scholarly journals Multidimensional Vascular Evaluation in Patients Treated with Tyrosine Kinase Inhibitors (TKIs): From Plaque Formation to Evolution and Follow up on 150 Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 54-54
Author(s):  
Elisabetta Abruzzese ◽  
Rossana Gloria ◽  
Andrea Siani ◽  
Carla Mazzone ◽  
Matteo Molica ◽  
...  

Background Among the unresolved issues concerning management of chronic myeloid leukemia (CML) patients, the most feared are long-term adverse events due to TKI treatment. Although TKIs have revolutionized CML outcomes, their use has also been associated with severe side effects including cardiovascular events, of which peripheral arterial occlusive disease (PAOD) is the most frequently reported. In 2010 we began a long-term collaboration with local angiologists and vascular surgeons to investigate, screen and follow patients on TKI therapy. Placque formation, evolution and follow up of 150 patients were studied and are presented here. Methods We analyzed 143 CML and 7 Ph+ Acute Lymphoid leukemia (ALL) patients, all of whom were treated with TKIs. Careful assessment of cardiovascular risk factors (i.e., age, smoking, obesity, diabetes, high blood pressure, high LDL or low HDL cholesterol levels, family history of heart disease or other cardiovascular disease) were done according to the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) risk charts. A complete vascular screening, including physical examination, and a series of instrumental tests were performed for all patients. Tests included doppler echocardiography (US) of supra-aortic arteries with measurement of pre-bulbar IMT, abdominal arteries and inferior limbs arteries and veins (IL), ABI of the posterior tibial artery and digital photoplethysmography (FPG). Patients needing surgical intervention were referred to a surgeon. The team of hematologists, angiologists and surgeons met periodically to discuss results and intervention approaches. Results Patients included 76 males and 74 females with a median age of 53.7 yo (range 18-85). All patients were treated with a TKI at diagnosis, 87 (58%) with imatinib, 63 (42%) with other TKIs, including ponatinib (2 LLA), and all received TKI therapy for a minimum of 12 months since 2010. For analyses purposes, patients were divided in 7 different age groups at diagnosis (18-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-85 years; patients incidence per group was 6%, 18%, 18.6%, 27.4%, 13.3%, 12.7% and 4%, respectively). Each patient in the study received yearly screening, and this increased to every 3-6 mo if abnormalities occurred. Of the 150 patients in the study, 10 (7%) developed severe PAOD (grade 3-4) requiring revascularization. Districts involved were: carotid (5), renal (2) and extremities (14 IL, 1 subclavian). Three patients were polyvascular requiring intervention in multiple regions. 18 patients with no malignancies requiring surgery were used as a control group and matched for sex, age, diabetes, smoking, district and intervention to compare patency rates, morbidity and mortality. At event, these 10 patients were taking imatinib (1), bosutinib (1), nilotinib (5) and ponatinib (3). None of them had a previous PAOD, but all had cardiovascular risk factors (100% were hypertensive). Median age was 66.8 yo (range 46-82) and the median number of PAOD risk factors (age >60, hypertension, diabetes, male gender, nicotine abuse and coronary heart disease) was 2 (range 1-5). Plaque was deemed significant when stenosis was >30%; at this point it developed very rapidly, with signs of arterial thrombosis within a year, requiring intervention. IMT scores (measuring thickness of carotid artery wall) and ABI followed by FPG and their variation over time proved predictive for plaque evolution. No patient died due to complications relating directly to surgical intervention or within 30 days post-surgery. One patient required a major limb amputation at 12 months. Patency rates were similar in the TKI and control group at 12 months (88.2% vs 80%), however the frequency of reintervention (endo or open) was 50% in TKI patients (n=5) and 11% in the control group (n=2; P<0.01). Discussion Multidisciplinary evaluation, comorbidity analysis and cardiovascular risk assessment in CML patients are highly recommended, at diagnosis if possible, to implement a tailored treatment strategy and to identify patients who require strict monitoring of risk factors during treatment. Extensive and detailed information on the 150 patients in this study will be presented with a focus on the onset and characteristics of thrombotic arterial events, medical/surgical interventions, analysis of instrumental parameters (ABI, IMT, FPG) and correlation with clinical data. Disclosures Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Isabella Naves Rosa ◽  
Alexandre Anderson de Sousa Munhoz Soares ◽  
Marcelo Palmeira Rodrigues ◽  
Luciana Ansaneli Naves

Abstract Background Hypopituitarism in the elderly population is an underdiagnosed condition and may increase comorbidities related to glucose metabolism, dyslipidemia, and cardiovascular risk factors. Optimization of hormone replacement that considers alterations in clearance rates of hormones, interaction with other medications, and evaluation of the risk-benefit ratio of treatment is a big challenge for clinical practice. Objectives This study aimed to evaluate classic cardiovascular risk factors in hypopituitary septuagenarians and octagenarians by diagnosis and after long-term hormone replacement. Methods This is a retrospective observational study, with patients recruited and selected from a registry in a tertiary medical center. We included patients aged 70–99 years with hypopituitarism, evaluated hormonal and biochemical parameters, and cardiovascular risk scores were calculated by diagnosis and compared after long-term follow-up. All patients gave informed consent. Patient data were compared to a sex and age-matched control group, with long-term geriatric follow-up, without endocrine diseases. Results Thirty-five patients were included, 16 patients aged 70–75 years (72.61), 12 patients 76–80 years (72.28), 7 patients 81–99 years (89.28). Pituitary macroadenomas were the main cause of hypopituitarism, mean maximal diameter 3.4 cm (2.9–4.3), and invasive craniopharyngiomas. At the moment of diagnosis, most patients were overweight, and abdominal adiposity was observed in 76.9% of women and 36.4% of men, primarily in octagenarians and nonagenarians. Comorbidities were frequent; 85.7% presented hypertension, 37.1% diabetes, 53.1% low HDL, 51.5% hypertriglyceridemia. Most patients presented more than two combined pituitary deficiencies; hypogonadism in 88.6%, central hypothyroidism in 82.9%, GH deficiency in 65.7%, and adrenal insufficiency in 25.7%. Analysis of cardiovascular risk prediction in the total cohort showed that 57.1% of patients presented a reduction in the General Cardiovascular Disease (CVD) Risk Prediction Score and 45.7% in atherosclerotic CVD risk estimated by ACC/AHA 2013 Pooled Cohort Equation, despite being submitted to conventional hormone replacement, during the mean follow-up of 14.5 years. This reduction was not observed in the control group. Discussion and conclusion In this study, aged hypopituitary patients presented a reduction in estimated general CVD risk during long-term follow-up, despite replacement with corticosteroids, levothyroxine, or gonadal steroids. Early diagnosis and treatment of hypopituitarism in the elderly remain challenging. Larger studies should be performed to assess the risk-benefit ratio of hormone replacement on the metabolic profile in septuagenarian and octogenarian patients.


2011 ◽  
Vol 164 (5) ◽  
pp. 675-684 ◽  
Author(s):  
Cristina L Ronchi ◽  
Elisa Verrua ◽  
Emanuele Ferrante ◽  
Gwendolyn Bender ◽  
Elisa Sala ◽  
...  

ObjectiveRadiation therapy (RT) is a useful adjuvant tool for acromegalic patients not cured by surgery and/or not responding to pharmacotherapy. However, its specific effects on cardio- and cerebrovascular morbidity are still on debate.DesignRetrospective analysis of 42 acromegalic patients cured after conventional radiotherapy (CRT, n=31) or radiosurgery by gamma-knife (GKRS, n=11) followed for a median period of 16.5 years (range: 2–40). Totally, 56 patients cured by surgery alone, with similar GH/IGF1 levels and duration of disease remission, served as control group.MethodsChanges in cardiovascular risk factors, such as body mass index, glucose metabolism, insulin resistance, blood pressure, and lipid profile (pre-defined primary end point) and occurrence of new major cardio- and cerebrovascular events (secondary end point) during follow-up.ResultsThe number of obese, hypertensive, and dyslipidemic subjects increased over time only in patients cured with RT. In contrast, the glucose response to the oral glucose tolerance test and the percentage of subjects with glucose alterations improved only in controls. As expected, the percentage of patients with pituitary failure was deeply higher among RT patients than among controls (86 vs 30%, P<0.0005). Despite these findings, a similar number of RT patients and controls developed major cardio- or cerebrovascular events (4/42 vs 3/56, P: NS). No differences were found between CRT and GKRS subgroups.ConclusionsPrevious RT seems to be associated with a worse metabolic profile in acromegalic patients studied after a long-term follow-up. Nevertheless, a direct link between RT and cardiovascular events remains to be proven.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Salazar ◽  
V Vilchez-Barboza ◽  
K Saez ◽  
T Paravic

Abstract Objective To establish the effect after 24 months of a face-to-face and telephone nursing counseling intervention, aimed at controlling cardiovascular risk factors (hypertension, dyslipidemia and overweight) and improving health-related quality of life (HRQoL) in patients of the cardiovascular health program of family health centers of Concepciόn, Chile. Methods Randomized controlled clinical trial with a 24 months post-intervention follow-up. 120 patients with cardiovascular risk factors under the cardiovascular health program were recruited from 6 family health centers and randomized into a control group (60) and an intervention group (60). The intervention group received the regular care in addition to face-to-face and telephone nursing counseling. Baseline measurements were taken and also at the end of the intervention (7 months). Participants returned then after 12 and 24 months for follow-up evaluations. A total of 109 subjects completed the intervention at 7 months and 45 returned at 24 months. During follow-up evaluations both groups continued to receive regular care given in the health centers. The measurements consisted of HRQoL (physical and mental health), systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), abdominal circumference (AC), total cholesterol (TC), low density lipoproteins (LDL-Chol), high density lipoprotein (HDL-Chol), atherogenicity index (LDL/HDL), cardiovascular risk factor (TC/HDL), 10-year coronary risk. Ethical requirements were considered and statistical analysis was carried out using MANCOVA and d-Cohen repeated measurements. Results The analysis of the effects of the intervention in the 24-month follow-up showed that subjects in the intervention group only maintained significant improvement of AC over time (F=3.18; p=0.03), compared to the control group. Conclusion Although participants in the intervention group only maintained the AC improvement over time, this can be regarded as an indirect indicator of the presence of intra-abdominal fat that makes it possible to predict and classify the risk of cardiovascular disease. Long-term follow-up studies are required to investigate behaviors and mechanisms that contribute to maintaining improvements in this indicator. Additionally, future research should include reinforcement activities, either face-to-face or by telephone, to help maintain the positive results of interventions. Acknowledgement/Funding Universidad de Concepciόn 214.082.049-1.0


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4610-4610
Author(s):  
Samar Kulkarni ◽  
John Murray ◽  
Charlotte Smith ◽  
Stephanie Cleaver ◽  
Michael Dennis ◽  
...  

Abstract Introduction: As the number of long-term survivors following HSCT is increasing, the long-term risks and associated morbidity has become important component of survivorship program. The known risk factors for developing cancer include use of chemotherapy agents, radiation exposure, immune dysfunction, previous malignancy in addition to other factors and as HSCT process involves all these factors, this single centre retrospective analysis was undertaken to evaluate the risk of developing SSC in the patients receiving transplant. Methods: From February 1982 to February 2016, 2231 patients received 2495 transplants (median age: 46yr., range: 14-76 yr.; M: 1586, F: 909) for haematological malignancies (Leuk: 744, lymphoma:767, myeloma:848, solid tumours/other:136). Donor was allogeneic (n=744) or autologous (n=1751) and conditioning was with (n=614) or without TBI (n=1881). Donor was sibling (n=375), matched unrelated (n=355), haploidentical relative (n=3) or umbilical cord blood (n=11). Source of stem cell was marrow (n=367), PBSC (n=2086), both (n=31) or cord blood (n=11). GVH prophylaxis included Campath or ATG in 369 cases. Of all the patients 1985 received single transplant, 231 had two, 13 had 3 and 2 had 4 HSCT procedures. Data was analysed as of 15/04/2016 using competing risk model with death as the competing event. Comparison of incidence to general population was performed by computing standardized incidence rates (SIR). Patients with second haematological malignancy were not included in this analysis. Results: Median follow-up was 5.3 years (range: 0-32 years). Patient follow-up was more than 10 years in 467 cases (19%), between 5 to 10 years in 430 (17%), 2 to 5 years in 607 (24%) and less than 1 year in 997 cases (40%). 36% patients were followed-up for more than 5 years. Second solid cancers developed in 116 patients with the incidence of 1% at 5yr (95% CI: 0.5-2.6), 3% at 10 yr (95% CI: 1.6-5.3), 6% at 15yr (95%CI: 3.6-8.8) and 10% (95% CI: 5.9-15.5) at 20 years. Median time to develop SSC from date of HSCT was 11 yr (range: 0.4-28.1 yr). Primary site for SSC included skin (n=37), breast (n=22), GI (n=15), GU (n=16), H&N (n=10), lung (n=6), CNS (n=4), Endocrine (n=4) & HPB (n=2). There was no difference with type of transplant i.e. auto or allograft. Autograft and allograft groups were analysed separately. In univariate analysis, allograft group showed higher cumulative incidence of SSC with use of PBSC (p<0.0001), campath/ATG (p=0.0002), donor other than sibling (P=0.0004), RIC (p<0.0001), non-TBI conditioning (p=0.007), older age at transplant (0.008), development of agvhd or cgvhd (p=0.023) and transplant year after 2000 (p=0.01). In multivariate analysis age above 50 (RR: 1.8, 95%CI: 1.2-1.8, p=0.046) and RIC (RR: 4.4, 95% CI: 1.2-8.3, p=0.03) were independently associated with higher risk of SSC. In autograft group, there were no independent risk factors in univariate or multivariate analysis. As compared to general population incidence was higher for all cancers (SIR=7.4) and also cancers at every primary site. Risk was highest for breast (SIR=14.3), Head/neck (SIR=25.6), brain (SIR=17.4) and colon (SIR=6.2). Overall survival is significantly shorter in patients who develop SSC (median: 12 yr vs. not reached, p<0.0001). The median time to develop SSC from the date of HSCT has significantly shortened over last three decades (years 1982-1990: 21yr, 1991-2000: 11.1 yr, 2001-2010: 6.34 yr, 2011-2016: 2.2 yr; p=0.0001) Conclusion: This single centre analysis confirms that the risk of developing SSC increases with advancing age, use of RIC allograft, longer follow-up and leads to inferior survival. Since the year 2000, SSC are developing early after transplant and it needs to be evaluated if this is a trend seen at other centers and if so, is it related to increasing use of RIC, increasing number of elderly patients, severity of immune-suppression or higher incidence of GVHD. Disclosures Somervaille: Novartis: Consultancy, Honoraria; Imago Biosciences: Consultancy. Bloor:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees.


2018 ◽  
Vol 37 (6) ◽  
pp. 2246-2251 ◽  
Author(s):  
Nicole Heussinger ◽  
Adela Della Marina ◽  
Andreas Beyerlein ◽  
Baerbel Leiendecker ◽  
Sofia Hermann-Alves ◽  
...  

2014 ◽  
Vol 22 (6) ◽  
pp. 762-770 ◽  
Author(s):  
Francesco Felicetti ◽  
Fabrizio D’Ascenzo ◽  
Claudio Moretti ◽  
Andrea Corrias ◽  
Pierluigi Omedè ◽  
...  

2013 ◽  
Vol 18 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Maital Kaidar ◽  
Michael Berant ◽  
Irit Krauze ◽  
Roxana Cleper ◽  
Eitan Mor ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Isabella Naves Rosa ◽  
Alexandre Anderson S M Soares ◽  
Luciana Ansaneli Naves

Abstract Background: Hypopituitarism in the elderly population is an underdiagnosed condition and may increase co-morbidities in glucose metabolism, dyslipidemia and cardiovascular risk factors. Pituitary macroadenomas are benign tumors, which prevalence is unknown in aged people, and is frequently associated to impairment in pituitary function. Objective: The aim of this study is to identify cardiovascular risk factors in hypopituitary septagenarians and octagenarians by diagnosis and after long term follow up of pituitary dysfunction. Methods: This is a retrospective observational study and the patients were recruited and selected from a service registry in a tertiary medical center. We included patients aged from 70-99 years with the diagnosis of pituitary macroadenomas, evaluated hormonal and biochemical parameters, cardiovascular risk scores were calculated by diagnosis and compared after long term follow up. All patients signed informed consent. Results: Thirty five patients were included, 21 patients aged 70-75 years (72.61 yo), 7 patients 76-80 years (77.28yo), 7 patients 81-99 years (89.28 yo). All tumors were macroadenomas, 40% of them Non Functioning Pituitary Macroadenomas, mean maximal diameter 3.4 cm (2.9-.4.3), 40% of them submitted to surgery, 14% adjuvant radiotherapy, 20% presented previous apoplexy. Co-morbidities were frequent by diagnosis, 85.71% presented Hypertension, 37.14% Diabetes, 62.8% Hypercholesterolemia and 45.71% Hypertriglyceridemia. Hypopituitarism was present in 71.42%, GH deficiency in 37.14%, hypogonadism in 60%, central hypothyroidism in 54.28%, adrenal insufficiency in 31.42%, 51.42 % presented more than two combined deficiencies. Analysis of cardiovascular risk prediction in total cohort showed, 57.14% of patients presented reduction of Framingham Score and 45.71% in Coronary Calcium Score, during mean time follow up of 13.09 years (3-32 years after diagnosis). According to ages, Framingham score and Coronary Calcium Score reduced respectively in 66% and 33.3% (70-75 yo), 57.15% and 85.71% (76-80 yo) and 42.85% and 28.57% (81-99 yo), during long term follow up. Discussion and Conclusion: In this study, most of hypopituitary aged patients presented reduction of cardiovascular risk factors during long term treatment and follow up, despite replacement with corticosteroids and gonadal steroids. Considering the importance of early diagnosis and the lack of data observed in the medical literature, larger scale studies should be performed with the objective to assess of the risk benefit ratio of hormonal replacement in metabolic control in septagenarian and octogenarian patients.


2020 ◽  
Author(s):  
Elena Izkhakov ◽  
Lital Keinan-Boker ◽  
Micha Barchana ◽  
Yacov Shacham ◽  
Iris Yaish ◽  
...  

Abstract Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors. Methods: Individuals diagnosed with TC during 2001-2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. Results: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5,677 (10.2%) TC patients and 1,235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR=1.89, 95%CI 1.71-2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR=1.49, 95%CI 1.33-1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P < 0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group. Conclusions: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.


Sign in / Sign up

Export Citation Format

Share Document