Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

BACKGROUND: With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. AIMS: The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. METHODS: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. RESULTS: This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. CONCLUSIONS: IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Intravascular lithotripsy in peripheral lesions with severe calcification and its use in TAVI procedure - a meta-analysis.

Background: Heavily calcified peripheral artery lesions increase the risk of vascular complications, constituting a severe challenge for the operator during catheter-based cardiovascular interventions. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and represents a promising technique for plaque modification in patients with severe calcification in peripheral arteries. Purpose: Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified peripheral arteries and its use in Transcatheter Aortic Valve Implantation (TAVI). Patients and methods: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL in the peripheral vasculature. The diameter of the vessel lumen before and after IVL was estimated. The occurrence of peri-procedural complications was assessed using a random-effects model. Results: 20 studies with a total of 1,223 patients with heavily calcified peripheral lesions were analysed. The mean age of the cohort was 70.6 ± 17.4 years. Successful IVL delivery achieved in 100% (95% CI: 100%-100%, I2 = 0%), with an increase in the luminal diameter (SMD: 4.66, 95% CI: 3.41-5.92, I2 = 90.8%) and reduction in diameter stenosis (SMD: -4.15, 95% CI: -4.75 to -3.55, I2 = 92.8%), and a concomitant low rate of complications. The procedure was free from dissection in 97% (95% CI: 91%-100%, I2 = 81.4%) while dissections of any type (A, B, C, or D) were observed in 6% (95% CI: 2%-10%, I2 = 85.3%) of the patients. Several rare cases of abrupt closure, no-reflow phenomenon, perforation, thrombus formation, and distal embolization were recorded. Finally, the subgroup analysis of patients who underwent a TAVI with IVL assistance presented successful implantation in 100% (95% CI: 100%-100%, I2 = 0%) of the cases, with only 4% (95% CI: 0%-12%, I2 = 68.96%) presenting dissections of any sort. Conclusions: IVL seems to be an effective and safe technique for modifying severely calcified lesions in peripheral arteries and it is a promising modality in TAVI settings. Future prospective studies are needed to validate our results.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial.

BACKGROUND: Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. METHODS: This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. FINDINGS: Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. INTERPRETATION: Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. FUNDING: Medtronic.

Anticoagulation Status and Left Atrial Appendage Occlusion Indications in Hospitalized Cardiology Patients with Atrial Fibrillation: A Hellenic Cardiorenal Morbidity Snapshot (HECMOS) Sub-Study.

Background and Objectives: The proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess anticoagulation status and LAAC indications in patients with AF from the HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: The HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on 3 March 2022 in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves or moderate-to-severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6 ± 11.7, 148 males) were included in our analysis. Most of them (n = 159; 62%) suffered from persistent AF. The mean CHA2DS2-VASc score was 4.28 ± 1.7, while the mean HAS-BLED score was 1.47 ± 0.9. Three out of three patients with a a CHA2DS2-VASc score of 0 or 1 (female) were inappropriately anticoagulated. Sixteen out of eighteen patients with a CHA2DS2-VASc score 1 or 2 (if female) received anticoagulants. Thirty-one out of two hundred thirty-five patients with a CHA2DS2-VASc score > 1 or 2 (if female) were inappropriately not anticoagulated. Relative indications for LAAC were present in 68 patients with NVAF (63 had only one risk factor and 5 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had an eGFR value < 15 mL/min/1.73 m2 for a total of 73 risk factors. Moreover, 33 had a HAS-BLED score ≥ 3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high-thromboembolic-risk population of cardiology patients who were mainly treated using NOACs. One out of four AF patients should be screened for LAAC.

Aspirin for Primary Prevention of Cardiovascular Diseases: "WALTZ" with the Evidence.

PURPOSE OF REVIEW: In this review article, a detailed analysis of the current literature is provided, along with a "glimpse" into what the future holds for aspirin in the context of primary prevention. RECENT FINDINGS: The role of aspirin in primary prevention of cardiovascular diseases (CVD) has been extensively evaluated; however, the results provided over the years have been controversial. Identification of individual subgroups who may benefit from aspirin administration at an acceptable risk of bleeding complications is of paramount importance. Additionally, questions emerge at everyday clinical practice regarding the optimal use of aspirin in different phenotypes of patients due to age, sex, obesity status, frailty and diabetes mellitus. Until further data become available, the effective management of the well-established CV risk factors constitutes the milestone in the primary prevention of CVD. Moreover, based on the available evidence, the beneficial addition of aspirin in the modern era of lifestyle and pharmacological interventions for primary CVD prevention remains largely undetermined and further research is needed.

Renal Functional Reserve Is Related to the Nondipping Phenotype and to the Exercise Heart Rate Response in Patients with Essential Hypertension and Preserved Renal Function.

BACKGROUND: Renal functional reserve (RFR), defined as the difference between stress and resting glomerular filtration rate (GFR), may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. Blunted RFR has been demonstrated in early stages of hypertension and has been attributed to impaired vascular reactivity due to an overactive sympathetic nervous system (SNS). OBJECTIVE: The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing overactivity of the SNS in patients with essential hypertension and preserved renal function. METHODS: Thirty-six patients with untreated essential hypertension and a GFR >60 mL/min/1.73 m2 were enrolled. The following parameters were measured: RFR, 24-h ambulatory blood pressure (BP) profile, a treadmill stress test, and an echocardiographic examination. Urine and venous samples were obtained at specific time points for the determination of clinical parameters, and both resting and stress GFR were calculated by using endogenous creatinine clearance for the measurement of RFR after an acute oral protein load (1 g/kg). RESULTS: Twenty-one patients had a RFR <30 mL/min/1.73 m2 and 15 had a RFR above this cutoff. A nondipping pattern of 24-h BP was significantly more frequent in patients with low RFR (57.1 vs. 25.0%, p < 0.05 for systolic BP and 52.3 vs. 10.0%, p < 0.02 for diastolic BP). Moreover, patients with lower RFR values showed a blunted heart rate (HR) response to exercise during treadmill test (r = 0.439, p < 0.05). None of the echocardiographic parameters differed between the two groups of patients. CONCLUSIONS: In hypertensive patients with preserved GFR, reduced RFR is related to nondipping BP phenotype as well as to attenuated exercise HR response. Overactivity of the SNS may be a common pathway. Since loss of RFR may represent a risk factor for acute or chronic kidney injury, hypertensive patients with blunted RFR might need a more careful renal follow-up.

ConfidenHT™ System for Diagnostic Mapping of Renal Nerves.

PURPOSE OF REVIEW: To summarize the evidence regarding the distribution of renal nerves and their patterns of anatomic variations in animal and human settings. Moreover, the methodology and results of studies regarding renal nerve stimulation (RNS) in both preclinical and clinical models are presented. RECENT FINDINGS: There are differences regarding the number and the size of renal fibers, as well as their distance from the lumen in the diverse parts of the main renal arteries and the branches. In both animals and humans, RNS is safe and results in an increase of blood pressure (BP) while the effect on heart rate varies. In this context, the ConfidenHT™ system constitutes an integrated solution for effective RNS in humans. Due to the diversity of renal nerve anatomy in humans, arterial areas for more effective renal denervation cannot be homogenously defined. The concept of mapping of renal nerves can improve completeness of renal denervation therapies by means of integrated RNS solutions such as the ConfidenHT™ system.

Uric acid as an independent predictor of coronary artery disease in essential hypertension: Data from an 8-year-follow-up study.

The role of serum uric acid (SUA) in cardiovascular risk prediction remains to be further determined. We assessed the predictive value of SUA for the incidence of coronary artery disease (CAD) in 2287 essential hypertensive patients who were followed up for a mean period of 8 years. The distribution of SUA levels at baseline was split by the median (5.2 mg/dL) and subjects were classified into those with high and low values. Hypertensives who developed CAD (n = 57) compared to those without CAD at follow-up (n = 2230) had at baseline higher SUA. In multivariate Cox regression model, among established confounders, high SUA (hazard ratio = 1.216, P = .016) turned out to be independent predictor of CAD. In essential hypertensive patients SUA independently predicts CAD.

Long-term efficacy and safety of renal denervation: an update from registries and randomised trials.

Hypertension remains the leading treatable global cause of mortality due to high incidence and poor control rates despite of safe and effective drug therapy.Animal studies do not support functional nerve regrowth after RF-RDN and accordingly clinical evidence verify that RDN leads to durable BP reduction.Renal denervation is safe, as up to 36 months after the procedure, there are no statistically significant difference in procedure-related adverse events, deterioration of renal function and adverse cardiovascular outcomeRenal denervation is efficient in reducing BP in patients with no drug therapy, independently of the number of antihypertensive drugs and phenotype of patient. This sustained and safe reduction in BP observed up to 36 months after RDN could be associated with lower rates of renal and cardiovascular events.

Intravascular ultrasound-guided, lithotrispy facilitated angioplasty for treating a heavily calcified renal artery stenosis.

A 63-year-old woman with uncontrolled hypertension despite taking 5 antihypertensive medications was referred for percutaneous renal artery intervention.

A "Snake-Like" Vessel in the Thorax.

We report a congenital extracardiac arteriovenous fistula revealed incidentally in a patient undergoing computed tomographic coronary angiography for angina. This clinical vignette panel describes the origin and the trajectory of this rare vascular lesion.

Multimodality Imaging in a Patient With Double Aortic Arch Undergoing Transcatheter Aortic Valve Implantation: J Am Coll Cardiol Case Rep 2024;29:102224.

[This retracts the article DOI: 10.1016/j.jaccas.2024.102224.].

Multimodality Imaging in a Patient With Double Aortic Arch Undergoing Transcatheter Aortic Valve Implantation.

Double aortic arch is a rare congenital malformation often identified as an incidental finding during routine imaging. In our case, we describe aortic hemodynamics of double aortic arch in a patient with severe aortic stenosis and the procedural process of transcatheter aortic valve implantation.

Gut Microbiome and Its Role in Valvular Heart Disease: Not a "Gutted" Relationship.

The role of the gut microbiome (GM) and oral microbiome (OM) in cardiovascular disease (CVD) has been increasingly being understood in recent years. It is well known that GM is a risk factor for various CVD phenotypes, including hypertension, dyslipidemia, heart failure and atrial fibrillation. However, its role in valvular heart disease (VHD) is less well understood. Research shows that, direct, microbe-mediated and indirect, metabolite-mediated damage as a result of gut dysbiosis and environmental factors results in a subclinical, chronic, systemic inflammatory state, which promotes inflammatory cell infiltration in heart valves and subsequently, via pro-inflammatory molecules, initiates a cascade of reaction, resulting in valve calcification, fibrosis and dysfunction. This relationship between GM and VHD adds a pathophysiological link to the pathogenesis of VHD, which can be aimed therapeutically, in order to prevent or regress any risk for valvular pathologies. Therapeutic interventions include dietary modifications and lifestyle interventions, in order to influence environmental factors that can promote gut dysbiosis. Furthermore, the combination of probiotics and prebiotics, as well as fecal m transplantation and targeted treatment with inducers or inhibitors of microbial enzymes have showed promising results in animal and/or clinical studies, with the potential to reduce the inflammatory state and restore the normal gut flora in patients. This review, thus, is going to discuss the pathophysiological links behind the relationship of GM, CVD and VHD, as well as explore the recent data regarding the effect of GM-altering treatment in CVD, cardiac function and systemic inflammation.

Transcatheter Structural Heart Interventions in the Acute Setting: An Emerging Indication.

Structural heart disease is increasingly prevalent in the general population, especially in patients of increased age. Recent advances in transcatheter structural heart interventions have gained a significant following and are now considered a mainstay option for managing stable valvular disease. However, the concept of transcatheter interventions has also been tested in acute settings by several investigators, especially in cases where valvular disease comes as a result of acute ischemia or in the context of acute decompensated heart failure. Tested interventions include both the mitral and aortic valve, mostly evaluating mitral transcatheter edge-to-edge repair and transcatheter aortic valve implantation, respectively. This review is going to focus on the use of acute structural heart interventions in the emergent setting, and it will delineate the available data and provide a meaningful discussion on the optimal patient phenotype and future directions of the field.

Aggressive Rhythm Control Strategy in Atrial Fibrillation Patients Presenting at the Emergency Department: The HEROMEDICUS Study Design and Initial Results.

Atrial fibrillation has progressively become a more common reason for emergency department visits, representing 0.5% of presenting reasons. Registry data have indicated that about 60% of atrial fibrillation patients who present to the emergency department are admitted, emphasizing the need for more efficient management of atrial fibrillation in the acute phase. Management of atrial fibrillation in the setting of the emergency department varies between countries and healthcare systems. The most plausible reason to justify a conservative rather than an aggressive strategy in the management of atrial fibrillation is the absence of specific guidelines from diverse societies. Several trials of atrial fibrillation treatment strategies, including cardioversion, have demonstrated that atrial fibrillation in the emergency department can be treated safely and effectively, avoiding admission. In the present study, we present the epidemiology and characteristics of atrial fibrillation patients presenting to the emergency department, as well as the impact of diverse management strategies on atrial-fibrillation-related hospital admissions. Lastly, the design and initial data of the HEROMEDICUS protocol will be presented, which constitutes an electrophysiology-based aggressive rhythm control strategy in patients with atrial fibrillation in the emergency department setting.

Management of dyslipidemia in coronary artery disease: the present and the future.

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality, necessitating continuous refinement in the management of dyslipidemia, one of its major risk factors, to mitigate cardiovascular risks. Previous studies have proven the critical role of immediate and robust low-density lipoprotein cholesterol (LDL-C) reduction in the aftermath of acute coronary syndrome (ACS). Emphasizing the evidence supporting this approach, we delve into the impact of early intervention on cardiovascular outcomes and propose optimal strategies for achieving rapid LDL-C lowering, while also providing the rationale for early proprotein convertase subtilisin/kexin 9 inhibitor use after an ACS. Given the importance of the residual lipidemic risk, we present an overview of emerging therapeutic avenues poised to reshape dyslipidemia management, such as bempedoic acid, lipoprotein(a) inhibition, ApoC3 modulation, and angiopoietin-like protein 3 targeting. This comprehensive review amalgamates current evidence with future prospects, offering a holistic perspective on the management of dyslipidemia in CAD. By exploring both the urgency for immediate post-ACS LDL-C reduction and the exciting advancements on the horizon, this article provides a roadmap for clinicians navigating the intricate landscape of lipid-lowering therapies in CAD.

Antitumor activity of 5-hydroxy-3',4',6,7-tetramethoxyflavone in glioblastoma cell lines and its antagonism with radiotherapy.

5-Hydroxy-3',4',6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.

LOX-1 Receptor: A Diagnostic Tool and Therapeutic Target in Atherogenesis.

Low-density lipoprotein (LDL) and oxidized LDL (oxLDL) are major contributors to atherogenesis, as endogenous antigens, via several receptors such as LOX 1. A PubMed search was conducted in order to identify relevant articles regarding LOX-1's role in the atherosclerosis, diagnosis, prognostic use and molecules that could be used for therapy. The references of the manuscripts obtained were also reviewed, in order to find additional relevant bibliography. LOX-1 is a lectin-like pattern recognition receptor, mostly expressed in endothelial cells (ECs) which can bind a variety of molecules, including oxLDL and C-reactive protein (CRP). LOX-1 plays a key role in oxLDL's role as a causative agent of atherosclerosis through several pathologic mechanisms, such as oxLDL deposition in the subintima, foam cell formation and endothelial dysfunction. Additionally, LOX-1 acts a scavenger receptor for oxLDL in macrophages and can be responsible for oxLDL uptake, when stimulated. Serum LOX-1 (sLOX-1) has emerged as a new, potential biomarker for diagnosis of acute coronary syndromes, and it seems promising for use along with other common biomarkers in everyday clinical practice. In a therapeutic perspective, natural as well as synthetic molecules exert anti-LOX-1 properties and attain the receptor's pathophysiological effects, thus extensive research is ongoing to further evaluate molecules with therapeutic potential. However, most of these molecules need further trials in order to properly assess their safety and efficacy for clinical use. The aim of this review is to investigate LOX-1 role in atherogenesis and explore its potential as diagnostic tool and therapeutic target.