RESUMEN
BACKGROUND: Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly high-risk of arrhythmias. OBJECTIVES: The aim of the study was to determine the association of QT interval on electrocardiogram for ventricular arrhythmic complications in patients with apical ballooning Takotsubo syndrome in a diverse population at a large urban hospital in the U.S. METHODS: We reviewed 105 cases of apical ballooning Takotsubo syndrome in patients admitted between 2011 and 2017. Two cardiologists reviewed the electrocardiograms to measure QT interval, adjusted for rate using the Fridericia formula (QTCF), and ventricular arrhythmic complications during the hospitalization. Data are reported as median and interquartile range or number and percentage. RESULTS: Of the 105 patients, 86 (82%) were female, and 34 (32%) were self-reported Black or African American. The mean age was 65 years (range: 58-72 years). Left ventricular ejection fraction was 25% (range: 25%-35%). Heart rate was 101 beats/min (range: 83-121 beats/min). Ten (11%) patients experienced a ventricular arrhythmic complication and had significantly longer QTCF (470 [range: 422-543] milliseconds) than did those without complications (417 [range: 383-456] milliseconds, P = 0.031). The area under the curve for QTCF was 0.708 (95% CI: 0.536-0.880; P = 0.031). Twenty-eight (27%) patients had a QTCF ≥460 milliseconds and significantly more arrhythmic complications (21% vs 5%, odds ratio 4.997 [95% CI: 1.288-19.237], P = 0.021). QTCF was an independent predictor of ventricular arrhythmias: odds ratio 1.090 for each 10-millisecond increase in QTCF (95% CI: 1.004-1.183; P = 0.040, corrected for sex). CONCLUSIONS: In a diverse population of patients with apical ballooning Takotsubo syndrome admitted to a large urban hospital in the United States, QTCF at admission ≥460 milliseconds identifies patients at high risk for in-hospital arrhythmic complications. Further studies are needed to determine strategies aimed at shortening QT interval to potentially prevent life-threatening arrhythmic events.
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Síndrome de QT Prolongado , Cardiomiopatía de Takotsubo , Humanos , Femenino , Anciano , Masculino , Cardiomiopatía de Takotsubo/complicaciones , Volumen Sistólico , Función Ventricular Izquierda , Síndrome de QT Prolongado/complicaciones , Síndrome de QT Prolongado/epidemiología , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/complicaciones , HospitalesRESUMEN
BACKGROUND: Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. METHODS: A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. RESULTS: Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs. 13.6% P=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 [95% CI 1.22-43.17], P=0.029), whereas angina was a protective factor (OR=0.11 [95% CI 0.02-0.65], P=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], P<0.001 and OR=1.64 [95% CI 1.15-2.58], P=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 [95% CI 0.03-0.88], P=0.004). CONCLUSIONS: Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.
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Síndrome Coronario Agudo , Cardiomiopatía de Takotsubo , Síndrome Coronario Agudo/diagnóstico , Negro o Afroamericano , Humanos , Estudios Retrospectivos , Cardiomiopatía de Takotsubo/epidemiología , Población BlancaRESUMEN
BACKGROUND: Cocaine use disorder (CUD) is a common problem in the United States and worldwide. The mechanisms by which cocaine induces acute cardiovascular toxicity are various. When systemically absorbed through inhaled or intravenous routes, cocaine induces an acute rise in the heart rate (HR) and blood pressure (BP) leading to a significant increase in the cardiac output (CO) and myocardial oxygen demand. Subjects with chronic CUD represent a special population that has experienced long-term cocaine exposure, often without showing signs of cardiovascular disease. We herein present prospectively collected data on the acute hemodynamic effects of intravenous cocaine in a cohort of nontreatment-seeking individuals with CUD without cardiovascular disease. METHODS AND RESULTS: Baseline physiologic data were collected while participants underwent infusion of escalating doses of cocaine (10, 20, and 40 mg administered over 2 minutes) at baseline and after receiving single-blind placebo treatment. Continuous noninvasive hemodynamic monitoring was performed throughout the infusion sessions using the ccNexfin finger cuffs (Edwards Lifesciences Corp, Irvine, CA). The recorded arterial BP tracings allowed for the measurement of beat-to-beat changes in HR, BP, stroke volume, CO, and systemic vascular resistance (SVR). None of the subjects experienced a treatment-related serious adverse event. Cocaine produced significant dose-dependent increases in median HR, BP, CO, and +dP/dt (a measure of cardiac contractility) and a significant dose-dependent reduction in median SVR. CONCLUSIONS: Intravenous cocaine in a cohort of otherwise healthy subjects with CUD produced dose-dependent increases in CO, largely explained by an increase in HR, accompanied by a dose-dependent decrease in SVR.
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Presión Arterial/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/efectos adversos , Trastornos Relacionados con Cocaína/fisiopatología , Cocaína/efectos adversos , Dedos/irrigación sanguínea , Frecuencia Cardíaca/efectos de los fármacos , Monitorización Hemodinámica , Resistencia Vascular/efectos de los fármacos , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Estimulantes del Sistema Nervioso Central/administración & dosificación , Cocaína/administración & dosificación , Trastornos Relacionados con Cocaína/diagnóstico , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
BACKGROUND: A comparison in acute thrombogenicity between the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold and the Absorb bioresorbable vascular scaffold has not been performed. This study assessed acute thrombogenicity of Magmaris compared with Absorb and the Orsiro hybrid drug-eluting stent in a porcine arteriovenous shunt model. METHODS AND RESULTS: An ex vivo porcine carotid jugular arteriovenous shunt was established and connected to SYLGARD tubing containing the Magmaris, Absorb, and Orsiro scaffolds/stents and allowed to run in the shunt for a maximum of 1 hour. Twelve shunts (2 shunt runs per pig) were run comparing the 3 scaffolds in alternating order. Nested generalized linear mixed models were used to compare variables between scaffold groups while adjusting for variability between shunt runs. Confocal fluorescent microscopy costaining CD61/CD42b demonstrated that both Magmaris (3.0%) and Orsiro (4.6%) had less platelet coverage of the total scaffold compared with Absorb (21.8%). Scanning electron microscopy demonstrated significantly less thrombus deposition to Magmaris as a percentage of the total scaffold compared with Absorb (5.0% versus 16.1%, P=0.02). Magmaris had significantly less PM-1-positive neutrophil and CD14-positive monocyte adherence compared with both Orsiro and Absorb. Orsiro had significantly less monocyte deposition compared with Absorb. CONCLUSIONS: Despite a similar scaffold strut thickness, the Magmaris sirolimus-eluting bioabsorbable magnesium scaffold was significantly less thrombogenic compared with the Absorb bioresorbable vascular scaffold in an ex vivo porcine arteriovenous shunt model. Further studies are needed to determine whether the reduced thrombogenicity of Magmaris will result in reductions in major cardiovascular events.
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Stents Liberadores de Fármacos/efectos adversos , Magnesio , Trombosis/etiología , Andamios del Tejido/efectos adversos , Animales , Adhesión Celular , Microscopía Electrónica de Rastreo , Porcinos , Trombosis/patologíaRESUMEN
RATIONALE: Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. OBJECTIVE: To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. METHODS AND RESULTS: Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O2, were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×106) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×106 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were randomized to tail-vein injection of 2×106 MSCs, with injection repeated at week 3 (n=16) versus PBS control (n=16). MSCs significantly increased LV ejection fraction and decreased LV end-systolic volume. CONCLUSIONS: Intravenously administered MSCs for acute myocardial infarction attenuate the progressive deterioration in LV function and adverse remodeling in mice with large infarcts, and in ischemic cardiomyopathy, they improve LV function, effects apparently modulated in part by systemic anti-inflammatory activities.
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Cardiomiopatías/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Infarto del Miocardio/terapia , Isquemia Miocárdica/terapia , Disfunción Ventricular Izquierda/terapia , Administración Intravenosa , Animales , Cardiomiopatías/inmunología , Cardiomiopatías/fisiopatología , Células Cultivadas , Humanos , Masculino , Células Madre Mesenquimatosas/inmunología , Ratones , Infarto del Miocardio/inmunología , Infarto del Miocardio/fisiopatología , Isquemia Miocárdica/inmunología , Isquemia Miocárdica/fisiopatología , Resultado del Tratamiento , Disfunción Ventricular Izquierda/inmunología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Newer P2Y12 inhibitors have more rapid onset of platelet inhibition compared with clopidogrel, especially the intravenous P2Y12 inhibitor cangrelor. Direct comparisons between cangrelor and oral P2Y12 inhibitors ticagrelor and prasugrel do not exist. Thus, we performed a network meta-analysis to directly and indirectly compare different P2Y12 inhibitors in patients undergoing percutaneous coronary intervention (PCI). METHODS: MEDLINE/PubMed and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared at least two P2Y12 inhibitors including cangrelor, clopidogrel, prasugrel, and ticagrelor. Network meta-analysis with a Bayesian approach was performed to directly and indirectly compare the effects of the aforementioned P2Y12 inhibitors on clinical outcomes. Odds ratios with credible intervals (OR [CrIs]) were generated with random-effects models to compare outcomes. RESULTS: This analysis included 15 RCTs with 54,025 patients randomized to cangrelor (n=12,475), clopidogrel (n=26,903), prasugrel (n=7455), or ticagrelor (n=7192) at time of PCI. Patients had a mean age of 63±10, 74% were male, and 82% underwent PCI for acute coronary syndrome. No significant differences between cangrelor and clopidogrel were found with respect to cardiovascular death (OR 1.01 [CrI 0.23-4.39]), myocardial infarction (OR 0.94 [CrI 0.69-1.25]), major adverse cardiac events (OR 0.91 [CrI 0.69-1.18]), stent thrombosis (OR 0.66 [CrI 0.37-1.19]), or major bleeding (OR 1.52 [CrI 0.79-2.98]). Rank probability data suggested that ticagrelor and prasugrel were better than cangrelor for reducing ischemic events, though these differences were not significant. CONCLUSION: Despite rapid platelet inhibition provided by cangrelor, newer oral P2Y12 inhibitors such as ticagrelor and prasugrel have comparable clinical outcomes.
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Adenosina Monofosfato/análogos & derivados , Adenosina/análogos & derivados , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticlopidina/análogos & derivados , Adenosina/efectos adversos , Adenosina/uso terapéutico , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/uso terapéutico , Clopidogrel , Humanos , Infarto del Miocardio/tratamiento farmacológico , Metaanálisis en Red , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Clorhidrato de Prasugrel/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Ticagrelor , Ticlopidina/efectos adversos , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
Treatment of acute myocardial infarction (AMI) has improved significantly in recent years, but many patients have adverse left ventricular (LV) remodeling, a maladaptive change associated with progressive heart failure. Although this change is usually associated with large infarcts, some patients with relatively small infarcts have adverse remodeling, whereas other patients with larger infarcts (who survive the first several days after AMI) do not. This paper reviews the relevant data supporting the hypothesis that individual differences in the intensity of the post-AMI inflammatory response, involving 1 or more inflammatory-modulating pathways, may contribute to adverse LV remodeling. It concludes by outlining how individual variations in the inflammatory response could provide important novel therapeutic targets and strategies.
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Inflamación/fisiopatología , Infarto del Miocardio/fisiopatología , Remodelación Ventricular/fisiología , Enfermedades Autoinmunes/complicaciones , Biomarcadores/metabolismo , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Humanos , Infecciones/complicaciones , Inflamasomas/antagonistas & inhibidores , Inflamación/prevención & control , Trasplante de Células Madre Mesenquimatosas , Miocardio/metabolismo , Neovascularización Fisiológica , Neutrófilos/metabolismo , Polimorfismo Genético , Volumen Sistólico/fisiologíaRESUMEN
INTRODUCTION: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model. METHODS: Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. RESULTS: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163±31% vs. 13±14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. CONCLUSIONS: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.
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Albúminas/farmacocinética , Medios de Contraste/farmacocinética , Colorantes Fluorescentes/farmacocinética , Gadolinio DTPA/farmacocinética , Imagen por Resonancia Magnética , Infarto del Miocardio/diagnóstico por imagen , Daño por Reperfusión Miocárdica/diagnóstico por imagen , Miocardio/metabolismo , Imagen Óptica/métodos , Fosfatidiletanolaminas/farmacocinética , Albúminas/administración & dosificación , Animales , Medios de Contraste/administración & dosificación , Modelos Animales de Enfermedad , Colorantes Fluorescentes/administración & dosificación , Gadolinio DTPA/administración & dosificación , Inmunohistoquímica , Inyecciones Intravenosas , Liposomas , Masculino , Ratones , Microscopía Fluorescente , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Nanopartículas , Tamaño de la Partícula , Fosfatidiletanolaminas/administración & dosificación , Distribución TisularRESUMEN
The use of statins to treat patients with heart failure (HF) is controversial due to conflicting results from large, prospective, randomized, placebo-controlled trials and other smaller studies. A recent comprehensive, well-conducted meta-analysis from Preiss and colleagues sought to determine whether statin therapy had an effect on major HF outcomes such as hospitalization and death. Although the study demonstrated a significant effect of statin therapy on HF hospitalizations, several limitations involving the participant data and nature of statin used in the analyzed trials raise questions about the inferences that can be drawn from the study results.