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Conflictos Armados , Inteligencia Artificial , Automatización , Armas , Inteligencia Artificial/ética , Federación de Rusia , Ucrania , Conflictos Armados/ética , Conflictos Armados/legislación & jurisprudencia , Armas/ética , Armas/legislación & jurisprudencia , Humanos , Automatización/ética , Automatización/legislación & jurisprudenciaRESUMEN
BACKGROUND: As heart transplant guidelines evolve, the clinical indication for 73% of durable left ventricular assist device (LVAD) implants is now destination therapy. Although completely magnetically levitated LVAD devices have demonstrated improved durability relative to previous models, LVAD replacement procedures are still required for a variety of indications. Thus, the population of patients with a replaced LVAD is growing. There is a paucity of data regarding the outcomes and risk factors for those patients receiving first-time LVAD replacements. METHODS: The study cohort consisted of all consecutive patients between 2006 and 2020 that received a first-time LVAD replacement at a single institution. Preoperative clinical and laboratory variables were collected retrospectively. The primary endpoint was death or need for an additional LVAD replacement. Data were subjected to Kaplan-Meier, univariate, and multivariate Cox hazard ratio analyses. RESULTS: In total, 152 patients were included in the study, of which 101 experienced the primary endpoint. On multivariate analysis, patients receiving HeartMate 3 (HM3) LVADs as the replacement device showed superior outcomes (HR 0.15, 95% CI 0.065-0.35, p < 0.0001). Independent risk factors for death or need for additional replacement included preoperative extracorporeal membrane oxygenation (ECMO) (HR 4.44, 95% CI 1.87-14.45, and p = 0.00042), increased number of sternotomies (HR 5.20, 95% CI 1.87-14.45, and p = 0.0016), and preoperative mechanical ventilation (HR 1.98, 95% CI 1.01-3.86, and p = 0.045). CONCLUSIONS: Replacement with HM3 showed superior outcomes compared to all other pump types when controlling for both initial pump type and other independent predictors of death or LVAD replacement. Preoperative ECMO, mechanical ventilation, and multiple sternotomies also increased the odds for death or the need for subsequent replacement.
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Humanos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Insuficiencia Cardíaca/terapia , Trasplante de Corazón/efectos adversos , Morbilidad , Resultado del TratamientoRESUMEN
Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced "beyond stage C" HF.
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Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Factores de Riesgo , Enfermedad CrónicaRESUMEN
Among the estimated 6.2 million Americans living with heart failure (HF), ≈5%/y may progress to advanced, or stage D, disease. Advanced HF has a high morbidity and mortality, such that early recognition of this condition is important to optimize care. Delayed referral or lack of referral in patients who are likely to derive benefit from an advanced HF evaluation can have important adverse consequences for patients and their families. A 2-step process can be used by practitioners when considering referral of a patient with advanced HF for consideration of advanced therapies, focused on recognizing the clinical clues associated with stage D HF and assessing potential benefits of referral to an advanced HF center. Although patients are often referred to an advanced HF center to undergo evaluation for advanced therapies such as heart transplantation or implantation of a left ventricular assist device, there are other reasons to refer, including access to the infrastructure and multidisciplinary team of the advanced HF center that offers a broad range of expertise. The intent of this statement is to provide a framework for practitioners and health systems to help identify and refer patients with HF who are most likely to derive benefit from referral to an advanced HF center.
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Insuficiencia Cardíaca/epidemiología , American Heart Association , Guías como Asunto , Humanos , Derivación y Consulta , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients. METHODS: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis. RESULTS: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; P<0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments. CONCLUSIONS: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
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Aloinjertos/trasplante , Ácidos Nucleicos Libres de Células/genética , Rechazo de Injerto/fisiopatología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Nonplatelet thromboxane generation, stimulated largely by oxidative stress, is a novel mortality risk factor in individuals with coronary artery disease. Though inversely associated with left ventricular ejection fraction (LVEF), a potential role in the pathobiology of heart failure (HF) remains poorly defined. Nonplatelet thromboxane generation and oxidative stress were assessed by measuring urine thromboxane-B2 metabolites (TXB2-M) and 8-isoPGF2α by ELISA in 105 subjects taking aspirin and undergoing right heart catheterization for evaluation of HF, valve disease, or after transplantation. Multivariable logistic regression and survival analyses were used to define associations of TXB2-M to invasive measures of cardiovascular performance and 4-year clinical outcomes. TXB2-M was elevated (>1,500 pg/mg creatinine) in 46% of subjects and correlated with HF severity by New York Heart Association (NYHA) functional class and brain natriuretic peptide level, modestly with LVEF, but not with HF etiology. There was no association of oxidative stress to HF type or etiology but a trend with NYHA functional class. Multiple invasive hemodynamic parameters independently associated with TXB2-M after adjustment for oxidative stress, age, sex, and race with pulmonary effective arterial elastance (Ea pulmonary), reflective of right ventricular afterload, being the most robust on hierarchical analysis. Similar to Ea pulmonary, elevated urinary TXB2-M is associated with increased risk of death (adjusted HR = 2.15, P = 0.037) and a combination of death, transplant, or mechanical support initiation (adjusted HR = 2.0, P = 0.042). Nonplatelet TXA2 thromboxane generation is independently associated with HF severity reflected by invasive measures of cardiovascular performance, particularly right ventricular afterload, and independently predicted long-term mortality risk.NEW & NOTEWORTHY Nonplatelet thromboxane generation in heart failure is independently associated with risk of death, transplant, or need for mechanical support. Measurement of urine thromboxane metabolites using a clinically available assay may be a useful surrogate for invasive measurement of cardiovascular hemodynamics and performance that could provide prognostic information and facilitate tailoring of therapy in patients with heart failure. Inhibiting thromboxane generation or its biological effects is a potential strategy for improving cardiovascular performance and outcomes in heart failure.
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Insuficiencia Cardíaca , Función Ventricular Izquierda , Insuficiencia Cardíaca/diagnóstico , Humanos , Volumen Sistólico , Tromboxano B2/orina , TromboxanosRESUMEN
BACKGROUND: Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes. METHODS AND RESULTS: We retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm3) and below-median (<219 cm3) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank Pâ¯=â¯0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.5%; log-rank Pâ¯=â¯0.67). CONCLUSIONS: In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Tejido Adiposo/diagnóstico por imagen , Adulto , Corazón Auxiliar/efectos adversos , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established. METHODS: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files. RESULTS: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.
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Insuficiencia Cardíaca/epidemiología , Anciano , Comorbilidad , Costo de Enfermedad , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Pruebas de Función Cardíaca , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Vigilancia en Salud PúblicaRESUMEN
BACKGROUND: Recurrent congestion in cardiac amyloidosis (CA) remains a management challenge, often requiring high dose diuretics and frequent hospitalizations. Innovative outpatient strategies are needed to effectively manage heart failure (HF) in patients with CA. Ambulatory diuresis has not been well studied in restrictive cardiomyopathy. Therefore, we aimed to examine the outcomes of an ambulatory diuresis clinic in the management of congestion related to CA. METHODS AND RESULTS: We retrospectively studied patients with CA seen in an outpatient HF disease management clinic for (1) safety outcomes of ambulatory intravenous (IV) diuresis and (2) health care utilization. Forty-four patients with CA were seen in the clinic a total of 203 times over 6 months. Oral diuretics were titrated at 96 (47%) visits. IV diuretics were administered at 56 (28%) visits to 17 patients. There were no episodes of severe acute kidney injury or symptomatic hypotension. There was a significant decrease in emergency department and inpatient visits and associated charges after index visit to the clinic. The proportion of days hospitalized per 1000 patient days of follow-up decreased as early as 30 days (147.3 vs 18.1/1000 patient days of follow-up, P< .001) and persisted through 180 days (33.6 vs 22.9/1000 patient days of follow-up, P< .001) pre- vs post-index visit to the clinic. CONCLUSIONS: We demonstrate the feasibility of ambulatory IV diuresis in patients with CA. Our findings also suggest that use of a HF disease management clinic may reduce acute care utilization in patients with CA. Leveraging multidisciplinary outpatient HF clinics may be an effective alternative to hospitalization in patients with HF due to CA, a population who otherwise carries a poor prognosis and contributes to high health care burden.
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Instituciones de Atención Ambulatoria , Amiloidosis/complicaciones , Cardiomiopatías/complicaciones , Diuréticos/uso terapéutico , Insuficiencia Cardíaca/terapia , Anciano , Instituciones de Atención Ambulatoria/economía , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Diuresis , Diuréticos/administración & dosificación , Servicio de Urgencia en Hospital/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Costos de la Atención en Salud , Necesidades y Demandas de Servicios de Salud , Insuficiencia Cardíaca/etiología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. METHODS: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (nâ¯=â¯330), HeartMate 3 (nâ¯=â¯22) and HeartWare (nâ¯=â¯48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. RESULTS: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28-627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank Pâ¯=â¯0 .013). CONCLUSIONS: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up.
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Insuficiencia Cardíaca , Corazón Auxiliar , Insuficiencia Renal Crónica , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Gastrointestinal bleeding (GIB) is common in left ventricular assist device (LVAD) patients. Serotonin release from platelets promotes platelet aggregation, and selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy inhibits the transporter responsible for re-uptake. METHODS: We reviewed the records of LVAD (HeartMateII™, Abbott Medical, Lake Bluff, IL, USA and Heartware™, Medtronic, Minneapolis, MN, USA) patients at the Medical University of South Carolina and Johns Hopkins Hospital between January 2009 and January 2016. After exclusions, 248 patients were included for analysis. After univariate analysis, logistic regression multivariate analysis was performed to adjust for any demographic, cardiovascular, and laboratory data variables found to be associated with GI bleeding post-LVAD. RESULTS: Gastrointestinal bleeding occurred in 85 patients (35%) with 55% of GIBs due to arteriovenous malformations (AVMs). Of the total cohort, 105 patients received an SSRI or SNRI during LVAD support. Forty-four (44) SSRI/SNRI (41.9%) and 41 non-SSRI/SNRI (28.7%) patients had a GIB (RR 1.46, p = 0.03). Twenty-six (26) (24.8%) of the SSRI/SNRI patients had a GIB due to AVMs versus 21 (14.7%) of the non-SSRI/SNRI patients (RR 1.69, p = 0.05). In fully-adjusted multivariate regression analysis, SSRI/SNRI therapy was independently associated with GIB (OR 1.78, p = 0.045). For GIB, the number needed to harm (NNH) was 7.6. CONCLUSION: In conclusion, SSRI/SNRI therapy is independently associated with an increased risk of GIB in LVAD patients.
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Hemorragia Gastrointestinal/inducido químicamente , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Medición de Riesgo/métodos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Femenino , Hemorragia Gastrointestinal/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex. METHODS: The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (≥55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40 173 events after accounting for sampling design (unweighted n=8746). RESULTS: Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ≈10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women -5.4%, black men -4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF -7.1%, black men HF with reduced ejection fraction -4.7%). CONCLUSIONS: Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.
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Insuficiencia Cardíaca/terapia , Evaluación de Procesos y Resultados en Atención de Salud/tendencias , Admisión del Paciente/tendencias , Negro o Afroamericano , Factores de Edad , Anciano , Femenino , Disparidades en el Estado de Salud , Insuficiencia Cardíaca/etnología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Función Ventricular Izquierda , Población BlancaRESUMEN
Cancer survivors might have an excess risk of cardiovascular disease (CVD) resulting from toxicities of cancer therapies and a high burden of CVD risk factors. We sought to evaluate the association of cancer survivorship with subclinical myocardial damage, as assessed by elevated high-sensitivity cardiac troponin T (hs-cTnT) test results. We included 3,512 participants of the Atherosclerosis Risk in Communities Study who attended visit 5 (2011-2013) and were free of CVD (coronary heart disease, heart failure, or stroke). We used multivariate logistic regression to evaluate the cross-sectional associations of survivorship from any, non-sex-related, and sex-related cancers (e.g., breast, prostate) with elevated hs-cTnT (≥14 ng/L). Of 3,512 participants (mean age, 76 years; 62% women; 21% black), 19% were cancer survivors. Cancer survivors had significantly higher odds of elevated hs-cTnT (OR = 1.26, 95% CI: 1.03, 1.53). Results were similar for survivors of non-sex-related and colorectal cancers, but there was no association between survivorship from breast and prostate cancers and elevated hs-cTnT. Results were similar after additional adjustments for CVD risk factors. Survivors of some cancers might be more likely to have elevated hs-cTnT than persons without prior cancer. The excess burden of subclinical myocardial damage in this population might not be fully explained by traditional CVD risk factors.
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Supervivientes de Cáncer/estadística & datos numéricos , Troponina T/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Cardiomiopatías/sangre , Cardiomiopatías/etiología , Estudios de Cohortes , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: The PIROUETTE (PIRfenidOne in patients with heart failUre and preserved lEfT venTricular Ejection fraction) trial is designed to evaluate the efficacy and safety of the anti-fibrotic pirfenidone in patients with chronic heart failure and preserved ejection fraction (HFpEF) and myocardial fibrosis. HFpEF is a diverse syndrome associated with substantial morbidity and mortality. Myocardial fibrosis is a key pathophysiological mechanism of HFpEF and myocardial fibrotic burden is strongly and independently associated with adverse outcome. Pirfenidone is an oral anti-fibrotic agent, without haemodynamic effect, that leads to regression of myocardial fibrosis in preclinical models. It has proven clinical effectiveness in pulmonary fibrosis. METHODS: The PIROUETTE trial is a randomised, double-blind, placebo-controlled phase II trial evaluating the efficacy and safety of 52 weeks of treatment with pirfenidone in patients with chronic HFpEF (symptoms and signs of heart failure, left ventricular ejection fraction ≥ 45%, elevated natriuretic peptides [BNP ≥ 100 pg/ml or NT-proBNP ≥ 300 pg/ml; or BNP ≥ 300 pg/ml or NT-proBNP ≥ 900 pg/ml if in atrial fibrillation]) and myocardial fibrosis (extracellular matrix (ECM) volume ≥ 27% measured using cardiovascular magnetic resonance). The primary outcome measure is change in myocardial ECM volume. A sub-study will investigate the relationship between myocardial fibrosis and myocardial energetics, and the impact of pirfenidone, using 31phosphorus magnetic resonance spectroscopy. DISCUSSION: PIROUETTE will determine whether pirfenidone is superior to placebo in relation to regression of myocardial fibrosis and improvement in myocardial energetics in patients with HFpEF and myocardial fibrosis (NCT02932566). CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT02932566) https://clinicaltrials.gov/ct2/show/NCT02932566.
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Insuficiencia Cardíaca/tratamiento farmacológico , Piridonas/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Femenino , Fibrosis , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Volumen Sistólico , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies are highly effective at preventing breast cancer recurrence but are associated with cardiotoxicity in some patients, and minimal data are available regarding racial disparities in the incidence of this toxicity. The authors conducted a retrospective study to analyze the association of black or white race with treatment-induced cardiotoxicity and incomplete therapy among patients with HER2-positive early breast cancer. METHODS: Women with HER2-positive, stage I through III breast cancer who initiated (neo)adjuvant HER2-targeted therapy (trastuzumab with or without pertuzumab) from January 2005 to March 2015 at the authors' institution were eligible. We analyzed differences in the incidence of cardiotoxicity (a decline in the left ventricular ejection fraction to <50% AND an absolute drop in the left ventricular ejection fraction of ≥10% from baseline) and incomplete therapy (<52 weeks of HER2-targeted therapy) between black and white women in univariate and multivariable analyses. RESULTS: The authors identified 59 black patients and 157 white patients who had a median follow-up 5.2 years. The median patient age was 53 years and was similar for black and white patients. The 1-year cardiotoxicity incidence was 12% overall (95% confidence interval [CI], 7%-16%), 24% in black women (95% CI, 12%-34%), and 7% in white women (95% CI, 3%-11%). Black patients had a significantly greater probability of incomplete therapy compared with white patients (odds ratio, 4.61; 95% CI, 1.70-13.07; P = .002). High correlation was observed between a cardiotoxicity event and incomplete therapy (96% concordance). CONCLUSIONS: Black patients have a higher rate of cardiotoxicity and resultant incomplete adjuvant HER2-targeted therapy than white patients. This patient population may benefit from enhanced cardiac surveillance, cardioprotective strategies, and early referral to cardiology when appropriate. Cancer 2018;124:1904-11. © 2018 American Cancer Society.
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Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/terapia , Cardiotoxicidad/etnología , Disparidades en el Estado de Salud , Receptor ErbB-2/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Población Negra/estadística & datos numéricos , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Femenino , Estudios de Seguimiento , Humanos , Mastectomía , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversos , Población Blanca/estadística & datos numéricosRESUMEN
OBJECTIVES: To characterize patient profile and hemodynamic profile of those undergoing intra-aortic balloon pump (IABP) for cardiogenic shock and define predictors of hemodynamic failure of IABP support. BACKGROUND: Clinical characteristics of IABP support in cardiogenic shock not related to acute myocardial infarction (AMI) remain poorly characterized. METHODS: We retrospectively studied a cohort of 74 patients from 2010 to 2015 who underwent IABP insertion for cardiogenic shock complicating acute decompensated heart failure not due to AMI. RESULTS: In the overall cohort, which consisted primarily of patients with chronic systolic heart failure (89%), IABP significantly augmented cardiac index and lowered systemic vascular resistance (P<.05). Despite this improvement, 28% of these patients died (24%) or require urgent escalation in mechanical circulatory support (MCS) (4%). Multivariable regression revealed that baseline left ventricular cardiac power index (LVCPI), a measure of LV power output derived from cardiac index and mean arterial pressure (P=.01), and history of ischemic cardiomyopathy (P=.003) were significantly associated with the composite adverse-event endpoint of death or urgent MCS escalation. An IABP Failure risk score using baseline LVCPI <0.28 W/m2 and ischemic history predicted 28-day adverse events with excellent discrimination. CONCLUSION: Despite hemodynamic improvements with IABP support, patients with non-AMI cardiogenic shock still suffer poor outcomes. Patients with ischemic cardiomyopathy and low LVPCI fared significantly worse. These patients may warrant closer observation or earlier consideration of more advanced hemodynamic support.
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Insuficiencia Cardíaca/etiología , Hemodinámica/fisiología , Contrapulsador Intraaórtico/efectos adversos , Infarto del Miocardio/complicaciones , Choque Cardiogénico/cirugía , Falla de Equipo , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Estudios Retrospectivos , Choque Cardiogénico/complicaciones , Resultado del Tratamiento , Estados Unidos/epidemiologíaAsunto(s)
Insuficiencia Cardíaca , Corazón Auxiliar , Femenino , Embarazo , Humanos , Estados Unidos , Insuficiencia Cardíaca/cirugíaRESUMEN
BACKGROUND: Patients with end-stage cardiomyopathy due to cardiac sarcoidosis (CS) may be referred for mechanical circulatory support (MCS) and heart transplantation (HT). We describe outcomes of patients with CS undergoing HT, focusing on the use of MCS as a bridge to transplant (BTT). METHODS: Using the United Network for Organ Sharing Scientific Registry of Transplant Recipients, we identified all adult waitlisted patients and isolated HT recipients from 2006 to 2015. These were divided into those with and without CS and further divided into those who did or did not receive MCS as BTT. Outcomes included 1- and 5-year post-transplantation freedom from mortality and 5-year freedom from primary graft failure. RESULTS: Over the study period, 31,528 patients were listed for HT, 148 (0.4%) of whom had CS. Among the CS patients, 34 (23%) received MCS as BTT. 18,348 patients (58%) eventually underwent HT, including 67 (0.4%) with CS, 20 (30%) of whom had received BTT MCS. Compared with non-CS diagnoses, CS patients had similar 1-year (91% vs 90%; log rank P = .88) and 5-year (83% vs 77%; log rank P = .46) freedom from mortality. Survival was also similar between CS BTT and non-CS BTT groups at 1 year (89% vs 89%; log-rank P = .92) and 5 years (72% vs 75%; log-rank P = .77). CONCLUSIONS: Survivals after HT were similar between CS and non-CS patients out to 5 years, and were also similar between CS and non-CS BTT cohorts. Both HT and BTT MCS should be considered in patients with CS.
Asunto(s)
Cardiomiopatías/cirugía , Trasplante de Corazón/métodos , Corazón Auxiliar , Sistema de Registros , Sarcoidosis/cirugía , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Cardiomiopatías/diagnóstico , Cardiomiopatías/mortalidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoidosis/diagnóstico , Sarcoidosis/mortalidad , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Living with a left ventricular assist device has significant psychosocial sequelae that affect health-related quality of life (HRQOL). OBJECTIVE: The purpose of this study was to (1) describe psychosocial indicators of stress including perceived stress, depression, fatigue, and coping; (2) examine relationships among stress indicators by level of perceived stress; (3) examine relationships among indicators of stress and clinical outcomes; and (4) test the moderation of social support on the relationship between stress and clinical outcomes. METHODS: Participants were recruited from 2 outpatient clinics in a cross-sectional study design. Standardized measures were self-administered via survey. Descriptive statistics, correlation, and multiple linear regression analysis were conducted. RESULTS: The sample (N = 62) was mostly male (78%), black (47%), and married (66%), with a mean age of 56.5 ± 13 years. The overall sample had a moderate stress profile: moderate perceived stress (mean, 11.7 ± 7), few depressive symptoms (mean, 3.2 ± 3.9), and moderate fatigue (mean, 14.3 ± 9.1). Increased perceived stress was associated with fatigue, depressive symptoms, and maladaptive coping (P < .001). Regression analysis demonstrated that perceived stress and fatigue were significant correlates of overall HRQOL (adj. R = 0.41, P < .0001). Social support moderated the relationship between perceived stress and HRQOL, controlling for fatigue (R = 0.49, P < .001). CONCLUSIONS: Individuals living with left ventricular assist device with high perceived stress have worse depressive symptoms, fatigue, and coping. The influence of high social support to improve the relationship between stress and HRQOL underscores the importance of a comprehensive plan to address psychosocial factors.