Association between Left Atrial Appendage Morphology and Clot Histology in Patients with Embolic Ischemic Stroke: An Exploratory Study.

BACKGROUND: Acute embolic ischemic stroke poses a significant healthcare challenge. Histological clot features' variability among patients with acute ischemic stroke treated by mechanical thrombectomy has potential implications for determining treatment and etiology. This study investigated the clot histological feature differences among patients who experienced cardioembolic stroke and embolic stroke of undetermined source with different left atrial appendage (LAA) morphologies. METHODS: We conducted a prospective observational study involving 79 patients with acute embolic ischemic stroke undergoing mechanical thrombectomy. Computed tomography angiography images were used to classify LAA morphologies. An artificial intelligence algorithm assessed the clot fibrin and red blood cell contents. RESULTS: Patients with chicken-wing LAA morphology exhibited lower mean clot fibrin proportions than did those with non-chicken-wing morphology (p < 0.001). Linear regression analysis showed that chicken-wing LAA was significantly associated with a lower clot fibrin proportion (estimate, -0.177; 95% CI [-0.259, -0.096]; p < 0.001). The successful recanalization rate and first-pass effect between the groups did not differ significantly. CONCLUSIONS: The chicken-wing LAA morphological type is associated with lower clot fibrin contents, suggesting potentially different embolism mechanisms or diverse embolic sources, compared with the non-chicken-wing LAA types. Further studies are required to investigate this association.

Randomized Pilot Trial on Optimal Treatment Strategy, Myocardial Changes, and Prognosis of Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains an unresolved challenge. Many different diagnostic approaches are often required to diagnose, confirm, and evaluate MINOCA. The prevalence can be as high as 13% of all acute myocardial infarction patients, indicating that this condition is not rare. At this time, there have been no completed randomized clinical trials involving MINOCA patients, and a better understanding of the mechanisms and management of these patients is important. This exploratory analysis seeks to find possible etiologic factors, the value of novel biomarkers, and the effect of different treatment strategies in patients with MINOCA. METHODS: This prospective randomized pilot trial will include 150 patients with MINOCA. A thorough clinical, laboratory, and imaging evaluation will be performed, including novel biomarkers and modern imaging techniques (heart magnetic resonance imaging and noninvasive testing). The duration of the enrollment is 18 months, and duration of the follow-up is 12 months from the enrollment of the first patient. RESULTS: The trial is registered under www.clinicaltrials.gov: NCT04538924. The study is currently recruiting participants. CONCLUSIONS: Because MINOCA is not a benign disease, the results of the current investigation could inform future diagnostic and therapeutic strategies and enhance the understanding of MINOCA patients.

Treatment of chronic total occlusion with percutaneous coronary intervention is associated with improved survival as compared to medical treatment alone: insights from a single-centre registry.

Symptom relief is currently the main indication to perform percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). So far, none of the randomized trials for CTO treatment have demonstrated improved survival after PCI compared to optimal medical treatment (OMT) alone. We investigated whether CTO PCI in addition to OMT could improve survival over OMT alone. Data of 1004 patients with a treated CTO was analysed. Patients with acute coronary syndrome and who underwent coronary artery bypass graft surgery (CABG) were excluded, thus final study population was 378. According to the treatment received, patients were divided into two groups: CTO PCI + OMT (n = 163) and OMT alone (n = 215). The primary endpoint was all-cause mortality during follow-up. The incidence of myocardial infarction (MI), revascularization (both CTO artery and non-CTO artery related) and stroke were also analysed as a secondary outcome. The mean follow-up period was 3.55 ± 0.93 years. Multiple regression analysis was performed to identify independent predictors of all-cause mortality. Occurrence of MI and repeat revascularization (both CTO vessel related and non-CTO vessel) and stroke did not differ significantly between groups. However, all-cause mortality was more frequent in OMT (19.1%) patients than PCI (10.4%). Patients age ≤70 years (odds ratio (OR) 0.47 [0.26; 0.84], p = 0.01) and CTO PCI (OR 0.51 [0.27; 0.94], p = 0.03) were independent predictors of reduced likelihood of all-cause death. The data from our centre registry demonstrates that CTO PCI is associated with reduced all-cause mortality as compared to medical treatment alone in a real-life setting.

Long-Term Effects of Renal Artery Denervation.

Background and Objectives: Renal artery denervation (RDN) procedure is a broadly discussed method in the treatment of resistant hypertension. Many studies report short-term (3-12 months) results for blood pressure and arterial stiffness. The primary endpoints were changes in 24 h mean systolic blood pressure (BP) and office systolic BP 48 months after RDN. The secondary endpoints were changes in aortic pulse wave velocity and impact of polypharmacy on these variables. Materials and Methods: Renal artery denervation was performed in 73 patients treated for resistant hypertension; 49 patients remained in final analysis. Patient examination was carried out before the procedure, and subsequently at 3, 6, 12, 24, and 48 months later. Patients' antihypertensive and overall medication regimens were carefully analysed. Results: Mean 24 h arterial blood pressure lowered and was sustained at lower levels for up to 48 months; median (interequartile range-IQR) from 158(23.5)/100(14.2) to 140(26.5)/86(16.2) mmHg. Mean reduction in 24 h ambulatory systolic BP was -11 ± 25 mmHg (95% CI, -20 to -2; p < 0.001), while office systolic BP reduced by -7 ± 23 mmHg (95%CI, -24 to -1; p < 0.02). A significant reduction in median aortic pulse wave velocity 12 months after the procedure (drop from baseline 11.2 [3.15] m/s (95%CI 6.1 to 16.2) to 9.8 [2.1] m/s (95%CI 6.1 to 13.7; p = 0.002)). After 48 months, there was no worsening compared to the baseline level of 10.3 [4.0] m/s (95% CI 6.9 to 17.8) (p > 0.05). The total mean number of antihypertensive drugs remained unchanged: 5.97(±1.1) vs. 5.24 (±1.45). A higher number of pills after 48 months was associated with higher aortic pulse wave velocity (1-5 pill group: 8.1 ± 1.6 m/s; 6-10 pill group: 10.9 ± 1.8 m/s; >11 pill group: 15.1 ± 2.6 m/s) (p = 0.003). Conclusions: Antihypertensive effect after renal denervation lasts up to 48 months with no worsening of arterial stiffness compared to baseline. In our study, polypharmacy was associated with increased arterial stiffness 48 months after the procedure.

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.

The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure.

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

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.

How to interpret 24-h arterial stiffness markers: comparison of 24-h ambulatory Mobil-O-Graph with SphygmoCor office values.

OBJECTIVES: Although applanation tonometry is the most widely used method for evaluating arterial stiffness, oscillometric ambulatory blood pressure monitoring devices using specific algorithms for pulse wave analyses have been validated more recently. Currently, it is not clear how to interpret 24-h mean values of arterial stiffness parameters. The objective of this study was to compare 24-h mean values of arterial stiffness parameters obtained using 24-h ambulatory blood pressure monitoring device (Mobil-O-Graph) against a validated single-measure tonometric system (SphygmoCor). MATERIALS AND METHODS: We measured brachial and central arterial pressure, augmentation index (AIx), and carotid-to-femoral pulse wave velocity (cfPWV) using SphygmoCor device in 82 high and very high cardiovascular risk patients. The Mobil-O-Graph device for the 24-h blood pressure and arterial stiffness parameter monitoring was used on the same day and started within 2 h after measurements using SphygmoCor were done. RESULTS: Mean AIx values were 26.38±9.95 for SphygmoCor office measurement and 26.69±8.45 for Mobil-O-Graph 24-h mean values. The mean difference was -0.31±9.78 (P=0.775). CfPWV values were 10.56±2.59 m/s for SphygmoCor office measurement and 8.72±1.29 m/s for Mobil-O-Graph 24-h mean values. The difference of 1.84±2.15 m/s was statistically significant (P<0.001). Correlation coefficients for AIx and cfPWV between two methods were 0.444 and 0.468, respectively (P<0.001). CONCLUSION: The agreement between SphygmoCor single measurement and Mobil-O-Graph 24-h mean values of arterial stiffness parameters is moderate. The 24-h mean values of cfPWV obtained by Mobil-O-Graph are significantly lower than SphygmoCor values obtained in the office, whereas 24-h AIx mean values do not have a significant bias.

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.