences between chest pain observation service patients and admitted "rule-out myocardial infarction" patients.
    (Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 1997-07) Dallara, J; Severance, HW; Davis, B; Schulz, G

    Objective

    To compare and contrast the patient characteristics of ED patients at low risk for acute cardiac ischemia who were assigned to a chest pain observation service vs those admitted to a monitored inpatient bed for "rule-out acute myocardial infarction" (R/O MI).

    Methods

    This was a retrospective, cross-sectional comparison of adult patients considered at relatively low risk for cardiac ischemia and who were evaluated in 1 of 2 settings: a short-term observation service and an inpatient monitored bed. All patients had an ED final diagnosis of "chest pain," "R/O MI," or "unstable angina" during the 7-month study period. Demographic features and presenting clinical features were examined as a function of site of patient evaluation.

    Results

    Of 531 study patients, 265 (50%) were assigned to the observation service. Younger age (OR = 1.75, 95% CI 1.26, 2.44, for each decrement of 20 years), the complaint of "chest pain" (OR = 2.35, 95% CI 1.34, 4.12), and the absence of prior known coronary artery disease (OR = 1.64, 95% CI 1.13, 2.38) were the principal independent factors associated with assignment to a chest pain observation service bed.

    Conclusions

    Patients evaluated in a chest pain observation service appear to have different clinical characteristics than other individuals admitted to a monitored inpatient bed for "R/O MI." Investigators should address differences in clinical characteristics when making outcome comparisons between these 2 patient groups.
  • Thumbnail Image
    ItemOpen Access
    Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.
    (J Am Heart Assoc, 2014-04-14) Sherwood, Matthew W; Wiviott, Stephen D; Peng, S Andrew; Roe, Matthew T; Delemos, James; Peterson, Eric D; Wang, Tracy Y
    BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.
  • Thumbnail Image
    ItemOpen Access
    Effect of home testing of international normalized ratio on clinical events.
    (The New England journal of medicine, 2010-10) Matchar, David B; Jacobson, Alan; Dolor, Rowena; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Vertrees, Julia E; Shih, Mei-Chiung; Holodniy, Mark; Lavori, Philip; THINRS Executive Committee and Site Investigators

    Background

    Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes.

    Methods

    We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death).

    Results

    The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001).

    Conclusions

    As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.).
  • Thumbnail Image
    ItemOpen Access
    Effectiveness and Safety of Aldosterone Antagonist Therapy Use Among Older Patients With Reduced Ejection Fraction After Acute Myocardial Infarction.
    (J Am Heart Assoc, 2016-01-21) Wang, Tracy Y; Vora, Amit N; Peng, S Andrew; Fonarow, Gregg C; Das, Sandeep; de Lemos, James A; Peterson, Eric D
    BACKGROUND: While aldosterone antagonists have proven benefit among post-myocardial infarction (MI) patients with low ejection fraction (EF), how this treatment is used among older MI patients in routine practice is not well described. METHODS AND RESULTS: Using ACTION Registry-GWTG linked to Medicare data, we examined 12 080 MI patients ≥65 years with EF ≤40% who were indicated for aldosterone antagonist therapy per current guidelines and without documented contraindications. Of these, 11% (n=1310) were prescribed aldosterone antagonists at discharge. Notably, 10% of patients prescribed an aldosterone antagonist were eligible for, but not concurrently treated with, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Spironolactone was the predominantly prescribed aldosterone antagonist. At 2-year follow-up, aldosterone antagonist use was not associated with lower mortality (unadjusted 39% versus 38%; HR 0.99, 95% CI 0.88-1.33 using inverse probability-weighted propensity adjustment) except in symptomatic HF patients (HR 0.84, 95% CI 0.72-0.99, Pinteraction=0.009). Risks of hyperkalemia were low at 30 days, but significantly higher among patients prescribed aldosterone antagonists (unadjusted 2.3% versus 1.5%; adjusted HR 2.04, 95% CI 1.16-3.60), as was 2-year risk of acute renal failure (unadjusted 6.7% versus 4.8%; adjusted HR 1.39, 95% CI 1.01-1.92) compared with patients not prescribed aldosterone antagonists. CONCLUSIONS: Aldosterone antagonist use among eligible older MI patients in routine clinical practice was not associated with lower mortality except in patients with HF symptoms, but was associated with increased risks of hyperkalemia and acute renal failure. These results underscore the importance of close post-discharge monitoring of this patient population.