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.

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.

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.

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.

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).

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.

Effects of heart rate reduction with ivabradine on vascular stiffness and endothelial function in chronic stable coronary artery disease.

INTRODUCTION: Epidemiological and clinical studies have shown a relevant association between heart rate and cardiovascular mortality. Experimental studies identified vascular effects of heart rate reduction with the If channel inhibitor ivabradine. Therefore, the effects of heart rate reduction on endothelial function and indices of arterial stiffness were examined in patients with stable coronary artery disease in a prospective, placebo-controlled clinical crossover study. METHODS AND RESULTS: Twenty-three patients (18 men and 5 women) with a resting heart rate (HR) of at least 70 beats per minute (bpm) and stable coronary artery disease were enrolled in this study. In a cross-over design, all patients were treated with ivabradine (Iva, 7.5 mg b.i.d.) and placebo for 6 months each. Iva reduced heart rate by 11.4 bpm (Iva 58.8 ±â€Š8.2 bpm vs. placebo 70.2 ±â€Š8.3 bpm, P < 0.0001). Augmentation index (AIx75), carotid-femoral pulse wave velocity (cfPWV) and central aortic blood pressure were measured using applanation tonometry (SphygmoCor). HRR by Iva increased AIx75 by 12.4% (Iva 24.3 ±â€Š10.5% vs. placebo 21.3 ±â€Š10.1%, P < 0.05) and reduced cfPWV by 14.1% (Iva 6.3 ±â€Š1.7 m/s vs. placebo 7.3 ±â€Š1.4 m/s, P < 0.01). Iva increased mean central blood pressure by 7.8% (Iva 107.5 ±â€Š15.4 mmHg vs. placebo 99.1 ±â€Š12.2 mmHg, P < 0.001). Endothelial function was determined measuring the flow-mediated vasodilation (FMD) of the brachial artery. HRR by Iva increased FMD by 18.5% (Iva 7.3 ±â€Š2.2% vs. placebo 6.0 ±â€Š2.0%, P < 0.001). Aortic distensibility was characterized by MRI. HRR by Iva increased aortic distensibility by 33.3% (Iva 0.003 ±â€Š0.001/mmHg vs. placebo 0.002 ±â€Š0.010/mmHg, P < 0.01) and circumferential cyclic strain by 37.1% (Iva 0.062 ±â€Š0.027 vs. placebo 0.039 ±â€Š0.018, P < 0.0001). CONCLUSION: Heart rate reduction with Iva increased endothelium-dependent vasodilation and reduced arterial stiffness in patients with stable CAD. These findings corroborate and expand the results collected in experimental studies and indicate the importance of heart rate as a determinant of vascular function.