bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bradycardia associated with ALK inhibitors in the treatment of non-small cell lung cancers: a systematic review and meta-analysis
Authors: Zhou S , Cirne F , Kappel C , El-Kadi A , Ellis P , Leong D P 
Published: October 2021

Abstract

Introduction
Anaplastic Lymphoma Kinase (ALK) inhibitors represent a major therapeutic advance in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). Bradycardia was initially observed with crizotinib, the first ALK inhibitor. The risk of bradycardia and whether it differs among various generations of ALK inhibitors has not been systematically described.

Purpose
The primary objective of this systematic review is to compare the risk of bradycardia in patients who received an ALK inhibitor or standard chemotherapy for the treatment of NSCLC in randomized controlled trials.

Methods
We conducted a systematic literature search in MEDLINE, EMBASE, Cochrane Central, Web of Science, and Clinical Trials registry. We included randomized controlled trials that compared two different ALK inhibitors, or an ALK inhibitor with standard chemotherapies in patients with NSCLC. The primary outcome of interest was the number of bradycardia events. Because bradycardia was not systematically reported in many trials, we also documented reports of dizziness (as a potential symptom of bradycardia) in a secondary analysis.

Results
We identified 12 eligible studies including 2915 participants. Bradycardia was reported as a treatment-emergent adverse event in 9 trials; dizziness was reported in the remaining 3 trials. The type of bradycardia and use of heart rate-slowing medications were not documented in most studies. The incidence of bradycardia among 1080 individuals prescribed crizotinib in 8 trials was 13% (95% CI 9–17%) during a mean follow-up of 1.26 years. A meta-analysis of four trials that compared crizotinib with standard chemotherapies (Figure 1) showed a higher risk of bradycardia with crizotinib (RR 19.33; 95% CI 5.40–69.22). Newer generations of ALK inhibitors (alectinib, brigatinib and lorlatinib) showed similar rates of bradycardia compared to crizotinib (RR 0.51; 95% CI 0.21–1.26; Figure 2). Dizziness was more common in ALK inhibitors than standard chemotherapies (RR 1.83; 95% CI 1.38–2.42).

Conclusions
Our findings suggest that crizotinib is associated with a higher rate of bradycardia than standard chemotherapies, while no difference was found between crizotinib and newer generations of ALK inhibitors. The higher rate of dizziness in ALK inhibitors could represent a symptom of bradycardia. Further research is needed to evaluate the incidence and types of ALK inhibitor-associated bradycardia and its relationship with patient symptoms.

Funding Acknowledgement
Type of funding sources: None. Figure 2
Ventricular arrhythmias in patients with immune checkpoint inhibitor myocarditis
Authors: Hassan M , Fradley M G , Drobni Z D , Mahmood S S , Nohria A , Thuny F , Michel C , Mahmoudi M , Thavendiranathan P , Garcia De Yebenes Castro M , Afilalo J , Nicolas E Z , Yang E H , Lyon A R , Neilan T 
Published: October 2021

Abstract

Background
Immune checkpoint inhibitor (ICI)-associated myocarditis is associated with a markedly increased risk of morbidity and mortality. The occurrence of ventricular arrhythmias (VA) in patients with ICI-associated myocarditis has not been well characterized.

Purpose
The aim of this study was to determine the characteristics and risk factors for severe VA in patients with ICI myocarditis.

Methods
The cohort consisted of 202 patients with ICI myocarditis. Ventricular arrhythmias were defined as a composite of sustained ventricular tachycardia and ventricular fibrillation. We used a multivariable logistic regression model to test the association between clinical variables and the development of VA.

Results
From a cohort of 202 patients with ICI myocarditis (67±13 years, 35% female, 60% hypertension, 23% diabetes mellitus), 41 (20.3%) developed VA, of which, 33 had VT and 8 had VF. The median time from admission to VF was 144 hours and to VT was 72 hours. A VA occurred in 17.5% of patients with a normal LVEF, and 25% of patients with reduced LVEF. On univariate analysis, a QRS duration &gt;110ms (OR 2.88, 95% CI 1.40 to 6.16, P=0.005) and a QTc duration &gt;470ms were associated with an increased probability of VA (OR 2.58, 95% CI 1.23, 5.41, P=0.012). The association remained significant after adjustment for age and gender. Additionally, a longer time from admission to initiation of corticosteroids was associated with a higher probability of VA (OR 1.06, 95% CI 1.01 to 1.13, P=0.027). The association between the time from admission to administration of corticosteroids and probability of VA remained significant after adjustment for age, gender, and LVEF on admission (OR, 1.06, 95% CI 1.00, 1.13, P=0.037) where each 6-hour delay in the initiation of corticosteroids was associated with a 4% increase in the risk for VA.

Conclusions
Ventricular arrhythmias are common in the setting of ICI myocarditis and are observed in patients presenting with both a preserved and a reduced LVEF. Wider QRS and longer QT at presentation and longer time from admission to initiation of corticosteroids were associated with an increased risk of VA.

Funding Acknowledgement
Type of funding sources: None.
Sensitivity and specificity of strain rate for the early detection of left ventricular dysfunction in breast cancer patients receiving adjuvant treatment with adriamycin with or without trastuzumab
Authors: Tettamanti M E , Gimenez I , Chacon C , Nadal J , Costanzo V , Nervo A , Losco F , Chacon R , Santos D A 
Published: October 2021

Abstract

Background
Medical literature states that a global longitudinal strain rate (GLS) &lt;−19% and further reductions in relation with baseline GLS may predict long term left ventricular dysfunction in breast cancer patients receiving adjuvant treatment with Adriamycin (A) with or without trastuzumab (T). However, there is not strong evidence to support the use of this technique in daily clinical practice.

Purpose
To analyze the sensitivity (S) and specificity (Sp) of GLS &lt;−19% or its relative 10, 15 and 20% reduction form baseline, for the early detection of left ventricular dysfunction in breast cancer patients receiving adjuvant treatment with A with or without T.

Methods
Patients were prospectively assessed with a cardiac echoDoppler + GLS at baseline, every 3 months during the first year and every 4 months thereafter. We assessed the S and Sp of GLS &lt;−19% or its relative &gt;10%, &gt;15% and &gt;20% reduction form baseline after treatment with A with or without T as predictors of cardiotoxicity (defined as a &gt;10 percentage points decrease of left ventricular ejection fraction to a value below the lower normal limit with respect to baseline).

Results
136 out of 884 patients (16%) had GLS measured at each visit: 83 patients (60%) and 53 patients (40%) treated with A or A+T respectively. Patients were followed up to 31±6 months. Mean age was 51±12 years. The table shows the baseline characteristics of both groups. 10 out of 83 patients in group A (12%) and 18 out of 53 P in group A+T (34%) developed cardiotoxicity. Baseline left ventricular ejection fraction and GLS were 61±4,7% and −20,18±2,6% in group A, and 58,7±5,8% and −19,5±2,6 post treatment. In this group, GLS S and Sp were 50 and 80%, respectively. In the group A+T, the best GLS cutoff was −19%, with a 60% sensitivity and 78% specificity.

Conclusions
In our non-selected cohort of patients, nor GLS or its percentage reductions along follow up predicted the reduction of left ventricular ejection fraction and the developing of cardiotoxic ventricular dysfunction in breast cancer patients receiving adjuvant treatment with A with or without T. The systematic use of this tool should be further investigated and validated at each center to help establish its usefulness in daily practice.

Funding Acknowledgement
Type of funding sources: None. Baseline characteristics
Impact of active and stable cancer on survival in patients undergoing percutaneous coronary intervention
Authors: Kang M G , Kim K H , Park H W , Koh J S , Park J R , Park Y H , Hwang S J , Jeong Y H , Kwak C H , Ahn J H , Song H N , Hwang J Y 
Published: October 2021

Abstract

Background
With advances in treatment of ischemic heart disease and cancer treatment, use of percutaneous coronary intervention (PCI) in cancer survivors and patients with active cancer (AC) is expanding.

Objectives
The purpose of this study was to determine the impact of cancer on survival and major cardiovascular events (MACE) in a long-term, single-center cohort of patients treated with PCI.

Methods
Patients treated with PCI between January 2010 and December 2017 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. AC was included patients with cancer diagnosed within the past 6 months, patients who had cancer-related therapy within the past 6 months, active metastatic disease, or active recurrence of the cancer. The primary endpoints were 5-year survival and a secondary endpoint was 5-year MACE.

Results
A total of 6,743 patients (age 66±12 years, 68.4% men) treated with PCI were included: 6,404 (95.0%) controls, 245 (3.6%) SC, and 94 (1.4%) AC. Predominant malignancies were gastrointestinal (37.4%), lung (22.7%), and genitourinary cancer (14.7%). No differences were observed between patients with AC, SC and controls regarding 5-year MACE (total MACE, 33.2% vs. 28.1% vs. 17.5%, p=0.072; cardiac death, 13.6% vs. 9.1% vs. 6.7%, p=0.066; non-fatal myocardial infarction, 2.9% vs. 7.5% vs. 7.8%, p=0.820; revascularization, 17.9% vs. 17.6% vs. 11.6%, p=0.794, respectively). Patients with AC and SC had reduced 5-year survival compared with controls (62.0% vs. 81.5% vs. 89.8%, p&lt;0.001) (Figure). AC was associated with a 1.76 (95% CI 1.22 to 2.54, p=0.002) fold increased risk of all-cause 5-year mortality in multivariable adjusted models.

Conclusions
Cumulative incidence of 5-year survival was discriminated by concurrent status of cancer following PCI. Individualized decision making is needed in the routine practice of PCI regarding concurrent cancer-specific treatment and prognosis.

Funding Acknowledgement
Type of funding sources: None.
Incident cardiovascular events among middle-age men are associated with increased risk of subsequent prostate cancer diagnosis
Authors: Fardman A , Tiosano S , Kaplan A , Kalstein M , Moshkovits Y , Segev S , Klempfner R , Segev A , Grossman E , Maor E 
Published: October 2021

Abstract

Introduction
Prostate cancer is the second most common malignancy in men worldwide, but incidence is highly dependent on screening.

Purpose
We aimed to examine whether incident cardiovascular disease (CVD) events are associated with increased risk of future prostate cancer in middle-aged men.

Methods
We evaluated asymptomatic self-referred men who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention, or stroke. Study endpoint was the development of cancer during follow up. Cancer and mortality data were available for all subjects from national registries. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event.

Results
Final study population included 18,282 subjects. Median age was 47 years (Interquartile range [IQR] 41–54). During median follow up time of 12 years (IQR 4–17) 2,047 (11%) subjects developed CVD, 406 (2.2%) developed prostate cancer and 694 (4%) died. Compared with patients who were free of CVD or prostate cancer during follow up, risk of death was 4, 6 and 15 times higher for patients who developed CVD event, prostate cancer, or both during follow up, respectively (p &lt;.001 for all). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop prostate cancer (95% Confidence Interval [CI] 1.2–2.1, p=.001). However, after multivariable adjustment, this association was no longer significant. Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in middle-aged men (age≤55 years; N=14,473) incident CVD was associated with a significant 70% increased risk of subsequent cancer diagnosis in multivariable model (95% CI 1.13–2.6, p=.011, p for interaction=.002). Exploratory analysis of men younger than 55 showed that independent association of incident CVD with subsequent cancer diagnosis was different among subjects with normal body mass index (BMI) (≤25 kg/m2) compared with those with increased BMI (HR 0.55; 95% CI [0.22–1.42]; p value=0.23 vs. 1.6; 95% CI [1.007–2.54]; p value=.047; p for interaction=.058, respectively).

Conclusion
Incident CVD is independently associated with increased risk of subsequent prostate cancer diagnosis among men ≤55 years. Routine prostate cancer surveillance should be considered after CVD event in this population.

Funding Acknowledgement
Type of funding sources: None.
Cardiovascular events among recipients of hematopoietic stem cell transplantation
Authors: Aghel N , Lui M , Mian H , Khalaf D , Hillis C , Petropoulos J , Wang V , Leber B , Lipton J , Walker I , Leong D 
Published: October 2021

Abstract

Background
Allogeneic and autologous hematopoietic stem cell transplantation (HSCT) are potential curative treatments for several hematological malignancies (1). Survival after HSCT has improved over the last decade, but survivors remain at risk for health issues after transplantation. Cardiovascular complications after HSCT are increasingly recognized (2). Cardiovascular diseases may be an important cause of mortality and morbidity in patients after HSCT owing to the toxicities of the cancer therapies; however, the incidence of cardiovascular events (CVEs) in this population has not been completely characterized. The objective of this systematic review is to summarize the evidence on the incidence of CVEs in HSCT recipients.

Methods
Medline and Embase were searched from inception to December 2020 without language restriction. Two authors independently screened the titles and abstracts. Inclusion criteria were: cohort studies and phase 3 randomized controlled trials that reported CVEs (i.e., heart failure, arrythmias, acute coronary syndrome, and stroke) or cardiovascular death among adults who underwent HSCT for a hematological malignancy. All-cause mortality, relapse-related mortality, and non-relapse-related mortality (NRM) were also collected. Studies in which the follow up period was not started immediately after HSCT were excluded due to the risk of immortal bias.

Results
Of 8151 nonduplicate articles, 30 studies including 14019 individuals post autologous HSCT, and 22 studies including 31049 individuals post allogeneic HSCT met the inclusion criteria.
The cumulative incidence of CVEs in the first 100 days post autologous HSCT was 9% and arrhythmia (i.e., atrial fibrillation) was the most common CVE. In recipients of allogeneic HSCT, the 100-day cumulative incidence of CVEs was 3%, and heart failure (HF) was the most common reported CVE. In recipients of autologous and allogeneic HSCT, cardiovascular death was responsible for 43% and 10% of NRM within 100 days, respectively (Table 1).
The incidence of CVEs was 4.96 per 1000-person years (95% CI; 4.21–5.80) in long-term survivors (beyond 100-days) of autologous HSCT, and HF was the most common CVE in this population. In long-term survivors of allogeneic HSCT, the incidence of CVEs was 1.90 per 1000-person years (95% CI: 1.59–2.24). Cardiovascular death was the most frequently reported CVE in long-term survivors of allogeneic HSCT (Table 2).

Conclusion
CVEs remain a major cause of non relapse morbidity and mortality in recipients of HSCT, especially recipients of autologous HSCT within the first 100 days. Future studies are needed to identify the risk factors for CVEs that are specific to HSCT recipients.

Funding Acknowledgement
Type of funding sources: None.
Pregnancy in women with hypertrophic cardiomyopathy: observational data from the tertiary referral center registry
Authors: Karelkina E , Zaitsev V , Konasov K , Svistelnikova E , Bautin A , Li O , Irtyuga O , Moiseeva O 
Published: October 2021

Abstract

Introduction
The number of cases of hypertrophic cardiomyopathy (HCM) in pregnancy increases every year. In most cases the course of pregnancy is favorable, however in certain high–risk scenarios there is an increased risk of complications (e.g., increased ventricular ectopic activity, heart failure exacerbation). Management heavily relies on the severity of the outflow tract obstruction, extent of left ventricular hypertrophy and sudden cardiac death (SCD) risk stratification.

Purpose
The main objective of this study is to assess risk factors and complications during pregnancy, childbirth and the postpartum period in women with HCM.

Methods
In this retrospective study we included 60 pregnant women with HCM who were admitted to the tertiary referral center between October 2010 and December 2019 with a mean age of 29.1±5.19 years. ECHO was performed in all patients.

Results
Twenty patients (33%) have obstructive HCM (HOCM), 31 patients (51,6%) were nulliparous, 20 patients (33%) had no clinical symptoms prior to pregnancy. Since the third trimester of pregnancy we observed the onset or exacerbation of heart failure in 26 (43.3%) cases, half of these patients presented with NYHA class III–IV. SCD risk was 3.64% (2.66 –5.84) in the third trimester. Six patients (9.23%) were required ICD implantation. Caesarean section (CS) delivery was performed in 38 patients (63.3%). However, the CS proportion has decreased from 80% to 51% in the last 5 years. Despite frequent complications during pregnancy and the postpartum period, no maternal mortality has been reported. The newborns' weight in HOCM cases was significantly lower than in patients without LVOT obstruction.

Conclusion
Despite the favorable course of pregnancy in HCM patients, the third trimester of pregnancy was often accompanied by the onset and progression of heart failure, as well as an increase in the proportion of patients with ventricular arrhythmias. In patients with HOCM, a decrease in the weight of newborns was revealed.

Funding Acknowledgement
Type of funding sources: None. Characteristics of women with HCP
Arterial hypertension in pregnant women: the effect of body mass index and smoking
Authors: Rublevskaya A , Bichan N A 
Published: October 2021

Abstract

Aim
To evaluate the effect of body mass index (BMI) and smoking, as well as their combination on the development of arterial hypertension (AH) during pregnancy.

Materials
The study included 312 pregnant women with hypertension (group I), with an average age of 32 [28–36] years. The diagnosis of moderate and severe hypertension was established before pregnancy on the basis of the national guidelines. The control group consisted of 358 pregnant women without hypertension (group II), with an average age of 28 [24–32] years. The study included the assessment of anthropometric data at 6–8 weeks of pregnancy, questionnaires and assessment of the smoking status of pregnant women (pack-years), ambulatory blood pressure monitoring (ABPM).

Results
At admission, the mean systolic blood pressure (SBP) in group I was 147 [140–164] mmHg, and the diastolic blood pressure (DBP) was 95.8 [84–100] mmHg. According to the ABPM data, the mean SBP was 142 [135–164] mmHg, and the mean DBP was 95.8 [84–98] mmHg When registered for pregnancy in the group 1, the BMI was significantly higher compared to the control group, 30.2 (25–34,9) and 22.3 (20.2–25.6), p&lt;0.001, respectively. Obesity and smoking were statistically more common in group I compared to the control group, p&lt;0.001 and p=0.01, respectively. The index of the smoker in the group with AH was 7.5 [2.5–15] pack-years, in the control group – 1.9 [1.0–7.5], p&lt;0.001.
Smoking pack-years ≥10, increased the chance of developing hypertension by 13.1 (5.5–29.9) times, in turn, with pack-years &lt;10 (compared to non-smokers), the chance of developing hypertension increased by 2.6 (1.6–3.9) times. Obesity significantly increased the chance of hypertension, Odds Ratio=12 (7.6–19.1). Among women with a normal BMI, smoking increased the chance of developing hypertension by 5 (2.7–9.3) times compared to its absence. The combination of smoking and an above-normal BMI compared to no smoking and a normal BMI increased the chance of developing hypertension by 31 (15.3–62) times. In women with a normal BMI, smoking (pack-years &lt;10) increased the chance of developing hypertension by 3.6 (1.8–6.8) times compared to its absence. Also in this group, smoking (pack-years ≥10) increased the chance of developing hypertension by 5 (1.2–21) times compared to IPL&lt;10 and by 17.7 (4.7–67) times compared to no smoking. In women with normal BMI, smoking (pack-years &lt;10), compared with non-smoking women, did not significantly affect the chance of developing hypertension. In obese women, pack-years did not significantly affect the chance of developing hypertension (p=0.07).

Conclusions
An increase in body mass index and smoking, either single or in combination, can increase the chance of developing hypertension.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Russian Medical Academy of Continuous Professional Education, Novokuznetsk
Predictors of inappropriate dosing of direct oral anticoagulants in nonagenarian patients with atrial fibrillation
Authors: Dominguez Erquicia P , Raposeiras-Roubin S , Abu-Asi E , Cespon-Fernandez M , Alonso Rodriguez D , Camacho Freire S J , Curbelos Fernandez N , Lopez Masjuan Rios A , Melendo Viu M , Iniguez Romo A 
Published: October 2021

Abstract

Background
Direct oral anticoagulants (DOACs) are presented as a good option for older patients owing to their safety profile. However, the dosing can become challenging especially in this population.

Objective
Our aim is to evaluate the predictors of inappropriate dosing of DOACs.

Methods
The authors analyzed the use of DOACs in 726 patients aged ≥90 years with a diagnosis of atrial fibrillation (AF) from a retrospective multicenter registry from 3 health areas in Spain. We studied the dosing, differentiating between appropriate dose, underdosing or overdosing. To evaluate the best predictive model, the Akaike information criterion (AIC) was used.

Results
Follow-up was 27.7±18.3 months. Mean age was 93.0±5.2 years, and 60.1% of patients were female. 339 patients received rivaroxaban (47.3%), 237 apixaban (33.1%), 105 dabigatran (14.7%) and 35 edoxaban (4.9%). An important proportion of patients received a suboptimal dose (41.5%, n=297): 35.3% underdosed and 6.1% overdosed. The rate of suboptimal dosing was higher for apixaban and lower for dabigatran (Figure 1A). In our registry we found as a predictors of inappropriate dosing: kidney function (Chronic Kidney Disease Epidemiology Collaboration), odds Ratio (OR) 1.04; 95% CI: 1.03–1.05, P&lt;0.001; weight measured in kilograms, OR 1.04; 95% CI: 1.01–1.07, P=0.012; and high blood pressure (HBP), OR 1.61; 95% CI: 1.02–2.53, P=0.041 (Figure 1B). Other variables such as HASBLED, CHADSVASc, anemia, prior bleeding, or concomitant use of antiplatelet therapy, were not significantly associated.

Conclusions
We want to highlight that the use of an inappropriate dose of DOAC in older patients is common, about 40% in our study. Apixaban was the most frequently underdosed DOAC. HBP, weight, and kidney function were associated with an inappropriate dosing prescription. Therefore, it is important to carefully evaluate the characteristics of the patient to prescribe the appropriate dose that guarantees a correct action.

Funding Acknowledgement
Type of funding sources: None. Dosing of DOACsPredictors of inappropriate dosing