Morbidity and mortality among children, adolescents, and young adults with cancer over six decades: a Swedish population-based cohort study (the Rebuc study).

Background: Despite progress in managing cancer in children, adolescents, and young adults (CAYAs), persistent complications may impact their quality of life. This study covers the morbidity and mortality, among CAYAs, with the aim to investigate the influence of socioeconomic factors on outcomes. Methods: This retrospective matched cohort study included the entire Swedish population of individuals under 25 with cancer 1958-2021. The population was identified from the Cancer Register, and controls were paired 1:5 based on age, sex, and residence. Multiple registers provided data on morbidity, mortality, and demographics. Findings: This survey covering 63 years, identified 65,173 CAYAs and matched controls, a total of 378,108 individuals (74% females). CAYAs exhibited a 3.04-times higher risk for subsequent cancer (Odds ratio (OR) 95% confidence interval (CI) 2.92-3.17, p < 0.0001), a 1.23-times higher risk for cardiovascular disease (OR 95% CI 1.20-1.26, p < 0.0001), and a 1.41-times higher risk for external affliction (OR 95% CI 1.34-1.49, p < 0.0001). CAYAs had a higher mortality hazard, and after adjusting for socioeconomic factors, males, individuals born outside Europe, and those with greater sick-leave had a higher association with mortality, while education and marriage showed a beneficial association. Interpretation: The Rebuc study, showed an increased risk for serious complications among young cancer patients in Sweden. Patient-specific variables, demographics, and socioeconomic factors influenced mortality. These results underscore the impact of cancer on the health and lifespan of young individuals and the necessity for further research to address socioeconomic disparities in cancer care. Funding: Grants from the Medical Research Council of Southeast Sweden (FORSS), ALF Grants, Region Ostergotland, and The Swedish Childhood Cancer Fund.

Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy Among Patients With Breast Cancer.

Importance: A large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy. Objective: To examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy. Design, Setting, and Participants: This population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022. Exposure: Discontinuation of adjuvant hormone therapy. Main Outcomes and Measures: The main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy. Results: A total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results. Conclusions and Relevance: In this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.

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

Background: The 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. Objective: To 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. Methods: Data 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. Results: The 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%. Conclusion: The 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.

Evidence-based prediction and prevention of cardiovascular morbidity in adults treated for cancer.

BACKGROUND: Cancer treatment-related morbidity relevantly compromises health status in cancer survivors, and efforts to optimise health-related outcomes in this population are vital to maximising healthy survivorship. A pre-treatment assessment - and possibly preventive management strategies - of cancer patients at increased risk for cardiovascular disease (CVD) seems a rational approach in this regard. Definitive evidence for such strategies is largely lacking, thereby impeding the formulation of firm recommendations. RESULTS: The current scoping review aims to summarise and grade the evidence regarding strategies for prediction and prevention of CVD in adults in relation to oncological treatments. We conducted a scoping literature search for different strategies for primary prevention, such as medical and lifestyle interventions, as well as the use of predictive risk scores. We identified studies with moderate to good strength and up to now limited evidence to recommend primary preventive strategies in unselected patients treated with potentially cardiotoxic oncologic therapies. CONCLUSION: Efforts to minimize the CVD burden in cancer survivors are needed to accomplish healthy survivorship. This can be done by means of robust models predictive for CVD events or application of interventions during or after oncological treatments. Up to now there is insufficient evidence to implement preventive strategies in an unselected group of patients treated with potential cardiotoxic oncological treatments. We conclude that randomised controlled trials are needed that evaluate medical and lifestyle interventions in groups at increased risk for complications, in order to be able to influence chronic illness risks, such as cardiovascular complications, for cancer survivors.

Randomized trial of a left ventricular assist device as destination therapy versus guideline-directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial.

AIMS: Patients with advanced heart failure (AdHF) who are ineligible for heart transplantation (HTx) can become candidates for treatment with a left ventricular assist device (LVAD) in some countries, but not others. This reflects the lack of a systematic analysis of the usefulness of LVAD systems in this context, and of their benefits, limitations and cost-effectiveness. The SWEdish evaluation of left Ventricular Assist Device (SweVAD) study is a Phase IV, prospective, 1:1 randomized, non-blinded, multicentre trial that will examine the impact of assignment to mechanical circulatory support with guideline-directed LVAD destination therapy (GD-LVAD-DT) using the HeartMate 3 (HM3) continuous flow pump vs. guideline-directed medical therapy (GDMT) on survival in a population of AdHF patients ineligible for HTx. METHODS: A total of 80 patients will be recruited to SweVAD at the seven university hospitals in Sweden. The study population will comprise patients with AdHF (New York Heart Association class IIIB-IV, INTERMACS profile 2-6) who display signs of poor prognosis despite GDMT and who are not considered eligible for HTx. Participants will be followed for 2 years or until death occurs. Other endpoints will be determined by blinded adjudication. Patients who remain on study-assigned interventions beyond 2 years will be asked to continue follow-up for outcomes and adverse events for up to 5 years. CONCLUSION: The SweVAD study will compare survival, medium-term benefits, costs and potential hazards between GD-LVAD-DT and GDMT and will provide a valuable reference point to guide destination therapy strategies for patients with AdHF ineligible for HTx.

Outcome and presentation of heart failure in breast cancer patients: findings from a Swedish register-based study.

AIMS: Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC. METHODS AND RESULTS: A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry. Two hundred and ninety-four iHF and 338 pHF patients with BC were age-matched to 1470 iHF and 1690 pHF patients without BC. Comorbidity and treatment characteristics were compared using the χ2 tests for categories. Cox proportional hazard models assessed the hazard ratio (HR) and 95% confidence intervals (95% CIs) of all-cause and cardiovascular mortality among HF patients with and without BC. In the pHF group, BC patients had less often myocardial infarction (21.6% vs. 28.6%, P < 0.01) and received less often aspirin (47.6% vs. 55.1%, P = 0.01), coronary revascularization (11.8% vs. 16.2%, P < 0.01), or device therapy (0.9% vs. 3.0%, P = 0.03). After median follow-up of 2 years, risk of all-cause mortality (iHF: HR = 1.04, 95% CI = 0.83-1.29 and pHF: HR = 0.94, 95% CI = 0.79-1.12), cardiovascular mortality (iHF: HR = 0.94, 95% CI = 0.71-1.24 and pHF: HR = 0.89, 95% CI = 0.71-1.10), and HF mortality (iHF: HR = 0.80, 95% CI = 0.34-1.90 and pHF: HR = 0.75, 95% CI = 0.43-1.29) were similar for patients with and without BC in the iHF and pHF groups. CONCLUSION: Risk of all-cause and cardiovascular mortality in HF patients did not differ by BC status. Differences in pre-existing myocardial infarction and HF treatment among pHF patients with and without BC may suggest differences in pathogenesis of HF.

Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial.

BACKGROUND: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive disease. METHODS: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse-free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up. RESULTS: There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P = .231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups. CONCLUSIONS: The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.

Sound analysis of the magnetically levitated left ventricular assist device HeartMate 3™.

INTRODUCTION: The HeartMate 3™ has shown lower rates of adverse events compared to previous devices due to the design and absence of mechanical bearings. For previous devices, sound analysis emerged as a way to assess pump function. The aims of this study were to determine if sound analysis can be applied to the HeartMate 3 in vivo and in vitro and to evaluate an electronic stethoscope. METHOD: Sound recordings were performed with microphones and clinical accessible electronic stethoscope. The recordings were studied in both the time and the frequency domains. Recordings from four patients were performed to determine if in vivo and in vitro recordings are comparable. RESULTS: The results show that it is possible to detect sound from HeartMate 3 and the sound spectrum is clear. Pump frequency and frequency of the pulsatile mode are easily determined. Frequency spectra from in vitro and in vivo recordings have the same pattern, and the major proportion (96.7%) of signal power is located at the pump speed frequency ±40 Hz. The recordings from the patients show low inter-individual differences except from location of peaks originating from pump speed and harmonics. Electronic stethoscopes could be used for sound recordings, but the dedicated equipment showed a clearer sound spectrum. DISCUSSION: The results show that acoustic analysis can also be performed with the HeartMate 3 and that in vivo and in vitro sound spectrum is similar. The frequency spectra are different from previous devices, and methods for assessing pump function or thrombosis need further evaluation.

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.

Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.

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

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.

Sound analysis of a left ventricular assist device: A technical evaluation of iOS devices.

INTRODUCTION: The use of left ventricular assist device (LVAD) has grown rapidly. Adverse events do continue to occur. In recent years, analysis of LVAD sound recordings emerged as a means to monitor pump function and detect pump thrombosis. The aim of this study was to characterize the sounds from HeartMate II and to evaluate the use of handheld iOS devices for sound recordings. METHOD: Signal analysis of LVAD sound recordings, with dedicated recording equipment and iOS devices, was performed. Two LVADs running in mock loop circuits were compared to an implanted LVAD. Spectral analysis and parametric signal models were explored to quantify the sound and potentially detect changes in it. RESULTS: The sound recordings of two LVADs in individual mock loop circuits and a third one implanted in a patient appeared to be similar. Qualitatively, sound characteristics were preserved following changes in pump speed. Recordings using dedicated equipment showed that HeartMate II sound comprises low-frequency components corresponding to pump impeller rotation, as well as high-frequency components due to a pulse width modulation of the electric power to the pump. These different signal components interact and result in a complicated frequency spectrum. The iPhone and iPod recordings could not reproduce the sounds as well as the dedicated equipment. In particular, lower frequencies were affected by outside disturbances. DISCUSSION: This article outlines a systematic approach to LVAD sound analysis using signal processing methods to quantify and potentially detect changes, and describes some of the challenges, for example, with the use of inexpensive recording devices.

Progressive multifocal leukoencephalopathy after heart transplantation: 4 years of clinically stable infection on low-dose immunosuppressive therapy.

Progressive multifocal leukoencephalopathy (PML), caused by reactivation of JC-virus is a relatively rare complication seen in patients with compromised immune system. There are no evidence-based treatment available and prognosis is poor. Withdrawal of immunosuppressant can result in further neurological deterioration and for patients with solid organ transplantations, fatal graft rejection. We report a 52-year-old women that presented with seizures within 1 month after heart transplantation. Initial diagnosis was vascular disease. After clinical deterioration 10 months after transplantation, further examinations led to the diagnosis. Minimizing tacrolimus, to a concentration of 2 ng/ml, and extensive physical therapy has improved the physical capacity of the patient. The patient has now been clinically stable for 4 years and extended survival for 5 years. This case adds to the limited adult cases of PML within the population of heart transplant recipients and the need for increased awareness to minimize diagnosis delay.

Clinical Implications of Physiologic Flow Adjustment in Continuous-Flow Left Ventricular Assist Devices.

There is increasing evidence for successful management of end-stage heart failure with continuous-flow left ventricular assist device (CF-LVAD) technology. However, passive flow adjustment at fixed CF-LVAD speed is susceptible to flow balancing issues as well as adverse hemodynamic effects relating to the diminished arterial pulse pressure and flow. With current therapy, flow cannot be adjusted with changes in venous return, which can vary significantly with volume status. This limits the performance and safety of CF-LVAD. Active flow adjustment strategies have been proposed to improve the synchrony between the pump and the native cardiovascular system, mimicking the Frank-Starling mechanism of the heart. These flow adjustment strategies include modulation by CF-LVAD pump speed by synchrony and maintenance of constant flow or constant pressure head, or a combination of these variables. However, none of these adjustment strategies have evolved sufficiently to gain widespread attention. Herein we review the current challenges and future directions of CF-LVAD therapy and sensor technology focusing on the development of a physiologic, long-term active flow adjustment strategy for CF-LVADs.

Endovascular Stenting of a LVAD Outflow Graft Thrombosis.

We report the endovascular stenting of an outflow tract thrombosis in a left ventricular assist device in a patient with relative contraindications to sternotomy and pump exchange. This report highlights the importance of simultaneous prevention of stroke using filter devices in the common carotid arteries.

Left Atrial Pressure Monitoring With an Implantable Wireless Pressure Sensor After Implantation of a Left Ventricular Assist Device.

After implantation of a continuous-flow left ventricular assist device (LVAD), left atrial pressure (LAP) monitoring allows for the precise management of intravascular volume, inotropic therapy, and pump speed. In this case series of 4 LVAD recipients, we report the first clinical use of this wireless pressure sensor for the long-term monitoring of LAP during LVAD support. A wireless microelectromechanical system pressure sensor (Titan, ISS Inc., Ypsilanti, MI) was placed in the left atrium in four patients at the time of LVAD implantation. Titan sensor LAP was measured in all four patients on the intensive care unit and in three patients at home. Ramped speed tests were performed using LAP and echocardiography in three patients. The left ventricular end-diastolic diameter (cm), flow (L/min), power consumption (W), and blood pressure (mm Hg) were measured at each step. Measurements were performed over 36, 84, 137, and 180 days, respectively. The three discharged patients had equipment at home and were able to perform daily recordings. There were significant correlations between sensor pressure and pump speed, LV and LA size and pulmonary capillary wedge pressure, respectively (r = 0.92-0.99, p < 0.05). There was no device failure, and there were no adverse consequences of its use.

[Cardiotoxicity relatively common in cancer treatment]. / Kardiotoxicitet relativt vanligt vid cancerbehandling - Samarbete mellan kardiologi och onkologi kan ge bättre vård.

Modern cancer therapy has noticeably improved the prognosis for various cancer diseases, but cardiovascular side effects are not uncommon, both in short and long term. The individual patient's cardiovascular risk profile affects the risk of developing side effects. Potential underestimation of this risk can lead to life-long severe cardiac disease for a patient that has been cured from cancer. Overestimation of the risk can lead to withdrawal of life-saving cancer treatment because of potentially reversible or mild cardiac side effects. A multidisciplinary approach will lead to better handling of cardio-oncologic patients.

Young woman with breast cancer and cardiotoxicity with severe heart failure treated with a HeartMate IITM for nearly 6 years before heart transplantation.

Cardiotoxicity is a multifactorial problem, which has emerged with the improvement of cancer therapies and survival. Heart transplantation is relatively contraindicated in patients with breast cancer, until at least 5 years after complete remission. We present a case where a young woman who in 2001, at the age of 31, was diagnosed with breast cancer. She was considered cured, but 4 years later she suffered a relapse. During her second treatment, in 2006, she suffered from severe heart failure. She received a HeartMate II, as a long-term bridge to transplantation and 6 years later she was successfully transplanted. In this case report we discuss the use of mechanical circulatory support in cancer patients with drug-induced heart failure.

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<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 ∼50% of the inner diameter (to mimic clot in the out- and inflow tubing), the frequency spectrum changed significantly (P<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 ∼50%. More significant (P<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.

Long-term left ventricular support in patients with a mechanical aortic valve.

OBJECTIVES: The presence of a mechanical prosthesis has been regarded as an increased risk of thromboembolic complications and as a relative contraindication for a left ventricular assist device (LVAD). Five patients in our center had a mechanical aortic valve at the time of device implantation and were studied regarding thromboembolic complications. DESIGN: Five patients operated upon with an LVAD (1 HeartMate I™, 4 HeartMate II™) between 2002 and 2011 had a mechanical aortic valve at the time of implantation. The first patient had a patch closure of the aortic valve. In four patients, the prosthesis was left in place. Anticoagulants included aspirin, warfarin, and clopidogrel. RESULTS: The average and accumulated treatment times were 150 and 752 days, respectively. Three of the five patients showed early signs of valve thrombosis on echo with concomitant valve dysfunction. Four patients were transplanted without thromboembolic events during pump treatment. One patient died from a hemorrhagic stroke after 90 days on the LVAD. CONCLUSIONS: The strategy of leaving a mechanical heart valve in place at the time of LVAD implantation in five patients led to valvular thrombosis in three but did not provoke embolic events. It increased the complexity of postoperative anticoagulation.