Long-term and real-life incidence of cancer therapy-related cardiovascular toxicity in patients with breast cancer: a Swedish cohort study

BackgroundThe administration of anticancer drugs in females with comorbidity increases the risk for cancer therapy-related cardiovascular toxicity (CTR-CVT), which in turn contributes to cardiovascular disease (CVD). Furthermore, a pathophysiological connection between cancer and cardiovascular disease may exist.ObjectiveTo assess the long-term risks and predictors of CTR-CVT, including clinical hypertension (HT), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), as well as all-cause mortality in women diagnosed with early breast cancer (BC) and eligible for adjuvant chemotherapy in Sweden.MethodsData were extracted from Swedish registers and medical records on 433 women, 18-60 years of age, diagnosed 1998-2002 with lymph node-positive BC, and considered for adjuvant chemotherapy. CTR-CVT was defined as HT, CAD, HF, or AF after the diagnosis of BC. Follow-up was from the date of BC diagnosis until November 30, 2021, or death. Prevalence of CTR-CVT and all-cause mortality were calculated. Hazard ratios (HR) were determined for factors associated with CTR-CVT.ResultsThe median age was 50 (interquartile range (IQR) 32) years. 910 CTR-CVT events were diagnosed in 311 women with a median of 19.3 (IQR 15,3) years follow-up. The proportions of CTR-CVT events were: HT 281 (64%); CAD 198 (46%); HF 206 (47%); and AF 225 (51%). The cumulative incidence of CTR-CVT was 71.8%, and 50% of all 433 patients developed CTR-CVT within 11.7 years of BC diagnosis (standard deviation (SD) 0.57, 95% confidence interval (CI) 10.6-12.9). Age was a risk factor for CTR-CVT. Anthracycline increased the risk for HF (p=0,001; HR 2,0; 95%CI 1,4-2,8), CAD (p= 0,002; HR 1,7; 95% CI 1,2-2,4), and AF (p=0,013; HR 1,5; 95% CI 1,0-2,0). At the end of the 24-year study period, 227 of the 433 women were alive, and the total cumulative mortality was 47,6%.ConclusionThe prevalence of CTR-CVT and all-cause mortality is high after BC diagnosis and treatment, particularly in older patients and those receiving anthracyclines. These findings and the onset of CTR-CVT support cardio-oncology guidelines recommending initial risk stratification and cardiovascular monitoring during treatment, followed by long-term annual screening for cardiovascular risk factors and CTR-CVT among BC survivors

Continuous-flow LVADs in the Nordic countries : complications and mortality and its predictors

Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries. Design: This was a retrospective, international, multicenter cohort study. Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p <.001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively. Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.Peer reviewe

Acoustic Analysis of a Mechanical Circulatory Support

Mechanical circulatory support technology is continually improving. However, adverse complications do occur with devastating consequences, for example, pump thrombosis that may develop in several parts of the pump system. The aim of this study was to design an experimental clot/thrombosis model to register and analyze acoustic signals from the left ventricular assist device (LVAD) HeartMate II (HMII) (Thoratec Corporation, Inc., Pleasanton, CA, USA) and detect changes in sound signals correlating to clots in the inflow, outflow, and pump housing. Using modern telecom techniques, it was possible to register and analyze the HMII pump-specific acoustic fingerprint in an experimental model of LVAD support using a mock loop. Increase in pump speed significantly (P less than 0.005) changed the acoustic fingerprint at certain frequency (0-23 000 Hz) intervals (regions: R1-3 and peaks: P1,3-4). When the ball valves connected to the tubing were narrowed sequentially by similar to 50% of the inner diameter (to mimic clot in the out-and inflow tubing), the frequency spectrum changed significantly (P less than 0.005) in P1 and P2 and R1 when the outflow tubing was narrowed. This change was not seen to the same extent when the lumen of the ball valve connected to the inflow tube was narrowed by similar to 50%. More significant (P less than 0.005) acoustic changes were detected in P1 and P2 and R1 and R3, with the largest dB figs. in the lower frequency ranges in R1 and P2, when artificial clots and blood clots passed through the pump system. At higher frequencies, a significant change in dB figs. in R3 and P4 was detected when clots passed through the pump system. Acoustic monitoring of pump sounds may become a valuable tool in LVAD surveillance

Controller and battery changes due to technical problems related to the HVAD® left ventricular assist device - a single center experience

Abstract Background The use of left ventricular assist devices (LVADs) has increased in the last decade. Major complications have been well described, but there is no data on device alarms and actual or threatening malfunction which impair quality of life and may impair outcomes. This study describes the technical problems related to the use of the HVAD® left ventricular assist device in a single center. Methods We retrospectively reviewed device malfunctions and outcomes in 22 patients with HVAD® left ventricular assist device followed at Karolinska University Hospital between 2011 and 2016. Device malfunction was defined by INTERMACS as a failure of one or more of the components of the LVAD system. The primary outcome was defined as death or hospitalization or unplanned urgent clinic visit due to device alarm of unknown significance or actual or threatening malfunction. Separate secondary outcomes were malfunction resulting in controller exchange and malfunction resulting in battery change. Exploratory outcomes were death, transplantation, or explantation because of recovery. Results Median age was 59 years and 19% were women. Over a mean follow-up time of 1.7 years (37 patient-years), the primary outcome occurred 30 times (0.8 events per patient-year; 0 deaths, 2 hospitalizations and 28 un-planned clinic visits). Secondary outcomes were 41 device malfunctions for 14 patients requiring 45 controller exchanges in 12 patients (1.1 events per patient-year) and 128 battery changes in 12 patients (3.5 events per patient-year). Exploratory outcomes were 8 deaths (36.4%), 7 transplantations (31.8%) and 2 explants due to recovery (9.1%). Conclusion The use of HVAD® was associated with technical problems requiring frequent un-planned clinic visits and changes of controller and/or batteries. There were no deaths due to device malfunction. Further studies are warranted to evaluate the risk of device malfunction and associated reductions in quality of life and cost