The association of catestatin and endocan with the effects of cardiac shock wave therapy: Biomarker sub-study of the randomized, sham procedure-controlled trial.

Introduction: Cardiac shock-wave therapy (CSWT) is a non-invasive regenerative treatment method based on low-frequency ultrasound waves, which stimulate angiogenesis. Current data about the effects of revascularization procedures on angiogenesis biomarkers is limited. Recently, an association of catestatin and endocan with coronary collateral development was shown in several trials. In this study, we aimed to evaluate the impact of CSWT on the dynamics of catestatin and endocan levels and to assess their correlation with parameters of myocardial perfusion and function. Methods: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria (NCT02339454). We measured biomarkers in 48 patients with stable angina (24 patients of CSWT group, 24 patients of sham-procedure group). Additionally, patients were divided into responders and non-responders according to improvement in myocardial perfusion and/or contractility assessed by myocardial scintigraphy and dobutamine echocardiography (30 and 13 patients, respectively). The blood samples were collected at baseline, after the last treatment procedure (9th treatment week) and at 6-month follow-up to evaluate biomarkers concentration and stored at -80° until analysis. Serum catestatin and endocan levels were determined by commercially available ELISA kits. Results: Serum catestatin concentration significantly increased in all patients. While endocan levels significantly decreased in the responders sub-group. The increase in catestatin levels at 9th week and 6 months was positively associated with improvement in summed difference score (rho = 0.356, p = 0.028) and wall motion score, WMS (rho = 0.397, p = 0.009) at 6 months in the whole study population. Meanwhile, the decrease in endocan levels over 6 months was positively correlated with improvement in WMS at 3- and 6- months (r = 0.378, p = 0.015 and r = 0.311, p = 0.045, respectively). ROC analysis revealed that a change at 6 months in catestatin and endocan levels significantly predicted improvement in myocardial perfusion and contractile function with 68.9% sensitivity and 75.0% specificity (p = 0.039) and 51.7% sensitivity, and 91.7% specificity (p = 0.017), respectively. Baseline endocan concentration and its change at 6 months predicted response to CSWT with 68.8% sensitivity and 83.3% specificity (p = 0.039) and 81.3% sensitivity and 100% specificity (p < 0.0001), respectively. Conclusion: This study demonstrates the association of increase in catestatin and decrease in endocan levels with the improvement of myocardial perfusion and contractile function. The potential predictive value of catestatin and endocan dynamics for the response to regenerative therapy is shown.

Intravenous r-tPA Dose Influence on Outcome after Middle Cerebral Artery Ischemic Stroke Treatment by Mechanical Thrombectomy.

Background and Objectives: Pretreatment with intravenous thrombolysis (IVT) is still recommended in all eligible acute ischemic stroke patients with large-vessel occlusion before mechanical thrombectomy (MTE). However, the added value and safety of bridging therapy versus direct MTE remains controversial. We aimed at evaluating the influence of r-tPA dose level in patients with middle cerebral artery (MCA) occlusion treated with MTE. Materials and Methods: We prospectively compared clinical and radiological outcomes in 38 bridging patients, with 65 receiving direct MTE for MCA stroke admitted to Vilnius University Hospital Santaros Clinics. Following our protocol, r-tPA infusion was stopped just before MTE in the operating room. Therefore, we divided all bridging patients into three groups according to the amount of r-tPA they received: bolus, partial dose or full dose. Functional independence at 90 days was assessed by a modified Rankin Scale score, i.e., from 0-2. The safety outcomes included 90-day mortality and any intracerebral hemorrhage (ICH). Results: Baseline characteristics and functional outcome at 90 days did not differ between the bridging and direct MTE groups. Shorter MTE procedure and hospitalization time (p = 0.025 and p = 0.036, respectively) were observed in the direct MTE group. An IVT treatment subgroup analysis showed higher rates of symptomatic ICH (p < 0.001) and longer intervals between imaging to MTE (p = 0.005) in the full r-tPA dose group. Conclusions: In patients with an MCA stroke, direct MTE seems to be a safe and equally effective as bridging therapy. The optimal r-tPA dose remains unclear. Randomized trials are needed to accurately evaluate the added value of r-tPA in patients treated with MTE.

Is Abdominal Aortic Aneurysm Behavior after Endovascular Repair Associated with Aneurysm Wall Density on Computed Tomography Angiography?

Background and objectives: Abdominal aortic aneurysm (AAA) growth is unpredictable after the endovascular aneurysm repair (EVAR). Continuing aortic wall degradation and weakening due to hypoxia may have a role in post-EVAR aneurysm sac growth. We aimed to assess the association of aortic wall density on computed tomography angiography (CTA) with aneurysm growth following EVAR. Materials and Methods: A total of 78 patients were included in the study. The control group consisted of 39 randomly assigned patients without aortic pathology. Post-EVAR aneurysm sac volumes on CTA were measured twice during the follow-up period to estimate aneurysm sac behavior. A maximum AAA sac diameter, aortic wall and lumen densities in Hounsfield units (HU) on CTA were measured. A relative aortic wall density (the ratio of aortic wall to lumen densities) was calculated. A statistical data analysis was performed using standard methods. Results: An increase in the AAA sac volume was observed in 12 (30.8%) cases. Median relative aortic wall density on CTA scores in both the patient and the control group at the level of the diaphragm were similar: 0.15 (interquartile range (IQR), 0.11-0.18) and 0.16 (IQR 0.11-0.18), p = 0.5378, respectively. The median (IQR) relative aortic wall density score at the level of the maximum AAA diameter in the patient group was lower than at the level below renal arteries in the control group: 0.10 (0.07-0.12) and 0.17 (0.12-0.23), p < 0.0001, respectively. The median (IQR) relative growing AAA sac wall density score was lower than a relative stable/shrinking AAA sac wall density score: 0.09 (0.06-0.10) and 0.11 (0.09-0.13), p = 0.0096, respectively. Conclusions: A lower aortic aneurysm wall density on CTA may be associated with AAA growth after EVAR.

Arterial Destiffening Starts Early after Renal Artery Denervation.

INTRODUCTION: Renal artery denervation (RDN) is a new widely discussed method in treatment of hypertension. Most of the RDN studies assessed BP and arterial changes 3 and 6 months after the procedure, but there is a lack of trials that investigated early changes after RDN. AIM: To investigate aortic stiffness 24-48 hours after the procedure and thus to examine whether RDN might have an early additive value for a cardiovascular risk decline beyond the lowering of blood pressure. METHODS: RDN was performed for 73 patients with resistant hypertension. Arterial stiffness and central haemodynamics were measured before the procedure, the next day after the procedure, and subsequently after 1, 3, 6, and 12 months. RESULTS: Within 48 hours, RDN significantly reduced aortic pulse wave velocity (AoPWV) from 11.3±2.7 to 10.3±2.6 m/s (p=0.001); reduction was sustained at months 1, 3, 6, and 12. Early changes in the AoPWV value did not correlate with changes in office systolic or diastolic BP (p=0.45; p=0.33). Furthermore, the higher the initial AoPWV value, the greater the reduction of AoPWV observed after 6 months: Q1 8.4±1, Δ0.05±1.6 / Q2 10.1±0.4, Δ1.1±1.4 / Q3 12.2±0.8, Δ1.8±1.7 / Q4 15.3±1.7, Δ2.8±2.1 (p=0.002). CONCLUSIONS: Early and sustained effects on AoPWV observed in our study suggest that RDN may have additional effects on reducing arterial stiffness and cardiovascular risk.

Aortic sac enlargement after endovascular aneurysm repair: volume-related changes and the impact of intraluminal thrombus.

PURPOSE: Abdominal aortic aneurysm (AAA) growth after endovascular aneurysm repair (EVAR) is still unpredictable. The issue of optimal frequency of computed tomography angiography for surveillance and its measurement method accuracy remain unclear. We aimed to assess the value of abdominal aneurysm sac volume measurement for detecting expansions and the association of preprocedural intraluminal thrombus (ILT) volume with aneurysm sac growth following EVAR. MATERIAL AND METHODS: A total of 107 patients underwent elective EVAR. Inclusion criteria provided a cohort of 39 patients. Changes of postoperative maximum aneurysm sac diameter and AAA volume were calculated. Volumetric AAA changes and demographic data of the cases with clinically irrelevant AAA diameter enlargement were evaluated. Preoperative ILT volumes were collected. ILT and AAA sac volume ratio was calculated. Statistical data analysis was performed using standard methods. RESULTS: The mean changes of maximum AAA diameter and volume in percentage after EVAR were -5.08 ± 8.20 mm and -13.39 ± 23.32%, respectively. A moderate positive linear correlation between those changes was found (R 2 = 0.731; p < 0.0001). The mean relative AAA volume increase in cases without clinically relevant diameter enlargement was 11.50 ± 8.27%. The means of ILT and AAA sac ratios were 0.59 ± 0.17 and 0.52 ± 1.8 in growing AAA sac and in stable or shrinking AAA sac groups, respectively (p = 0.308). CONCLUSIONS: Volumetric AAA measurement may be useful as an additional method to diameter measurement after EVAR to identify clinically relevant sac growth. Preoperative volume of ILT may not significantly affect the growth rate of AAA after EVAR.

Outcomes of a percutaneous coronary intervention versus coronary artery bypass grafting in octogenarians.

BACKGROUND: The data on long-term outcomes for elderly patients with coronary artery disease who undergo invasive treatment is limited. This study aimed to assess long-term outcomes and risk factors for patients over 80 years of age who underwent revascularisation. METHODS: This single-centre retrospective study included ≥80-year-old patients who underwent coronary angiography between 2012 and 2014. Among 590 study patients, 411 patients had significant angiographic changes and had either a percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) performed. Baseline patient characteristics, including demographics, comorbidities, survival to hospital discharge, and long term mortality were analysed. Three-year mortality was assessed. RESULTS: Three hundred sixty-nine (89.8%) patients underwent PCI and in 42 (10.2%) CABG was performed. Significant differences between groups were detected in heart failure (PCI - 51.2% vs. CABG - 78.6%; p = 0.001), previous CABG (11.4% vs. 0%; p = 0.014), cardiogenic shock (12.2% vs. 0%; p = 0.008). Hospital mortality rate in the PCI group - 10.6%, CABG - 7.1%; p = 0.787. A median 3-year survival rate in the PCI group - 66.1%, CABG - 66.7%; p = 1.000. Chronic heart failure (OR 2.442; 95% CI: 1.530-3.898, p < 0.001), atrial fibrillation (OR 0.425; 95% CI: 0.261-0.692, p < 0.001), cardiogenic shock (OR 0.120; 95% CI: 0.054-0.270, p = 0.001), and LMCA stenosis (OR 2.104; 95% CI: 1.281-3.456, p = 0.003) were identified as independent 3-year all-cause mortality predictors in multivariate regression analysis. CONCLUSIONS: There was no significant difference in hospital mortality and survival rates between elderly patients who underwent PCI or CAGB. The majority of elderly patients underwent a PCI and these patients appeared to experience cardiogenic shock more frequently.

Could careful patient selection for renal denervation warrant a positive effect on arterial stiffness and left ventricular mass reduction?

AIMS: After the sequence of Symplicity HTN trials, the impact of the procedure on lowering blood pressure (BP) and cardiovascular risk is still debatable. We present initial results of the multimodal pilot study that aimed at carefully selecting proper patients and investigating the effects of RASD on cardiac morphology and central haemodynamic parameters in 15 patients with resistant arterial hypertension prior and 6 months after RASD. METHODS AND RESULTS: The multimodal (applanation tonometry, echocardiography and cardiac magnetic resonance (CMR)) study findings have shown a significant BP decrease (190/112 ± 23/12 to 153/91 ± 18/11 mm Hg, P < 0.002), a decrease of the arterial markers (carotid-femoral pulse wave velocity decreased from 11.46 ± 2.92 m/s to 9.17 ± 2.28 m/s and the augmentation index decreased from 25.47 ± 10.55 to 21 ± 12.19, P < 0.006), a significant left ventricular mass index decrease by 10% both by echocardiography (140.83 ± 38.46 to 115.26 ± 25.37 g/m2, n = 14, P < 0.001) and CMR (108.32 ± 39.02 to 97.25 ± 30.06 g/m2, n = 15, P = 0.003). A significant decrease of CMR retrograde flow volume in the ascending aorta non-dependent on BP was also found. CONCLUSIONS: Our study is characterised by strict and extensive patient selection criteria for renal artery sympathetic denervation (RASD), which seem to warrant a positive effect of the procedure on BP, arterial stiffness and left ventricular mass 6 months after RASD, although it should be confirmed in larger controlled trials.

Impact of renal sympathetic denervation on cardiac sympathetic nerve activity evaluated by cardiac MIBG imaging.

AIMS: The objective of the present study was to investigate an effect of renal artery sympathetic denervation (RASD) on patients with resistant hypertension and RASD effect on cardiac sympathetic nerve activity. It is known that an abnormally activated sympathetic tone is associated with progression of heart failure (HF). METHODS AND RESULTS: We investigated 16 patients with resistant arterial hypertension (mean age 54.88±7.89 years, mean 24-hr ambulatory blood pressure [BP] systolic 161.07±20.12 mmHg, diastolic 97.6±16.25 mmHg, using 6.44±0.96 antihypertensive drugs), who underwent bilateral RASD. Echocardiography, 24-hr ambulatory BP and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy were performed before and six months after RASD. There were no significant changes in 24-hr ambulatory systolic and diastolic BP before RASD and six months after it: systolic BP before RASD was 161.07±20.12 mmHg and 144.93±17.27 mmHg after (p=0.050); diastolic BP before RASD was 97.6±16.25 mmHg and 89.87±12.33 mmHg after (p=0.182). We observed a significant change in cardiac sympathetic nerve activity assessed by 123I-MIBG scintigraphy, as an increase of late heart-to-mediastinum (H/M) ratio, varying from 2.21±0.47 to 2.35±0.52 m/s (p=0.02). CONCLUSIONS: Selective RASD significantly reduces cardiac sympathetic overdrive assessed by 123I-MIBG scintigraphy. Presumably, this positively affects HF progression in patients with resistant arterial hypertension.

Complicated congenital gluteal arteriovenous malformation with hemorrhage in pregnancy.

Extracranial congenital arteriovenous malformations (AVMs) are rare clinical entities that can be progressive in nature. The influence of pregnancy on lesion progression has been discussed in the past. This report presents an unusual case of 23-year-old primigravida woman who presented at 36 weeks' gestation with complicated necrotic ulceration and hemorrhage of the right gluteal region. A hyperpigmented mark with varicosities was initially noted at birth, but during pregnancy it showed remarkable progression and was first identified as an AVM. After hemorrhage control and induced delivery, the lesion was successfully treated with several embolizations. Complete wound healing was achieved, but because of partial recurrence at 3 years, repeat embolization was performed, with satisfactory clinical improvement and residual 25% arteriovenous shunting on transarterial lung perfusion scintigraphy study. AVM complications during pregnancy are uncommon, and this case supports the prior opinion that pregnancy can stimulate lesion progression. Especially in undiagnosed and previously untreated cases, this can lead to life-threatening complications for the mother and fetus. Long-term lesion management usually requires combined endovascular and surgical treatment.

Diagnostic methods, treatment modalities, and follow-up of extracranial arteriovenous malformations.

OBJECTIVE: Arteriovenous malformations (AVMs) are an uncommon vascular pathology that remains challenging to accurately diagnose and successfully treat. This study introduces a novel way to evaluate AVM treatment outcomes using transarterial lung perfusion scintigraphy (TLPS) and reports our treatment results. MATERIAL AND METHODS: The patients treated for extracranial AVMs were studied retrospectively. Diagnosis and outcomes were based on clinical data, ultrasonography, magnetic resonance imaging, computed tomography, angiography, and TLPS studies. The influence of gender; location, form, and stage of AVMs; first attempt at treatment; and treatment modalities was analyzed. Outcomes were defined as positive (cure, improvement, and remission) or negative (no remission and aggravation). RESULTS: Of the 324 patients with congenital vascular malformations, 129 (39.8%) presented with AVMs, and the data of 56 treated patients with AVMs were analyzed. Of the 29 patients in the endovascularly treated group, 15 in the surgically treated group, and 12 in the combined treatment group, 24 (82.8%), 14 (93.3%), and 10 patients (83.3%), respectively, had positive outcomes (P>0.05). All outcomes were positive in surgically treated patients with extratruncular limited AVMs, and these patients were more likely to be cured as compared with those who had other forms of AVMs (OR, 5.8; 95% CI, 1.1-29; P=0.02). The patients with more advanced AVMs (stages III and IV) and with AVMs in the gluteal and pelvic region were more likely to have the worst outcomes than those with stage II AVMs (OR, 8.2; 95% CI, 1-72; P=0.03) and with AVMS in other locations (OR, 5.8; 95% CI, 1.1-29; P=0.02), respectively. Gender and age did not significantly influence treatment results (P>0.05). The TLPS data of 17 patients showed AV shunting ranging from 0% to 92%, which combined with other results helped identify 9 patients who needed further interventions, 6 who were treated successfully, and 2 who had insignificant shunting. CONCLUSIONS: The best outcomes were achieved in surgically treated patients with localized lesions and less advanced AVMs. For the first time in Lithuania, a modified TLPS method has been introduced that enhances a hemodynamic assessment of AV shunting and provides with a more accurate evaluation of AVMs to better serve in planning future treatments.

Classic dissection of thoracic aorta complicated by ascending aortic intramural hematoma: promt diagnosis and successful endovascular repair.

We reported a case of 68-year-old man, with a previous history of hypertension. Patient was admitted to our institution for evaluation of a severe, constant, tearing anterior chest pain radiated to the neck with suspicion of acute aortic dissection. A multidetector computed tomography scan of thorax and abdomen demonstrated a dissection starting from the middle part of aortic arch and extending downward to the descending aorta till the middle part of the thoracic aorta. The dissection was classified as Stanford A, De Bakey I. Surgical treatment of patient was started with bypass graft from the right common carotid artery to the left common carotid with subsequent revascularization of left subclavian artery. Lower parts of above-mentioned arteries were ligated. At the second stage an emergent prosthetic stent-graft was placed distally from the truncus brachiocephalicus up to the proximal part of the descending aorta. We reported a case report to present diagnostic and possible interventional treatment for patient with acute aortic type A dissection.

Translesional pressure gradients to predict blood pressure response after renal artery stenting in patients with renovascular hypertension.

BACKGROUND: In previous studies on the effect of renal stenting on arterial hypertension, patients were selected mainly on the basis of angiographic parameters of the renal artery stenosis. The aim of the present study was to evaluate whether translesional pressure gradients could identify the patients with renal artery stenosis who might benefit from stenting. METHODS AND RESULTS: A total of 53 consecutive hypertensive patients with unilateral RAS scheduled for renal artery intervention were recruited. Transstenotic pressure gradients were measured at baseline and during maximal hyperemia, before renal artery stenting. Twenty-four-hour ambulatory blood pressure measurements were performed in all patients before and 3 months after the intervention. Average reductions in systolic blood pressure and diastolic blood pressure at follow-up were -20±30 mm Hg and -2±12 mm Hg, respectively. At multivariate analysis, dopamine-induced mean gradient was the only independent predictor of the variations of both systolic blood pressure (regression coefficient=-4.03, standard error=1.11; P<0.001) and diastolic blood pressure (regression coefficient=-3.11, standard error=1.20; P=0.009). Patients who showed a decline in systolic blood pressure from the baseline value >20 mm Hg were considered as "responders." The optimal cutoff for identification of "responders" was a dopamine-induced mean gradient ≥20 mm Hg (area under the curve, 0.77; 95% confidence interval, 0.64 to 0.90; P=0.001). CONCLUSIONS: A dopamine-induced mean pressure gradient of ≥20 mm Hg is highly predictive of arterial hypertension improvement after renal stenting, and therefore this measurement is useful for appropriate selection of patients with arterial hypertension.