Between the Probe and the Pump : An experimental study on cardiac performance analysis based on Echocardiography, tissue and laser Doppler

Echocardiography is an ultrasound-based bedside, non-invasive and easily available cardiac diagnostic technique visualising the heart’s morphology and function. Quantification of cardiac wall motion can be measured with the tissue Doppler Imaging (TDI) modality which provides in humans a high diagnostic capacity to differentiate healthy from diseased myocardium with reduced function. Heart failure, as a consequence of, for example, myocardial or ischaemic heart disease, demands both bedside and intraoperative diagnostic procedures for myocardial functional and perfusion assessment. In the late stages of heart failure cardiac left ventricular assist devices (LVAD) may be the treatment of choice. Such new technologies are commonly evaluated in large animals before application in humans is accepted. With the aim of evaluating TDI´s applicability and feasibility in a large animal model 21 calves (aged 3 months and weight around 70 kg), were studied with colour TDI (Paper I). Analysis was performed either during coronary artery occlusion when the laser Doppler perfusion imaging technique (LDMP) was refined (Paper II), or after implantation of the LVAD, Heart Mate II® (Papers III, IV). All animals were haemodynamically monitored (pressures, flows, heart rate) and ECG was continuously recorded. Transthoracic and epicardial echocardiography (TTE) were performed before and after sternotomy and intraoperatively during experimental progressive heart failure. Heart chamber dimensions, native stroke volume, systolic and diastolic regional basal myocardial peak velocities (cm/s; systolic S´, early diastolic E´, and atrial A´, strain (%), strain rate (s-1) and displacement (mm) were determined. Second harmonic imaging (SHI) was applied in order to better visualise air bubbles (Paper IV). In Paper I compiled baseline values were established before and after sternotomy for central haemodynamic and echocardiographic parameters, including the TDI myocardial motion variables velocity, strain rate, strain and displacement. Blood pressure and heart rate changed significantly after sternotomy, but the TDI derived data did not change significantly. In Paper II we report that movement artifacts of the laser Doppler myocardial perfusion measurements can be reduced, both when myocardium is normally perfused and during coronary occlusion, by using the TDI velocity registrations showing wall motion to be minimal. The optimum interval depends on the application but late systole as well as late diastole is preferred. After LVAD implantation in Paper III the flow characteristics and myocardial motion during variations in afterload TDI show that myocardial velocities decrease concomitantly with myocardial depression and are significantly correlated to native stroke volume, heart rate, systemic arterial resistance and cardiac output, but not with left ventricular size, fractional shortening or pump speed. Echocardiography together with TDI thereby offers additional means for monitoring and quantifying residual myocardial function during LVAD treatment. SHI is superior in the early detection of single air-bubbles in the ascending aorta prior to significant air embolism during manipulation of the LVAD pump speed, as shown in Paper IV. A prompt decrease in size of the left atrium during speed adjustment may be a warning that massive air embolism is imminent whereas the commonly used left atrial pressure not provide the same warning.The title of article II is in the list of publications "Correlation between laser Doppler perfusion monitoring and myocardial tissue Doppler echocardiography in the beating heart" and in the published article the title is "Myocardial tissue motion influence on laser Doppler perfusion monitoring using tissue Doppler imaging".</p

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

The place of skin cancer screening in heart transplant recipient follow-up protocols: a case series

ObjectivesFor solid organ transplant recipients the risk of skin cancer is markedly increased due to immunosuppression. Many studies propose an annual, or morefrequent, skin screening program by a dermatologist. As the number of transplant recipients increases and survival times improve, the need for screeningand rapid response (as required) access is increasing. DesignIn a quality control study we retrospectively examined the medical records of patients participating in an annual screening program between 1997 and2012. A total of 69 medical records were studied and we here describe the program and present the findings. ResultsWe found malignant melanoma in 3 cases. Cutaneous squamous cell carcinoma occurred in 16 patients and basal cell carcinoma in 12 patients. Themost frequent skin lesions were actinic keratoses, reported in 20 patients. ConclusionsIncidence rates for all diagnoses were elevated compared to the general population. Awareness of the increased risk for skin malignancies is of importanceto those involved in the care of solid organ transplant recipients. Routines for early discovery of skin tumors are needed both in the form of screening,which can also establish risk group status and give preventive education, and as rapid response access for skin lesion diagnosis and treatment

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.Funding Agencies|Swedish Research Council [2022-00584]; Swedish Cancer Society [22 2207]; Forte [2016-00081, 2018-00877]; Stockholm County Council [20200102]; China Scholarship Council [201807930004]; Robert Lundberg Memorial Foundation [2022-01161]; Zhejiang University through the Hundred Talents Program</p

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

Approaches to management of cardiovascular morbidity in adult cancer patients : cross-sectional survey among cardio-oncology experts

In cardio-oncology, a range of clinical dilemmas can be identified where high-quality evidence for management is still lacking. The aim of this project was to study clinical practices and expert approaches to several clinical cardio-oncological dilemmas regarding prediction, prevention and treatment of cardiovascular disease in adult cancer patients

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.Funding Agencies|Karolinska InstituteKarolinska Institutet</p

The place of skin cancer screening in heart transplant recipient follow-up protocols: a case series

ObjectivesFor solid organ transplant recipients the risk of skin cancer is markedly increased due to immunosuppression. Many studies propose an annual, or morefrequent, skin screening program by a dermatologist. As the number of transplant recipients increases and survival times improve, the need for screeningand rapid response (as required) access is increasing. DesignIn a quality control study we retrospectively examined the medical records of patients participating in an annual screening program between 1997 and2012. A total of 69 medical records were studied and we here describe the program and present the findings. ResultsWe found malignant melanoma in 3 cases. Cutaneous squamous cell carcinoma occurred in 16 patients and basal cell carcinoma in 12 patients. Themost frequent skin lesions were actinic keratoses, reported in 20 patients. ConclusionsIncidence rates for all diagnoses were elevated compared to the general population. Awareness of the increased risk for skin malignancies is of importanceto those involved in the care of solid organ transplant recipients. Routines for early discovery of skin tumors are needed both in the form of screening,which can also establish risk group status and give preventive education, and as rapid response access for skin lesion diagnosis and treatment