First experiences of ultrasound vector flow imaging at the femoropopliteal artery in peripheral arterial disease.

Background: The femoropopliteal artery (FPA) plays a central role in diagnosing and treating peripheral arterial disease (PAD). FPA lesions are the most frequent cause of intermittent claudication, and no other artery of the lower extremities is recanalised more frequently. Generally, ultrasound is the primary imaging tool in PAD, particularly FPA. With the development of high-frame-rate ultrasound technology in addition to traditional ultrasound modes, vector flow imaging (VFI) has provided deeper haemodynamic insights when used in the carotid artery. Here, we report the use of VFI at the FPA level in routine PAD examinations. Patients and methods: In this single-centre prospective study, we evaluated consecutive patients with PAD using B-mode imaging, colour Doppler, pulsed wave Doppler (PW) and vector flow. Hemodynamic parameters at predefined locations at the carotid artery and FPA were compared. Results: Qualitatively adequate VFI at all sites was possible in 76% of the patients with PAD. With decreasing volume flow from the common carotid artery to the internal carotid artery and from the common femoral artery via the superficial femoral artery to the popliteal artery, the correlation between VFI- and PW-derived-volume flow was high at every site. Based on different techniques, the VFI-derived values were significantly lower than the PW-derived values. The mean wall shear stress was significantly lower at all femoropopliteal sites than at the carotid sites, whereas the oscillatory shear index at the femoral site was higher than that at the carotid sites rather than at the popliteal location. Conclusions: Our findings suggest that vector flow data acquisition in the FPA is feasible in most patients with PAD. Therefore, with knowledge of the method and its limitations, VFI provides haemodynamic information beyond traditional ultrasound techniques and is a promising new tool for flow analysis in PAD.

Gender aspects in cardiooncology.

BACKGROUND: Cardiooncology is a relatively new subspeciality, investigating the side effects of cytoreductive therapies on the cardiovascular (CV) system. Gender differences are well known in oncological and CV diseases, but are less elucidated in cardiooncological collectives. METHODS: Five hundred and fifty-one patients (278 male, 273 female) with diagnosed cancer who underwent regular cardiological surveillance were enrolled in the 'MAnnheim Registry for CardioOncology' and followed over a median of 41 (95% confidence interval: 40-43) months. RESULTS: Female patients were younger at the time of first cancer diagnosis [median 60 (range 50-70) vs. 66 (55-75), P = 0.0004], while the most common tumour was breast cancer (49.8%). Hyperlipidaemia was more often present in female patients (37% vs. 25%, P = 0.001). Male patients had a higher cancer susceptibility than female patients. They suffered more often from hypertension (51% vs. 67%, P = 0.0002) or diabetes (14% vs. 21%, P = 0.02) and revealed more often vitamin D deficiency [(U/l) median 26.0 (range 17-38) vs. 16 (9-25), P = 0.002] and anaemia [(g/dl) median 11.8 (range 10.4-12.9) vs. 11.7 (9.6-13.6), P = 0.51]. During follow-up, 140 patients died (male 77, female 63; P = 0.21). An increased mortality rate was observed in male patients (11.4% vs. 14%, P = 0.89), with even higher mortality rates of up to 18.9% vs. 7.7% (P = 0.02) considering tumours that can affect both sexes compared. CONCLUSIONS: Although female patients were younger at the time of first cancer diagnosis, male patients had both higher cancer susceptibility and an increased mortality risk. Concomitant CV diseases were more common in male patients.

First experiences of local pulse wave velocity measurements in 4D-MRI in focally stented femoropopliteal arteries.

Background: In peripheral arterial disease (PAD) the femoropopliteal (FP) artery is the most frequently recanalized lower limb artery. Stent-based interventions change the biomechanical properties of FP arteries. However, no clinical tool for functional imaging is established for quantitative measurements in vivo. Four-dimensional-flow magnetic resonance imaging enables a detailed evaluation of the hemodynamics of the central and - more challenging - the peripheral arteries. The present study aimed to determine the feasibility of assessing pulse wave velocities (PWV) as a marker of vessel stiffness in PAD patients with multiple spot stents and to compare the values with age-matched subjects and young-adult healthy subjects. Patients and methods: Contrast-free 4D-flow MRI was performed in seven PAD patients with focally stented FP arteries, five age-matched subjects after exclusion of PAD, and five young, healthy adults. PWV values were calculated from flow curves by using the foot-to-foot method. Results: Four-D-flow MRI sequences offering high spatial and temporal resolution enables quantification of flow velocity measurements and estimation of PWVs. Assessment of segmental PWV as a surrogate of vascular stiffness in focally stented femoral arteries is feasible. PWV values across all groups were 15.6±5.2 m/s, 13.3±4.1 m/s, and 9.9±2.2 m/s in PAD patients, senior-aged volunteers, and young-adult volunteers respectively. PWV values in PAD patients were similar with those in the senior-aged volunteers group (15.6±5.2 vs. 13.3 ±4.1 years, p=0.43). However, when compared to the young-adult volunteers, PAD patients had a statistically significantly higher mean local PWV (15.6±5.2 m/s vs. 9.9±2.2 m/s, p<0.05). Conclusions: Calculating segmental PWV in the femoral arteries is feasible in PAD patients with focally stented FP arteries. PWV values in PAD patients were similar to those in senior-aged volunteers, both of which were higher than in young-adult volunteers.

Extent of Late Gadolinium Enhancement Predicts Thromboembolic Events in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Thromboembolic complications such as ischemic stroke or peripheral arterial thromboembolism are known complications in hypertrophic cardiomyopathy (HCM). We sought to assess the clinical and cardiovascular magnetic resonance (CMR) characteristics of patients with HCM suffering from thromboembolic events and analyzed the predictors of these unfavorable outcomes.Methods and Results:The 115 HCM patients underwent late gadolinium enhanced (LGE) CMR and were included in the study. Follow-up was 5.6±3.6 years. The primary endpoint was the occurrence of thromboembolic events (ischemic stroke or peripheral arterial thromboembolism). It occurred in 17 (14.8%) patients (event group, EG), of whom 64.7% (11) were men. During follow-up, 10 (8.7%) patients died. Patients in the EG showed more comorbidities, such as heart failure (EG 41.2% vs. NEG (non-event group) 14.3%, P<0.01) and atrial fibrillation (AF: EG 70.6% vs. NEG 36.7%, P<0.01). Left atrial end-diastolic volume was significantly higher in the EG (EG 73±24 vs. NEG 50±33 mL/m2, P<0.01). Both the presence and extent of LGE were enhanced in the EG (extent% EG 23±15% vs. NEG 8±9%, P<0.0001). No patient without LGE experienced a thromboembolic event. Multivariate analysis revealed AF and LGE extent as independent predictors. CONCLUSIONS: LGE extent (>14.4%) is an independent predictor for thromboembolic complications in patients with HCM and might therefore be considered as an important risk marker. The risk for thromboembolic events is significantly elevated if accompanied by AF.

Prevalence of abdominal aortic aneurysm and associated lower extremity artery aneurysm in men hospitalized for suspected or known cardiopulmonary disease.

BACKGROUND: AAA is a disease affecting predominantly male patients ≥65 years and its dreaded complications such as rupture led to population-based screening programs as preventive measure. Nonetheless, the supposed prevalence may have been overestimated, so that targeted screening of high risk populations may be more effective. This study was performed to evaluate the prevalence of abdominal aortic aneurysm (AAA) of an inpatient high-risk cohort and to estimate the co-prevalence of lower extremity arterial aneurysms. METHODS: Participants: 566 male inpatients, ≥ 65 years of age, hospitalized for suspected or known cardiopulmonary disease. Primary and secondary outcome measures: Maximal infrarenal aortic diameters using abdominal ultrasound (leading edge to leading edge method). Upon detection of an AAA (diameter ≥ 30 mm), the lower extremity arteries were examined with regard to associated aneurysms. RESULTS: In 40 of 566 patients (7.1%) AAAs were detectable. Fourteen patients (2.5%) had a first diagnosis of AAA, none of which was large (> 55 mm), the remaining 26 patients were either already diagnosed (14 patients, 2.5%) or previously repaired (12 patients, 2.1%). The three most common main diagnoses at discharge were acute coronary syndrome (43.3%), congestive heart failure (32.2%), and chronic obstructive pulmonary disease (12%). The cohort showed a distinct cardiovascular risk profile comprising arterial hypertension (82.9%), diabetes mellitus (44.4%), and a history of smoking (57.6%). In multivariate analysis, three-vessel coronary artery disease (Odds ratio (OR): 4.5, 95% confidence interval (CI): 2.3-8.9, p <  0.0001) and history of smoking (OR: 3.7, CI: 1.6-8.6, p <  0.01) were positively associated with AAA, while diabetes mellitus (OR: 0.5, CI: 0.2-0.9, p = 0.0295) showed a negative association with AAA. Among the subjects with AAA, we found two large iliac and two large popliteal aneurysms. CONCLUSION: Ultrasound screening in male inpatients, hospitalized for suspected or known cardiopulmonary disease, revealed a high AAA prevalence in comparison to the present epidemiological screening programs. There was a moderate proportion of newly-screen detected AAA and additional screening of the lower extremity arteries yielded some associated aneurysms with indication for possible intervention.

Protective effect of acquired long QT syndrome in Takotsubo syndrome.

BACKGROUND: Clinical variables that predict long-term mortality and recurrence of Takotsubo syndrome (TTS) are not completely understood as the role of acquired corrected QT interval (QTc) prolongation. AIM: To detect the prevalence of QTc interval prolongation in patients with TTS and to evaluate its long-term prognostic impact. METHODS: QTc intervals were analysed in 105 patients presenting with symptoms of TTS. These patients were included in an ongoing retrospective cohort database. The cohort was subsequently subdivided into two groups based on the presence (long QT (LQT) group, n = 73, 69.52%) or absence (non-long QT (non-LQT) group, n = 32, 30.43%) of QTc interval prolongation. Patients were followed up over a mean period of 4.2 years. The rate of life-threatening arrhythmia during the first 30 days in the LQT group was comparable with the non-LQT group (10.9 vs 12.5%), whereas in-hospital mortality and 30-day mortality occurred less frequently in the LQT group (2.7 vs 18.75%, P < 0.01). RESULTS: During this time span, 17 (23.3%) patients with acquired LQT syndrome died, whereas 14 (43.7%) patients with non-LQT duration died. Kaplan-Meier survival rates were significantly higher in the LQT group than those in the non-LQT group (Log-rank-test, P = 0.02). On multivariate analysis, the QTc interval was an independent negative predictor of all-cause mortality (P = 0.02). CONCLUSION: The QTc interval at admission is an independent negative predictor of long-term adverse outcome in patients with TTS.

Therapy optimization in patients with heart failure: the role of the wearable cardioverter-defibrillator in a real-world setting.

BACKGROUND: The wearable cardioverter-defibrillator (WCD) has emerged as a valuable tool to temporarily protect patients at risk for sudden cardiac death (SCD). The aim of this study was to determine the value of the WCD for therapy optimization of heart failure patients. METHODS: One hundred five consecutive patients that received WCD between 4/2012 and 9/2016 were included in the study. All patients were followed for clinical outcome and echocardiographic parameters during WCD therapy and had continued follow-up after WCD therapy, irrespective of subsequent implantable cardioverter-defibrillator (ICD) implantation. RESULTS: The most common indication for WCD were newly diagnosed ischemic (ICM) or non-ischemic cardiomyopathy (NICM) with left ventricular ejection fraction (LVEF) ≤35%. Mean WCD wear time was 68.8 ± 50.4 days with a mean daily use of 21.5 ± 3.5 h. Five patients (4.8%) received a total of five appropriate WCD shocks. During WCD wear, patients with ICM and NICM showed significant improvement in LVEF, reducing the proportion of patients with a need for primary preventive ICD implantation to 54.8% (ICM) and 48.8% (NICM). An ICD was finally implanted in 51.4% of the study patients (24 trans-venous ICDs, 30 subcutaneous ICDs). After discontinuation of WCD therapy, all patients were followed for a mean of 18.6 ± 12.3 months. 5.6% of patients with implanted ICDs received appropriate therapies. No patient with subcutaneous ICD needed change to a trans-venous device. None of the patients without an implanted ICD suffered from ventricular tachyarrhythmias and no patient died suddenly. In patients with NICM a significant LVEF improvement was observed during long-term follow-up (from 34.8 ± 11.1% to 41.0 ± 10.2%). CONCLUSIONS: WCD therapy successfully bridged all patients to either LVEF recovery or ICD implantation. Following WCD, ICD implantation could be avoided in almost half of the patients. In selected patients, prolongation of WCD therapy beyond 3 months might further prevent unnecessary ICD implantation. The WCD as an external monitoring system contributed important information to optimize device selection in patients that needed ICD implantation.

Hemodynamic and Stress Response After Sound Intervention with Different Headphone Systems: A Double-Blind Randomized Study in Healthy Volunteers Working in the Health Care Sector.

Objectives: Two headphone systems using different sound systems were compared to investigate the effects of a sound intervention on cardiovascular parameters, indicators of stress, and subjective feelings. Methods: One hundred volunteers who work in the health care sector reporting elevated workplace-related stress were enrolled and randomized to a 12-min sound intervention (classical music) with either conventional headphones ("MEZE 99 Classic") or with the same-but internally modified-headphone (called "Lautsaenger"). Cardiovascular parameters were measured with the VascAssist2.0, both before and after sound interventions. In addition, participants were asked to complete questionnaires on burnout risk and emotions/stress. Results: The study population consisted mainly of female participants (n = 83), with the majority being students (42%). Median age was 32.5 years (range 21-71). In terms of cardiovascular parameters, a significant reduction in aortic pulse wave velocity, as measure of arterial stiffness, and heart rate was observed within both treatment arms. Both systolic blood pressure and arterial flow resistance were reduced by sound intervention, while these effects were only documented with Lautsaenger. Treatment groups were comparable in terms of subjective feedback by participants: a significant increase in emotional wellbeing was achieved with both headphone systems. Conclusions: A single short-term sound intervention seems to be able to achieve objective cardiovascular improvements in healthy volunteers reporting subjective symptoms of workplace-related stress, using two different headphone systems. Moreover, significant emotional improvement was reported within both arms. Trial Registration: ISRCTN registry 70947363, date of registration August 13, 2021.

Comparison of Functional and Morphological Estimates of Vascular Age.

BACKGROUND/AIM: Vascular age (VA) is an emerging metric in preventive cardiovascular (CV) medicine. VA can be derived from morphological parameters such as carotid intima-media thickness (CIMT), or functional parameters such as pulse wave analysis (PWA), which celebrates its 100th birthday. This study aimed to investigate whether the results of both approaches are comparable. PATIENTS AND METHODS: On the occasion of the double 100th anniversary of PWA and the Mannheim Clinic, 100 volunteers underwent a) bilateral CIMT assessment using high-resolution ultrasound and b) oscillometric PWA at the brachial forearm site. The respective VAs were calculated using previously published equations. RESULTS: Median age of the participants was 53.6 years (range=39.8-62.6 years), and 56% were female. Median CIMT was 632.5 µm (range=548.8-730.0 µm). Median PWA-derived VA was 55.3 years (36.5-70.5 years). Different values were obtained for CIMT-derived VA, depending on the reference cohort used as calculation basis, ranging from median 43.7 (26.2-59.5 years) to median 64.0 years (43.5-82.1 years). In 46% of the participants divergent VAs were found, that is, the calculated age was higher according to one method and lower according to the other. Correlation analysis revealed a strong dependence of VA (both PWA- and CIMT-derived) and chronological age, as well as an increase in CV risk factors and the detection of plaques with age. CONCLUSION: Different approaches for estimating VA are not comparable and often produce contradictory results. The current methods and their validity must be critically assessed if they are not standardized.

Description of a new clinical syndrome: thoracic constriction without evidence of the typical funnel-shaped depression-the "invisible" pectus excavatum.

Pectus excavatum (PE) is a congenital malformation with a funnel-shaped depression of the sternum that can lead to cardiac symptoms. However, there are patients with thoracic constriction (defined as elevated Haller-Index > 3.25 determined by cardiac magnetic resonance imaging (CMR)) without visible evidence of PE, leading to similar complaints. Between January 2004 till June 2020, patients who underwent CMR for further evaluation of the heart, due to cardiac symptoms were enrolled and compared to controls. Biventricular global strain analysis was assessed using feature tracking (CMR-FT). ECG and/or Holter recordings were performed to detect rhythm events. Cardiac symptoms were evaluated in detail using a questionnaire. Finally, 88 patients (male 35, female 53) with elevated Haller-Index (3.9 ± 0.8) were included and compared to CMR data from 25 individuals with confirmed PE and 25 healthy controls (HC). Mean age at time of CMR was 35 ± 16 years. The most common symptoms at presentation were palpitations (41%), followed by dyspnea (24%) and atypical chest pain (14%). Three patients (3%) had atrial fibrillation or atrial flutter. Concomitant phenomena were pericardial effusion in 39% and mitral valve prolapse (MVP) in 27% of the study cohort. While there were no differences in left ventricular function or volumes, right ventricular function (RVEF) was significantly lower in patients with internal PE compared to HC (RVEF (%) 50 ± 5 vs 59 ± 4, p < 0.01). Strain analysis revealed only discrete changes in RV strain, implying a purely mechanical problem in the absence of structural changes. RV dimensions were negatively correlated with the size of thoracic indices (r = 0.41), reflecting the extent of thoracic constriction. MVP was more prevalent in patients with greater thoracic indices (r = 0.24). The described cohort, referred to as internal PE because of the absence of external changes, showed similar CMR morphologic findings as patients with real PE (especially altered dimensions of the right heart and a lower RVEF). In addition, there was a high incidence of rhythm disturbances, such as extrasystoles or arrhythmias. In one-third of the study cohort additional abnormalities such as pericardial effusion or MVP were present, with MVP being found more frequently in patients with larger thoracic indices, suggesting a possible common pathogenesis.Trial registration: ISRCTN registry, ISRCTN15355937, retrospectively registered 03.06.2022, https://www.isrctn.com/ISRCTN15355937?q=15355937&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10 .

Patients with Advanced Pancreatic Cancer Treated with Mistletoe and Hyperthermia in Addition to Palliative Chemotherapy: A Retrospective Single-Center Analysis.

This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in the study, whereof 142 patients (68.9%) received palliative chemotherapy (gemcitabine/nab-paclitaxel 33.8%; FOLFIRINOX 35.9%; gemcitabine 30.3%) while the remainder were treated with best supportive and integrative care. Integrative therapies were used in 117 of 142 patients (82.4%) in addition to conventional chemotherapy, whereby mistletoe was used in 117 patients (82.4%) and hyperthermia in 74 patients (52.1%). A total of 107/142 patients (86.3%) died during the observation period, whereby survival times differed significantly depending on the additional use of integrative mistletoe or hyperthermia: chemotherapy alone 8.6 months (95% CI 4.7-15.4), chemotherapy and only mistletoe therapy 11.2 months (95% CI 7.1-14.2), or a combination of chemotherapy with mistletoe and hyperthermia 18.9 months (95% CI 15.2-24.5). While the survival times observed for patients with advanced pancreatic cancer receiving chemotherapy alone are consistent with pivotal phase-III studies and German registry data, we found significantly improved survival using additional mistletoe and/or hyperthermia.

Effects of a Sound Intervention on Physical and Emotional Well-Being in Patients with Cancer: A Prospective Randomized Trial.

AIM: Cancer remains a disease with a significant impact on morbidity and mortality but also on quality of life. This prospective randomized pilot study investigated the effects of a sound intervention on physical and emotional well-being in outpatients with cancer. METHODS: Two self-applied sound interventions were used for this purpose, either active "music playing" with a body monochord or passive sound intervention with headphones to listen to a given music compilation. Interventions were carried out over a period of 4 weeks for at least 15 min in the evening before bedtime. The following self-assessment questionnaires were completed both at baseline and after 4 weeks to evaluate the response: the Pittsburgh Sleep Quality Index (PSQI), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Visual Analogue Scale (VAS) for pain and fatigue, and the Fear of Progression (FoP) questionnaire. Primary endpoint of this exploratory trial was to describe the rate of patients with improvement in at least one dimension without worsening of any other. RESULTS: 73 patients (29 male, 44 female) were included in the study and randomized to either active (n = 34, 47%) or passive sound intervention (n = 39, 53%). Median age was 52.0 years (range 21-79). Fourteen patients (19%) stated that they were musically active. The sound intervention was carried out on a median of 26 days (range 5-28). A higher percentage of patients in the passive group reached the primary endpoint: n = 15 (39%) versus n = 9 (27%). Response differences in favour of the passive group were seen with the VAS fatigue and with QLQ-30 questionnaires. Overall, an improvement in QLQ-30 questionnaire was seen in 12 patients (31%) in the passive group versus 3 patients (9%). Moreover, sound intervention significantly improved social functioning and shortness of breath in the passive group according to QLQ-C30. Significant improvements were also noticed in the passive group in terms of affective reactions as a domain of the FoP questionnaire. No effects on pain or sleep quality could be observed. CONCLUSION: A 4-week self-administered sound intervention was feasible in outpatients suffering from cancer. Using a panel of 5 questionnaires, passive sound interventions appeared to be more likely to positively influence patient-reported outcomes. In particular, a positive impact was documented in social functioning and fatigue.

Adverse Cardiovascular Effects of Anti-tumor Therapies in Patients With Breast Cancer: A Single-center Cross-sectional Analysis.

BACKGROUND/AIM: Cardiotoxicity due to antitumor therapy is a dreaded complication and could thus impact the prognosis of patients with breast cancer. This study sought to analyze the occurrence of adverse cardiovascular events and to identify potential risk factors. PATIENTS AND METHODS: A total of 136 patients with breast cancer were divided into two groups based on the occurrence of treatment-related cardiovascular toxicity [event 47 (35%) vs. no event 89 (65%)]. Patients were followed over a median of 45 months (range=37-83 months). RESULTS: Most common events were thromboembolic complications (26%), followed by heart failure (15%) and acute toxic cardiomyopathy (5%), with a reduced left ventricular ejection fraction [LVEF (%), no event 59±5.0 vs. event 55±11, p=0.01 ]. Patients with leftsided breast cancer and an advanced stage disease had a higher risk of developing adverse cardiovascular events. The highest risk was found for patients with a high number of cardiovascular risk factors. In addition to LVEF, mitral annular plane systolic excursion was also significantly reduced in the event group, while there was a trend for higher global longitudinal strain. During follow-up, 26 patients (19.1%) deceased, whereof 12 had a treatment-related cardiovascular event, but without statistical difference. CONCLUSION: Treatment-related cardiovascular events are relatively common in about one third of patients with breast cancer. Women with a cardiovascular risk profile or an advanced stage disease had a higher risk for adverse events. Despite the treatment-related cardiac deterioration, no difference in mortality was observed during follow up.

Diagnostic Value of sST2, VCAM-1, and Adiponectin in Patients with Breast Cancer to Predict Anti-Tumour Treatment-Related Cardiac Events: A Pilot Study.

AIM: The present exploratory study investigated the diagnostic value of inflammatory markers in patients with breast cancer to predict anti-tumour treatment-related cardiac events. METHODS: Twenty-one patients with breast cancer were enrolled in this prospective observational study and followed over 6 months. Transthoracic echocardiography and measurement of cardiac (N-terminal prohormone of brain natriuretic peptide (NT-proBNP), troponin I (TnI)) and inflammatory biomarkers (vascular adhesion molecule 1 (VCAM-1), soluble suppression of tumorigenesis-2 (sST2), adiponectin) was performed at 3-month intervals (baseline, follow-up, final visit). Cardiac events were defined as decrease in left ventricular ejection fraction (LVEF, decrease by 10% or <50%) or increase in global longitudinal strain (GLS, increase by 15% or > -16%), as a more sensitive marker of LV function. RESULTS: Cardiac deterioration was observed in 9 out of 21 patients (event group). While LVEF did not differ significantly between the two groups (event vs. no event) at any visit, GLS was significantly higher during follow-up (follow-up: event -16 ± 3.3% vs. no event -18 ± 1.6%, p = 0.04; final visit: event -16 ± 2.1% vs. no event -19 ± 1.9%, p = 0.003). NT-proBNP was numerically higher in patients with a cardiac event during all visits, with NT-proBNP negatively correlated with LVEF and MAPSE (both r = -0.33, p = 0.02), whereas GLS (r = 0.40, p = 0.006), TnI (r = 0.44, p = 0.001), and VCAM-1 (r = 0.48, p = 0.003) showed a positive association with NT-proBNP. In comparison, higher VCAM-1 and sST2 concentrations were detected in the event group at both baseline and the final visit, with a significant difference for baseline (VCAM-1: p = 0.02; sST2: p = 0.03). Adiponectin was also lower in patients with a treatment-related event. Thresholds for VCAM-1 >762 ng/mL and sST2 >18.7 ng/mL, as detected by ROC analysis, correlated best with the primary endpoint. CONCLUSION: Cardiac events during anti-tumour treatment in patients with breast cancer are relatively common. Inflammatory markers such as VCAM-1 or sST2 were associated with an increased likelihood for occurrence of a treatment-related event, which may therefore hold the promise to better identify patients at high risk.

Prediction of cardiac events with non-contrast magnetic resonance feature tracking in patients with ischaemic cardiomyopathy.

AIMS: The aim of this study was to evaluate the prognostic value of feature tracking (FT) derived cardiac magnetic resonance (CMR) strain parameters of the left ventricle (LV)/right ventricle (RV) in ischaemic cardiomyopathy (ICM) patients treated with an implantable cardioverter-defibrillator (ICD). Current guidelines suggest a LV-ejection fraction ≤35% as major criterion for ICD implantation in ICM, but this is a poor predictor for arrhythmic events. Supplementary parameters are missing. METHODS AND RESULTS: Ischaemic cardiomyopathy patients (n = 242), who underwent CMR imaging prior to primary and secondary implantation of ICD, were classified depending on EF ≤ 35% (n = 188) or >35% (n = 54). FT parameters were derived from steady-state free precession cine views using dedicated software. The primary endpoint was a composite of cardiovascular mortality (CVM) and/or appropriate ICD therapy. There were no significant differences in FT-function or LV-/RV-function parameters in patients with an EF ≤ 35% correlating to the primary endpoint. In patients with EF > 35%, standard CMR functional parameters, such as LV-EF, did not reveal significant differences. However, significant differences in most FT parameters correlating to the primary endpoint were observed in this subgroup. LV-GLS (left ventricular-global longitudinal strain) and RV-GRS (right ventricular-global radial strain) revealed the best diagnostic performance in ROC curve analysis. The combination of LV-GLS and RV-GRS showed a sensitivity of 85% and a specificity of 76% for the prediction of future events. CONCLUSIONS: The impact of FT derived measurements in the risk stratification of patients with ICM depends on LV function. The combination of LV-GLS/RV-GRS seems to be a predictor of cardiovascular mortality and/or appropriate ICD therapy in patients with EF > 35%.

Blood Cholesterol and Outcome of Patients with Cancer under Regular Cardiological Surveillance.

Cardiovascular (CV) diseases and cancer share several similarities, including common risk factors. In the present investigation we assessed the relationship between cholesterol levels and mortality in a cardiooncological collective. In total, 551 patients receiving anticancer treatment were followed over a median of 41 (95% CI 40, 43) months and underwent regular cardiological surveillance. A total of 140 patients (25.4%) died during this period. Concomitant cardiac diseases were more common in patients who deceased (53 (37.9%) vs. 67 (16.3%), p < 0.0001), as well as prior stroke. There were no differences in the distribution of classical CV risk factors, such as hypertension, diabetes or nicotine consumption. While total cholesterol (mg/dL) was significantly lower in patients who deceased (157 ± 59 vs. 188 ± 53, p < 0.0001), both HDL and LDL cholesterol were not differing. In addition, cholesterol levels varied between different tumour entities; lowest levels were found in patients with tumours of the hepatopancreaticobiliary system (median 121 mg/dL), while patients with melanoma, cerebral tumours and breast cancer had rather high cholesterol levels (median > 190 mg/dL). Cholesterol levels were significantly lower in patients who died of cancer; lowest cholesterol levels were observed in patients who died of tumours with higher mitotic rate (mesenchymal tumours, cerebral tumours, breast cancer). Cox regression analysis revealed a significant mortality risk for patients with stem cell transplantation (HR 4.31) and metastasised tumour stages (HR 3.31), while cardiac risk factors were also associated with a worse outcome (known cardiac disease HR 1.58, prior stroke/TIA HR 1.73, total cholesterol HR 1.70), with the best discriminative performance found for total cholesterol (p = 0.002).

Prognostic Impact of Pretherapeutic Hemoglobin Levels on All-cause Mortality in Cardiooncology.

BACKGROUND/AIM: We investigated the prognostic impact of hemoglobin (Hb) levels in tumour patients receiving routine cardiological surveillance during anticancer treatment. The aim of the study was to identify independent predictors of all-cause mortality in a cardio-oncological collective. PATIENTS AND METHODS: A total of 551 patients (273 males, 278 females) were enrolled in the Mannheim Registry for Cardiooncology and were included in the present analysis. Median follow-up was 41 months (95% CI=40-43). RESULTS: Patients were grouped according to a pretherapeutic Hb-threshold (determined by ROC analysis) into cohorts with Hb<11.4 g/dl (n=232, 42.1%) and Hb >11.4 g/dl (n=319, 57.9%). Patients with lower Hb levels were older at the time of first diagnosis (63.8±14.4 vs. 59.9±15.4 years, p=0.003) and were more likely to have advanced tumour stages (92 (39.7%) vs. 83 (26.0%), p=0.0007). There were no differences regarding cardiovascular comorbidities such as hypertension or diabetes, while chronic kidney disease was more common in patients with lower Hb. Anticoagulants were used more often in patients with lower Hb (88 (37.9%) vs. 84 (26.3%), p=0.01). Left ventricular ejection fraction (LVEF) was lower in patients with Hb <11.4 g/dl (51.9±11.0% vs. 55.1±9.7%, p=0.003). Correlation analysis revealed a significant correlation of Hb levels and LVEF (R2=0.07, p<0.0001). During follow-up, a total of 140 patients (25.4%) were deceased, with significantly more deaths occurring in the group of patients with low Hb values [108 (46.6%) vs. 32 (10.0%), p<0.0001]. In multivariable analysis, Hb was identified as independent predictor for mortality (OR=5.3, CI=0.41-0.89, p<0.0001). CONCLUSION: Low Hb levels were identified as an independent predictor of mortality in patients with cancer. There was a significant correlation of Hb and LVEF, suggesting that low Hb values are not solely due to anaemia, but rather reflect the severity of cancer.

Effects of selective heart rate reduction with ivabradine on LV function and central hemodynamics in patients with chronic coronary syndrome.

OBJECTIVES: We assessed left ventricular (LV) function and central hemodynamic effects in patients with a heart rate (HR) at rest of ≥70 beats per minute (bpm) and chronic coronary syndrome (CCS) after long-term treatment with ivabradine compared to placebo by cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS: In a randomized, double-blinded, prospective cross-over design, 23 patients (18 male, 5 female) were treated with ivabradine (7.5 mg bid) or placebo for 6 months. CMR imaging was performed at baseline and after 6 and 12 months to determine LV functional parameters.Mean resting HR on treatment with ivabradine was 58 ± 8.2 bpm and 70.2 ± 8.3 bpm during placebo (p < 0.0001).There was no difference in systolic LV ejection fraction (ivabradine 57.4 ± 11.2% vs placebo 53.0 ± 10.9%, p = 0.18), indexed end-diastolic (EDVi) or end-systolic volumes (ESVi). Indexed stroke volume (SVi) (ml/m2) remained unchanged after treatment with ivabradine. Volume time curve parameters reflecting systolic LV function (peak ejection rate and time) were unaffected by ivabradine, while both peak filling rate (PFR) and PFR/EDV were significantly increased. Mean aortic velocity (cm/s) was significantly reduced during treatment with ivabradine (ivabradine 6.7 ± 2.7 vs placebo 9.0 ± 3.4, p = 0.01). Aortic flow parameters were correlated to parameters of vascular stiffness. The strongest correlation was revealed for mean aortic velocity with aortic distensibility (AD) (r = -0.86 [-0.90 to -0.85], p < 0.0001). CONCLUSION: Long-term reduction of HR with ivabradine in patients with CCS improved diastolic function and reduced mean aortic flow velocity.

Differential Effects of Sound Intervention and Rest on Cardiovascular Parameters in Cancer Patients: A Randomized Cross-over Trial.

BACKGROUND: Music therapy or sound interventions were shown to confer beneficial effects in patients with cancer for instance in terms of pain or fear relief and improvement of other patient reported outcomes. Cardiovascular parameters, especially heart rate variability (HRV) were found to have prognostic implications in cancer patients. In this trial we aimed to investigate the effects of a sound intervention on cardiovascular parameters compared to rest in patients with cancer. METHODS AND RESULTS: Using a randomized cross-over design, 52 patients (male 13, female 39) with cancer were recruited to receive both a 15-minute sound intervention and a 15-minute rest intervention within 4 weeks with at least a one-week blanking period. Cardiovascular parameters (among others HRV, aortic pulse wave velocity [PWV], augmentation index [Aix], aortic blood pressure [BP], heart rate [HR]) were assessed immediately before (pre) and after (post) the intervention had taken place. HRV (Root mean square of successive RR interval differences [RMSSD, ms]) significantly increased, during sound intervention (median RMSSD pre 24 [range 5-112] vs post 22 [range 9-141], P = .03). Likewise, median PWV, as a direct marker of arterial stiffness, was significantly reduced by sound intervention ([m/s] pre 8.5 [range 5.6-19.6] vs post 8.3 [range 5.6-15.6], P = .04). For both parameters no statistically significant change during rest was observed. HR was lowered by both, rest (P < .0001) and sound intervention (P = .02), with a more pronounced effect by rest. A significant increase in systolic aortic blood pressure was shown by rest ([mmHg] median 101 [range 78-150] vs post median 103 [range 71-152], P = .04) but not during sound intervention (P = .59), while rest intervention led to a decrease in resistance index (pre median 33 [range 13-92] vs post median 32 [11-84], P = .02). CONCLUSION: In comparison with rest, a single sound intervention in patients with cancer improved cardiovascular parameters commonly associated with increased stress levels. Studies with longer follow-up and multiple interventions are warranted. TRIAL REGISTRATION: ISRCTN registry 70947363.

Risk stratification of patients with Brugada syndrome: the impact of myocardial strain analysis using cardiac magnetic resonance feature tracking.

OBJECTIVE: This study evaluated the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in patients with Brugada syndrome (BrS) to detect subclinical alterations and predict major adverse events (MAE). METHODS: CMR was performed in 106 patients with BrS and 25 healthy controls. Biventricular global strain analysis was assessed using CMR-FT. Patients were followed over a median of 11.6 [8.8 ± 13.8] years. RESULTS: The study cohort was subdivided according to the presence of a spontaneous type 1 ECG (sECG) into sBrS (BrS with sECG, n = 34 (32.1%)) and diBrS (BrS with drug-induced type 1 ECG, n = 72 (67.9%)). CMR-FT revealed morphological differences between sBrS and diBrS patients with regard to right ventricular (RV) strain (circumferential (%) (sBrS -7.9 ± 2.9 vs diBrS - 9.5 ± 3.1, p = 0.02) and radial (%) (sBrS 12.0 ± 4.3 vs diBrS 15.4 ± 5.4, p = 0.004)). During follow-up, MAE occurred in 11 patients (10.4%). Multivariable analysis was performed to identify independent predictors for the occurrence of events during follow-up. The strongest predictive value was found for RV circumferential strain (OR 3.2 (95% CI 1.4 - 6.9), p = 0.02) and RVOT/BSA (OR 3.1 (95% CI 1.0 - 7.0), p = 0.03). CONCLUSIONS: Myocardial strain analysis detected early subclinical alterations, prior to apparent changes in myocardial function, in patients with BrS. While usual functional parameters were within the normal range, CMR-FT revealed pathological results in patients with an sECG. Moreover, RV circumferential strain and RVOT size provided additional prognostic information on the occurrence of MAE during follow-up, which reflects electrical vulnerability.