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High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever Cardiovascular Outcomes in 154,052 Participants.

Sat, 07/29/2017 - 12:45
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High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever Cardiovascular Outcomes in 154,052 Participants.

J Am Coll Cardiol. 2017 Aug 01;70(5):558-568

Authors: Willeit P, Welsh P, Evans JDW, Tschiderer L, Boachie C, Jukema JW, Ford I, Trompet S, Stott DJ, Kearney PM, Mooijaart SP, Kiechl S, Di Angelantonio E, Sattar N

Abstract
BACKGROUND: High-sensitivity assays can quantify cardiac troponins I and T (hs-cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury.
OBJECTIVES: The goal of this study was to assess associations of cardiac troponin concentration with cardiovascular disease (CVD) outcomes in primary prevention studies.
METHODS: A search was conducted of PubMed, Web of Science, and EMBASE for prospective studies published up to September 2016, reporting on associations of cardiac troponin concentration with first-ever CVD outcomes (i.e., coronary heart disease [CHD], stroke, or the combination of both). Study-specific estimates, adjusted for conventional risk factors, were extracted by 2 independent reviewers, supplemented with de novo data from PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using random effects meta-analysis.
RESULTS: A total of 28 relevant studies were identified involving 154,052 participants. Cardiac troponin was detectable in 80.0% (hs-cTnI: 82.6%; hs-cTnT: 69.7%). In PROSPER, positive associations of log-linear shape were observed between hs-cTnT and CVD outcomes. In the meta-analysis, the relative risks comparing the top versus the bottom troponin third were 1.43 (95% confidence interval [CI]: 1.31 to 1.56) for CVD (11,763 events), 1.67 (95% CI: 1.50 to 1.86) for fatal CVD (7,775 events), 1.59 (95% CI: 1.38 to 1.83) for CHD (7,061 events), and 1.35 (95% CI: 1.23 to 1.48) for stroke (2,526 events). For fatal CVD, associations were stronger in North American studies (p = 0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027).
CONCLUSIONS: In the general population, high cardiac troponin concentration within the normal range is associated with increased CVD risk. This association is independent of conventional risk factors, strongest for fatal CVD, and applies to both CHD and stroke.

PMID: 28750699 [PubMed - in process]

Exosomes from pediatric dilated cardiomyopathy patients modulate a pathological response in cardiomyocytes.

Sat, 07/29/2017 - 12:45
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Exosomes from pediatric dilated cardiomyopathy patients modulate a pathological response in cardiomyocytes.

Am J Physiol Heart Circ Physiol. 2017 Apr 01;312(4):H818-H826

Authors: Jiang X, Sucharov J, Stauffer BL, Miyamoto SD, Sucharov CC

Abstract
Stimulation of the renin-angiotensin-aldosterone system (RAAS) and β-adrenergic receptors plays an important role in adult heart failure (HF). Despite the demonstrated benefits of RAAS inhibition and β-adrenergic receptor blockade in adult HF patients, no substantial improvement in survival rate has been observed in children with HF. This suggests that the underlying disease mechanism is uniquely regulated in pediatric HF. Here, we show that treatment of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and neonatal rat ventricular myocytes (NRVMs) with serum from pediatric dilated cardiomyopathy (DCM) patients induces pathological changes in gene expression, which occur independently of the RAAS and adrenergic systems, suggesting that serum circulating factors play an important role in cardiac remodeling. Furthermore, exosomes purified from DCM serum induced pathological changes in gene expression in NRVMs and iPSC-CMs. Our results suggest that DCM serum exosomes mediate pathological responses in cardiomyocytes and may propagate the pediatric HF disease process, representing a potential novel therapeutic target specific to this population.NEW & NOTEWORTHY The results of this work could alter the present paradigm of basing clinical pediatric heart failure (HF) treatment on outcomes of adult HF clinical trials. The use of serum-treated primary cardiomyocytes may define age-specific mechanisms in pediatric HF with the potential to identify unique age-appropriate and disease-specific therapy.

PMID: 28130338 [PubMed - indexed for MEDLINE]

Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice.

Sat, 07/29/2017 - 12:45
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Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice.

PLoS One. 2016;11(7):e0158745

Authors: Czapla J, Matuszczak S, Wiśniewska E, Jarosz-Biej M, Smolarczyk R, Cichoń T, Głowala-Kosińska M, Śliwka J, Garbacz M, Szczypior M, Jaźwiec T, Langrzyk A, Zembala M, Szala S

Abstract
AIMS: The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation.
METHODS AND RESULTS: MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed.
CONCLUSION: In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart.

PMID: 27415778 [PubMed - indexed for MEDLINE]

The incidence of aspirin resistance in heart transplantation recipients.

Fri, 07/28/2017 - 12:45
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The incidence of aspirin resistance in heart transplantation recipients.

Kardiochir Torakochirurgia Pol. 2017 Jun;14(2):115-119

Authors: Urbanowicz T, Komosa A, Michalak M, Mularek T, Cassadei V, Grajek S, Jemielity M

Abstract
INTRODUCTION: Coronary allograft vasculopathy can cause as many deaths as infections or rejection episodes within 3 years following heart transplantation.
AIM: To compare the aspirin resistance rate in an allograft heart transplantation population and in a control group by laboratory tests including the Aspirin-Resistant Patients Identification Test (ASPItest).
MATERIAL AND METHODS: A total of 24 heart recipients (20 men and 4 women) at a mean age of 48 ±13 years who underwent routine clinical follow-up were consecutively enrolled in group 1. The control group consisted of 24 patients (19 men and 5 women) at a mean age of 64 ±7 years waiting for coronary artery bypass grafting in our department. All patients were treated with a standard dose of 75 mg aspirin (ASA) daily.
RESULTS: Aspirin resistance was evaluated by the Multiplate platelet function test. The ASPItest revealed a mean value of 27 ±22 U in the transplant group. Results above 30 U were obtained in 8 (34%) patients, with a mean value of 50.3 ±20.6 U, indicating aspirin resistance. In the control group ASPItest results above 30 U were obtained in 5 (20%) patients, with a mean value of 43.3 ±6.4 U.
CONCLUSIONS: There is a high incidence (34% vs. 20%, NS) of ASA resistance in heart transplantation recipients and in the general population, respectively.

PMID: 28747943 [PubMed]

Impact of peak provoked left ventricular outflow tract gradients on clinical outcomes in hypertrophic cardiomyopathy.

Fri, 07/28/2017 - 12:45
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Impact of peak provoked left ventricular outflow tract gradients on clinical outcomes in hypertrophic cardiomyopathy.

Int J Cardiol. 2017 Sep 15;243:290-295

Authors: Lu DY, Hailesealassie B, Ventoulis I, Liu H, Liang HY, Nowbar A, Pozios I, Canepa M, Cresswell K, Luo HC, Abraham MR, Abraham TP

Abstract
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is traditionally classified based on a left ventricular outflow tract (LVOT) pressure gradient of 30mmHg at rest or with provocation. There are no data on whether 30mmHg is the most informative cut-off value and whether provoked gradients offer any information regarding outcomes.
METHODS: Resting and provoked peak LVOT pressure gradients were measured by Doppler echocardiography in patients fulfilling guidelines criteria for HCM. A composite clinical outcome including new onset atrial fibrillation, ventricular tachycardia/fibrillation, heart failure, transplantation, and death was examined over a median follow-up period of 2.1years.
RESULTS: Among 536 patients, 131 patients had resting LVOT gradients greater than 30mmHg. Subjects with higher resting gradients were older with more cardiovascular events. For provoked gradients, a bi-modal risk distribution was found. Patients with provoked gradients >90mmHg (HR 3.92, 95% CI 1.97-7.79) or <30mmHg (HR 2.15, 95% CI 1.08-4.29) have more events compared to those with gradients between 30 and 89mmHg in multivariable analysis. The introduction of two cut-off points for provoked gradients allowed HCM to be reclassified into four groups: patients with "benign" latent HCM (provoked gradient 30-89mmHg) had the best prognosis, whereas those with persistent obstructive HCM had the worst outcome.
CONCLUSIONS: Provoked LVOT pressure gradients offer additional information regarding clinical outcomes in HCM. Applying cut-off points at 30 and 90mmHg to provoked LVOT pressure gradients further classifies HCM patients into low-, intermediate- and high-risk groups.

PMID: 28747034 [PubMed - in process]

Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM).

Thu, 07/27/2017 - 12:45
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Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM).

Eur Surg Res. 2017 Jul 26;58(5-6):246-262

Authors: Tolba RH, Czigány Z, Osorio Lujan S, Oltean M, Axelsson M, Akelina Y, Di Cataldo A, Miko I, Furka I, Dahmen U, Kobayashi E, Ionac M, Nemeth N

Abstract
BACKGROUND: Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training.
SUMMARY: Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro)surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed.

PMID: 28746936 [PubMed - as supplied by publisher]

Novel Cardiac Coordinate Modeling System for Three-Dimensional Quantification of Inflow Cannula Malposition of HeartMate II LVADs.

Thu, 07/27/2017 - 12:45
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Novel Cardiac Coordinate Modeling System for Three-Dimensional Quantification of Inflow Cannula Malposition of HeartMate II LVADs.

ASAIO J. 2017 Jul 25;:

Authors: Lima B, Dur O, Chuang J, Chamogeorgakis T, Farrar DJ, Sundareswaran KS, Felius J, Joseph SM, Hall SA, Gonzalez-Stawinski GV

Abstract
Optimal function of left ventricular assist devices (LVADs) depends on proper alignment of the inflow cannula (IC). Quantitative guidelines for IC angulation are lacking because of variation in cardiac geometry and difficulty in analyzing three-dimensional (3D) cannula orientation relative to the left ventricle (LV). Based on contrast-enhanced computed tomography images from five normal and five clinically malpositioned IC cases in patients with HeartMate II LVADs, we developed a method for 3D quantification of IC malpositioning. Using Mimics image software (Materialise, Leuven, Belgium), the native heart, major arteries, and LVAD were segmented to create patient-specific 3D models, allowing LV cavity volume and long-axis length to be measured directly. The deviation of the IC was quantified in a cylindrical coordinate system at the IC insertion point relative to the mitral valve and septum, and IC occlusion was assessed by the distance between cannula inlet and the proximal endocardium. Compared with normal cases, patients with malpositioned pumps had shorter LV length (p = 0.03) and reduced pump pocket depth (p = 0.009). Malpositioned pumps may experience greater obstruction by the nearby myocardium. This quantitative 3D modeling tool may help identify different modes of pump malalignment and migration and may facilitate preoperative planning and minimally invasive approaches via virtual LVAD implantation.

PMID: 28746083 [PubMed - as supplied by publisher]

HeartWare Ventricular Assist Device as a Bridge-to-Transplant in a Small Boy with Complicated Kawasaki Disease.

Thu, 07/27/2017 - 12:45
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HeartWare Ventricular Assist Device as a Bridge-to-Transplant in a Small Boy with Complicated Kawasaki Disease.

ASAIO J. 2017 Jul 25;:

Authors: Mascio CE, Malankar DP, Rome JJ

Abstract
We report a case of HeartWare ventricular assist device (HVAD) implant as a Bridge-to-Transplant in the smallest and the youngest known patient, a 32-month-old boy (body surface area of 0.66 m2) with known Kawasaki disease and giant coronary artery aneurysms. The disease course was complicated by coronary thromboembolism resulting in acute myocardial infarction, ventricular fibrillation, and cardiac arrest. After short-term support with extracorporeal membrane oxygenation for 7 days and long-term support with an HVAD for 5 months, he underwent heart transplantation and is doing well 2 months after the transplant.

PMID: 28746082 [PubMed - as supplied by publisher]

Determination of Optimal Coronary Flow for the Preservation of "Donation after Circulatory Death" in Murine Heart Model.

Thu, 07/27/2017 - 12:45
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Determination of Optimal Coronary Flow for the Preservation of "Donation after Circulatory Death" in Murine Heart Model.

ASAIO J. 2017 Jul 25;:

Authors: Quader M, Toldo S, Torrado J, Mishra S, Mauro AG, Mezzaroma E, Heather R, Abbate A, Kasirajan V, Mangino M

Abstract
Donation after circulatory death donors (DCD) have the potential to increase the number of heart transplants. The DCD hearts undergo an extended period of warm ischemia, which mandates the use of machine perfusion preservation if they are to be successfully recovered for transplantation. Because the minimum coronary artery flow needed to meet the basal oxygen demand (DCRIT) of a DCD heart during machine perfusion preservation is critical and yet unknown, we studied this in a DCD rat heart model. Adult male rats were anesthetized, intubated, heparinized, and paralyzed with vecuronium. The DCD hearts (n = 9) were recovered 30 minutes after circulatory death whereas non-DCD control hearts (n = 12) were recovered without circulatory death. Hearts were perfused through the aorta with an oxygenated Belzer Modified Machine Perfusion Solution at 15°C or 22°C starting at a flow index of 300 ml/min/100 gm and decreasing by 40 ml/min/100 gm every 10 minutes. Inflow (aortic) and outflow (inferior vena cava) perfusate samples were collected serially to assess the myocardial oxygen consumption index (MVO2) and O2 extraction ratio. The DCRIT is the minimum coronary flow below which the MVO2 becomes flow dependent. The MVO2, DCRIT, and oxygen extraction ratios were higher in DCD hearts compared with control hearts. The DCRIT for DCD hearts was achieved only at 15°C and was significantly higher (131.6 ± 7 ml/min/100 gm) compared with control hearts (107.7 ± 8.4 ml/100 gm/min). The DCD hearts sustain warm ischemic damage and manifest higher metabolic needs during machine perfusion. Establishing adequate coronary perfusion is critical to preserving organ function for potential heart transplantation.

PMID: 28746080 [PubMed - as supplied by publisher]

Trend of Socio-Demographic Index and Mortality Estimates in Iran and its Neighbors, 1990-2015; Findings of the Global Burden of Diseases 2015 Study.

Thu, 07/27/2017 - 12:45
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Trend of Socio-Demographic Index and Mortality Estimates in Iran and its Neighbors, 1990-2015; Findings of the Global Burden of Diseases 2015 Study.

Arch Iran Med. 2017 Jul;20(7):419-428

Authors: Moradi-Lakeh M, Sepanlou SG, Karimi SM, Khalili N, Djalalinia S, Karimkhani C, Krohn K, Afshin A, Farzadfar F, Kiadaliri AA, Asadi-Lari M, Asayesh H, Esteghamati AR, Farvid MS, Fereshtehnejad SM, Heydarpour P, Khosravi A, Khubchandani J, Kasaeian A, Rana SM, Mahdavi M, Masoudifarid H, Mohammadi A, Pourmalek F, Qorbani M, Radfar A, Rahimi K, Rahimi-Movaghar V, Roshandel G, Safi S, Salamati P, Tehrani-Banihashemi A, Bazargan-Hejazi S, Vos T, Malekzadeh R, Mokdad AH, Murray CJL, Naghavi M

Abstract
BACKGROUND: The Global burden of disease and injuries study (GBD 2015) reports expected measures for years of life lost (YLL) based on socio-demographic index (SDI) of countries, as well as the observed measures. In this extended GBD 2015 report, we reviewed total and cause-specific deaths and YLL for Iran and all its neighboring countries between 1990 and 2015.
METHODS: We extracted data from the GBD 2015 database. Observed YLL measures were calculated by multiplying the number of deaths by standard life expectancy at each age. SDI was a composite index, calculated based on income per capita, average years of schooling, and total fertility rate. The GBD world population was used for age standardization.
RESULTS: All-ages crude death rate in Iran reduced from 665.6 per 100,000 population (95% uncertainty interval: 599.3-731.6) in 1990 to 487.2 (414.9-566.1) in 2015. The ratio of observed to expected YLL (O/E ratio) for all-causes ranged between 0.54 (Turkey) and 1.95 (Russia) in 2015. For Iran, the all-causes O/E ratio was less than 1 in all years (1990-2015), except 2003. However, cause-specific O/E ratio was more than 1 for some causes, including the top leading causes of YLL (ischemic heart disease, road injuries, and cerebrovascular disorders). Ischemic heart disease was the first or second cause of YLL in all comparator countries except Afghanistan.
CONCLUSION: The leading YLL causes with high O/E ratios should be prioritized in public health efforts. In addition to research evidence, countries with low O/E ratios should be scrutinized to find feasible innovative interventions.

PMID: 28745903 [PubMed - in process]

Role of miR-29 as marker of risk of acute rejection after heart transplant.

Thu, 07/27/2017 - 12:45
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Role of miR-29 as marker of risk of acute rejection after heart transplant.

Br J Biomed Sci. 2017 Jul 26;:1-6

Authors: Guo S, Guo X, Wang S, Nie Q, Ni G, Wang C

Abstract
BACKGROUND: Circulating miRNAs are potential biomarkers of the pathogenesis of certain diseases and in monitoring therapeutic responses. We hypothesized that serum miR-29 can determine risk of acute cardiac allograft rejection.
METHODS: Peripheral vein blood was collected from 50 healthy volunteers and 506 patients during post-transplant surveillance. Serum cardiac troponin I (cTnI) and miR-29 was detected by ELISA and qRT-PCR assay respectively. Rejection risk was defined as International Society of Heart and Lung Transplant score from leukocyte infiltration of an endomyocardial biopsy. No evidence of rejection was defined as grade R0, mild as R1, moderate as 2R and severe as 3R. Specificity and sensitivity of miR-29 to discriminate rejection was determined by the area under the curve (AUC) of receiver operating characteristic curve analysis. Correlations between miR29 and rejection grade were compared.
RESULTS: Serum miR-29 was 100.8 ± 42.4 copies/μl in R0 groups (P = 0.164 versus controls), 537.5 ± 84.3 copies/μl in R1 groups (P = 0.024) and 1478.4 ± 198.7 copies/μl in the joint R2/R3 groups (P = 0.001). MiR-29 was 1963.5 ± 214.7 six months after transplantation, 1242.5 ± 103.8 after a year, 825.6 ± 58.2 after 2 years, 413.8 ± 61.9 after 3 years and 270.6 ± 34.6 ng/mL after 4 years (P < 0.001). The level of miR-29 correlated positively with cTnI, NT-proBNP, white blood cell counts, and negatively with lymphocyte counts (all P < 0.001). The AUC values (95% CI) for discriminating R0 and R1 was 0.81 (0.75-0.89), and was 0.79 (0.72-0.86) for R0 and R2/R3 (both P < 0.01).
CONCLUSION: miR-29 is a promising predictor of the risk of heart transplant rejection.

PMID: 28745139 [PubMed - as supplied by publisher]

Acute effects of power and resistance exercises on hemodynamic measurements of older women.

Thu, 07/27/2017 - 12:45
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Acute effects of power and resistance exercises on hemodynamic measurements of older women.

Clin Interv Aging. 2017;12:1103-1114

Authors: Coelho-Júnior HJ, Irigoyen MC, Aguiar SDS, Gonçalves IO, Câmara NOS, Cenedeze MA, Asano RY, Rodrigues B, Uchida MC

Abstract
PURPOSE: The purpose of this study was to compare the acute effects of resistance training (RT) and power training (PT) on the hemodynamic parameters and nitric oxide (NO) bioavailability of older women.
MATERIALS AND METHODS: A randomized experimental design was used in this study. Twenty-one older women (age: 67.1±4.6 years; body mass index: 28.03±4.9 kg/m(2); systolic blood pressure: 135.1±21.1 mmHg) were recruited to participate in this study. Volunteers were randomly allocated into PT, RT, and control session (CS) groups. The PT and RT groups underwent a single session of physical exercise equalized by training volume, characterized by 3 sets of 8-10 repetitions in 8 different exercises. However, RT group performed exercise at a higher intensity (difficult) than PT (moderate) group. On the other hand, concentric contractions were faster in PT group than in RT group. Hemodynamic parameters and saliva samples (for NO quantification) were collected before and during an hour after exercise completion.
RESULTS: Results demonstrated post-exercise hypotension during 35 minutes in the PT when compared to rest period (P=0.001). In turn, RT showed decreased heart rate and double product (P<0.001) during the whole evaluation period after exercise completion compared with the rest period. NO levels increased in the PT and RT during the whole evaluation period in relation to rest period. However, there were no differences between PT, RT, and CS regarding hemodynamic and NO evaluations.
CONCLUSION: Data indicate that an acute session of power and resistance exercise can be effective to cause beneficial changes on hemodynamic parameters and NO levels in older women.

PMID: 28744114 [PubMed - in process]

Pre-transplant depression as a predictor of adherence and morbidities after orthotopic heart transplantation.

Thu, 07/27/2017 - 12:45
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Pre-transplant depression as a predictor of adherence and morbidities after orthotopic heart transplantation.

J Cardiothorac Surg. 2017 Jul 25;12(1):62

Authors: Delibasic M, Mohamedali B, Dobrilovic N, Raman J

Abstract
BACKGROUND: Psychosocial factors are useful predictors of adverse outcomes after solid organ transplantation. Although depression is a known predictor of poor outcomes in patients who undergo orthotopic heart transplantation (OHT) and is actively screened for during pre-transplant evaluation, the effects of early identification of this entity on post-transplant outcomes are not clearly understood. The purpose of this study was to evaluate the impact of pre-transplant depression on outcomes after OHT.
METHOD: In this retrospective study, 51 patients that underwent psychosocial evaluation performed by a social worker prior to the transplant and followed up in our center post-transplant were enrolled. Patients were stratified by the presence/absence of depression during the initial encounter. Primary end-points were overall survival, 1st-year hospitalizations, overall hospitalizations, rejections, and compliance with medications and outpatient appointments.
RESULTS: Depressed patients were 3.5 times more likely to be non-compliant with medications; RR = 3.5, 95% CI (1.2,10.2), p = 0.046 and had higher incidence of first year hospitalizations (4.7 ± 3.1 vs. 2.2 ± 1.9, p = 0.046), shorter time to first hospitalization 25 days (IQR 17-39) vs. 100 days (IQR 37-229), p = 0.001. Patients with depression also had higher overall hospitalizations (8.3 ± 4.4 vs. 4.6 ± 4.2, p = 0.025,) and higher number of admissions for infections (2.8 ± 1.3 vs. 1.5 ± 1.4, p = 0.018) compared to patients without depression. There were no statistically significant differences in total number of rejections or compliance with outpatient appointments. Kaplan-Meier survival analysis did not reveal differences between the two groups (mean 3705 vs. 3764 days, log-rank p = 0.52).
CONCLUSION: Depression was a strong predictor of poor medication compliance and higher rates of hospitalization in transplant recipients. No difference in survival between depressed and non-depressed patients after OHT was noted.

PMID: 28743270 [PubMed - in process]

Engineered Heart Repair.

Thu, 07/27/2017 - 12:45
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Engineered Heart Repair.

Clin Pharmacol Ther. 2017 Aug;102(2):197-199

Authors: Fujita B, Zimmermann WH

Abstract
There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM).

PMID: 28661033 [PubMed - indexed for MEDLINE]

Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

Thu, 07/27/2017 - 12:45
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Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

Biochem Pharmacol. 2017 Aug 15;138:193-204

Authors: Ahmed LA, Rizk SM, El-Maraghy SA

Abstract
Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

PMID: 28450224 [PubMed - indexed for MEDLINE]

Heart failure and anemia: Effects on prognostic variables.

Thu, 07/27/2017 - 12:45
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Heart failure and anemia: Effects on prognostic variables.

Eur J Intern Med. 2017 Jan;37:56-63

Authors: Cattadori G, Agostoni P, Corrà U, Sinagra G, Veglia F, Salvioni E, Bonomi A, La Gioia R, Scardovi AB, Ferraironi A, Emdin M, Metra M, Di Lenarda A, Limongelli G, Raimondo R, Re F, Guazzi M, Belardinelli R, Parati G, Caravita S, Magrì D, Lombardi C, Frigerio M, Oliva F, Girola D, Mezzani A, Farina S, Mapelli M, Scrutinio D, Pacileo G, Apostolo A, Iorio A, Paolillo S, Filardi PP, Gargiulo P, Bussotti M, Marchese G, Correale M, Badagliacca R, Sciomer S, Palermo P, Contini M, Giannuzzi P, Battaia E, Cicoira M, Clemenza F, Minà C, Binno S, Passino C, Piepoli MF, MECKI score Research Group (appendix)

Abstract
BACKGROUND: Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown.
METHODS: Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively.
RESULTS: Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb.
CONCLUSIONS: Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

PMID: 27692931 [PubMed - indexed for MEDLINE]

Pulmonary Pressure Assessment with the Total Artificial Heart.

Wed, 07/26/2017 - 12:45
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Pulmonary Pressure Assessment with the Total Artificial Heart.

ASAIO J. 2017 Jul 24;:

Authors: Joyce DL, Redfield MM, Kushwaha SS, Behfar A, Borlaug BA, Daly RC, Sandhu GS, Joyce LD

Abstract
Reversal of pulmonary hypertension has been observed in patients during a bridge to transplant with a left ventricular assist device. Total artificial heart (TAH) implant prevents subsequent right heart catheterization. Consequently, controversy exists over whether the prosthetic right ventricle improves or exacerbates pulmonary hypertension. A pulmonary artery (PA) pressure monitor was placed in two patients undergoing TAH implant, as a bridge to transplant. One patient had pulmonary hypertension at implant; the other had normal pulmonary pressures. Daily measurements were taken of systolic, diastolic, and mean PA pressures throughout support. Patient 1 received successful transplant after TAH support of 91 days. Systolic/diastolic (mean) PA pressures steadily decreased from 55/39 (28) mm Hg at implant to 29/18 (7) mm Hg currently. Patient 2 received support for 101 days before death due to abdominal ischemic complications. Pulmonary arterial pressures stayed consistent throughout this period, from 26/17 (20) mm Hg at implant to 23/13 (17) mm Hg at the time of death. These findings suggest that an implantable PA pressure monitor may be useful in optimizing hemodynamics and planning appropriate timing of transplant with TAH support.

PMID: 28742532 [PubMed - as supplied by publisher]

Cost-effectiveness of left ventricular assist devices for patients with end-stage heart failure: analysis of the French hospital discharge database.

Wed, 07/26/2017 - 12:45
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Cost-effectiveness of left ventricular assist devices for patients with end-stage heart failure: analysis of the French hospital discharge database.

ESC Heart Fail. 2017 Jul 25;:

Authors: Tadmouri A, Blomkvist J, Landais C, Seymour J, Azmoun A

Abstract
AIMS: Although left ventricular assist devices (LVADs) are currently approved for coverage and reimbursement in France, no French cost-effectiveness (CE) data are available to support this decision. This study aimed at estimating the CE of LVAD compared with medical management in the French health system.
METHODS AND RESULTS: Individual patient data from the 'French hospital discharge database' (Medicalization of information systems program) were analysed using Kaplan-Meier method. Outcomes were time to death, time to heart transplantation (HTx), and time to death after HTx. A micro-costing method was used to calculate the monthly costs extracted from the Program for the Medicalization of Information Systems. A multistate Markov monthly cycle model was developed to assess CE. The analysis over a lifetime horizon was performed from the perspective of the French healthcare payer; discount rates were 4%. Probabilistic and deterministic sensitivity analyses were performed. Outcomes were quality-adjusted life years (QALYs) and incremental CE ratio (ICER). Mean QALY for an LVAD patient was 1.5 at a lifetime cost of €190 739, delivering a probabilistic ICER of €125 580/QALY [95% confidence interval: 105 587 to 150 314]. The sensitivity analysis showed that the ICER was mainly sensitive to two factors: (i) the high acquisition cost of the device and (ii) the device performance in terms of patient survival.
CONCLUSIONS: Our economic evaluation showed that the use of LVAD in patients with end-stage heart failure yields greater benefit in terms of survival than medical management at an extra lifetime cost exceeding the €100 000/QALY. Technological advances and device costs reduction shall hence lead to an improvement in overall CE.

PMID: 28741873 [PubMed - as supplied by publisher]

Novel centrifugal pump for heart failure patients: initial success and future challenges.

Wed, 07/26/2017 - 12:45
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Novel centrifugal pump for heart failure patients: initial success and future challenges.

J Thorac Dis. 2017 Jun;9(6):1429-1431

Authors: Feldmann C, Chatterjee A, Hanke JS, Dogan G, Haverich A, Schmitto JD

PMID: 28740649 [PubMed]

Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure.

Wed, 07/26/2017 - 12:45
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Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure.

J Am Soc Nephrol. 2017 Jul 24;:

Authors: Rao VS, Planavsky N, Hanberg JS, Ahmad T, Brisco-Bacik MA, Wilson FP, Jacoby D, Chen M, Tang WHW, Cherney DZI, Ellison DH, Testani JM

Abstract
Understanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (n=128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine. The mean±SD prediuretic FELi was 16.2%±9.5%, similar to that in a control cohort without HF not receiving diuretics (n=52; 16.6%±9.2%; P=0.82). Administration of a median of 160 (interquartile range, 40-270) mg intravenous furosemide equivalents increased FELi by 12.6%±10.8% (P<0.001) but increased FENa by only 4.8%±3.3%. Thus, only 34% (interquartile range, 15.6%-75.7%) of the estimated diuretic-induced sodium release did not undergo distal reabsorption. After controlling for urine diuretic levels, the increase in FELi explained only 6.4% of the increase in FENa (P=0.002). These data suggest that administration of high-dose loop diuretics to patients with HF yields meaningful increases in sodium exit from the proximal tubule/loop of Henle. However, little of this sodium seems to reach the urine, consistent with findings from animal models that indicate that distal tubular compensatory sodium reabsorption is a primary driver of DR.

PMID: 28739647 [PubMed - as supplied by publisher]

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