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Pubblicazioni recenti - cardiac failure
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ECG Monitoring of Reactions to Sacubitril-valsartan in Heart Failure with Reduced Ejection Fraction.
J Cardiovasc Imaging -
Changes in QRS Duration Are Associated with a Therapeutic Response to Sacubitril-valsartan in Heart Failure with Reduced Ejection Fraction.
J Cardiovasc Imaging2020 Oct;28(4):244-253. doi: 10.4250/jcvi.2020.0025.
Kim Bong Joon, Park Han Su, Im Sung Il, Kim Hyun Su, Heo Jung Ho, Cha Tae Joon, Cho Kyoung Im,
Abstract
BACKGROUND:
Recent studies have demonstrated that angiotensin receptor neprilysin inhibitors (ARNIs) can reverse the cardiac remodeling effects that occur in heart failure with reduced ejection fraction (HFrEF). These studies have also suggested that ARNIs have favorable effects on ventricular dyssynchrony. We assessed the changes in QRS duration associated with ARNIs in patients with HFrEF.
METHODS:
We retrospectively investigated patients with HFrEF (defined by a left ventricular ejection fraction [LVEF] ? 35%) who were treated with ARNIs for at least six months. We divided the patients into QRS shortening and non-QRS shortening groups according to their electrocardiogram (ECG) findings. We also compared changes in echocardiographic parameters between the groups.
RESULTS:
A total of 68 patients with HFrEF were included (mean age: 62.5 years, 74.6% male). Twenty-one patients had significant ischemic heart disease (IHD). Thirty-five patients exhibited QRS-duration shortening on follow-up ECGs (mean change: -7.8 msec), and 33 patients showed no changes or increased QRS duration (mean change: 5.1 msec). The QRS shortening group exhibited significant improvement in LVEF (12.5 ± 15.3% vs. 1.7 ± 9.5%; p < 0.001) when compared with the non-QRS shortening group. The QRS shortening group also had significantly lower LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD) and LV mass index (LVMI) than did the non-QRS shortening group. The change in QRS duration was significantly correlated with the change in LVEF (r = -0.329, p = 0.011) and LVESD (r = 0.298, p = 0.022).
CONCLUSIONS:
Among patients with HFrEF treated with ARNIs, the QRS shortening group showed favorable LV systolic function recovery, and reversal of cardiac remodeling compared to those of the non-QRS shortening group. Change in the QRS duration, which reflects LV synchrony, may be associated with response to ARNIs in patients with HFrEF.
Copyright © 2020 Korean Society of Echocardiography.
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Clinical characteristics and outcomes of chronic heart failure in adult Takayasu arteritis: A cohort study of 163 patients.
Int J Cardiol2020 Oct;():. doi: S0167-5273(20)33984-X.
Zhang Ying, Fan Peng, Zhang Huimin, Ma Wenjun, Song Lei, Wu Haiying, Cai Jun, Luo Fang, Zhou Xianliang,
Abstract
BACKGROUND:
Chronic heart failure (CHF) is a serious complication and a major cause of mortality in patients with Takayasu arteritis (TA). We aimed to explore the clinical features and long-term outcomes in TA patients with CHF.
METHODS AND RESULTS:
Adult TA patients admitted to our hospital between January 2009 to April 2018 were classified as HF and non-HF group. The adverse events were defined as a composite of all-cause mortality and hospitalization for HF. The outcome of the HF-group was further analyzed. A total of 61 HF patients and 102 non-HF patients were identified. In the HF group, the median age at assessment was 41.9?years, and female was predominant (82.0%). The multivariable logistic regression model revealed that pulmonary hypertension, aortic regurgitation, mitral regurgitation, level albumin, and uric acid were independently associated with CHF. After a median follow-up of 1347?days, 25 adverse events occurred in HF patients, and the 5-year event-free rate was 54.7%. The Cox model showed that coronary artery involvement, aortic regurgitation, without interventional treatment were related to adverse events.
CONCLUSIONS:
The 5-year event-free rate was not satisfying. Aggressive intervention may decreased the likelihood of adverse events in patients with CHF.
Copyright © 2020. Published by Elsevier B.V.
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Prdm16 Deficiency Leads to Age-Dependent Cardiac Hypertrophy, Adverse Remodeling, Mitochondrial Dysfunction, and Heart Failure.
Cell Rep2020 Oct;33(3):108288. doi: S2211-1247(20)31277-8.
Cibi Dasan Mary, Bi-Lin Kathleen Wung, Shekeran Shamini Guna, Sandireddy Reddemma, Tee Nicole, Singh Anamika, Wu Yajun, Srinivasan Dinesh Kumar, Kovalik Jean-Paul, Ghosh Sujoy, Seale Patrick, Singh Manvendra K,
Abstract
Hypertrophic cardiomyopathy (HCM) is a well-established risk factor for cardiovascular mortality worldwide. Although hypertrophy is traditionally regarded as an adaptive response to physiological or pathological stress, prolonged hypertrophy can lead to heart failure. Here we demonstrate that Prdm16 is dispensable for cardiac development. However, it is required in the adult heart to preserve mitochondrial function and inhibit hypertrophy with advanced age. Cardiac-specific deletion of Prdm16 results in cardiac hypertrophy, excessive ventricular fibrosis, mitochondrial dysfunction, and impaired metabolic flexibility, leading to heart failure. We demonstrate that Prdm16 and euchromatic histone-lysine N-methyltransferase factors (Ehmts) act together to reduce expression of fetal genes reactivated in pathological hypertrophy by inhibiting the functions of the pro-hypertrophic transcription factor Myc. Although young Prdm16 knockout mice show normal cardiac function, they are predisposed to develop heart failure in response to metabolic stress. Our study demonstrates that Prdm16 protects the heart against age-dependent cardiac hypertrophy and heart failure.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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Doxorubicin and subsequent risk of cardiovascular diseases among survivors of diffuse large B-cell lymphoma in Hong Kong.
Blood Adv2020 Oct;4(20):5107-5117. doi: 10.1182/bloodadvances.2020002737.
Lee Shing Fung, Luque-Fernandez Miguel Angel, Chen Yu Hui, Catalano Paul J, Chiang Chi Leung, Wan Eric Yuk-Fai, Wong Ian Chi-Kei, Chen Ming Hui, Ng Andrea K,
Abstract
Evidence regarding the dose-related impact of doxorubicin on subsequent cardiovascular diseases (CVDs) in Asian patients with diffuse large B-cell lymphoma (DLBCL) without preexisting CVDs is lacking. From a territory-wide electronic database in Hong Kong, we identified adults who were diagnosed with DLBCL and treated with chemotherapy between 2000 and 2018. We evaluated the patients for incident CVDs (including ischemic heart disease, heart failure, and cardiomyopathy). We evaluated the cause-specific cumulative incidence (csCI) of CVD with levels of doxorubicin exposure by using flexible parametric competing risk analysis and adjusting for demographics, comorbidities, therapeutic exposure, cardiovascular risk factors, and lifestyle factors. Controls were age- and sex-matched to DLBCL patients. We analyzed 2600 patients and 13?000 controls. The adjusted cause-specific hazard ratio (HR) for CVD in patients treated with >500 mg doxorubicin compared with non-doxorubicin regimens was 2.65 (95% confidence interval [CI], 1.23-5.74; P = .013). The 5-, 10-, and 15-year csCIs were 8.2%, 11.3%, and 12.8% in patients vs 3.1%, 4.4%, and 5.2% in controls, respectively. Hypertension (HR, 6.20; 95% CI, 0.79-48.44; P = .082) and use of aspirin/angiotensin-converting enzyme inhibitor/beta-blocker at baseline (HR, 2.13-4.63; P < .001 to .002) might confer a higher risk of subsequent CVDs. In this Hong Kong population-based study, doxorubicin exposure (absolute dose >500 mg), together with hypertension or baseline use of medication for cardiovascular risk factors, was found to be associated with an increase in csCIs of CVDs. Tailoring therapeutic strategies to underlying CVD risk factors and risk-adapted monitoring and follow-up of susceptible DLBCL patients are advisable.
© 2020 by The American Society of Hematology.
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Treatment strategies in ischaemic left ventricular dysfunction: a network meta-analysis.
Eur J Cardiothorac Surg2020 Oct;():. doi: ezaa319.
Gaudino Mario, Hameed Irbaz, Khan Faiza M, Tam Derrick Y, Rahouma Mohamed, Yongle Ruan, Naik Ajita, Di Franco Antonino, Demetres Michelle, Petrie Mark C, Jolicoeur E Marc, Girardi Leonard N, Fremes Stephen E,
Abstract
OBJECTIVES:
The optimal revascularization strategy for patients with ischaemic left ventricular systolic dysfunction (iLVSD) remains controversial. We aimed to compare percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical therapy (MT) in a network meta-analysis.
METHODS:
All randomized controlled trials and observational studies comparing any combination of PCI, CABG and MT in patients with iLVSD were analysed in a frequentist network meta-analysis (generic inverse variance method). Primary outcome was mortality at longest available follow-up. Secondary outcomes were cardiac death, stroke, myocardial infarction (MI) and repeat revascularization (RR).
RESULTS:
Twenty-three studies were included (n?=?23 633; 4 randomized controlled trials). Compared to CABG, PCI was associated with higher mortality [incidence rate ratio (IRR) 1.32, 95% confidence interval (CI) 1.13-1.53], cardiac death (IRR 1.65, 95% CI 1.18-2.33), MI (IRR 2.18, 95% CI 1.70-2.80) and RR (IRR 3.75, 95% CI 2.89-4.85). Compared to CABG, MT was associated with higher mortality (IRR 1.52, 95% CI 1.26-1.84), cardiac death (IRR 3.83, 95% CI 2.12-6.91), MI (IRR 3.22, 95% CI 1.52-6.79) and RR (IRR 3.37, 95% CI 1.67-6.79). Compared to MT, PCI was associated with lower cardiac death (IRR 0.43, 95% CI 0.24-0.78). CABG ranked as the best revascularization strategy for mortality, cardiac death, MI and RR; MT ranked as the strategy associated with the lowest incidence of stroke. Left ventricular ejection fraction, year of study, use of drug-eluting stents did not affect relative treatment effects.
CONCLUSIONS:
CABG appears to be the best therapy for iLVSD, although mainly based on observational data. Definitive randomized controlled trials comparing CABG and PCI in iLVSD are required.
PROSPERO REGISTRATION ID:
132414.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Burden, predictors and short-term outcomes of peripartum cardiomyopathy in a black African cohort.
PLoS One2020 ;15(10):e0240837. doi: 10.1371/journal.pone.0240837.
Nabbaale Juliet, Okello Emmy, Kibirige Davis, Ssekitoleko Isaac, Isanga Joseph, Karungi Patience, Sebatta Elias, Zhu Zhang Wan, Nakimuli Annettee, Omagino John, Kayima James,
Abstract
BACKGROUND:
Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with acute heart failure during the peripartum period. It is common in patients of African ancestry. Currently, there is paucity of data on the burden, predictors and outcomes of PPCM in Uganda. This study aimed to investigate the prevalence, predictors and six-month outcomes of PPCM in an adult cohort attending a tertiary specialised cardiology centre in Kampala, Uganda.
METHODS:
This study consecutively enrolled 236 women presenting with features of acute heart failure in the peripartum period. Clinical evaluation and echocardiography were performed on all the enrolled women. PCCM was defined according to recommendations of the Heart Failure Association of the European Society of Cardiology Working Group on PPCM. Poor outcome at six months of follow-up was defined as presence of any of the following: death of a mother or her baby, New York Heart Association (NYHA) functional class III-IV or failure to achieve complete recovery of left ventricular function (left ventricular ejection fraction ?55%).
RESULTS:
The median age, BMI and parity of the study participants was 31.5 (25.5-38.0) years, 28.3 (26.4-29.7) and 3 (2-4) respectively. The prevalence of PPCM was 17.4% (n = 41/236). Multiple pregnancy was the only predictor of PPCM in this study population (OR 4.3 95% CI 1.16-16.05, p = 0.029). Poor outcome at six-months was observed in about 54% of the patients with PPCM (n = 4, 9.8% in NYHA functional class III-IV and n = 22, 53.7% with LVEF <55%). No maternal or foetal mortality was documented.
CONCLUSION:
PPCM is relatively common in Uganda and is associated with multiple pregnancy. Poor outcomes especially absence of complete recovery of left ventricular function are also common. Large studies to further investigate long-term maternal and foetal outcomes in Uganda are justified.
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Pulmonary artery pressures and outcomes after MitraClip.
ESC Heart Fail2020 Oct;():. doi: 10.1002/ehf2.13018.
Rashi Yonatan, Haberman Dan, Tonchev Ivaylo, Peretz Alona, Medvedovsky Anna Turyan, Gotsman Israel, Minha Saar, Poles Lion, Shimoni Sara, Goland Sorel, Perlman Gidon Y, Danenberg Haim D, Beeri Ronen, Shuvy Mony,
Abstract
AIMS:
We evaluated the impact of MitraClip on systolic pulmonary artery pressure (sPAP) and the effects of baseline sPAP on outcomes.
METHODS AND RESULTS:
In a cohort of patients who underwent MitraClip implantation, three groups were defined according to pre-procedure sPAP levels. Clinical and echocardiographic data were compared. The study included 177 patients: 59 had severe pulmonary hypertension (PHT), 96 had mild to moderate PHT, and 22 had no PHT. In patients with pre-existing severe PHT, sPAP was reduced from 70.8 ± 9.2 to 56.8 ± 13.7 mmHg (P < 0.001), sPAP remained unchanged in patients with mild to moderate PHT but was significantly increased from 30.8 ± 4.3 to 38.6 ± 8.3 mmHg in the no-PHT group (P < 0.001). Improvement of sPAP was observed in 77% of severe PHT group, while worsening of sPAP was more common among patients with no-PHT [57% compared with 33% among the mild to moderate PHT and 7% in the severe PHT group, respectively, (P < 0.001)]. One year survival was similar among the study groups.
CONCLUSIONS:
MitraClip decreases PHT among patients with severe PHT. A concerning finding is that most patients with no-PHT increase their sPAP.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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Towards dissecting the mechanism of protein phosphatase-1 inhibition by its C-terminal phosphorylation.
Chembiochem2020 Oct;():. doi: 10.1002/cbic.202000669.
Köhn Maja, Salvi Francesca, Hoermann Bernhard, Del Pino Garcia Javier, Fontanillo Miriam, Derua Rita, Beullens Monique, Bollen Mathieu, Barabas Orsolya,
Abstract
Phosphoprotein Phosphatase-1 (PP1) is a key player in the regulation of phospho-serine (pSer) and phospho-threonine (pThr) dephosphorylation and is involved in a large fraction of cellular signaling pathways. Aberrant activity of PP1 has been linked to many diseases, including cancer and heart failure. Besides a well-established activity control by regulatory proteins, an inhibitory function for phosphorylation (p) of a Thr residue in the C -terminal intrinsically disordered tail of PP1 has been demonstrated. The associated phenotype of cell-cycle arrest was repeatedly proposed to be due to autoinhibition of PP1 through either conformational changes or substrate competition. Here, we use PP1 variants created by mutations and protein semisynthesis to differentiate between these hypotheses. Our data supports that pThr exerts its inhibitory function by mediating protein complex formation rather than by a direct mechanism of structural changes or substrate competition.
© 2020 Wiley-VCH GmbH.
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VVI Pacing with normal QRS duration and ventricular function: MOST trial findings relevant to leadless pacemakers.
Pacing Clin Electrophysiol2020 Oct;():. doi: 10.1111/pace.14100.
Loring Zak, North Rebecca, Hellkamp Anne S, Atwater Brett D, Frazier-Mills Camille G, Jackson Kevin P, Pokorney Sean D, Lamas Gervasio A, Piccini Jonathan P,
Abstract
BACKGROUND:
Leadless pacemakers (LPs) provide ventricular pacing without the risks associated with transvenous leads and device pockets. LPs are appealing for patients who need pacing, but do not need defibrillator or cardiac resynchronization therapy. Most implanted LPs provide right ventricular pacing without atrioventricular synchrony (VVIR mode). The Mode Selection Trial in Sinus Node Dysfunction Trial (MOST) showed similar outcomes in patients randomized to dual chamber (DDDR) vs ventricular pacing (VVIR). We compared outcomes by pacing mode in LP-eligible patients from MOST.
METHODS:
Patients enrolled in the MOST study with an LVEF >35%, QRSd <120ms and no history of ventricular arrhythmias or prior implantable cardioverter defibrillators were included (LP-eligible population). Cox proportional hazards models were used to test the association between pacing mode and death, stroke or heart failure hospitalization and atrial fibrillation (AF).
RESULTS:
Of the 2,010 patients enrolled in MOST, 1,284 patients (64%) met inclusion criteria. Baseline characteristics were well balanced across included patients randomized to DDDR (N = 630) and VVIR (N = 654). Over four years of follow-up, there was no association between pacing mode and death, stroke or heart failure hospitalization (VVIR HR 1.28 [0.92-1.75]). VVIR pacing was associated with higher risk of AF (HR 1.32 [1.08-1.61], p = 0.007), particularly in patients with no history of AF (HR 2.38 [1.52-3.85], p<0.001).
CONCLUSION:
In patients without reduced LVEF or prolonged QRS duration who would be eligible for LP, DDDR and VVIR pacing demonstrated similar rates of death, stroke or heart failure hospitalization; however, VVIR pacing significantly increased the risk of AF development. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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Is it better to treat bypass graft or native coronary artery following early graft failure?
J Card Surg2020 Oct;():. doi: 10.1111/jocs.15144.
Sef Davorin, Predrijevac Mladen, Raja Shahzad G, Turina Marko I,
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Prognostic value of DCTA scoring system in heart failure.
Herz2020 Oct;():. doi: 10.1007/s00059-020-04993-1.
Zhao Tian-Jun, Yang Qian-Kun, Bi Li-Dan, Li Jie, Tan Chun-Yu, Miao Zhi-Lin,
Abstract
OBJECTIVE:
The aim of this study was to evaluate the prognostic value of a novel scoring system, based on D?dimer, total cholesterol, high-sensitivity cardiac troponin T (hs-cTnT), and serum albumin levels, in patients with heart failure.
METHODS:
A total of 221 patients diagnosed with heart failure between May 2016 to January 2020 were enrolled in this retrospective study. The prognostic significance of the biomarkers D?dimer, total cholesterol, hs-cTnT, and serum albumin was determined with univariate and multivariate Cox proportional hazard models. A novel prognostic score based on these predictors was established. The Kaplan-Meier method and log-rank test were used to compare the adverse outcomes of patients in different risk groups.
RESULT:
Results from univariate and multivariate analyses showed that high D?dimer, low serum albumin, high hs-cTnT, and low total cholesterol levels were independent prognostic factors for adverse outcomes (D-dimer >0.63?mg/l, HR?=?1.84, 95% CI?=?1.16-2.94, p?=?0.010; serum albumin >34?g/l, HR?=?0.67, 95% CI?=?0.45-0.99, p?=?0.046; hs-cTnT >24.06?pg/ml, HR?=?1.65, 95% CI?=?1.08-2.53, p?=?0.020; total cholesterol >3.68?mmol/l, HR?=?0.63, 95% CI?=?0.43-0.92, p?=?0.017). Moreover, all the patients were stratified into low-risk or high-risk group according to a scoring system based on these four markers. Kaplan-Meier analyses demonstrated that patients in the high-risk group were more prone to having adverse outcomes compared with patients in the low-risk group.
CONCLUSION:
D?dimer, total cholesterol, hs-cTnT, and serum albumin levels were independent prognostic factors in the setting of heart failure. A novel and comprehensive scoring system based on these biomarkers is an easily available and effective tool for predicting the adverse outcomes of patients with heart failure.
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Circulating sDPP-4 is increased in obesity and insulin resistance but is not related to systemic metabolic inflammation.
J Clin Endocrinol Metab2020 Oct;():. doi: dgaa758.
Rohmann Nathalie, Schlicht Kristina, Corinna Geisler, Hollstein Tim, Knappe Carina, Krause Laura, Hagen Stefanie, Beckmann Alexia, Seoudy Anna Katharina, Wietzke-Braun Perdita, Hartmann Katharina, Schulte Dominik, Türk Kathrin, Beckmann Jan, von Schönfels Witigo, Hägele Franziska Anna, Bosy-Westphal Anja, Franke Andre, Schreiber Stefan, Laudes Matthias,
Abstract
CONTEXT:
Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. It exists in a membrane bound form and a soluble form (= sDPP-4). Initial human studies suggested sDPP-4 to be an adipokine involved in metabolic inflammation. However, recent mechanistic data in genetically modified mice questioned these findings.
OBJECTIVES:
We examined circulating sDPP-4 in a cohort of n = 451 humans with different metabolic phenotypes and during three different weight loss interventions (n = 101) to further clarify its role in human physiology and metabolic diseases.
DESIGN:
sDPP-4 serum concentrations were measured by ELISA and related to several phenotyping data including gut microbiome analysis.
RESULTS:
sDPP-4 increased with age and body weight and was positively associated with insulin resistance and hypertriglyceridemia but was reduced in manifest type 2 diabetes. In addition, we found reduced serum concentrations of sDPP-4 in subjects with arterial hypertension. In contrast to earlier reports, we did not identify an association with systemic markers of inflammation. Impaired kidney and liver functions significantly altered sDPP-4 concentrations while no relation to biomarkers for heart failure was observed. Having found increased levels of sDPP-4 in obesity, we studied surgical (gastric bypass and sleeve gastrectomy) and non-surgical interventions revealing a significant association of sDPP-4 with the improvement of liver function tests but not with changes in body weight.
CONCLUSIONS:
Our data suggest that sDPP-4 is related to hepatic abnormalities in obesity rather than primarily functioning as an adipokine and that sDPP-4 is implicated both, in glucose and lipid metabolism, but not fundamentally in systemic inflammation.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Maximal Oxygen Uptake and Ventilation Improvement Following Sacubitril-Valsartan Therapy.
Arq Bras Cardiol2020 Oct;():. doi: S0066-782X2020005013202.
Gonçalves António Valentim, Pereira-da-Silva Tiago, Galrinho Ana, Rio Pedro, Soares Rui, Feliciano Joana, Moreira Rita Ilhão, Silva Sofia, Alves Sandra, Capilé Eunice, Ferreira Rui Cruz,
Abstract
BACKGROUND:
Sacubitril/valsartan had its prognosis benefit confirmed in the PARADIGM-HF trial. However, data on cardiopulmonary exercise testing (CPET) changes with sacubitril-valsartan therapy are scarce.
OBJECTIVE:
This study aimed to compare CPET parameters before and after sacubitril-valsartan therapy.
METHODS:
Prospective evaluation of chronic heart failure (HF) patients with left ventricular ejection fraction ?40% despite optimized standard of care therapy, who started sacubitril-valsartan therapy, expecting no additional HF treatment. CPET data were gathered in the week before and 6 months after sacubitril-valsartan therapy. Statistical differences with a p-value <0.05 were considered significant.
RESULTS:
Out of 42 patients, 35 (83.3%) completed the 6-month follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6±11.1 years. New York Heart Association class improved in 26 (74.3%) patients. Maximal oxygen uptake (VO2max) (14.4 vs. 18.3 ml/kg/min, p<0.001), VE/VCO2slope (36.7 vs. 31.1, p<0.001), and exercise duration (487.8 vs. 640.3 sec, p<0.001) also improved with sacubitril-valsartan. Benefit was maintained even with the 24/26 mg dose (13.5 vs. 19.2 ml/kg/min, p=0.018) of sacubitril-valsartan, as long as this was the highest tolerated dose.
CONCLUSIONS:
Sacubitril-valsartan therapy is associated with marked CPET improvement in VO2max, VE/VCO2slope, and exercise duration. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).
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Overview of Riociguat and Its Role in the Treatment of Pulmonary Hypertension.
J Pharm Pract2020 Oct;():897190020961291. doi: 10.1177/0897190020961291.
Kenny Marianne, Clarke Megan M, Pogue Kristen T,
Abstract
Pulmonary hypertension (PH), which includes pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), is a progressive condition with significant morbidity and mortality due to right heart failure if left untreated. Riociguat is a soluble guanylate cyclase (sGC) stimulator and is the only treatment approved for both PAH and CTEPH. The objectives of this review are to describe the epidemiology and pathophysiology of PAH and CTEPH; synthesize the pharmacology, efficacy, safety, and utilization of riociguat; and discuss the role of the pharmacist in managing patients with these conditions. Data presented in this review is supported by peer reviewed literature, using PubMed and key words including pulmonary hypertension, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and riociguat. The review draws on key studies and review articles that discuss the pathophysiology of PAH and CTEPH, as well as articles discussing the safety and efficacy of riociguat. The overall goal in the treatment of PAH and CTEPH is to improve long-term survival. Treatment planning depends on the type of PH, treatment goals, comorbidities, and risk profiles. Pharmacists serve a valuable role as part of the multidisciplinary team in the care of patients with PH, many of whom may have comorbidities that contribute to high costs and resource utilization. Riociguat is a first-in-class medication and the only approved treatment for both PAH and CTEPH. In clinical trials, riociguat has demonstrated favorable efficacy and tolerability. Riociguat is a valuable addition to the armamentarium of options for treating patients with PH.
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The role of renin-angiotensin system in patients with left ventricular assist devices.
J Renin Angiotensin Aldosterone Syst;21(4):1470320320966445. doi: 10.1177/1470320320966445.
Briasoulis Alexandros, Ruiz Duque Ernesto, Mouselimis Dimitrios, Tsarouchas Anastasios, Bakogiannis Constantinos, Alvarez Paulino,
Abstract
End-stage heart failure is a condition in which the up-regulation of the systemic and local renin-angiotensin-aldosterone system (RAAS) leads to end-organ damage and is largely irreversible despite optimal medication. Left ventricular assist devices (LVADs) can downregulate RAAS activation by unloading the left ventricle and increasing the cardiac output translating into a better end-organ perfusion improving survival. However, the absence of pulsatility brought about by continuous-flow devices may variably trigger RAAS activation depending on left ventricular (LV) intrinsic contractility, the design and speed of the pump device. Moreover, the concept of myocardial recovery is being tested in clinical trials and in this setting LVAD support combined with intense RAAS inhibition can promote recovery and ensure maintenance of LV function after explantation. Blood pressure control on LVAD recipients is key to avoiding complications as gastrointestinal bleeding, pump thrombosis and stroke. Furthermore, emerging data highlight the role of RAAS antagonists as prevention of arteriovenous malformations that lead to gastrointestinal bleeds. Future studies should focus on the role of angiotensin receptor inhibitors in preventing myocardial fibrosis in patients with LVADs and examine in greater details the target blood pressure for these patients.
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Reliability of contralateral suppression of otoacoustic emissions in children.
Int J Audiol2020 Oct;():1-8. doi: 10.1080/14992027.2020.1834630.
Jedrzejczak W Wiktor, Pilka Edyta, Skarzynski Piotr Henryk, Skarzynski Henryk,
Abstract
OBJECTIVE:
The purpose of the study was to determine the reliability in children of the medial olivocochlear reflex when measured as decibels of suppression of transiently evoked otoacoustic emissions (TEOAEs) by contralateral acoustic stimulation (CAS).
DESIGN:
TEOAEs with and without CAS (white noise) were measured. In each subject, measurements were performed twice. Of particular interest was the suppression of TEOAEs by CAS and its reliability. Reliability was evaluated by calculating the standard error of measurement (SEM) and minimum detectable change (MDC).
STUDY SAMPLE:
Fifty-one normally hearing girls aged 3-6?years.
RESULTS:
The average global TEOAE suppression was around 0.6?dB. The highest reliability was for global values, with SEM of 0.2?dB and MDC of ±0.55?dB for the standard 2.5-20?ms recording window and slightly higher values for an 8-18?ms window. The worst reliability in the studied group was for the 1?kHz half-octave frequency band. Additionally, ears without spontaneous otoacoustic emissions had higher suppression levels than those with, but they also had lower signal-to-noise ratios, which may limit their clinical utility.
CONCLUSIONS:
The current study shows that, under the studied paradigm, TEOAE suppression does not have satisfactory reliability since MDC was similar to the level of suppression.
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The Association of Advance Care Planning Documentation and End-of-Life Healthcare Use Among Patients With Multimorbidity.
Am J Hosp Palliat Care2020 Oct;():1049909120968527. doi: 10.1177/1049909120968527.
McDermott Cara L, Engelberg Ruth A, Khandelwal Nita, Steiner Jill M, Feemster Laura C, Sibley James, Lober William B, Curtis J Randall,
Abstract
PURPOSE:
Multimorbidity is associated with increased intensity of end-of-life healthcare. This association has been examined by number but not type of conditions. Our purpose was to understand how intensity of care is influenced by multimorbidity within specific chronic conditions to provide guidance for interventions to improve end-of-life care for these patients.
METHODS:
We identified adults cared for in a multihospital healthcare system who died between 2010-2017. We categorized patients by 4 primary chronic conditions: heart failure, pulmonary disease, renal disease, or dementia. Within each condition, we examined the effect of multimorbidity (presence of 4 or more chronic conditions) on hospital and ICU admission in the last 30 days of life, in-hospital death, and advance care planning (ACP) documentation >30 days before death. We performed logistic regression to estimate associations between multimorbidity and end-of-life care utilization, stratified by the presence or absence of ACP documentation.
RESULTS:
ACP documentation >30 days before death was associated with lower odds of in-hospital death for all 4 conditions both in patients with and without multimorbidity. With the exception of patients with renal disease without multimorbidity, we observed lower odds of hospitalization and ICU admission for all patients with ACP >30 days before death.
CONCLUSIONS:
Patients with dementia and multimorbidity had the highest odds of high-intensity end-of-life care. For patients with dementia, heart failure, or pulmonary disease, ACP documentation >30 days before death was associated with lower likelihood of in-hospital death, hospitalization, and ICU use at end-of-life, regardless of multimorbidity.
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Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin.
J Cachexia Sarcopenia Muscle2020 Oct;():. doi: 10.1002/jcsm.12631.
Janovska Petra, Melenovsky Vojtech, Svobodova Michaela, Havlenova Tereza, Kratochvilova Helena, Haluzik Martin, Hoskova Eva, Pelikanova Terezie, Kautzner Josef, Monzo Luca, Jurcova Ivana, Adamcova Katerina, Lenkova Lucie, Buresova Jana, Rossmeisl Martin, Kuda Ondrej, Cajka Tomas, Kopecky Jan,
Abstract
BACKGROUND:
Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment.
METHODS:
The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ?7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment.
RESULTS:
Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both ?-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = -0.94; P = 0.036).
CONCLUSIONS:
Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and 'healthy' EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and ?-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia.
© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
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Endothelial dysfunction and the risk of heart failure in a community-based study: the Multi-Ethnic Study of Atherosclerosis.
ESC Heart Fail2020 Oct;():. doi: 10.1002/ehf2.13054.
Ärnlöv Johan, Sang Yingying, Ballew Shoshana H, Vaidya Dhananjay, Michos Erin D, Jacobs David R, Lima Joao, Shlipak Michael G, Bertoni Alain G, Coresh Josef, Blaha Michael, Post Wendy S, Matsushita Kunihiro,
Abstract
AIMS:
We aimed to investigate the association between endothelial dysfunction, assessed by brachial flow-mediated dilation (FMD), and the incidence of heart failure (HF) in the community-based Multi-Ethnic Study of Atherosclerosis.
METHODS AND RESULTS:
Brachial artery FMD was measured in a nested case-cohort sample including 3496 of 6814 Multi-Ethnic Study of Atherosclerosis participants without prevalent cardiovascular disease (mean age 61 years, 50% women). Multivariable probability-weighted Cox proportional hazards analysis was used to examine the association between FMD and incident HF. We also investigated the association between FMD and HF with reduced vs. preserved ejection fraction [HFrEF (left ventricular ejection fraction <45%) vs. HFpEF (left ventricular ejection fraction ?45%)]. During follow-up (median 12 years), 149 participants developed incident HF (incidence rate 3.7 events per 1000 person years). There were 56 HFrEF and 69 HFpEF events (incidence rates 1.4 and 1.7 events per 1000 person years, respectively). In multivariable models adjusted for established HF risk factors (age, sex, race/ethnicity, body mass index, systolic blood pressure, antihypertensive treatment, heart rate, diabetes mellitus, history of myocardial infarction, current smoker, and former smoker status), individuals in the highest quartile of FMD (reflecting better endothelial function) had a lower HF risk compared with individuals in the lowest quartile [hazard ratio 0.53, 95% confidence interval (CI) 0.31-0.95]. Lower risk according to higher FMD was particularly evident for HFrEF, but not for HFpEF (hazard ratio per standard deviation increase 0.79, 95% CI 0.64-0.97 vs. 0.99, 95% CI 0.78-1.26, respectively). Results remained similar after adjustment for baseline natriuretic peptide levels. The addition of FMD to established HF risk factors generally rendered no or only modest improvement in C-statistics [C-statistics for model with established HF risk factors: 0.774, and with the addition of FMD: 0.776 (delta C 0.002, 95% confidence interval -0.002 to 0.006)].
CONCLUSIONS:
Endothelial dysfunction was independently associated with HF in this community cohort, suggesting a pathophysiological contribution of endothelial function to the development of HF, in particular HFrEF. However, the value of FMD measurements for HF risk prediction seems limited.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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