Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 310
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Am Heart Assoc ; 9(13): e015026, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32552264

RESUMO

Background Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that modulation of the phosphodiesterase type 3/cyclic AMP using a novel oral formulation of milrinone might exert favorable effects HFpEF via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with HFpEF. Methods and Results The MilHFPEF (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double-blind, placebo-controlled pilot study in 23 patients with symptomatic HFpEF. Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6-minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone-treated patients compared with placebo (+10±13 versus -3±15; P=0.046). Six-minute walk distance also tended to improve in the treatment group compared with placebo (+22 [-8 to 49] versus -47 [-97 to 12]; P=0.092). Heart rate (-1±5 versus -2±9 bpm; P=0.9) and systolic blood pressure (-3±18 versus +1±12 mm Hg; P=0.57) were unchanged. Early filling velocity/early mitral annular velocity (-0.3±3.0 versus -1.9±4.8; P=0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone. Conclusions In this novel pilot study, extended release oral milrinone was well tolerated and associated with improved quality of life in patients with HFpEF. Further longer-term studies are warranted to establish the role of this therapeutic approach in HFpEF. Registration URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12616000619448.

2.
Heart Lung Circ ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32359870

RESUMO

BACKGROUND: Patients admitted to hospital with acute heart failure (AHF) are at increased risk of readmission and mortality post-discharge. The aim of the study was to examine health service utilisation within 30 days post-discharge from an AHF hospitalisation. METHODS: This was a prospective, observational, non-randomised study of consecutive patients hospitalised with acute HF to one of 16 Victorian hospitals over a 30-day period each year and followed up for 30 days post-discharge. The project was conducted annually over three consecutive years from 2015 to 2017. RESULTS: Of the 1,197 patients, 56.3% were male with an average age of 77±13.23 years. Over half of the patients (711, 62.5%) were referred to an outpatient clinic and a third (391, 34.4%) to a HF disease management program. In-hospital mortality was 5.1% with 30 day-mortality of 9% and readmission rate of 24.4%. Patients who experienced a subsequent readmission less than 10 days post-discharge and between 11 and 20 days post-discharge had a five- to six-fold increase in risk of mortality (adjusted OR 5.02, 95% CI 2.11-11.97; OR 6.45, 95% CI 2.69-15.42; respectively) compared to patients who were not readmitted to hospital. An outpatient appointment within 30 days post-discharge significantly reduced the risk of 30-day mortality by 81% (95% CI 0.09-0.43). CONCLUSION: Patients admitted to hospital with AHF who experience a subsequent readmission within 20 days post-discharge are at increased risk of dying. However, early follow-up post-discharge may reduce this risk. Early post-discharge follow-up is vital to address this vulnerable period after a HF admission.

3.
Heart Lung Circ ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32418875

RESUMO

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

4.
Interv Cardiol Clin ; 9(3): 395-401, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32471679

RESUMO

Contrast-induced acute kidney injury is not uncommon after percutaneous coronary intervention, particularly in high-risk patients. Pharmacologic approaches have not demonstrated significant benefit, and numerous device-based approaches exist targeting a variety of pathways. In this review, we summarize the most recent interventions and the evidence behind them.

5.
Curr Hypertens Rep ; 22(5): 38, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385705

RESUMO

PURPOSE OF REVIEW: To summarize the recent evidence that supports a role for the gut microbiota, microbiota-derived metabolites, and dysbiosis on cardiovascular risk factors, and to discuss the neuro-cardio-metabolic mechanisms that link gut microbiota and heart failure. RECENT FINDINGS: There is growing evidence that the gut microbiota communicates with and impacts the cardiovascular system, contributing to the development of heart failure once it becomes out of balance (i.e. gut dysbiosis). The exact mechanisms of how the gut microbiota influences cardiovascular outcomes are not fully understood, but immune dysregulation and disturbance of neuro-enteroendocrine hormones seem to be involved. The disturbances in the gut microbiota influence the progression of several risk factors for heart failure, including atherosclerosis, obesity, diabetes, kidney disease and hypertension. In turn, these conditions also act to regulate the gut microbiota through the deterioration of the integrity of the intestinal barrier and the release of neurotransmitters and gastrointestinal hormones. In normal and healthy physiological conditions, these interactions are homeostatic and tightly controlled. However, a combination of environmental exposures (e.g. antibiotics use and Western diet) and the host's intrinsic conditions (e.g. genetics and fluid status) can result in the breakdown of intestinal homeostasis and further progression of cardiovascular risk factors, which lead to the development of heart failure. Manipulation of the gut microbiota may have the potential to improve cardiovascular outcomes by ameliorating immune system dysregulation, enteroendocrine disruptions, and neurohormonal activation in patients with cardiovascular risk factors for heart failure.

6.
Cell Signal ; 72: 109629, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32278008

RESUMO

Cardiac fibrosis and myocyte hypertrophy are hallmarks of the cardiac remodelling process in cardiomyopathies such as heart failure (HF). Dyslipidemia or dysregulation of lipids contribute to HF. The dysregulation of high density lipoproteins (HDL) could lead to altered levels of other lipid metabolites that are bound to it such as sphingosine-1- phosphate (S1P). Recently, it has been shown that S1P and its analogue dihydrosphingosine-1-phosphate (dhS1P) are bound to HDL in plasma. The effects of dhS1P on cardiac cells have been obscure. In this study, we show that extracellular dhS1P is able to increase collagen synthesis in neonatal rat cardiac fibroblasts (NCFs) and cause hypertrophy of neonatal cardiac myocytes (NCMs). The janus kinase/signal transducer and activator (JAK/STAT) signalling pathway was involved in the increased collagen synthesis by dhS1P, through sustained increase of tissue inhibitor of matrix metalloproteinase 1 (TIMP1). Extracellular dhS1P increased phosphorylation levels of STAT1 and STAT3 proteins, also caused an early increase in gene expression of transforming growth factor-ß (TGFß), and sustained increase in TIMP1. Inhibition of JAKs led to inhibition of TIMP1 and TGFß gene and protein expression. We also show that dhS1P is able to cause NCM hypertrophy through S1P-receptor-1 (S1PR1) signalling which is opposite to that of its analogue, S1P. Taken together, our results show that dhS1P increases collagen synthesis in cardiac fibroblasts causing fibrosis through dhS1P-JAK/STAT-TIMP1 signalling.

7.
Br J Pharmacol ; 177(13): 2906-2922, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32250449

RESUMO

Cardiorenal syndrome (CRS) is a multi-organ disease, encompassing heart, kidney and vascular system dysfunction. CRS is a worldwide problem, with high morbidity, mortality, and inflicts a significant burden on the health care system. The pathophysiology is complex, involving interactions between neurohormones, inflammatory processes, oxidative stress and metabolic derangements. Therapies remain inadequate, mainly comprising symptomatic care with minimal prospect of full recovery. Challenges include limiting the contradictory effects of multi-organ targeted drug prescriptions and continuous monitoring of volume overload. Novel strategies such as multi-organ transplantation and innovative dialysis modalities have been considered but lack evidence in the CRS context. The adjunct use of pharmaceuticals targeting alternative pathways showing positive results in preclinical models also warrants further validation in the clinic. In recent years, studies have identified the involvement of gut dysbiosis, uraemic toxin accumulation, sphingolipid imbalance and other unconventional contributors, which has encouraged a shift in the paradigm of CRS therapy.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32111559

RESUMO

PURPOSE: To report long-term survival and to identify potential determinants of survival among patients receiving treatment for functional mitral regurgitation (FMR) with the Carillon device. METHODS: This was a post hoc analysis in which we pooled prospectively collected data from three studies of the Carillon device with available long-term vital status data. Patient eligibility in these trials specified symptomatic congestive heart failure despite guideline-directed medical therapy, grade 2 to 4 FMR, left ventricular enlargement, and reduced ejection fraction. Echocardiographic parameters were available through the 12-month visit and vital status was available through 5 years. The association of patient characteristics and changes in echocardiographic parameters at 6 and 12 months with long-term survival was analyzed using Cox proportional hazards regression. RESULTS: A total of 74 patients (mean age 67 years, 72% male, 59% MR grade 3 or 4) were treated with the Carillon device. Over 1 year of follow-up, the New York Heart Association (NYHA) class decreased in 64% of patients, distance on the 6-minute walk test increased, and echocardiographic measures indicated significant decreases in MR grade and favorable left ventricular remodeling. The Kaplan-Meier survival rate was 83.6% at 1 year, 73.1% at 2 years, 67.9% at 3 years, and 56.2% at 4 and 5 years of follow-up. Primary determinants of long-term survival were a decrease in NYHA class, an increase in 6-minute walk test distance, and a decrease in regurgitant volume during the first year of follow-up. CONCLUSIONS: Among patients with congestive heart failure and grade 2 to 4 FMR who were symptomatic despite guideline-directed medical therapy, transcatheter mitral valve repair with the Carillon device resulted in a favorable 5-year survival rate. The survival benefit was greatest among patients with improvement in clinical and hemodynamic parameters during the first year of follow-up.

9.
J Am Soc Echocardiogr ; 33(5): 583-593, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173204

RESUMO

BACKGROUND: Left ventricular (LV) assist devices (LVADs) are known to elicit reverse remodeling by mechanically unloading the left ventricle. Current guidelines target a reduction in LV end-diastolic diameter (LVEDD) of 15% compared with pre-LVAD dimensions; however, there is significant heterogeneity in the degree of unloading achieved. We sought to investigate factors associated with mechanical unloading at 6 months of LVAD support. METHODS: Data were retrospectively collected for 75 LVAD recipients at five time points: pre-LVAD, within 14 days post-LVAD, and at 1, 3, and 6 months post-LVAD. The percentage change in LVEDD between the pre-LVAD and 6 months post-LVAD time points was termed ΔLVEDD. Optimal LV unloading was defined as ΔLVEDD of ≥15% at 6 months. Patients who achieved optimal unloading (group A, n = 30) were compared with patients who did not (group B, n = 45). RESULTS: At 6 months, optimally unloaded patients (group A) demonstrated higher fractional shortening (15% ± 10% vs 10% ± 7%, P = .007), lower rates of moderate or severe mitral regurgitation (10% vs 33%, P = .02), and lower pulmonary capillary wedge pressure (9 ± 4 vs 16 ± 7 mm Hg, P = .02). Right ventricular dysfunction was more prevalent at 6 months in poorly unloaded (group B) patients (73% vs 43%, P = .008). Between hospital discharge and 6 months, the percentage increase in pump speed (Δ revolutions per minute) was higher in group A patients (4.4% ± 3.7% vs 0.1% ± 2.6%, P < .001). In a multivariate analysis, Δ revolutions per minute and tricuspid annular systolic velocity (S') at 6 months were independently associated with 6-month ΔLVEDD. CONCLUSIONS: Recipients of LVADs who undergo progressive pump speed up-titration during outpatient follow-up are more likely to sustain optimal LV unloading. Progressive LVAD-related right ventricular failure is prevalent in suboptimally unloaded patients.

10.
Circulation ; 141(17): 1393-1403, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32093510

RESUMO

BACKGROUND: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, a diet poor in fiber is associated with prevalence of high BP. The impact of lack of prebiotic fiber and the associated mechanisms that lead to higher BP are unknown. Here we show that lack of prebiotic dietary fiber leads to the development of a hypertensinogenic gut microbiota, hypertension and its complications, and demonstrate a role for G-protein coupled-receptors (GPCRs) that sense gut metabolites. METHODS: One hundred seventy-nine mice including C57BL/6J, gnotobiotic C57BL/6J, and knockout strains for GPR41, GPR43, GPR109A, and GPR43/109A were included. C57BL/6J mice were implanted with minipumps containing saline or a slow-pressor dose of angiotensin II (0.25 mg·kg-1·d-1). Mice were fed diets lacking prebiotic fiber with or without addition of gut metabolites called short-chain fatty acids ([SCFA)] produced during fermentation of prebiotic fiber in the large intestine), or high prebiotic fiber diets. Cardiac histology and function, BP, sodium and potassium excretion, gut microbiome, flow cytometry, catecholamines and methylation-wide changes were determined. RESULTS: Lack of prebiotic fiber predisposed mice to hypertension in the presence of a mild hypertensive stimulus, with resultant pathological cardiac remodeling. Transfer of a hypertensinogenic microbiota to gnotobiotic mice recapitulated the prebiotic-deprived hypertensive phenotype, including cardiac manifestations. Reintroduction of SCFAs to fiber-depleted mice had protective effects on the development of hypertension, cardiac hypertrophy, and fibrosis. The cardioprotective effect of SCFAs were mediated via the cognate SCFA receptors GPR43/GPR109A, and modulated L-3,4-dihydroxyphenylalanine levels and the abundance of T regulatory cells regulated by DNA methylation. CONCLUSIONS: The detrimental effects of low fiber Westernized diets may underlie hypertension, through deficient SCFA production and GPR43/109A signaling. Maintaining a healthy, SCFA-producing microbiota is important for cardiovascular health.

11.
Intern Med J ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043694

RESUMO

BACKGROUND: We identified variation in delivery of guideline recommended care at our institution, and undertook a project to design a HF model of care. AIM: To maximize time patients with HF spend well in the community by delivering best practice guidelines to reduce variation in care improving overall outcomes. METHOD: This quality improvement project focused on reducing variation in process measures of care. The HF model of care included electronic HF care bundles, a patient education pack with staff training on delivering HF patient education, referral of all HF patients to the Hospital Admissions Risk Program for phone call within 72 h, and a nurse-pharmacist early follow-up clinic. Outcomes were assessed using interrupted time series analyses. RESULTS: The pre-intervention group comprised 1585 patients, and post-intervention 1720 patients with a primary diagnosis of HF admitted under general cardiology and general medicine. Interrupted Time Series analysis indicated 30-day readmissions did not change in overall trend (-0.2% per month, p = 0.479) but with significant step-down of 7.8% (p = 0.018). For 90-day readmissions, a significant trend reduction over the time period was seen (-0.6% per month, p = 0.017) with a significant immediate step-down (-9.4%, p = 0.001). Emergency department re-presentations, in-patient mortality and length of stay did not change significantly. Improvements in process measures were seen at audit. CONCLUSION: This model of care resulted in overall trends of reductions in 30 and 90 day readmissions, without increasing ED representations, mortality and length of stay. This model will be adapted to the electronic medical record at our institution. This article is protected by copyright. All rights reserved.

12.
N Engl J Med ; 382(1): 20-28, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31893513

RESUMO

BACKGROUND: Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear. METHODS: We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up. RESULTS: Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01). CONCLUSIONS: Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).


Assuntos
Abstinência de Álcool , Consumo de Bebidas Alcoólicas/efeitos adversos , Fibrilação Atrial/prevenção & controle , Idoso , Fibrilação Atrial/etiologia , Austrália , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Prevenção Secundária
13.
ESC Heart Fail ; 7(1): 213-222, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31960599

RESUMO

AIMS: Women are overrepresented amongst patients with heart failure with preserved ejection fraction (HFpEF); however, the underpinning mechanism for this asymmetric distribution is unclear. Pregnancy represents a potential gender-specific risk factor for HFpEF. It leads to significant physiological adaption, and increasing parity has been associated with some cardiovascular risk. We sought to examine the relationship between prior parity with the rest and exercise haemodynamic and echocardiographic profile of women with HFpEF. METHODS AND RESULTS: Patients referred for assessment of exertional dyspnoea and confirmed to have a haemodynamic and clinical profile consistent with HFpEF were included. Detailed evaluation consisted of rest and exercise right heart catheterization and echocardiography. A socio-economic and obstetric history was also documented. Fifty-eight women were assessed and categorized as having either 0-2 births or ≥3 births, dividing the cohort equally. Women with ≥3 births achieved a lower symptom-limited workload than those with 0-2 births [38 (24-51) vs. 46 (31-68) W, P = 0.04]. Women with ≥3 births had a greater rise in pulmonary capillary wedge pressure indexed to workload with exercise [0.5 (0.3-0.8) vs. 0.3 (0.2-0.5) mmHg/W, P = 0.03], paralleled by a greater rise in right atrial pressure [10 (8-12) vs. 7 (3-11), P = 0.01]. Pulmonary vascular resistance was also higher in women with ≥3 births [1.9 (1.6-2.4) vs. 1.6 (1.4-1.9) mmHg/L/min rest, P = 0.046, and 1.9 (2.4-2.4) vs. 1.4 (1-1.8) mmHg/L/min exercise, P = 0.024]. Left ventricular ejection fraction was lower at rest [60 (57-61) vs. 63 (60-66), P = 0.008] and during exercise [65 (62-67) vs. 68 (66-70), P = 0.038] in women with higher parity. CONCLUSIONS: Higher parity is associated with greater impairments in multiple physiologic parameters of HFpEF severity in women, including diastolic reserve, pulmonary vascular resistance, and systolic dysfunction.

14.
Heart ; 106(1): 58-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31530572

RESUMO

OBJECTIVE: The aim of the meta-analysis was to determine the association of obesity and heart failure (HF) and the cardiac impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obese subjects. METHODS: MEDLINE, Embase and Web of Science were searched up to 3 April 2018. Studies reporting association and prognostic impact of obesity in HF and the impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obesity were included in the meta-analysis. RESULTS: 4959 citations were reviewed. After exclusions, 29 studies were analysed. A 'J curve' relationship was observed between body mass index (BMI) and risk of HF with maximum risk in the morbidly obese (1.73 (95% CI 1.30 to 2.31), p<0.001, n=11). Although 'obesity paradox' was observed for all-cause mortality, the overweight group was associated with lower cardiovascular (CV) mortality (OR=0.86 (95% CI 0.79 to 0.94), n=11) with no significant differences across other BMI groups. Intentional weight loss induced by bariatric surgery in obese patients (n=9) without established HF, atrial fibrillation or known coronary artery disease, was associated with a reduction in left ventricular mass index (p<0.0001), improvement in left ventricular diastolic function (p≤0.0001) and a reduction in left atrial size (p=0.02). CONCLUSIONS: Despite the increased risk of HF with obesity, an 'obesity paradox' is observed for all-cause mortality. However, the nadir for CV mortality is observed in the overweight group. Importantly, intentional weight loss was associated with improvement in indices of cardiac structure and myocardial function in obese patients. TRIAL REGISTRATION NUMBER: APP 74412.

17.
Eur Heart J ; 40(47): 3859-3868c, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31800034

RESUMO

The overall lifetime risk of heart failure (HF) is similar between men and women, however, there are marked sex differences in the landscape of this condition that are both important and under-recognized. Men are predisposed to HF with reduced ejection fraction (HFrEF), whereas women predominate in HF with preserved ejection fraction (HFpEF). Sex differences are also notable in the penetrance of genetic cardiomyopathies, risk factors, e.g. breast cancer which may be associated with cancer treatment-induced cardiomyopathy, as well as sex-specific conditions such as peripartum cardiomyopathy (PPCM). This review outlines the key sex differences with respect to clinical characteristics, pathophysiology, and therapeutic responses to HF treatments. Finally, we address important differences in the prognosis of HF. A central hypothesis is that the higher risk of HFrEF in men compared to women may be attributable to their predisposition to macrovascular coronary artery disease and myocardial infarction, whereas coronary microvascular dysfunction/endothelial inflammation has been postulated to play a key role in HFpEF and maybe the common link among HF syndromes that women are predisposed to Takotsubo cardiomyopathy, PPCM, and breast cancer radiotherapy-induced cardiomyopathy. Under-pinning current sex disparities in HF, there is a paucity of women recruited to HF clinical trials (20-25% of cohorts) and thus treatment guidelines are predominantly based on male-derived data. Large gaps in knowledge exist in sex-specific mechanisms, optimal drug doses for women and sex-specific criteria for device therapy.

18.
Cardiovasc Drugs Ther ; 33(6): 687-692, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31885055

RESUMO

PURPOSE: Drug-eluting balloon catheters (DEBc) coated with paclitaxel (PTX) have been associated with potential safety concerns. An efficacious but less toxic balloon coating may reduce these outcomes. We evaluated a novel DEBc, Epi-Solve, coated with metacept-3 (MCT-3), a member of the histone deacetylase inhibitor (HDACi) class of epigenetic agents, in a large animal model of neointimal hyperplasia (NIH). METHODS: Plain balloon angioplasty (PABA) catheters were ultrasonically coated with MCT-3 to generate Epi-Solve DEBc. An ovine model of NIH formation was established utilising partial left common carotid artery (LCA) ligation. Twenty-eight days post neointima (NI) induction, PABA, Epi-Solve or PTX-coated DEBc were deployed at the site of induced NI formation. Twenty-eight days post-intervention, ligated vessels were evaluated for attenuation of NI formation, gene expression profiles and immunohistochemical analysis. RESULTS: Epi-Solve DEBc demonstrated attenuation of NIH over no intervention and a trend to inhibition of NIH over PABA. Gene expression analysis and immunohistochemical studies identified significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA. CONCLUSIONS: Epi-Solve is a novel HDACi-coated DEBc which demonstrates significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA in an ovine model and may afford endothelial protection.


Assuntos
Angioplastia com Balão/instrumentação , Doenças das Artérias Carótidas/terapia , Artéria Carótida Primitiva/patologia , Materiais Revestidos Biocompatíveis , Epigênese Genética/efeitos dos fármacos , Inibidores de Histona Desacetilases/administração & dosagem , Neointima , Dispositivos de Acesso Vascular , Animais , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Desenho de Equipamento , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Mediadores da Inflamação/metabolismo , Paclitaxel/administração & dosagem , Carneiro Doméstico , Fatores de Tempo
19.
J Am Coll Cardiol ; 74(21): 2539-2550, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31753198

RESUMO

BACKGROUND: Implantation of an interatrial shunt device (IASD) in patients with heart failure (HF) reduces left atrial hypertension by shunting oxygenated blood to the right heart and lungs. The attendant increases in pulmonary blood flow (Qp) and oxygen content may alter pulmonary vascular function, while left-to-right shunting might compromise systemic perfusion. OBJECTIVES: The authors hypothesized that IASD would improve indexes of pulmonary artery (PA) function at rest and during exercise in HF patients without reducing systemic blood flow (Qs). METHODS: This is a pooled analysis from 2 trials assessing the effects of the IASD on resting and exercise hemodynamics in HF patients (n = 79) with EF ≥40% with baseline and repeated hemodynamic evaluation between 1 and 6 months. Patients with pulmonary vascular resistance (PVR) >4 WU or right ventricular dysfunction were excluded. RESULTS: Qp and PA oxygen content increased by 27% and 7% following IASD. These changes were associated with salutary effects on pulmonary vascular function (17% reduction in PVR, 12% reduction in PA elastance [pulmonary Ea], and 24% increase in PA compliance). Qp increased during exercise to a greater extent following IASD compared with baseline, which was associated with reductions in exercise PVR and pulmonary Ea. Patients with increases in PA compliance following IASD experienced greater improvements in supine exercise duration. There was no reduction in Qs following IASD at rest or during exercise. CONCLUSIONS: Implantation of an IASD improves pulmonary vascular function at rest and during exercise in selected patients with HF and EF ≥40%, without compromising systemic perfusion. Further study is warranted to identify underlying mechanisms and long-term pulmonary hemodynamic effects of IASD. (REDUCE LAP-HF Trial [REDUCE LAP-HF]; NCT01913613; and REDUCE LAP-HF Randomized Trial I [REDUCE LAP-HF I]; NCT02600234).


Assuntos
Átrios do Coração/cirurgia , Insuficiência Cardíaca/cirurgia , Circulação Pulmonar , Idoso , Anastomose Cirúrgica , Fibrilação Atrial/fisiopatologia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico
20.
Int J Spine Surg ; 13(5): 423-428, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31741831

RESUMO

Background: Surgical site infections (SSIs) represent a devastating complication after spine surgery. Many factors have been identified, but the influence of operating room (OR) size on infection rate has not been assessed. Methods: Two thousand five hundred and twenty-three patients who underwent open lumbar spine fusion at a single institution between 2010 and 2016 were included. Patients were dichotomized into large versus small groups based on OR volume. Bivariate logistic regression and a final multivariate model following a multicollinearity check were used to calculate odds of infection for all variables. Results: A total of 63 patients (2.5%) developed SSIs with 46 (73%) in the larger OR group and 17 (27%) in the smaller OR group. The rate of SSIs in larger ORs was 3.02% compared with 1.81% in smaller ORs. Significant parameters impacting SSI in bivariate analysis included an earlier year of surgery, BMI > 30, more comorbidities, more levels decompressed and fused, smoking, and larger OR volumes. Multivariate analysis identified BMI > 30, Elixhauser scores, smoking, and increasing levels decompressed as significant predictors. Topical vancomycin was found to significantly decrease rate of infection in both analyses. Conclusions: OR size (large versus small) was ultimately not a significant predictor of infection related to rates of SSIs, although it did show a clinical trend toward significance, suggesting association. Future prospective analysis is warranted. Level of Evidence: 3.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA