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1.
J Card Fail ; 25(7): 553-560, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30978507

RESUMO

BACKGROUND: Polymorphisms in adrenergic signaling affect the molecular function of adrenergic receptors and related proteins. The ß1 adrenergic receptor (ADRB1) Arg389Gly, G-protein receptor kinase type 5 (GRK5) Gln41Leu, G-protein ß-3 subunit (GNB3) 825 C/T, and α2c deletion affect adrenergic tone, impact heart failure outcomes and differ in prevalence by ethnicity. Their combined effect within black cohorts remains unknown. METHODS AND RESULTS: We analyzed subjects from the African American Heart Failure Trial (A-HeFT) by assessing event-free survival, quality of life, and gene coinheritance. Significant coinheritance effects on survival included GRK5 Leu41 among subjects co-inheriting GNB3 825 C alleles (n = 166, 90.4% vs 69.0%, P < 0.001). By contrast, the impact of ADRB1 Arg389Arg genotype was magnified among subjects with GNB3 825 TT genotype (n = 181, 66.3% vs 85.7%, P = .002). The lack of the α2c deletion (ie, insertion) led to a greater impact of the ARG389Arg genotype (n = 289, 76.4% vs 86.1%, P = .007). CONCLUSIONS: Polymorphisms in adrenergic signaling affects outcomes in black subjects with heart failure. Coinheritance patterns in genetic variation may help determine heart failure survival.

2.
Clin Cardiol ; 42(5): 524-529, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30843220

RESUMO

BACKGROUND: There is limited data on electrocardiographic (ECG) abnormalities and their prognostic significance in women with peripartum cardiomyopathy (PPCM). We sought to characterize ECG findings in PPCM and explore the association of ECG findings with myocardial recovery and clinical outcomes. HYPOTHESIS: We hypothesized that ECG indicators of myocardial remodeling would portend worse systolic function and outcomes. METHODS: Standard 12-lead ECGs were obtained at enrollment in the Investigations of Pregnancy-Associated Cardiomyopathy study and analyzed for 88 women. Left ventricular ejection fraction (LVEF) was measured by echocardiography at baseline, 6 months, and 12 months. Women were followed for clinical events (death, mechanical circulatory support, and/or cardiac transplantation) until 1 year. RESULTS: Half of women had an "abnormal" ECG, defined as atrial abnormality, ventricular hypertrophy, ST-segment deviation, and/or bundle branch block. Women with left atrial abnormality (LAA) had lower LVEF at 6 months (44% vs 52%, P = 0.02) and 12 months (46% vs 54%, P = 0.03). LAA also predicted decreased event-free survival at 1 year (76% vs 97%, P = 0.008). Neither left ventricular hypertrophy by ECG nor T-wave abnormalities predicted outcomes. A normal ECG was associated with recovery in LVEF to ≥50% (84% vs 49%, P = 0.001) and event-free survival at 1 year (100% vs 85%, P = 0.01). CONCLUSIONS: ECG abnormalities are common in women with PPCM, but a normal ECG does not rule out the presence of PPCM. LAA predicted lower likelihood of myocardial recovery and event-free survival, and a normal ECG predicted favorable event-free survival.

3.
Am J Transplant ; 19(7): 2067-2076, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30659754

RESUMO

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.

4.
J Am Heart Assoc ; 8(2): e008968, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30638108

RESUMO

Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.

5.
Case Rep Cardiol ; 2018: 6195045, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402296

RESUMO

There is an increasing prevalence of patients with concomitant implantable cardioverter-defibrillators (ICDs) and left ventricular devices (LVADs). The potential for negative interactions between these continually evolving technologies is a valid concern. Previously reported interactions include inappropriate ICD therapy and interference with ICD telemetry function. Understanding the nature of such interactions and developing a comprehensive strategy to approach such situations are important. In this report, we describe a case of electromagnetic interference from LVAD inhibiting the pacing function of an ICD that was corrected by reprograming the device. We would encourage investigators to review patients with ICD and LVAD in their institutions in order to help assess the frequency and nature of these and other interactions.

6.
Am J Perinatol ; 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30184556

RESUMO

OBJECTIVE: To examine the association between maternal obesity on left ventricular (LV) size and recovery in women with peripartum cardiomyopathy (PPCM). STUDY DESIGN: This was a prospective analysis of 100 women enrolled within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body mass index (BMI) definitions for under/normal weight, overweight, and obesity. Demographic, clinical, and biomarker variables were compared across weight categories. OUTCOMES: LV end-diastolic diameter (LVEDD) and ejection fraction were measured at entry, 6, and 12 months postpartum. Multivariable regression models examined the relationship between adiposity, LV size, and leptin levels with cardiac recovery at 6 and 12 months postpartum. RESULTS: Obese and nonobese women had similar LV dysfunction at entry. Obese women had greater LV size and less LV recovery at 6 and 12 months postpartum. BMI was positively associated with leptin and ventricular diameter. Greater BMI at entry remained associated with less ventricular recovery at 6 months (p = 0.02) in adjusted race-stratified models. LVEDD at entry predicted lower ejection fraction at 6 months (p < 0.001) and similarly at 12 months. CONCLUSION: Obese women with PPCM had greater cardiac remodeling, higher leptin levels, and diminished cardiac recovery.

7.
JAMA Cardiol ; 3(10): 929-938, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30140897

RESUMO

Importance: The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants. Objective: We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM. Design: This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh. Main Outcomes and Measures: The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations. Results: Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P < .001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P = .01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation. Conclusions and Relevance: This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

9.
J Clin Invest ; 128(3): 1154-1163, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29457789

RESUMO

SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was previously shown to reproducibly associate with cardiac electrophysiological parameters, but was not considered to be causal. Here, we show that miR-24 potently suppresses SCN5A expression and that rs1805126 modulates this regulation. We found that the rs1805126 minor allele associates with decreased cardiac SCN5A expression and that heart failure subjects homozygous for the minor allele have decreased ejection fraction and increased mortality, but not increased ventricular tachyarrhythmias. In mice, we identified a potential basis for this in discovering that decreased Scn5a expression leads to accumulation of myocardial reactive oxygen species. Together, these data reiterate the importance of considering the mechanistic significance of synonymous SNPs as they relate to miRs and disease, and highlight a surprising link between SCN5A expression and nonarrhythmic death in heart failure.

10.
J Card Fail ; 24(1): 33-42, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29079307

RESUMO

OBJECTIVE: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. BACKGROUND: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. METHODS: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM). RESULTS: Entry NK cell levels (CD3-CD56+CD16+; reported as % of CD3- cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3- cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4-CD8-CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4-CD8- cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4-CD8-CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. CONCLUSIONS: Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4-CD8-CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and "double negative" (CD4-CD8-) T regulatory cells in PPCM requires further investigation.

12.
Circ Heart Fail ; 10(6)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28611123

RESUMO

BACKGROUND: There are sex differences in mortality while awaiting heart transplantation, and the reason remains unclear. METHODS AND RESULTS: We included all adults in the Scientific Registry of Transplant Recipients placed on the heart transplant active waitlist from 2004 to 2015. The primary end point was all-cause mortality. Multivariable Cox proportional hazards models were performed to evaluate survival by United Network for Organ Sharing (UNOS) status at the time of listing. Random survival forest was used to identify sex interactions for the competing risk of death and transplantation. There were 33 069 patients (25% women) awaiting heart transplantation. This cohort included 7681 UNOS status 1A (26% women), 13 027 UNOS status 1B (25% women), and 12 361 UNOS status 2 (26% women). During a median follow-up of 4.3 months, 1351 women and 4052 men died. After adjusting for >20 risk factors, female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.29) and UNOS status 1B (adjusted hazard ratio, 1.17; 95% confidence interval, 1.05-1.30). In contrast, female sex was significantly protective for time to death among UNOS status 2 (adjusted hazard ratio, 0.85; 95% confidence interval, 0.76-0.95). Sex differences in probability of transplantation were present for every UNOS status, and >20 sex interactions were identified for mortality and transplantation. CONCLUSIONS: When stratified by initial UNOS status, women had a higher mortality than men as UNOS status 1 and a lower mortality as UNOS status 2. With >20 sex interactions for mortality and transplantation, further evaluation is warranted to form a more equitable allocation system.


Assuntos
Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Sistema de Registros , Obtenção de Tecidos e Órgãos/métodos , Listas de Espera/mortalidade , Adulto , Fatores Etários , Feminino , Seguimentos , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
13.
J Am Heart Assoc ; 6(4)2017 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-28373243

RESUMO

BACKGROUND: In peripartum cardiomyopathy, the prevalence of focal myocardial damage detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is important to elucidate mechanisms of myocardial injury and cardiac dysfunction. LGE equates irreversible myocardial injury, but LGE prevalence in peripartum cardiomyopathy is uncertain. METHODS AND RESULTS: Among 100 women enrolled within the Investigations of Pregnancy Associated Cardiomyopathy cohort, we recruited 40 women at 13 centers to undergo LGE cardiovascular magnetic resonance, enrolled within the first 13 weeks postpartum. Follow-up scans occurred at 6 months postpartum, and death/transplant rates at 12 months. Baseline characteristics did not differ significantly in the parent cohort according to cardiovascular magnetic resonance enrollment except for mechanical circulatory support. LGE was noted only in 2 women (5%) at baseline. While left ventricular dysfunction with enlargement was prevalent at baseline cardiovascular magnetic resonance scans (eg, ejection fraction 38% [Q1-Q3 31-50%], end diastolic volume index=108 mL/m2 [Q1-Q3 83-134 mL/m2]), most women demonstrated significant improvements at 6 months, consistent with a low prevalence of LGE. LGE was not related to baseline clinical variables, ejection fraction, New York Heart Association heart failure class, or mortality. Neither of the 2 women who died exhibited LGE. LGE was inversely associated with persistent left ventricular ejection fraction at 6 months (P=0.006). CONCLUSIONS: Factors other than focal myocardial damage detectable by LGE explain the initial transient depressions in baseline left ventricular ejection fraction, yet focal myocardial damage may contribute to persistent myocardial dysfunction and hinder recovery in a small minority. Most women exhibit favorable changes in ventricular function over 6 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01085955.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Compostos Organometálicos/administração & dosagem , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Canadá , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Feminino , Fibrose , Gadolínio/administração & dosagem , Transplante de Coração , Humanos , Período Periparto , Valor Preditivo dos Testes , Gravidez , Complicações Cardiovasculares na Gravidez/mortalidade , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/terapia , Estudos Prospectivos , Recuperação de Função Fisiológica , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Função Ventricular Direita
14.
J Heart Lung Transplant ; 36(6): 657-665, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28209402

RESUMO

BACKGROUND: Right ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF. METHODS: Expression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR Array; Qiagen). Results were expressed as polymerase chain reaction (PCR) cycles to threshold and normalized to the average of 3 control genes, glyceraldehyde phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and ß2-microglobulin (B2M). Secondary outcomes studied were 1-year mortality and long-term RV failure (RVF-LT). RESULTS: CCR3, CCR4, CCR6, CCR7 and CCR8 were downregulated in LVAD recipients with RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further downregulated in those who required RV mechanical support. In addition, under-expression of CCR3 to CCR8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. CCR expression did not predict RVF-LT in our patient cohort. CONCLUSIONS: Pre-LVAD CCR downregulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play a major role in prognostication in this patient population.


Assuntos
Insuficiência Cardíaca/sangue , Coração Auxiliar , Receptores de Quimiocinas/sangue , Medição de Risco , Disfunção Ventricular Direita/sangue , Biomarcadores/sangue , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Disfunção Ventricular Direita/mortalidade , Disfunção Ventricular Direita/cirurgia
15.
J Am Coll Cardiol ; 69(8): 968-977, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28231950

RESUMO

BACKGROUND: Among various cardiac autoantibodies (AAbs), those recognizing the ß1-adrenergic receptor (ß1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by ß-blockers and immunoglobulin G3 (IgG3) immunoadsorption. OBJECTIVES: The goal of this study was to investigate the role of ß1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. METHODS: Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-ß1AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. RESULTS: Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-ß1AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-ß1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, ß = 0.20, p = 0.01; change in LVEF, ß = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. CONCLUSIONS: IgG3-ß1AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Autoanticorpos/sangue , Insuficiência Cardíaca Sistólica/sangue , Receptores Adrenérgicos beta 1/imunologia , Adulto , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do Tratamento , Função Ventricular Esquerda
17.
J Heart Lung Transplant ; 35(11): 1277-1283, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27836022

RESUMO

The National Institutes of Health National Heart, Lung, and Blood Institute convened a working group in March 2008 to discuss how therapies for heart failure (HF) might be best advanced using clinical trials involving left ventricular assist devices (LVAD). This group opined that the field was ready for a trial to assess the use of long-term ventricular assist device therapy in patients who are less ill than patients currently eligible for destination therapy, which resulted in the Randomized Evaluation of VAD InterVEntion before Inotropic Therapy (REVIVE-IT) pilot study. The specific objective of REVIVE-IT was to compare LVAD therapy with optimal medical management in patients with less advanced HF than current LVAD indications to determine if wider application of permanent LVAD use to less ill patients would be associated with improved survival, quality of life, or functional capacity. REVIVE-IT represented an extraordinary effort to provide data from a randomized clinical trial to inform clinicians, scientists, industry, and regulatory agencies about the efficacy and safety of LVAD therapy in a population with less advanced HF. Despite significant support from the medical community, industry, and governmental agencies, REVIVE-IT failed to accomplish its goal. The reasons for its failure are instructive, and the lessons learned from the REVIVE-IT experience are likely to be relevant to any future study of LVAD therapy in a population with less advanced HF.


Assuntos
Ensaios Clínicos como Assunto/métodos , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Qualidade de Vida , Suspensão de Tratamento , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Projetos Piloto , Estados Unidos
19.
Circ Heart Fail ; 9(5)2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27166247

RESUMO

BACKGROUND: Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery. We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome. METHODS AND RESULTS: Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) <45% within 13 weeks after delivery. Baseline RV function was assessed by echocardiographic end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane excursion, and RV speckle-tracking longitudinal strain. LV recovery was defined as LVEF of ≥50% at 1 year, persistent severe LV dysfunction as LVEF of ≤35%, and major events as death, transplant, or LV assist device implantation. RV measurements were feasible for 90 of the 96 patients (94%) with echocardiograms available. Mean baseline LVEF was 36±9%. RV fractional area change was <35% in 38% of patients. Of 84 patients with 1-year follow-up data, 63 (75%) had LV recovery and 11 (13%) had LVEF of ≤35% or a major event (4 LV assist devices and 2 deaths). Tricuspid annular plane excursion and RV strain did not predict outcome. Baseline RV fractional area change by multivariable analysis was independently associated with subsequent LV recovery and clinical outcome. CONCLUSIONS: Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year. RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important.


Assuntos
Cardiomiopatias/fisiopatologia , Período Periparto , Complicações Cardiovasculares na Gravidez/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Função Ventricular Direita , Área Sob a Curva , Canadá , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/mortalidade , Cardiomiopatias/terapia , Ecocardiografia , Feminino , Humanos , Estimativa de Kaplan-Meier , Valor Preditivo dos Testes , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/mortalidade , Complicações Cardiovasculares na Gravidez/terapia , Prognóstico , Estudos Prospectivos , Curva ROC , Recuperação de Função Fisiológica , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Estados Unidos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/terapia
20.
JACC Heart Fail ; 4(9): 689-97, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27179836

RESUMO

OBJECTIVES: The aim of this study was to identify differences in survival on the basis of type of heart disease while awaiting orthotopic heart transplantation (OHT). BACKGROUND: Patients with restrictive cardiomyopathy (RCM), congenital heart disease (CHD), or hypertrophic cardiomyopathy (HCM) may be at a disadvantage while awaiting OHT because they often are poor candidates for mechanical circulatory support and/or inotropes. METHODS: The study included all adults in the Scientific Registry of Transplant Recipients database awaiting OHT from 2004 to 2014, and outcomes were evaluated on the basis of type of heart disease. The primary endpoint was time to all-cause mortality, censored at last patient follow-up and time of transplantation. Multivariate Cox proportional hazards modeling was performed to evaluate survival by type of cardiomyopathy. RESULTS: There were 14,447 patients with DCM, 823 with RCM, 11,799 with ischemic cardiomyopathy (ICM), 602 with HCM, 964 with CHD, 584 with valvular disease, and 1,528 in the "other" category (including 1,216 for retransplantation). During median follow-up of 3.7 months, 4,943 patients died (1,253 women, 3,690 men). After adjusting for possible confounding variables including age, renal function, inotropes, mechanical ventilation, and mechanical circulatory support, the adjusted hazard ratios by diagnoses relative to DCM were 1.70 for RCM (95% confidence interval [CI]: 1.43 to 2.02), 1.10 for ICM (95% CI: 1.03 to 1.18), 1.23 for HCM (95% CI: 0.98 to 1.54), 1.30 for valvular disease (95% CI: 1.07 to 1.57), 1.37 for CHD (95% CI: 1.17 to 1.61), and 1.51 for "other" diagnoses (95% CI: 1.34 to 1.69). Sex was a significant modifier of mortality for ICM, RCM, and "other" diagnoses (p < 0.05 for interaction). CONCLUSIONS: In the United States, patients with RCM, CHD, or prior heart transplantation had a higher risk for death while awaiting OHT than patients with DCM, ICM, HCM, or valvular heart disease.


Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Restritiva/mortalidade , Cardiopatias Congênitas/mortalidade , Insuficiência Cardíaca/mortalidade , Transplante de Coração , Doenças das Valvas Cardíacas/mortalidade , Listas de Espera/mortalidade , Adulto , Idoso , Cardiomiopatias/etiologia , Cardiomiopatias/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Modelos de Riscos Proporcionais , Estados Unidos
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