Novel Treatments in Refractory Recurrent Pericarditis.

Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid dependence. In the most recent decade, the introduction of interleukin-1 blockers in clinical practice has revolutionized the treatment of glucocorticoid-dependent and colchicine-resistant recurrent pericarditis due to their excellent efficacy and good safety profile. The rationale for the introduction of this class of medications in clinical practice is the autoinflammatory nature of recurrent pericarditis in a substantial rate of cases, with interleukin-1 being the main pro-inflammatory cytokine involved in this context. This review aims to discuss the contemporary available evidence from original research and real-world data on interleukin-1 blocker use in refractory recurrent pericarditis, in terms of indications, mechanism of action, efficacy, side effects, and recommended treatment protocols. Moreover, novel treatment proposals, such as hydroxychloroquine, beta blockers, and cannabidiol, which showed encouraging preliminary results, are addressed. Finally, gaps in knowledge, unmet needs, and future perspectives related to recurrent pericarditis are thoroughly discussed.

Perivascular Fat: A Novel Risk Factor for Coronary Artery Disease.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

Markers of Vascular Dysfunction in Hypertension.

Hypertension is a modifiable cardiovascular risk factor and displays a rapidly growing incidence due to aging and the acquisition of an unhealthy lifestyle. Hypertension is linked to the development of target organ damage in several vascular beds such as coronary arteries, peripheral, cerebral, and renal arteries. Besides, along with the presence of other cardiovascular risk factors, it aggravates vascular dysfunction due to the aging process. The mechanisms of vascular dysfunction in hypertension are complex and involve excessive salt intake and water retention, activation of neurohormonal systems, induction of endothelial dysfunction of large arteries and microcirculation, development of arterial stiffness, and complex interactions with cellular pathways of inflammation, oxidative stress, and thrombosis. The extent of vascular dysfunction in patients with hypertension can be assessed by evaluating endothelial function, measuring arterial stiffness, and testing the levels of circulating biomarkers of oxidative stress, pro-inflammatory cytokines, and thrombosis. Assessing these markers in subjects with and without hypertension could aid in identifying those at risk of vascular damage and improving risk prediction for future cardiovascular events. While several lifestyle and pharmacological therapies have shown promise in addressing vascular dysfunction in hypertension, none of these biomarkers have been established as an independent risk factor or treatment target. Therefore, in this article, we review the literature on the evidence that exists regarding the role of vascular dysfunction in the pathophysiology, diagnosis, progression, and treatment of hypertension, highlighting the lack of conclusive evidence in this field.

A More Targeted and Selective Use of Implantable Loop Recorders Improves the Effectiveness of Syncope Units: A Single-Center Experience.

PURPOSE: Syncope remains a common medical problem. Recently, the role of dedicated syncope units and implantable loop recorders has emerged in the investigation of unexplained syncope. This study aims to investigate the possibilities for a more rational and targeted use of various diagnostic tools. METHODS: In this retrospective single-center study, 196 patients with unexplained syncope were included between March 2019 and February 2023. Various diagnostic tools were utilized during the investigation, according to clinical judgement. Patients were retrospectively allocated into Group A (including those who, among other tests, underwent loop recorder insertion) and Group B (including patients investigated without loop recorder implantation). Data were compared with Group C, including patients assessed prior to syncope unit establishment. RESULTS: There was no difference between Group A (n = 133) and Group B (n = 63) in the diagnostic yield (74% vs. 76%, p = 0.22). There were significant differences between Groups A and B regarding age (67.3 ± 16.9 years vs. 48.3 ± 19.1 years, p < 0.001) and cause of syncope (cardiogenic in 69% of Group A, reflex syncope in 77% of Group B, p < 0.001). Electrocardiography-based diagnosis occurred in 55% and 19% of Groups A and B, respectively (p < 0.001). The time to diagnosis was 4.2 ± 2.7 months in Group A and 7.5 ± 5.6 months in Group B (p < 0.001). In Group C, the diagnostic yield was 57.9% and the electrocardiography-based diagnostic yield was 18.3%. CONCLUSIONS: A selective use of loop recorders according to clinical and electrocardiographic characteristics increases the effectiveness of the structured syncope unit approach and further preserves financial resources.

Bridge to Life: Current Landscape of Temporary Mechanical Circulatory Support in Heart-Failure-Related Cardiogenic Shock.

Acute heart failure (HF) presents a significant mortality burden, necessitating continuous therapeutic advancements. Temporary mechanical circulatory support (MCS) is crucial in managing cardiogenic shock (CS) secondary to acute HF, serving as a bridge to recovery or durable support. Currently, MCS options include the Intra-Aortic Balloon Pump (IABP), TandemHeart (TH), Impella, and Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO), each offering unique benefits and risks tailored to patient-specific factors and clinical scenarios. This review examines the clinical implications of recent advancements in temporary MCS, identifies knowledge gaps, and explores promising avenues for future research and clinical application. Understanding each device's unique attributes is crucial for their efficient implementation in various clinical scenarios, ultimately advancing towards intelligent, personalized support strategies.

Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients (BMI ≥ 30 kg/m2) with Atrial Fibrillation or Venous Thromboembolism: An Updated Systematic Review and Meta-Analysis.

Background: Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m2) due to concerns regarding their efficacy and safety in this demographic. Aim: This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods: A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results: A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions: DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.

The Efficacy of Coronary Sinus Reducer in Patients with Refractory Angina: A Systematic Review and Meta-Analysis.

Background: Refractory angina is a frequently encountered phenomenon in patients with coronary artery disease, often presenting therapeutic challenges to the clinical cardiologist. Novel treatment methods have been explored in this direction, with the coronary sinus reducer (CSR) being among the most extensively-investigated. Methods: We conducted a systematic review of the literature for studies assessing the efficacy of CSR in patients with refractory angina. The primary endpoints of interest were procedural success and the improvement in angina according to the Canadian Cardiovascular Society (CCS) by at least one class. Secondary endpoints were the rate of periprocedural adverse events, the improvement by at least 2 CCS classes, and the mean change in CCS class. A random-effects meta-analysis of proportions (procedural success, improvement by ≥ 1 or ≥ 2 classes, periprocedural adverse events) or means (mean CCS class change) were performed. I 2 was chosen as the metric for between-study heterogeneity. Publication bias was assessed by the inspection of funnel plots and Egger's regression test. We examined the risk of bias according to the Newcastle-Ottawa Scale. Results: From a total of 515 studies identified from the original search, 12 studies were finally included for data extraction. Based on their meta-analysis, we observed a high CSR procedural success (98%, 95% confidence interval (CI) 96 to 99%) with a low rate of periprocedural complications (6%, 95% CI 5 to 7%), while most patients exhibited an improvement by at least 1 CCS class (75%, 95% CI 66 to 83%) after the intervention. A significant proportion of patients demonstrated an improvement by at least 2 CCS classes (39%, 95% CI 34 to 45%), with a mean change of -1.24 CCS class (95% CI -1.40 to -1.08). Conclusions: CSR is associated with high implantation success rates and significant improvements in angina symptoms for patients with refractory angina.

Coronary Plaque Erosion: Epidemiology, Diagnosis, and Treatment.

Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.

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.

The Association of Systemic Endothelial Dysfunction With Diffuse Diabetic Macular Edema.

Our aim was to assess whether systemic endothelial dysfunction, evaluated non-invasively by flow mediated dilation (FMD), is associated with diabetic macular edema (DME) and to determine if it is further impaired in patients with diffuse-DME. Consecutive patients (n = 84) with type-2 diabetes mellitus (T2DM) and diabetic retinopathy were enrolled. DME was not present in 38 (non-DME) and present in 46 patients; 25 with focal and 21 with diffuse-DME. No differences were detected between DME and non-DME groups regarding the clinical and demographic characteristics, except for the age of T2DM initiation (lower in non-DME). FMD values were significantly impaired in DME compared with non-DME patients, even after adjustment for multiple covariates (3.56 ± 1.03 vs 4.57 ± 1.25%, P = .003). Among DME patients, no differences were found concerning the clinical and demographic data, while FMD levels were significantly lower in diffuse-DME patients, compared with the focal-DME ones, regardless of the impact several confounders (2.88 ± 0.65 vs 4.08 ± 0.95%, P = .002). It is noteworthy that FMD values of non-DME and focal-DME patients did not differ significantly (4.52 ± 1.24 vs 4.21 ± 1.06%, P = .307). Moreover, among DME patients, impaired FMD was an independent predictor of diffuse-DME (odds ratio: 0.06, 95% CI 0.01-0.47, P = .007).

Young and older patients with acute myocardial infarction: differences in risk factors and angiographic characteristics.

OBJECTIVE: Although coronary artery disease mainly affects older individuals, the incidence of myocardial infarction (MI) among younger adults (<55 years) has increased during the past decade. Young and older MI patients have different underlying pathophysiologic characteristics, atherosclerotic plaque morphology, and risk factor profiles. METHODS: We studied 977 patients (≤55 years old: 322, >55 years old: 655) who were hospitalized for MI in the previous 5 years. Patients' baseline characteristics and daily habits were recorded. Angiographic characteristics and vascular lesions were detected, and further examinations, including flow-mediated dilation (FMD), pulse wave velocity (PWV), and central augmentation index (AIx), were performed. Biomarkers of inflammation (Interleukin-6, Tumor-Necrosis factor-a, Intercellular Adhesion Molecule 1, and Osteopontin) were also tested. RESULTS: The median age in the younger age group was 49 years [interquartile range (IQR: 44-53)] and 66 years (IQR: 61-73) in the older age group. Arterial hypertension was less prevalent in the young compared to the elderly with MI (47.4% vs. 76.2%, p < 0.01). The younger counterparts presented significantly lower rates of diabetes mellitus (19.3% vs. 30.6%, p < 0.01), dyslipidemia (59% vs. 70.8%, p < 0.01), and atrial fibrillation (2.6% vs. 9.7%, p < 0.01) and were more casual smokers (49.3% vs. 23.8%, p < 0.01) compared to older patients with MI. In terms of arterial stiffness, lower PWV [7.3 m/s (IQR: 6.5-8.4 m/s) vs. 9 m/s (IQR: 8-10.8 m/s), p < 0.01] and AIx (20.5 ± 10.8 vs. 25.5 ± 7.8, p < 0.01) were recorded in the young compared to the elderly with MI. Concerning angiographic characteristics, younger patients were more likely to have none or single-vessel disease (55.6% vs. 45.8%, p < 0.02), whereas the older participants more frequently had three or more vessel disease (23.5% vs. 13.6% in the young, p < 0.02). Although significant disparities in blood test results were detected during the acute phase, the great majority of young MI patients were undertreated. CONCLUSION: Younger patients with MI are more likely to be smokers with impaired PWV measures, present with non-obstructive or single-vessel disease, and often remain undertreated. A better knowledge of the risk factors as well as the anatomic and pathophysiologic processes in young adults will help enhance MI prevention and treatment options in this patient population.

The Role of Inflammasomes in Heart Failure.

Heart failure (HF) poses a significant world health challenge due to the increase in the aging population and advancements in cardiac care. In the pathophysiology of HF, the inflammasome has been correlated with the development, progression, and complications of HF disease. Discovering biomarkers linked to inflammasomes enhances understanding of HF diagnosis and prognosis. Directing inflammasome signaling emerges as an innovative therapeutic strategy for managing HF. The present review aims to delve into this inflammatory cascade, understanding its role in the development of HF, its potential role as biomarker, as well as the prospects of modulating inflammasomes as a therapeutic approach for HF.

Congenital heart "Challenges" in Down syndrome.

In this editorial, we comment on the article by Kong et al published in the recent issue of the World Journal of Cardiology. In this interesting case, the authors present the challenges faced in managing a 13-year-old patient with Down syndrome (DS) and congenital heart disease (CHD) associated with pulmonary arterial hypertension. In this distinct population, the Authors underscore the need for early diagnosis and management as well as the need of a multidisciplinary approach for decision making. It seems that the occurrence of CHD in patients with DS adds layers of complexity to their clinical management. This editorial aims to provide a comprehensive overview of the intricate interplay between DS and congenital heart disorders, offering insights into the nuanced diagnostic and therapeutic considerations for physicians.

Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a systematic review and network meta-analysis of 32 randomized trials.

INTRODUCTION: Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF. MATERIALS AND METHODS: MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]). CONCLUSIONS: MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.

Myocardial Ischemia-Reperfusion Injury: Unraveling Pathophysiology, Clinical Manifestations, and Emerging Prevention Strategies.

Myocardial ischemia-reperfusion injury (MIRI) remains a challenge in the context of reperfusion procedures for myocardial infarction (MI). While early revascularization stands as the gold standard for mitigating myocardial injury, recent insights have illuminated the paradoxical role of reperfusion, giving rise to the phenomenon known as ischemia-reperfusion injury. This comprehensive review delves into the intricate pathophysiological pathways involved in MIRI, placing a particular focus on the pivotal role of endothelium. Beyond elucidating the molecular intricacies, we explore the diverse clinical manifestations associated with MIRI, underscoring its potential to contribute substantially to the final infarct size, up to 50%. We further navigate through current preventive approaches and highlight promising emerging strategies designed to counteract the devastating effects of the phenomenon. By synthesizing current knowledge and offering a perspective on evolving preventive interventions, this review serves as a valuable resource for clinicians and researchers engaged in the dynamic field of MIRI.

MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential.

Atrial fibrillation (AFib), the most prevalent arrhythmia in clinical practice, presents a growing global health concern, particularly with the aging population, as it is associated with devastating complications and an impaired quality of life. Its pathophysiology is multifactorial, including the pathways of fibrosis, inflammation, and oxidative stress. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as substantial contributors in AFib pathophysiology, by affecting those pathways. In this review, we explore the intricate relationship between miRNAs and the aforementioned aspects of AFib, shedding light on the molecular pathways as well as the potential diagnostic applications. Recent evidence also suggests a possible role of miRNA therapeutics in maintenance of sinus rhythm via the antagonism of miR-1 and miR-328, or the pharmacological upregulation of miR-27b and miR-223-3p. Unraveling the crosstalk between specific miRNA profiles and genetic predispositions may pave the way for personalized therapeutic approaches, setting the tone for precision medicine in atrial fibrillation.

Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis.

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

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.

Expression of Circulating miR-21 and -29 and their Association with Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is characterized by myocardial hypertrophy, fibrosis, and sarcomeric disarray. OBJECTIVE: To evaluate the expression levels of circulating miR-21 and -29 in patients with HCM and their association with clinical characteristics and myocardial fibrosis. METHODS: In this case-control study, 27 subjects with HCM, 13 subjects with hypertensive cardiomyopathy, and 10 control subjects were enrolled. Evaluation of patients' functional capacity was made by the six-minute walk test. Echocardiographic measurements of left ventricle systolic and diastolic function were conducted. Cardiac magnetic resonance late gadolinium enhancement (LGE) -through a semiquantitative evaluation- was used in the assessment of myocardial fibrosis extent in HCM patients. The expression of miR-21 and -29 in peripheral blood samples of all patients was measured via the method of quantitative reverse transcription polymerase chain reaction. RESULTS: Circulating levels of miR-21 were higher in both hypertensive and HCM (p<0.001) compared to controls, while expression of miR-29 did not differ between the three studied groups. In patients with HCM and LGE-detected myocardial fibrosis in more than 4 out of 17 myocardial segments, delta CT miR-21 values were lower than in patients with myocardial LGE in 3 or fewer myocardial segments (2.71 ± 1.06 deltaCT vs. 3.50 ± 0.55 deltaCT, p<0.04), indicating the higher expression of circulating miR-21 in patients with more extensive myocardial fibrosis. CONCLUSION: MiR-21 was overexpressed in patients with HCM and hypertensive cardiomyopathy. Importantly, in patients with HCM, more extensive myocardial fibrosis was associated with higher levels of miR-21.