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Left ventricular outflow tract closure during LVAD implantation: 2 cases of patients supported for over 6 years.

Sat, 10/07/2017 - 12:45

Left ventricular outflow tract closure during LVAD implantation: 2 cases of patients supported for over 6 years.

J Artif Organs. 2017 Oct 05;:

Authors: Critsinelis A, Kurihara C, Kawabori M, Sugiura T, Civitello AB, Frazier OH, Morgan JA

Abstract
We previously reported a series of 5 patients with advanced heart failure and aortic insufficiency (AI) who underwent concomitant left ventricular outflow tract (LVOT) closure at the time of continuous-flow left ventricular assist device (CF-LVAD) implantation. Although this technique of treating AI has been shown to be effective in the short term, its long-term durability has not been well studied. Here, we report the long-term outcomes of two patients with severe AI who underwent LVOT closure at the time of CF-LVAD implantation. Each of the two patients survived for more than 6 years without any complications related to LVOT closure.

PMID: 28983673 [PubMed - as supplied by publisher]

Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.

Sat, 10/07/2017 - 12:45

Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.

Circulation. 2017 Oct 05;:

Authors: Emdin CA, Khera AV, Klarin D, Natarajan P, Zekavat SM, Nomura A, Haas ME, Aragam K, Ardissino D, Wilson JG, Schunkert H, McPherson R, Watkins H, Elosua R, Bown MJ, Samani NJ, Baber U, Erdmann J, Gormley P, Palotie A, Stitziel N, Gupta N, Danesh JN, Saleheen D, Gabriel SB, Kathiresan S

Abstract
Background -Nitric oxide signaling plays a key role in regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacologic stimulation of the nitric oxide pathway as a therapeutic strategy. Methods -We analyzed the association of common and rare genetic variants in two genes that mediate nitric oxide signaling [Nitric Oxide Synthase 3 (NOS3) and Guanylate Cyclase 1, Soluble, Alpha 3 (GUCY1A3)] with a range of human phenotypes. We selected two common variants (rs3918226 in NOS3 and rs7692387 in GUCY1A3) known to associate with increased NOS3 and GUCY1A3 expression and reduced mean arterial pressure, combined them into a genetic score, and standardized this exposure to a 5 mm Hg reduction in mean arterial pressure. Using individual-level data from 335,464 participants in the UK Biobank and summary association results from seven large-scale genome wide association studies, we examined the effect of this nitric oxide signaling score on cardiometabolic and other diseases. We also examined whether rare loss-of-function mutations in NOS3 and GUCY1A3 were associated with coronary heart disease using gene sequencing data from the Myocardial Infarction Genetics Consortium (n=27,815). Results -A genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease [OR 0.37 95% CI 0.31, 0.45; p=5.5*10(-26)], peripheral arterial disease (OR 0.42 CI 0.26, 0.68; p=0.0005) and stroke (OR 0.53 CI 0.37, 0.76; p=0.0006). In a mediation analysis, the effect of the genetic score on decreased coronary heart disease risk extended beyond its effect on blood pressure. Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes were associated with a 23 mm Hg higher systolic blood pressure (CI 12, 34 mm Hg; p=5.6*10(-5)) and a three-fold higher risk of coronary heart disease (OR 3.03 CI 1.29, 7.12, p=0.01). Conclusions -A genetic predisposition to enhanced nitric oxide signaling is associated with reduced risks of coronary heart disease, peripheral arterial disease and stroke. Pharmacologic stimulation of nitric oxide signaling may prove useful in the prevention or treatment of cardiovascular disease.

PMID: 28982690 [PubMed - as supplied by publisher]

Short- and Long-term Prognosis of Patients With Acute Heart Failure With and Without Diabetes: Changes Over the Last Three Decades.

Sat, 10/07/2017 - 12:45

Short- and Long-term Prognosis of Patients With Acute Heart Failure With and Without Diabetes: Changes Over the Last Three Decades.

Diabetes Care. 2017 Oct 05;:

Authors: van den Berge JC, Constantinescu AA, Boiten HJ, van Domburg RT, Deckers JW, Akkerhuis KM

Abstract
OBJECTIVE: We studied differences in long-term (i.e., 10 year) prognosis among patients with acute heart failure (HF) with and without diabetes over the last three decades. In addition, we investigated whether the degree of prognostic improvement in that period was comparable between patients with and without diabetes.
RESEARCH DESIGN AND METHODS: This prospective registry included all consecutive patients aged 18 years and older admitted to the Intensive Coronary Care Unit with acute HF in the period of 1985-2008. A total of 1,810 patients were included; 384 patients (21%) had diabetes. The outcome measure was the composite of all-cause mortality, heart transplantation, and left ventricular assist device implantation after 10-year follow-up.
RESULTS: The 10-year outcome in patients with diabetes was significantly worse than in those without diabetes (87% vs. 76%; adjusted hazard ratio [HR] 1.17 [95% CI 1.02-1.33]). Patients admitted in the last decade had a significantly lower 10-year event rate than patients admitted in the first two decades, both among patients without diabetes (adjusted HR 0.86 [95% CI 0.75-0.99]) and patients with diabetes (adjusted HR 0.80 [95% CI 0.63-1.00]).
CONCLUSIONS: The long-term outcome of patients with diabetes is worse than that of patients without diabetes. However, the long-term prognosis improved over time in both groups. Importantly, this improvement in long-term prognosis was comparable in patients with and without diabetes. Despite these promising results, more awareness for diabetes in patients with acute HF is necessary and there is still need for optimal treatment of diabetes in acute HF.

PMID: 28982652 [PubMed - as supplied by publisher]

Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome.

Fri, 10/06/2017 - 12:45

Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome.

Atherosclerosis. 2017 Sep 21;266:58-63

Authors: Tolva J, Paakkanen R, Jarva H, Pussinen P, Havulinna AS, Salomaa V, Sinisalo J, Lokki ML

Abstract
BACKGROUND & AIMS: Elevated soluble HLA-DR (sHLA-DR) serum levels have been reported in HLA class II-associated inflammatory disorders. We have previously shown that the HLA class II allele HLA-DRB1*01 may predispose to acute coronary syndromes (ACS). To our knowledge, sHLA-DR serum levels have not been studied in ACS.
METHODS: sHLA-DR serum levels were measured in 477 ACS patients as cases and 475 area- and sex-matched controls by sandwich enzyme-linked immunosorbent assay. Binary logistic regression and ordinal logistic regression analyses adjusted for clinical parameters were conducted to evaluate the associations of sHLA-DR levels.
RESULTS: ACS patients had lower sHLA-DR serum levels compared to controls (OR = 0.837; 95% CI = 0.704-0.994; p = 0.043). After adjustment for smoking status, this association was no longer significant. This was explained by the notion that current smoking was inversely associated with sHLA-DR levels both in cases (OR = 0.592; 95% CI = 0.553-0.908; p = 0.016) and in controls (OR = 0.356; 95% CI = 0.226-0.563; p = 0.000010). A similar effect was not seen with other cardiovascular risk factors.
CONCLUSIONS: The results indicate, for the first time, that lower sHLA-DR levels are associated with smoking, but not with ACS. This is an important finding because previous studies of sHLA-DR have not accounted for the possible associations between smoking and sHLA-DR levels. Further studies are required to confirm these novel results and explore the mechanisms behind the observed associations.

PMID: 28982023 [PubMed - as supplied by publisher]

Heart Toxicity Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 4 of 5.

Fri, 10/06/2017 - 12:45

Heart Toxicity Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 4 of 5.

J Diet Suppl. 2017 Oct 05;:1-40

Authors: Brown AC

Abstract
BACKGROUND: The purpose of this review was to create an online research summary table of heart toxicity case reports related to dietary supplements (DS; includes herbs).
METHODS: Documented PubMed case reports of DS appearing to contribute to heart-related problems were used to create a "Toxic Table" that summarized the research (1966 to April, 2016, and cross-referencing). Keywords included "herb," "dietary supplement," and cardiac terms. Case reports were excluded if they were herb combinations (some exceptions), Chinese herb mixtures, teas of mixed herb contents, mushrooms, poisonous plants, self-harm (e.g. suicide), excess dose (except vitamins/minerals), drugs or illegal drugs, drug-herbal interactions, and confounders of drugs or diseases. The spectrum of heart toxicities included hypertension, hypotension, hypokalemia, bradycardia, tachycardia, arrhythmia, ventricular fibrillation, heart attack, cardiac arrest, heart failure, and death.
RESULTS: Heart related problems were associated with approximately seven herbs: Four traditional Chinese medicine herbs - Don quai (Angelica sinensis), Jin bu huan (Lycopodium serratum), Thundergod vine or lei gong teng (Tripterygium wilfordii Hook F), and Ting kung teng (Erycibe henryi prain); one an Ayruvedic herb - Aswagandha, (Withania somnifera); and two North American herbs - blue cohosh (Caulophyllum thalictroides), and Yohimbe (Pausinystalia johimbe). Aconitum and Ephedra species are no longer sold in the United States. The DS included, but are not limited to five DS - bitter orange, caffeine, certain energy drinks, nitric oxide products, and a calming product. Six additional DS are no longer sold. Licorice was the food related to heart problems.
CONCLUSION: The online "Toxic Table" forewarns clinicians, consumers and the DS industry by listing DS with case reports related to heart toxicity. It may also contribute to Phase IV post marketing surveillance to diminish adverse events that Government officials use to regulate DS.

PMID: 28981338 [PubMed - as supplied by publisher]

Analysis of public discourse on heart transplantation in Japan using Social Network Service data.

Fri, 10/06/2017 - 12:45

Analysis of public discourse on heart transplantation in Japan using Social Network Service data.

Am J Transplant. 2017 Oct 05;:

Authors: Nawa N, Ishida H, Suginobe H, Katsuragi S, Baden H, Takahashi K, Narita J, Kogaki S, Ozono K

Abstract
The clarification of public concerns regarding heart transplantation is important for improving low organ donation rates in Japan. In the present study, we used the Twitter data of 4986 (between August 2015 and January 2016) and 1429 tweets (between April 2016 and May 2016) to analyze public discourse on heart transplantation in Japan and identify the reasons for low organ donation rates. We manually categorized all tweets relevant to heart transplantation into nine categories and counted the number of tweets in each category per month. During the study period, the most popular category of tweets was related to the media followed by money (tweets questioning or even criticizing the high price of fundraising goals to go overseas for heart transplants), while some tweets were misconceptions. We also conducted a sentiment analysis, which revealed that the most popular negative tweets were related to money, while the most positive tweets were related to reports on the favorable outcomes of recipients. Our results suggest that listening to concerns, providing correct information (particularly for some misconceptions), and emphasizing the outcomes of recipients will facilitate an increase in the number of people contemplating heart transplantation and organ donation. This article is protected by copyright. All rights reserved.

PMID: 28980431 [PubMed - as supplied by publisher]

Real-world experience of tocilizumab in rheumatoid arthritis: sub-analysis of data from the Italian biologics' register GISEA.

Fri, 10/06/2017 - 12:45

Real-world experience of tocilizumab in rheumatoid arthritis: sub-analysis of data from the Italian biologics' register GISEA.

Clin Rheumatol. 2017 Oct 05;:

Authors: Iannone F, Ferraccioli G, Sinigaglia L, Favalli EG, Sarzi-Puttini P, Atzeni F, Gorla R, Bazzani C, Govoni M, Farina I, Gremese E, Carletto A, Giollo A, Galeazzi M, Foti R, Bianchino L, La Grasta L, Lapadula G

Abstract
To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics' registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.

PMID: 28980085 [PubMed - as supplied by publisher]

A clinical-genetic approach to assessing cardiovascular risk in patients with CKD.

Fri, 10/06/2017 - 12:45

A clinical-genetic approach to assessing cardiovascular risk in patients with CKD.

Clin Kidney J. 2017 Oct;10(5):672-678

Authors: Rodrigo E, Pich S, Subirana I, Fernandez-Fresnedo G, Barreda P, Ferrer-Costa C, M de Francisco ÁL, Salas E, Elosua R, Arias M

Abstract
BACKGROUND: Coronary heart disease (CHD) is the primary cause of death in individuals with chronic kidney disease (CKD), but current equations for assessing coronary risk have low accuracy in this group. We have reported that the addition of a genetic risk score (GRS) to the Framingham risk function improved its predictive capacity in the general population. The aims of this study were to evaluate the association between this GRS and coronary events in the CKD population and to determine whether the addition of the GRS to coronary risk prediction functions improves the estimation of coronary risk at the earliest possible stages of kidney disease.
METHODS: A total of 632 CKD patients, aged 35-74 years, who had Stage 4-5 CKD, were on dialysis, had a functioning renal transplant or had returned to dialysis after transplant failure were included and followed up for a mean of 9.3 years. The transitions between disease states and the development of coronary events were registered. The increase in predictive ability that was obtained by including the GRS was measured as the improvement in the C-statistic and as the net reclassification index.
RESULTS: The GRS was independently associated with the risk of CHD (hazards ratio 1.34; 95% confidence interval 1.04-1.71; P = 0.022), especially in Stages 4 and 5 CKD, and kidney transplant patients. A coronary risk prediction function that incorporated chronic kidney disease (CKD) disease state, age, sex and the GRS had significantly greater predictive capacity (AUC 70.1, P = 0.01) and showed good reclassification (net reclassification improvement 28.6).
CONCLUSION: This new function, combining genetic and clinical data, identifies CKD patients with a high risk of coronary events more accurately, allowing us to prevent such events more effectively.

PMID: 28979779 [PubMed]

Acute kidney injury in octogenarians after heart valve replacement surgery: a study of two periods over the last decade.

Fri, 10/06/2017 - 12:45

Acute kidney injury in octogenarians after heart valve replacement surgery: a study of two periods over the last decade.

Clin Kidney J. 2017 Oct;10(5):648-654

Authors: Thongprayoon C, Cheungpasitporn W, Lin J, Mao MA, Qian Q

Abstract
BACKGROUND: Data on postoperative acute kidney injury (AKI) in octogenarians are limited. This study examines the AKI occurrence and clinical impact in octogenarians following open-heart valve replacement surgery in two periods over the last 15 years.
METHODS: A total of 452 consecutive octogenarians (non-kidney transplant and non-dialysis) who underwent heart valve replacement at the Mayo Clinic during the years 2011-13 (contemporary cohort) were examined. The results were compared with a comparable 209 consecutive octogenarians in 2002-03 (past cohort). Pre-existing chronic kidney disease (CKD) was defined based on estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula). Outcomes included postoperative AKI defined by the Acute Kidney Injury Network (AKIN) criteria, length of hospital stay (LOS), discharge disposition and patient survival (hospital and 1 year).
RESULTS: AKI occurrence in the contemporary cohort was lower than the past cohort (35% versus 47%, respectively, P < 0.003). Compared with the past cohort, the contemporary cohort had fewer known perioperative AKI risk factors (pre-existing CKD, comorbidity, heart failure, surgical duration, cross-clamp time, blood transfusion and large-volume intravenous fluids). In both periods, AKI adversely impacts mortality, LOS and discharge to a care facility.
CONCLUSIONS: Postoperative AKI in octogenarians following heart valve replacement surgery has declined over the last decade. As a result, the AKI-attributable percentage mortality has accordingly decreased. However, AKI continues to exert a heavy morbidity and mortality burden. These results are highly pertinent to practice since the octogenarian population is growing.

PMID: 28979775 [PubMed]

Left Ventricular Unloading during Peripheral Extracorporeal Membrane Oxygenator Support: A Bridge To Life In Profound Cardiogenic Shock.

Fri, 10/06/2017 - 12:45

Left Ventricular Unloading during Peripheral Extracorporeal Membrane Oxygenator Support: A Bridge To Life In Profound Cardiogenic Shock.

J Extra Corpor Technol. 2017 Sep;49(3):201-205

Authors: Centofanti P, Attisani M, La Torre M, Ricci D, Boffini M, Baronetto A, Simonato E, Clerici A, Rinaldi M

Abstract
A limit of peripheral veno-arterial Extracorporeal Membrane Oxigenator (VA-ECMO) is the inadequate unloading of the left ventricle. The increase of end-diastolic pressure reduces the possibility of a recovery and may cause severe pulmonary edema. In this study, we evaluate our results after implantation of VA-ECMO and Transapical Left Ventricular Vent (TLVV) as a bridge to recovery, heart transplantation or long-term left ventricular assit devices (LVAD). From 2011 to 2014, 24 consecutive patients with profound cardiogenic shock were supported by peripheral VA-ECMO as bridge to decision. In all cases, TLVV was implanted after a mean period of 12.2 ± 3.4 hours through a left mini-thoracotomy and connected to the venous inflow line of the VA-ECMO. Thirty-day mortality was 37.5% (9/24). In all patients, hemodynamics improved after TLVV implantation with an increased cardiac output, mixed venous saturation and a significant reduced heart filling pressures (p < .05). Recovery of the cardiac function was observed in 11 patients (11/24; 45.8%). Three patients were transplanted (3/24; 12.5%) and three patients (3/24; 12.5%) underwent LVAD implantation as destination therapy, all these patients were discharged from the hospital in good clinical conditions. In these critical patients, systematic TLVV improved hemodynamic seemed to provide better in hospital survival and chance of recovery, compared to VA-ECMO results in the treatment of cardiogenic shock reported in the literature . TLVV is a viable alternative to standard VA-ECMO to identify the appropriate long-term strategy (heart transplantation or long-term VAD) reducing the risk of treatment failure. A larger and multicenter experience is mandatory to validate these hypothesis.

PMID: 28979045 [PubMed - in process]

Treatment strategy for patients with Hodgkin lymphoma.

Fri, 10/06/2017 - 12:45

Treatment strategy for patients with Hodgkin lymphoma.

Rinsho Ketsueki. 2017;58(10):1973-1982

Authors: Yoshida I

Abstract
Although Hodgkin lymphoma is a disease with a low incidence rate, there is a significant social resources perspective associated with this disease to ensure that adolescents and young adults are adequately treated and receive social reintegration. Consequently, Hodgkin lymphoma is considered an important disease in the field of oncology. Combined modality therapy, which combines chemotherapy and radiotherapy, has resulted in cure rates of more than 80% in patients with early stages of this disease, although long-term sequelae remain a problem. Response-adapted therapy using FDG-PET is being studied as a treatment strategy in an attempt to attenuate treatment to reduce toxicity in interim-PET negative cases and to enhance therapeutic intensity for interim-PET positive cases. In addition, brentuximab vedotin, which targets CD30 and anti-PD-1 antibodies, which represent immune checkpoint inhibitors, is effective even when treatment resistance develops after autologous transplantation. Both high cure rates and toxicity control are essential targets for treatment modalities of Hodgkin lymphoma. Long-term follow-up of secondary malignancy and heart and lung failure should be incorporated into such treatment strategies. In this review, I explore comprehensive treatment strategies for Hodgkin lymphoma in the early stage with both favorable and unfavorable prognosis, in the advanced stage, and relapsed or refractory disease.

PMID: 28978839 [PubMed - in process]

CTRP9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways.

Fri, 10/06/2017 - 12:45

CTRP9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways.

Circulation. 2017 Oct 04;:

Authors: Yan W, Guo Y, Tao L, Lau WB, Gan L, Yan Z, Guo R, Gao E, Wong GW, Koch WL, Wang Y, Ma XL

Abstract
Background -Cell therapy remains the most promising approach against ischemic heart injury. However, the poor survival of engrafted stem cells in the ischemic environment limits their therapeutic efficacy for cardiac repair post myocardial infarction (MI). C1q/tumor necrosis factor-related protein-9 (CTRP9) is a novel pro-survival cardiokine with significantly downregulated expression after MI. Here, we tested a hypothesis that CTRP9 might be a cardiokine required for a healthy microenvironment promoting implanted stem cell survival and cardioprotection. Methods -Mice were subjected to MI and treated with adipose-derived mesenchymal stem cells (ADSCs, intramyocardial transplantation), CTRP9, or their combination. Survival, cardiac remodeling and function, cardiomyocytes apoptosis, and ADSCs engraftment were evaluated. Whether CTRP9 directly regulates ADSCs function was determined in vitro. Discovery-drive approaches followed by cause-effect analysis were employed to uncover the molecular mechanisms of CTRP9. Results -Administration of ADSCs alone failed to exert significant cardioprotection. However, administration of ADSCs in addition to CTRP9 further enhanced the cardioprotective effect of CTRP9 (P<0.05 or P<0.01 vs. CTRP9 alone), suggesting a synergistic effect. Administration of CTRP9 at a dose recovering physiological CTRP9 levels significantly prolonged ADSCs retention/survival after implantation. Conversely, the number of engrafted ADSCs was significantly reduced in the CTRP9KO heart. In vitro study demonstrated that CTRP9 promoted ADSCs proliferation and migration, and protected ADSCs against hydrogen peroxide-induced cellular death. CTRP9 enhances ADSCs proliferation/migration by ERK1/2-MMP-9 signaling and promotes anti-apoptotic/cell survival via ERK-Nrf2/anti-oxidative protein expression. N-cadherin was identified as a novel CTRP9 receptor mediating ADSCs signaling. Blockade of either N-cadherin or ERK1/2 completely abolished the above noted CTRP9 effects. Although CTRP9 failed to promote ADSCs cardiogenic differentiation, CTRP9 promotes Sod-3 expression and secretion from ADSCs, protecting cardiomyocytes against oxidative stress-induced cell death. Conclusions -We provide the first evidence that CTRP9 promotes ADSCs proliferation/survival, stimulates ADSCs migration, and attenuates cardiomyocyte cell death by previously unrecognized signaling mechanisms. These include binding with N-cadherin, activation of ERK/MMP-9 and ERK/Nrf2 signaling, and upregulation/secretion of anti-oxidative proteins. These results suggest that CTRP9 is a cardiokine critical in maintaining a healthy microenvironment facilitating stem cell engraftment in infarcted myocardial tissue, thereby enhancing stem cell therapeutic efficacy.

PMID: 28978553 [PubMed - as supplied by publisher]

Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses.

Fri, 10/06/2017 - 12:45
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Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses.

Oncotarget. 2017 Sep 15;8(40):68780-68794

Authors: Wang B, Zhang L, Cao H, Yang J, Wu M, Ma Y, Fan H, Zhan Z, Liu Z

Abstract
Myocardial infarction (MI) is a highly prevalent cardiac emergency, which results in adverse cardiac remodeling and then exacerbates progressive heart failure. Inflammatory responses in cardiac tissue after MI is necessary for myocardium repair and wound healing. However, the excessive inflammation is also a key component of subsequent heart failure pathology. Myoblast transplantation after MI have been fulfilled attractive effects on cardiac repair, but the complications of transplantation and the underlying mechanisms have not been fully elucidated. Here, we found that human myoblast transplantation into minipig myocardium decreased the infiltration of inflammatory cells, the expression levels of many pro-inflammatory genes and the activation of inflammation-related signal pathways, while upregulated the expression levels of anti-inflammatory genes such as IL-10 in cardiac tissue of minipig post-MI, which was contributed to the improved cardiac function, the decreased infarct area and the attenuated myocardial fibrosis. Moreover, co-culture of human myoblasts inhibited the production of IL-1β and TNF-α as well as activation of MAPK and NF-κB signaling pathway induced by damage-associated molecular patterns such as HMGB1 and HSP60 in human THP-1 cells, which was partially attributed to the up-regulated production of IL-10. Collectively, these results indicate that myoblast transplantation ameliorates heart injury and improves cardiac function post-MI through inhibiting the inflammatory response, which provides the novel mechanism for myoblast transplantation therapy of MI.

PMID: 28978156 [PubMed]

Frontline treatment with chemoimmunotherapy for limited-stage ocular adnexal MALT lymphoma with adverse factors: a phase II study.

Fri, 10/06/2017 - 12:45
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Frontline treatment with chemoimmunotherapy for limited-stage ocular adnexal MALT lymphoma with adverse factors: a phase II study.

Oncotarget. 2017 Sep 15;8(40):68583-68590

Authors: Kim SY, Yang SW, Lee WS, Yang JW, Oh SY, Ahn HB, Yang DH, Park SK, Chang JH, Kim HJ, Lee MJ, Cho SG

Abstract
BACKGROUND: Radiotherapy is a commonly used treatment for limited-stage ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) but showed a substantial relapse risk if the disease involves beyond-conjunctiva or bilateral conjunctivae. Systemic chemoimmunotherapy may be an alternative frontline therapy for the limited disease with those adverse prognostic factors.
PATIENTS AND METHODS: We designed a multicenter, phase II study of the chemoimmunotherapy, rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) for the treatment of patients with limited-stage OAML with bilateral or beyond-conjunctival involvement. Thirty-three patients with Ann Arbor stage I OAML with the adverse factors were enrolled. Patients received six cycles of R-CVP followed by two cycles of rituximab therapy.
RESULTS: At the end of treatment, all the enrolled patients had responded. The cumulative complete response achievement was 93.9% at 2 years. At a median follow-up of 50.6 months, three patients had progressed. Progression-free survival and overall survival at 4 years was 90.3±5.3% and 100%, respectively.
CONCLUSIONS: This phase II study demonstrated durable efficacy of R-CVP chemoimmunotherapy, which has promise as an alternative frontline therapy for the limited-stage OAML patients with adverse prognostic factors.
CLINICAL TRIAL REGISTRATION: NCT01427114.

PMID: 28978139 [PubMed]

An Alternative Strategy for Bridge-to-Transplant/Recovery in Small Children with Dilated Cardiomyopathy.

Fri, 10/06/2017 - 12:45
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An Alternative Strategy for Bridge-to-Transplant/Recovery in Small Children with Dilated Cardiomyopathy.

Pediatr Cardiol. 2017 Jun;38(5):902-908

Authors: Mets G, Panzer J, De Wolf D, Bové T

Abstract
Dilated cardiomyopathy in children still has a poor prognosis with high rates of mortality and cardiac transplantation (resp. around 20 and 25%). Awaiting transplantation or possible recovery, these pediatric patients are mechanically supported with extracorporeal membrane oxygenation or a paracorporeal ventricular assist device, both resulting in higher survival rates but also entailing considerable risks of infection, thrombosis, or bleeding. A new indication for an old technique, i.e., pulmonary artery banding, presents itself as an interesting alternative to mechanical circulatory support in selected infants and small children with dilated LV cardiomyopathy and preserved RV function. Here we present a brief review of literature and report on two patients in whom PAB has been successfully implemented as either bridge-to-recovery or bridge-to-transplant.

PMID: 28357450 [PubMed - indexed for MEDLINE]

Even mild reversible myocardial perfusion defects predict mortality in patients evaluated for kidney transplantation.

Thu, 10/05/2017 - 12:45

Even mild reversible myocardial perfusion defects predict mortality in patients evaluated for kidney transplantation.

Eur Heart J Cardiovasc Imaging. 2017 Aug 04;:

Authors: Helve S, Laine M, Sinisalo J, Helanterä I, Hänninen H, Lammintausta O, Lehtonen J, Finne P, Nieminen T

Abstract
Aims: The value of single-photon emission tomography (SPECT) in patients with severe chronic kidney disease is controversial, and the implications of SPECT finding with lower level of ischaemia are unknown. We assessed the prognostic value of SPECT in patients evaluated for kidney transplantation.
Methods and results: Five hundred and forty-eight patients underwent SPECT as a part of routine evaluation for kidney transplantation. During the median follow-up of 43.7 months (IQR 22.4-68.4 months), 112 patients (20.4%) died, 49 of cardiovascular (CV) causes (8.9%). In comparison to those with no perfusion defects, mild perfusion abnormalities (1%-9.9%) had an adjusted Cox hazard ratio (HR) of 1.80 [95% confidence interval (95% CI) 1.02-3.17, P = 0.041] for all-cause mortality, while large perfusion defects (≥10%) demonstrated an HR of 2.20 (95% CI 1.38-3.50, P = 0.001). A competing risk analysis produced a similar prognostic capacity for CV mortality. SPECT also offered incremental prognostic impact with two reclassification methods. Revascularization was performed clearly more often on patients with severely than mildly abnormal or normal SPECT (28.0%, 4.3%, and 1.3%, respectively, P < 0.001). However, revascularization was not linked with better survival. Patients with a normal SPECT received a kidney transplant more often than patients with a mildly or severely abnormal SPECT (50.5%, 36.2%, and 36.6%, respectively, P = 0.010).
Conclusion: Myocardial ischaemia in SPECT is clearly linked with mortality in patients screened for kidney transplantation. Contrary to populations with coronary artery disease, even a mild perfusion defect in SPECT predicts poor prognosis in this patient population. The finding deserves further attention in forthcoming trials.

PMID: 28977433 [PubMed - as supplied by publisher]

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for improving diagnosis of infection in patients on CF-LVAD: longing for more 'insights'.

Thu, 10/05/2017 - 12:45

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for improving diagnosis of infection in patients on CF-LVAD: longing for more 'insights'.

Eur Heart J Cardiovasc Imaging. 2017 Jul 12;:

Authors: Dell'Aquila AM, Avramovic N, Mastrobuoni S, Motekallemi A, Wisniewski K, Scherer M, Sindermann JR, Wenning C

Abstract
Aim: Presence and consequent extent of infection in patients on continuous-flow left ventricular assist devices (CF-LVADs) can be challenging with the current diagnostic tools. The present study sought to demonstrate the diagnostic power of 18F-Fluorodeoxyglucose-Positron-Emission Tomography/Computed Tomography (18F-FDG PET/CT) in detecting infection in patients supported with CF-LVAD.
Background: The present study sought to demonstrate the diagnostic power of 18F-fluorodeoxyglucose-positron-emission tomography/computed tomography (18F-FDG PET/CT) in detecting infection in patients supported with CF-LVAD.
Methods and results: Between July 2009 and April 2016, 61 PET/CT examinations were performed in 47 patients (median age 64.13 years, IQR 18.77) supported with a CF-LVAD. PET/CT assessments were performed qualitatively and quantitatively at three different levels: at the piercing site of driveline (first level), along the intracorporeal course of driveline (second level), and around the device (third level). Final diagnosis of LVAD infection was prospectively performed and was based upon microbiological samples taken at hospital admission, during the surgical revision/transplantation and recurrence of symptoms on long-term follow-up. At last follow-up a total of 40 (65.57%) final diagnoses of LVAD-infection could be ascertained. Matching the final diagnosis with the PET/CT assessments the sensitivity, specificity, and positive and negative predictive value were 90.0, 71.4, 85.71, and 78.94%, respectively. Level sub-analyses of SUV max showed an optimal discriminator power for levels 1 and 2 (AUC of level 1-0.824, P < 0.001; AUC of level 2-0.849, P < 0.001, respectively). At the third level semi-quantitative analysis showed poor discriminator power (AUC 0.589, P = 0.33). Qualitative visual analysis instead indicated a trend toward significance (P = 0.07).
Conclusions: Quantitative 18F-FDG PET/CT is an optimal diagnostic tool in detecting superficial and deep driveline infections. However, diagnostic accuracy with regard to the diagnosis of pump housing infection is limited. Here, clinical and qualitative PET/CT analyses must be better considered.

PMID: 28977417 [PubMed - as supplied by publisher]

Use of very old donors for lung transplantation: a dual-centre retrospective analysis.

Thu, 10/05/2017 - 12:45

Use of very old donors for lung transplantation: a dual-centre retrospective analysis.

Eur J Cardiothorac Surg. 2017 Jul 17;:

Authors: Hecker M, Hecker A, Kramm T, Askevold I, Kuhnert S, Reichert M, Mayer E, Seeger W, Padberg W, Mayer K

Abstract
OBJECTIVES: To reduce the shortage of organs for transplantation by expanding organ selection criteria as a means to increase the pool of potential lung donors. In this study, we sought to investigate the impact of using lungs from very old donors aged >70 years on outcomes after lung transplantation.
METHODS: Between January 2010 and November 2016, 96 patients with end-stage lung disease underwent lung transplantation in our centres. Lung donors were divided into 3 groups according to age (donor aged <60 years, 60-69 years and ≥70 years). We examined the effect of donor age on various short- and long-term outcome parameters.
RESULTS: Lungs harvested from very old donors had a lower percentage of smoking history and shorter ventilation time. Survival rates of recipients did not show significant differences between older and younger donor groups. Most of the short- and long-term outcome parameters in recipients of lungs from very old donors did not differ significantly among the 3 age groups, except for post-transplant best forced expiratory volume in 1 s and treated acute rejections, which were lower and higher, respectively, in donors aged ≥70 years.
CONCLUSIONS: This dual-centre analysis showed that lung transplantation from donors aged ≥70 years was not associated with worse outcomes compared with the younger donors. This study supports the idea that it might be possible to use an extraordinarily cautious selection of lungs from very old donors to increase the pool of suitable donors, given the shortage of suitable organ donors available for lung transplantation.

PMID: 28977370 [PubMed - as supplied by publisher]

Novel mouse model of cardiopulmonary bypass.

Thu, 10/05/2017 - 12:45

Novel mouse model of cardiopulmonary bypass.

Eur J Cardiothorac Surg. 2017 Jul 18;:

Authors: Madrahimov N, Boyle EC, Gueler F, Goecke T, Knöfel AK, Irkha V, Maegel L, Höffler K, Natanov R, Ismail I, Maus U, Kühn C, Warnecke G, Shrestha ML, Cebotari S, Haverich A

Abstract
OBJECTIVES: Cardiopulmonary bypass (CPB) is an essential component of many cardiac interventions, and therefore, there is an increasing critical demand to minimize organ damage resulting from prolonged extracorporeal circulation. Our goal was to develop the first clinically relevant mouse model of CPB and to examine the course of extracorporeal circulation by closely monitoring haemodynamic and oxygenation parameters.
METHODS: Here, we report the optimization of device design, perfusion circuit and microsurgical techniques as well as validation of physiological functions during CPB in mice after circulatory arrest and reperfusion. Validation of the model required multiple blood gas analyses, and therefore, this initial report describes an acute model that is incompatible with survival due to the need of repetitive blood draws.
RESULTS: Biochemical and histopathological assessment of organ damage revealed only mild changes in the heart and lungs and signs of the beginning of acute organ failure in the liver and kidneys.
CONCLUSIONS: This new CPB mouse model will facilitate preclinical testing of therapeutic strategies in cardiovascular diseases and investigation of CPB in relation to different insults and pre-existing comorbidities. In combination with genetically modified mice, this model will be an important tool to dissect the molecular mechanisms involved in organ damage related to extracorporeal circulation.

PMID: 28977367 [PubMed - as supplied by publisher]

Incremental value of right heart metrics and exercise performance to well-validated risk scores in dilated cardiomyopathy.

Thu, 10/05/2017 - 12:45

Incremental value of right heart metrics and exercise performance to well-validated risk scores in dilated cardiomyopathy.

Eur Heart J Cardiovasc Imaging. 2017 Jul 21;:

Authors: Moneghetti KJ, Giraldeau G, Wheeler MT, Kobayashi Y, Vrtovec B, Boulate D, Kuznetsova T, Schnittger I, Wu JC, Myers J, Ashley E, Haddad F

Abstract
Aims: Risk stratification in heart failure (HF) relies on several established clinical risk scores, however, myocardial deformation, right heart metrics, and exercise performance have not usually been considered. This study sought to assess the incremental value of advanced echocardiographic and cardiopulmonary exercise testing (CPX) parameters to validated risk scores in HF.
Methods and results: The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) and Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI) scores were applied to 208 ambulatory patients with dilated cardiomyopathy (DCM) who completed echocardiography in conjunction with CPX as part of the Stanford Exercise Testing registry. Patients were followed for the composite end point of death, heart transplant, left ventricular device implantation, and hospitalization for acute HF. Mean age, left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) were 47 ± 13 years, 33 ± 13%, and -10.6 ± 4.4%, respectively, while right ventricular free-wall longitudinal strain was -18.8 ± 5.5%. Partial correlation mapping identified strong correlations between LVEF, LVGLS, and LV systolic strain rate, with a moderate correlation between these metrics and peak VO2. Over a median follow up of 5.3 years, the composite end point occurred in 60 patients. Cox proportional hazards identified MAGGIC score [hazard ratio (HR) (2.04 [1.39-3.01], P < 0.01], peak VO2 HR (0.52 [0.28-0.97], P = 0.04), and right atrial volume indexed (RAVI) HR (1.31 [1.07-1.61], P < 0.01) as independent correlates of outcome. RAVI remained an independent correlate when combined with the MECKI score (2.21 [1.59-3.07]), P < 0.01, RAVI, 1.33 [1.06-1.67], P = 0.01).
Conclusion: Our study demonstrates that RAVI is complementary to well-validated HF risk scores and highlights the importance of exercise performance in DCM.

PMID: 28977353 [PubMed - as supplied by publisher]

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