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Pubblicazioni recenti - cardio-oncology
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Adverse Cardiovascular Events in Cancer Trials: Missing in Action?
J Am Coll Cardiol2020 Feb;75(6):629-631. doi: S0735-1097(19)38753-4.
Bishopric Nanette H, Lippman Marc E,
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Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.
J Am Coll Cardiol2020 Feb;75(6):620-628. doi: S0735-1097(19)38752-2.
Bonsu Janice M, Guha Avirup, Charles Lawrence, Yildiz Vedat O, Wei Lai, Baker Brandee, Brammer Jonathan E, Awan Farrukh, Lustberg Maryam, Reinbolt Raquel, Miller Eric D, Jneid Hani, Ruz Patrick, Carter Rebecca R, Milks Michael W, Paskett Electra D, Addison Daniel,
Abstract
BACKGROUND:
Cardiovascular disease (CVD) has become an increasingly common limitation to effective anticancer therapy. Yet, whether CVD events were consistently reported in pivotal trials supporting contemporary anticancer drugs is unknown.
OBJECTIVES:
The authors sought to evaluate the incidence, consistency, and nature of CVD event reporting in cancer drug trials.
METHODS:
From the Drugs@FDA, clinicaltrials.gov, MEDLINE, and publicly available U.S. Food and Drug Administration (FDA) drug reviews, all reported CVD events across latter-phase (II and III) trials supporting FDA approval of anticancer drugs from 1998 to 2018 were evaluated. The primary outcome was the report of major adverse cardiovascular events (MACE), defined as incident myocardial infarction, stroke, heart failure, coronary revascularization, atrial fibrillation, or CVD death, irrespective of treatment arm. The secondary outcome was report of any CVD event. Pooled reported annualized incidence rates of MACE in those without baseline CVD were compared with reported large contemporary population rates using relative risks. Population risk differences for MACE were estimated. Differences in drug efficacy using pooled binary endpoint hazard ratios on the basis of the presence or absence of reported CVD were also assessed.
RESULTS:
Overall, there were 189 trials, evaluating 123 drugs, enrolling 97,365 participants (58.5 ± 5 years, 46.0% female, 72.5% on biologic, targeted, or immune-based therapies) with 148,138 person-years of follow-up. Over a median follow-up of 30 months, 1,148 incidents of MACE (375 heart failure, 253 myocardial infarction, 180 strokes, 65 atrial fibrillation, 29 revascularizations, and 246 CVD deaths; 792 in the intervention vs. 356 in the control arm; p < 0.01) were reported from the 62.4% of trials noting any CVD. The overall weighted-average incidence was 542 events per 100,000 person-years (716 per 100,000 in the intervention arm), compared with 1,408 among similar-aged non-cancer trial subjects (relative risk: 0.38; p < 0.01), translating into a risk difference of 866. There was no association between reporting CVD events and drug efficacy (hazard ratio: 0.68 vs. 0.67; p = 0.22).
CONCLUSIONS:
Among pivotal clinical trials linked to contemporary FDA-approved cancer drugs, reported CVD event rates trail expected population rates.
Copyright © 2020. Published by Elsevier Inc.
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Optimal management of coronary artery disease in cancer patients.
Chronic Dis Transl Med2019 Dec;5(4):221-233. doi: 10.1016/j.cdtm.2019.12.007.
Han Xue-Jie, Li Jian-Qiang, Khannanova Zulfiia, Li Yue,
Abstract
Owing to early diagnosis and rapid development of treatments for cancers, the five-year survival rate of all cancer types has markedly improved worldwide. Over time, however, there has been an increase in the number of cancer patients who develop coronary artery disease (CAD) due to different causes. First, many risk factors are shared between cancer and CAD. Second, inflammation and oxidative stress are common underlying pathogeneses in both disorders. Lastly, cancer therapy can result in endothelial injury, coronary artery spasm, and coagulation, thereby increasing the risk of CAD. As more cancer patients are being diagnosed with CAD, specialized cardiac care should be established to minimize the cardiovascular mortality of cancer survivors.
© 2019 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
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Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia.
Blood Adv2020 Feb;4(3):530-538. doi: 10.1182/bloodadvances.2019000268.
Chan Onyee, Talati Chetasi, Isenalumhe Leidy, Shams Samantha, Nodzon Lisa, Fradley Michael, Sweet Kendra, Pinilla-Ibarz Javier,
Abstract
Ponatinib is associated with cardiovascular adverse events (CAEs), and its frequency in the real world is limited. In this retrospective study, we examined the survival outcomes and associated toxicities in 78 consecutive ponatinib-treated patients with chronic myeloid leukemia (CML) at the Moffitt Cancer Center from January 2011 through December 2017. The most common non-CAE was thrombocytopenia (39.7%), occurring in a dose-dependent fashion. Eighteen patients (23.1%) experienced some form of CAE, with the most common being arrhythmia (9%) and hypertension (7.7%), whereas 3 patients experienced myocardial infarction (3.8%). Before 2014, most patients were started on ponatinib 45 mg daily. There was an inverse correlation between cardio-oncology referral and the number of CAEs (P = .0440); however, a lower ponatinib starting dose, more frequent dose reduction, and increased cardio-oncology referral all were likely to have contributed to the observed decrease in CAEs after 2014. The response rate and 5-year overall survival (OS) were higher than those observed in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial (major molecular response, 58.7% vs 40% and OS, 76% vs 73%; median follow-up of 32.5 months). Ponatinib-treated patients with chronic phase-CML did not show a significant improvement with allogeneic stem cell transplantation, whereas those with accelerated phase/blast phase-CML had a much better outcome (median OS of 32.9 months vs 9.2 months; P = .01). These results demonstrate that ponatinib is highly effective. Dose adjustments and increased awareness of the cardiotoxicities associated with ponatinib may help maximize its benefits.
© 2020 by The American Society of Hematology.
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Longitudinal kidney function outcome in aging testicular cancer survivors.
Acta Oncol2020 Feb;():1-8. doi: 10.1080/0284186X.2020.1724328.
Nome Ragnhild V, Cvancarova Småstuen Milada, Bjøro Trine, Kiserud Cecilie E, Fosså Sophie D,
Abstract
Testicular cancer survivors (TCSs) have increased risk of reduced kidney function related to treatment burden, but longitudinal studies of renal outcome in aging TCSs have been lacking. This longitudinal study describes age- and treatment-related kidney function changes in TCSs compared to a comparison group from the general population. Estimated glomerular filtration rate (eGFR) was determined in blood samples from Norwegian TCSs (diagnosed 1980-1994) and surveyed median 11, 19 and 26?years since diagnosis (Survey1 [ = 1273], 2 [ = 849] and 3 [ = 670]) defining four treatment groups; Surgery only, Radiotherapy (RT) only, Cisplatin-based chemotherapy (CBCT) ?850?mg and High CBCT/RT >850?mg cisplatin or any combination of CBCT with RT. A comparison group was constructed from similarly aged men who participated in a population-based health survey. By multiple linear regressions and generalized mixed models for repeated measurements, we studied difference in eGFR between TCSs and the comparison group for all TCSs combined and stratified by treatment modality. At Survey 1, the kidney function for the youngest TCSs combined versus the comparison group was significantly reduced by mean six units (mL/min/1.73 m) with further decline to mean 12 units at Survey 3. The kidney function was significantly reduced in all treatment groups with the largest differences emerging for TCSs from the High CBCT/RT Group, thus indicating a deteriorating impact of high cumulative doses of cisplatin. Collated to the comparison group, the kidney function in TCSs became increasingly impaired during nearly three post-treatment decades, related to the treatment modality. Early detection and intervention of kidney dysfunction is important to reduce the risk of TCSs' long-term morbidity and mortality related to nephrotoxicity, such as cardio-vascular diseases.
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International expert consensus on the management of bleeding during VATS lung surgery.
Ann Transl Med2019 Dec;7(23):712. doi: 10.21037/atm.2019.11.142.
Liu Lunxu, Mei Jiandong, He Jie, Demmy Todd L, Gao Shugeng, Li Shanqing, He Jianxing, Liu Yang, Huang Yunchao, Xu Shidong, Hu Jian, Chen Liang, Zhu Yuming, Luo Qingquan, Mao Weimin, Tan Qunyou, Chen Chun, Li Xiaofei, Zhang Zhu, Jiang Gening, Xu Lin, Zhang Lanjun, Fu Jianhua, Li Hui, Wang Qun, Liu Deruo, Tan Lijie, Zhou Qinghua, Fu Xiangning, Jiang Zhongmin, Chen Haiquan, Fang Wentao, Zhang Xun, Li Yin, Tong Ti, Yu Zhentao, Liu Yongyu, Zhi Xiuyi, Yan Tiansheng, Zhang Xingyi, Pu Qiang, Che Guowei, Lin Yidan, Ma Lin, Embun Raul, Aragón Javier, Evman Serdar, Kocher Gregor J, Bertolaccini Luca, Brunelli Alessandro, Gonzalez-Rivas Diego, Dunning Joel, Liu Hui-Ping, Swanson Scott J, Borisovich Ryabov Andrey, Sarkaria Inderpal S, Sihoe Alan Dart Loon, Nagayasu Takeshi, Miyazaki Takuro, Chida Masayuki, Kohno Tadasu, Thirugnanam Agasthian, Soukiasian Harmic J, Onaitis Mark W, Liu Chia-Chuan, ,
Abstract
Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.
2019 Annals of Translational Medicine. All rights reserved.
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Stereoselective Four-Component Synthesis of Functionalized 2,3-Dihydro-4-Nitropyrroles.
Front Chem2019 ;7():810. doi: 10.3389/fchem.2019.00810.
Wang Dong, Ma Xinyue, Dong Linru, Feng Hairong, Yu Peng, Désaubry Laurent,
Abstract
We report a metal-free and stereoselective four-component reaction between ?-ketoamides, amines, aromatic aldehydes and ?-nitroalkenes or ?-pivaloxy-nitroalkanes to obtain 2,3-dihydro-4-nitropyrroles functionalized in every position. The heterocycles accessible using this reaction may have utility in the synthesis of pharmacologically active compounds.
Copyright © 2019 Wang, Ma, Dong, Feng, Yu and Désaubry.
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The Multi-Modal Effect of the Anti-fibrotic Drug Pirfenidone on NSCLC.
Front Oncol2019 ;9():1550. doi: 10.3389/fonc.2019.01550.
Marwitz Sebastian, Turkowski Kati, Nitschkowski Dörte, Weigert Andreas, Brandenburg Julius, Reiling Norbert, Thomas Michael, Reck Martin, Drömann Daniel, Seeger Werner, Rabe Klaus F, Savai Rajkumar, Goldmann Torsten,
Abstract
Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed and effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.
Copyright © 2020 Marwitz, Turkowski, Nitschkowski, Weigert, Brandenburg, Reiling, Thomas, Reck, Drömann, Seeger, Rabe, Savai and Goldmann.
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Non-Invasive Hemodynamic Whole-Body Bioimpedance Indices for the Early Detection of Cancer Treatment-Related Cardiotoxicity: A Retrospective Observational Study.
Cardiology2020 Feb;():1-6. doi: 10.1159/000505809.
Schamroth Pravda Nili, Lev Shaul, Itzhaki Ben Zadok Osnat, Kornowski Ran, Iakobishvili Zaza,
Abstract
INTRODUCTION:
Patients undergoing chemotherapy are extremely vulnerable to cardiotoxicity. Early detection of cardiac dysfunction is of vital importance to optimize the management of these patients.
OBJECTIVE:
The aim of this study was to test the effectiveness of non-invasive hemodynamic whole-body bioimpedance (WBI) technology as a modality to detect heart failure in patients undergoing chemotherapy treatment.
METHODS:
This retrospective observational trial included 84 patients treated at the cardio-oncology outpatient clinic of the Rabin Medical Center. Clinical assessments were performed including biomarker testing and measurement of hemodynamic and volume status parameters as measured by WBI.
RESULTS:
We included 84 patients with a median age of 64.8 years, and 40.5% were males. Clinical heart failure was detected in 43% of the whole group. Patients were divided into two groups according to baseline NT-proBNP levels with a cut-off of 900 pg/mL. Left ventricular ejection fraction did not differ between the groups. Those with NT-proBNP >900 pg/mL had lower levels of stroke index, cardiac index, and Granov-Goor index (GGI; 25.9 vs. 34.0, 2.0 vs. 2.3, 8.3 vs. 11.4, respectively, with p < 0.001 for all comparisons). The optimal cut-off value for the GGI to detect NT-proBNP >900 pg/mL was 8.3. The area under the curve of a GGI cut-off <8.3 to detect NT-proBNP >900 pg/mL was 0.81 (positive predictive value 95% and negative predictive value 72%), with a 51% sensitivity and 98% specificity.
CONCLUSION:
GGI, a parameter measured by WBI, can reliably correlate to biomarker evidence of heart failure in patients after chemotherapy. Its use as a screening tool for cardiotoxicity in patients with ongoing anticancer therapy is promising.
© 2020 S. Karger AG, Basel.
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Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.
J Am Coll Cardiol2020 Feb;75(5):467-478. doi: S0735-1097(19)38682-6.
Awadalla Magid, Mahmood Syed S, Groarke John D, Hassan Malek Z O, Nohria Anju, Rokicki Adam, Murphy Sean P, Mercaldo Nathaniel D, Zhang Lili, Zlotoff Daniel A, Reynolds Kerry L, Alvi Raza M, Banerji Dahlia, Liu Shiying, Heinzerling Lucie M, Jones-O'Connor Maeve, Bakar Rula B, Cohen Justine V, Kirchberger Michael C, Sullivan Ryan J, Gupta Dipti, Mulligan Connor P, Shah Sachin P, Ganatra Sarju, Rizvi Muhammad A, Sahni Gagan, Tocchetti Carlo G, Lawrence Donald P, Mahmoudi Michael, Devereux Richard B, Forrestal Brian J, Mandawat Anant, Lyon Alexander R, Chen Carol L, Barac Ana, Hung Judy, Thavendiranathan Paaladinesh, Picard Michael H, Thuny Franck, Ederhy Stephane, Fradley Michael G, Neilan Tomas G,
Abstract
BACKGROUND:
There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.
OBJECTIVES:
This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.
METHODS:
This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death.
RESULTS:
Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8).
CONCLUSIONS:
GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.
Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.
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Cardiovascular diseases in survivors of childhood cancer.
Cancer Metastasis Rev2020 Feb;():. doi: 10.1007/s10555-020-09859-w.
Bansal Neha, Blanco Javier G, Sharma Umesh C, Pokharel Saraswati, Shisler Shannon, Lipshultz Steven E,
Abstract
Over the past few decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, there are an increasing number of children who are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades after treatment. These problems are serious enough that all caregivers of childhood cancer survivors, including oncologists, cardiologists, and other health care personnel, must pay close attention to the short- and long-term effects of chemotherapy and radiotherapy on these children. This review discusses the effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy and the methods for preventing, screening, and treating these complications.
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Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib.
Heart Fail Rev2020 Feb;():. doi: 10.1007/s10741-020-09926-y.
Casavecchia Grazia, Galderisi Maurizio, Novo Giuseppina, Gravina Matteo, Santoro Ciro, Agricola Eustachio, Capalbo Silvana, Zicchino Stefano, Cameli Matteo, De Gennaro Luisa, Righini Francesca Maria, Monte Ines, Tocchetti Carlo Gabriele, Brunetti Natale Daniele, Cadeddu Cristian, Mercuro Giuseppe,
Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.
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Effectiveness of sacubitril-valsartan in cancer patients with heart failure.
ESC Heart Fail2020 Feb;():. doi: 10.1002/ehf2.12627.
Martín-Garcia Ana, López-Fernández Teresa, Mitroi Cristina, Chaparro-Muñoz Marinela, Moliner Pedro, Martin-Garcia Agustin C, Martinez-Monzonis Amparo, Castro Antonio, Lopez-Sendon Jose L, Sanchez Pedro L,
Abstract
AIMS:
Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD.
METHODS AND RESULTS:
We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty-nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ?II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N-terminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ?0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril-valsartan dose (low or medium/high doses).
CONCLUSIONS:
Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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Childhood obesity, cardiovascular and liver health: a growing epidemic with age.
World J Pediatr2020 Feb;():. doi: 10.1007/s12519-020-00341-9.
Faienza Maria Felicia, Chiarito Mariangela, Molina-Molina Emilio, Shanmugam Harshitha, Lammert Frank, Krawczyk Marcin, D'Amato Gabriele, Portincasa Piero,
Abstract
BACKGROUND:
The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences.
DATA SOURCES:
The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health.
RESULTS:
We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences.
CONCLUSIONS:
The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood.
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The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.
J Card Surg2020 Feb;():. doi: 10.1111/jocs.14444.
Guha Avirup, McKinley Grant, Dey Amit K, Carter Rebecca, Miller P Elliott, Deshmukh Abhishek J, Zaghlol Raja, Barac Ana, Desai Nihar R, Addison Daniel,
Abstract
BACKGROUND:
Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure.
METHODS:
We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states).
RESULTS:
In those presenting with VTE during index-admission (619?241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10?776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P?
CONCLUSION:
The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.
© 2020 Wiley Periodicals, Inc.
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The Cardiovascular Complications of Chimeric Antigen Receptor T Cell Therapy.
Curr Hematol Malig Rep2020 Feb;():. doi: 10.1007/s11899-020-00567-4.
Jamal Faizi A, Khaled Samer K,
Abstract
PURPOSE OF REVIEW:
Chimeric antigen receptor T cell therapy is gaining clinical use in the management of B cell lymphomas. As the use of this unique treatment option increases, its associated toxicities will require recognition and treatment. In this review, we aim to discuss the cardiovascular toxicities of chimeric antigen receptor T cell therapy and our approach to their clinical management.
RECENT FINDINGS:
Cardiotoxicity may be due to direct or indirect effects of infused chimeric antigen receptor T cells. The cytokine release syndrome has been described extensively in the literature. Studies have also reported cardiovascular dysfunction including hypotension, left ventricular dysfunction, heart failure, and cardiogenic shock in the setting of cytokine release syndrome. While there are no standardized guidelines for the treatment of cytokine release syndrome or associated cardiotoxicity, we present our current clinical practices. Further research is indicated into the pathophysiology of therapy-associated cardiac dysfunction and effective management strategies to optimize patient outcomes.
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Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry.
Eur Heart J2020 Feb;():. doi: ehaa006.
López-Sendón José, Álvarez-Ortega Carlos, Zamora Auñon Pilar, Buño Soto Antonio, Lyon Alexander R, Farmakis Dimitrios, Cardinale Daniela, Canales Albendea Miguel, Feliu Batlle Jaime, Rodríguez Rodríguez Isabel, Rodríguez Fraga Olaia, Albaladejo Ainara, Mediavilla Guiomar, González-Juanatey Jose Ramón, Martínez Monzonis Amparo, Gómez Prieto Pilar, González-Costello José, Serrano Antolín José María, Cadenas Chamorro Rosalía, López Fernández Teresa,
Abstract
AIM:
Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking.
METHODS AND RESULTS:
We prospectively studied 865 patients, aged 54.7?±?13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ?50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ?40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24?months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P?
CONCLUSIONS:
The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
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Response by Salem et al to Letter Regarding Article, "Androgenic Effects on Ventricular Repolarization: A Translational Study From the International Pharmacovigilance Database to iPSC-Cardiomyocytes".
Circulation2020 Feb;141(5):e63-e64. doi: 10.1161/CIRCULATIONAHA.119.045215.
Salem Joe-Elie, Moslehi Javid J, Funck Brentano Christian, Roden Dan M,
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Intraabdominal Pressure Targeted Positive End-expiratory Pressure during Laparoscopic Surgery: An Open-label, Nonrandomized, Crossover, Clinical Trial.
Anesthesiology2020 Jan;():. doi: 10.1097/ALN.0000000000003146.
Mazzinari Guido, Diaz-Cambronero Oscar, Alonso-Iñigo Jose Miguel, Garcia-Gregorio Nuria, Ayas-Montero Begoña, Ibañez Jose Luis, Serpa Neto Ary, Ball Lorenzo, Gama de Abreu Marcelo, Pelosi Paolo, Maupoey Javier, Argente Navarro Maria Pilar, Schultz Marcus J,
Abstract
WHAT WE ALREADY KNOW ABOUT THIS TOPIC:
Transpulmonary driving pressure (ratio of tidal volume to respiratory system compliance) increases with increased intraabdominal pressure during laparoscopic surgery. High transpulmonary driving pressure during laparoscopic surgery is associated with increased risk of postoperative pulmonary complications.Intraoperative positive end-expiratory pressure prevents atelectasis, but may also cause overdistension.
WHAT THIS ARTICLE TELLS US THAT IS NEW:
This single-center study found that titrating intraoperative positive end-expiratory pressure in relation to observed intraabdominal pressure may counterbalance pneumoperitoneum-related rises in transpulmonary driving pressure during laparoscopic cholecystectomies.
BACKGROUND:
Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure.
METHODS:
Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. "Targeted PEEP" (2 cm H2O above intraabdominal pressure) was compared with "standard PEEP" (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure.
RESULTS:
Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels.
CONCLUSIONS:
Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes.
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miR-940 inhibits cell proliferation and promotes apoptosis in esophageal squamous cell carcinoma cells and is associated with post-operative prognosis.
Exp Ther Med2020 Feb;19(2):833-840. doi: 10.3892/etm.2019.8279.
Wang Haiwen, Song Tao, Qiao Yanping, Sun Jiangtao,
Abstract
The present study aimed to examine microRNA (miR)-940 expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, analyze its association with the clinicopathological features and prognosis of patients, and explore the potential underlying mechanisms. miR-940 expression in ESCC cell lines and a normal esophageal cell line was detected using reverse transcription-quantitative (RT-q)PCR. Furthermore, 210 resected ESCC tissue and para-carcinoma tissue specimens were collected, and miR-940 expression in those tissues was detected by RT-qPCR. In addition, the association of miR-940 with the clinicopathological features and prognosis of patients was analyzed. In an experiment, miR-940 mimics were transduced into ESCC cells by the liposome method. An MTT assay was used to detect the effect of miR-940 on the viability of ESCC cells. The influence of miR-940 on the cell cycle and apoptotic rate of ESCC cells was detected by flow cytometry. The present results indicated that the expression levels of miR-940 in human ESCC tissues and cell lines were markedly downregulated, and that low expression of miR-940 in ESCC tissues was significantly associated with a poor degree of differentiation, positive lymph node metastasis and advanced clinical stage. Kaplan-Meier survival analysis suggested that low miR-940 expression was associated with poor prognosis. Cox regression analysis revealed that lymph node metastasis, clinical stage and miR-940 expression were independent risk factors affecting the prognosis of patients. Overexpression of miR-940 in ESCC cells markedly reduced the cell viability, blocked the cell cycle at G0/G1 phase and promoted cell apoptosis. These results suggest that miR-940 is downregulated in ESCC, which is linked to the occurrence and progression of ESCC. Conversely, overexpression of miR-940 reduced the cell viability and promoted apoptosis of ESCC cells. Therefore, miR-940 may be a promising novel prognostic marker and anti-cancer target in ESCC.
Copyright: © Wang et al.
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