Residual leaks following percutaneous left atrial appendage occlusion and outcomes: a meta-analysis.

BACKGROUND AND AIMS: Residual leaks are not infrequent after left atrial appendage occlusion. However, there is still uncertainty regarding their prognostic implications. The aim of this study is to evaluate the impact of residual leaks after left atrial appendage occlusion. METHODS: A literature search was conducted until 19 February 2023. Residual leaks comprised peri-device leaks (PDLs) on transoesophageal echocardiography (TEE) or computed tomography (CT), as well as left atrial appendage patency on CT. Random-effects meta-analyses were performed to assess the clinical impact of residual leaks. RESULTS: Overall 48 eligible studies (44 non-randomized/observational and 4 randomized studies) including 61 666 patients with atrial fibrillation who underwent left atrial appendage occlusion were analysed. Peri-device leak by TEE was present in 26.1% of patients. Computed tomography-based left atrial appendage patency and PDL were present in 54.9% and 57.3% of patients, respectively. Transoesophageal echocardiography-based PDL (i.e. any reported PDL regardless of its size) was significantly associated with a higher risk of thromboembolism [pooled odds ratio (pOR) 2.04, 95% confidence interval (CI): 1.52-2.74], all-cause mortality (pOR 1.16, 95% CI: 1.08-1.24), and major bleeding (pOR 1.12, 95% CI: 1.03-1.22), compared with no reported PDL. A positive graded association between PDL size and risk of thromboembolism was noted across TEE cut-offs. For any PDL of >0, >1, >3, and >5 mm, the pORs for thromboembolism were 1.82 (95% CI: 1.35-2.47), 2.13 (95% CI: 1.04-4.35), 4.14 (95% CI: 2.07-8.27), and 4.44 (95% CI: 2.09-9.43), respectively, compared with either no PDL or PDL smaller than each cut-off. Neither left atrial appendage patency, nor PDL by CT was associated with thromboembolism (pOR 1.45 and 1.04, 95% CI: 0.84-2.50 and 0.52-2.07, respectively). CONCLUSIONS: Peri-device leak detected by TEE was associated with adverse events, primarily thromboembolism. Residual leaks detected by CT were more frequent but lacked prognostic significance.

Major clinical outcomes in symptomatic vs. asymptomatic atrial fibrillation: a meta-analysis.

BACKGROUND AND AIMS: Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. METHODS: Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. RESULTS: Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80-1.17], cardiovascular mortality (HR 1.04, 95% CI .72-1.49), thromboembolism (HR 1.06, 95% CI .87-1.28), stroke (HR 1.06, 95% CI .84-1.34), hospitalization (HR 1.34, 95% CI .89-2.02), and myocardial infarction (HR .98, 95% CI .70-1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19-1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54-.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76-1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33-2.03) and ablation therapy (OR 1.47, 95% CI 1.06-2.05) compared to asymptomatic cases. CONCLUSIONS: The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF.

Prognostic role of inflammatory cytokines and novel adipokines in acute myocardial infarction: An updated and comprehensive review.

Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality worldwide. The inflammation response during and after AMI is common and seems to play a key role in the peri-AMI period, related with ischaemia-reperfusion injury, adverse cardiac remodelling, infarct size and poor prognosis. In this article, we provide an updated and comprehensive overview of the most important cytokines and adipokines involved in the complex pathophysiology mechanisms in AMI, summarizing their prognostic role post-AMI. Data so far support that elevated levels of the major proinflammatory cytokines TNFα, IL-6 and IL-1 and the adipokines adiponectin, visfatin and resistin, are linked to high mortality and morbidity. In contrary, there is evidence that anti-inflammatory cytokines and adipokines as IL-10, omentin-1 and ghrelin can suppress the AMI-induced inflammatory response and are correlated with better prognosis. Mixed data make unclear the role of the novel adipokines leptin and apelin. After all, imbalance of pro-inflammatory and anti-inflammatory cytokines may result in worst AMI prognosis. The incorporation of these inflammation biomarkers in established prognostic models could further improve their prognostic power improving overall the management of AMI patients.

Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). METHODS: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. RESULTS: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. CONCLUSION: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Intracoronary Thrombolysis in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: an Updated Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the standard reperfusion treatment in ST-segment elevation myocardial infarction (STEMI). Intracoronary thrombolysis (ICT) may reduce thrombotic burden in the infarct-related artery, which is often responsible for microvascular obstruction and no-reflow. METHODS: We conducted, according to the PRISMA statement, the largest meta-analysis to date of ICT as adjuvant therapy to PPCI. All relevant studies were identified by searching the PubMed, Scopus, Cochrane Library, and Web of Science. RESULTS: Thirteen randomized controlled trials (RCTs) involving a total of 1876 patients were included. Compared to the control group, STEMI ICT-treated patients had fewer major adverse cardiac events (MACE) (OR 0.65, 95% CI, 0.48-0.86, P = 0.003) and an improved 6-month left ventricular ejection fraction (MD 3.78, 95% CI, 1.53-6.02, P = 0.0010). Indices of enhanced myocardial microcirculation were better with ICT (Post-PCI corrected thrombolysis in myocardial infarction (TIMI) frame count (MD - 3.57; 95% CI, - 5.00 to - 2.14, P < 0.00001); myocardial blush grade (MBG) 2/3 (OR 1.76; 95% CI, 1.16-2.69, P = 0.008), and complete ST-segment resolution (OR 1.97; 95% CI, 1.33-2.91, P = 0.0007)). The odds for major bleeding were comparable between the 2 groups (OR 1.27; 95% CI, 0.61-2.63, P = 0.53). CONCLUSIONS: The present meta-analysis suggests that ICT was associated with improved MACE and myocardial microcirculation in STEMI patients undergoing PPCI, without significant increase in major bleeding. However, these findings necessitate confirmation in a contemporary large RCT.

Plasma nesfatin-1 and DDP-4 levels in patients with coronary artery disease: Kozani study.

BACKGROUND: Nesfatin-1, a novel adipokine and dipeptidyl peptidase-4 (DPP4), a mam malian serine protease, are potent factors of atherosclerosis. In the present cross-sectional study, we investigated whether the plasma nesfatin-1 and DPP4 is associated with the prevalence and severity of coronary artery disease (CAD) with and without diabetes mellitus (DM). METHODS: We consecutively enrolled a total of 240 patients with significant CAD (previous revascularization or angiographically-proven coronary artery stenosis > 50%) presented with either unstable angina (UA, N = 76) or stable chronic CAD (SCAD, N = 165). 85 patients with at least 2 classical cardiovascular risk factors but without significant CAD served as controls. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), nesfatin-1 and DPP4 levels were assayed. RESULTS: No differences were found for age, sex, hypertension and diabetes distribution between groups. Low nesfatin-1 levels were found in both CAD groups (UA & SCAD) with respect to controls. The difference between UA and SCAD groups was marginally non-significant. There was a significant increase of DPP4 along UA to SCAD and control groups. Differences between groups remained unchanged in non-diabetic participants. Nesfatin-1 significantly correlated to hsCRP (r = - 0.287, p = 0.036), HOMA-IR (r = - 0.587, p = 0.007) and hyperlipidemia (r = - 0.331, p = 0.034). DPP4 was significantly associated with hs-CRP (r = 0.353 p < 0.001) and FPG (r = 0.202, p = 0.020) in univariate analysis, but those correlations were lost in multiple regression analysis. There was a negative correlation between nesfatin-1 and the severity of CAD, quantified by the Gensini score (r = - 0.511, p < 0.001), but no association was found for DPP4. CONCLUSIONS: Serum DPP4 levels are increased in patients with CAD, while serum nesfatin-1 levels have a negative association with both the incidence and the severity of CAD. These results are independent of the presence of diabetes mellitus. In addition, both peptides have a strong association with hsCRP. Trial registration ClinicalTrials.gov Identifier: NCT00306176.

The interplay between statins and adipokines. Is this another explanation of statins' 'pleiotropic' effects?

Statin therapy comprises an integral part of secondary and to a lesser extent of primary cardiovascular disease prevention. This is attributed not only to their lipid-lowering properties, but as well to a plethora of pleiotropic actions. Recently, the cytokines secreted by adipose tissue, the so-called adipokines, have been proved to play a critical role in various pathophysiological functions, among which inflammation and atherosclerosis development and vulnerability. The aim of this literature review was to summarize the effects of statins and the underlying mechanisms on the circulating levels of the most common adipokines regulating atherosclerosis process, as a part of their pleiotropic function. Up to now, robust evidence implicates a significant statin-induced reduction of pro-inflammatory adipokines IL-6, TNF-a and visfatin. Weak evidence from limited, small and mostly non-randomized studies suggest increased levels of anti-inflammatory adipokines apelin, vaspin and omentin-1 after statin therapy. In the rest of most known adipokines, statins have shown either controversial (adiponectin, retinol binding protein-4 and fetuin-A) or negligible effects (leptin and resistin) on their circulating levels. Therefore, statins may favourably alter the balance of inflammatory/anti-inflammatory adipokines, implicating a novel atheroprotective mechanism. However, the interplay between statins and adipokines is still not fully elucidated and its potential clinical relevance is warranted.

Omentin-1 and vaspin serum levels in patients with pre-clinical carotid atherosclerosis and the effect of statin therapy on them.

BACKGROUND: Omentin-1 and vaspin are novel adipokines, and their association with atherosclerosis is still under investigation. The present study aimed to assess the relationship of those adipokines with preclinical, non-significant carotid atherosclerosis and the impact of statin therapy on their levels, suggesting a link between adiposity and atherosclerosis. METHODS: Eighty-four statin-free subjects with non-significant, preclinical carotid atherosclerosis and elevated LDL- cholesterol levels (>130 mg/dl) were recruited to receive atorvastatin (from 10 to 80 mg per day) (atorvastatin group - AG group). Forty-six age- and gender-matched healthy individuals, without any chronic disease served as controls (control group - CG). Clinical parameters, metabolic profile, serum omentin-1, vaspin concentrations and ultrasound measurements of carotid thickening were obtained at the beginning and after 12 months. RESULTS: At baseline, AG showed lower omentin-1 and vaspin serum levels than CG (p ≤ 0.001). Along the entire study population at baseline, omentin-1 levels were independently related to LDL-cholesterol, while vaspin levels were independently associated with hsCRP and the presence of carotid atherosclerosis (p < 0.05). Within AG, 12-months atorvastatin treatment significantly increased omentin-1 (from 202.79 ± 91.41 ng/ml to 262.56 ± 101 ng/ml, p < 0.001) and vaspin concentrations (from 1.29 ± 0.51 ng/ml to 1.70 ± 0.5 ng/ml, p = 0.002). In standard multiple regression analysis, the presence of carotid atherosclerosis related to baseline vaspin levels (ß = -0.232, p < 0.001), while the atorvastatin-induced increase of vaspin was independently associated with hsCRP reduction (ß = -0.198, p = 0.045). CONCLUSION: Low omentin-1 and vaspin serum levels associated with preclinical, non-significant carotid atherosclerosis. Notably, atorvastatin administration significantly increased both adipokines, but the underlying mechanisms and the clinical impact of those changes requires further investigation.

How to Manage a Patient with Haemophilia and ACS Requiring PCI: A Battle between Bleeding and Thrombosis.

We present the case of a 70-year-old man with a history of haemophilia B, who presented to our hospital with a non-ST-elevation myocardial infarction. The patient, following consultation by a haemophilia expert, was revascularized with percutaneous coronary intervention (PCI) under adequate clotting factor administration. Patients with haemophilia and acute coronary syndrome, are susceptible to periprocedural bleeding and thrombotic events during PCI, and therefore a balanced management plan should always be implemented by a multidisciplinary team.

Contemporary management of stent thrombosis: Predictors of mortality and the role of new-generation drug-eluting stents.

OBJECTIVES: We sought to evaluate mortality predictors and the role of new-generation drug-eluting stents (NG-DES) in stent thrombosis (ST) management. BACKGROUND: No data are available regarding the outcome of patients with ST after interventional management that includes exclusively NG-DES. METHODS: Patients with definite ST of DES or BMS who underwent urgent/emergent angiography between 2015 and 2018 at our institution were considered for the study. After excluding patients who achieved TIMI-flow<2 after intervention or received an old-generation stent, 131 patients were included. Management classification was stent or non-stent treatment (medical management, thromboaspiration, balloon-angioplasty). Follow-up was performed to document all-cause death (ACD) and target-lesion-revascularization (TLR) that was used for censorship. RESULTS: Mode of presentation was STEMI in 88% and UA/NSTEMI in 12%. Type of ST was early, late, and very late in 11, 4, and 85%, respectively. Eighty four patients received stent and 47 non-stent treatment. After 926 ± 34 days, 21 ACDs, 7 TLRs and no cases of definite, recurrent ST were observed. Univariate predictors of in-hospital mortality were LVEF and presentation with shock or cardiac arrest. For patients discharged alive, non-stent treatment (HR 4.2, p = .01), TIMI-2 flow (HR 7.4, p = .002) and GFR < 60 mL/min (HR 3.8, p = .01) were independent predictors of ACD. The stent-treatment group had significantly better ACD-free survival after discharge, both unadjusted (p = .022) and adjusted (p = .018). CONCLUSIONS: After ST management, different predictors were observed for in-hospital mortality and mortality in patients discharged alive. The better outcome with NG-DES treatment is a novel observation, warranting further studies to elucidate if it is associated with stent-related or patient-related factors.

Omitting aspirin in PCI patients: Myth or reality?

In the current era of percutaneous coronary intervention (PCI), with the use of contemporary drug-eluting stents, refined techniques, and adjunctive pharmacotherapy, the role of aspirin peri-PCI remains undisputable. Beyond the initial period, dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 receptor inhibitor for 6 months in stable coronary artery disease and 12 months in acute coronary syndromes is the standard of care. However, concerns regarding bleeding adverse events caused by aspirin have led to shortened DAPT duration or even omission of aspirin. Aspirin free-strategies have been increasingly encountered in several studies and showed a significant reduction in bleeding events, without any sign of increased ischemic risk. Individualization of DAPT duration particularly in high bleeding risk patients appears therefore mandatory, making aspirin not necessary in several cases. Moreover, recent randomized trials have shed light on how to treat PCI patients in the presence of concomitant anticoagulant treatment with P2Y12 monotherapy and excluding aspirin. These aspirin-free strategies have been proved safer than the "older" standard triple antithrombotic treatment, without compromising safety. Ongoing studies may further dispel the myths and establish real facts regarding post-PCI-tailored treatment with or without aspirin.

How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction?

AIMS: Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation. METHODS AND RESULTS: In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2-95.8] to 36.7 (IQR: 22.7-59.5), P < 0.001. However, after stenting, IMR remained elevated (>40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: -0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: -0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR - pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm(3) of stent), P: 0.01] were associated with a potentially deleterious increase in IMR. CONCLUSION: Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burden.

Adenosine as an Adjunct Therapy in ST Elevation Myocardial Infarction Patients: Myth or Truth?

Early reperfusion represents the key strategy in ST elevation myocardial infarction. However, reperfusion may induce myocardial damage due to the reperfusion myocardial injury, compromising the full potential of reperfusion therapy and accounting for unfavourable results in high risk patients. Adenosine seems to attenuate ischemia reperfusion injury, and thus represents a promising therapeutic option for treating such patients. However, previous randomized clinical trials have collectively failed to demonstrate whether adenosine can effectively reduce measures of myocardial injury and improve clinical outcome, despite its good basic evidence. The failure of such trials to show a real beneficial action may be in part related to specific factors other than adenosine's clinical efficacy. The purpose of this review is to explain the rationale for the use of adenosine as an adjunctive pharmacological cardio-protective agent following reperfusion of the ischemic myocardium, to address the weakness of previous trials and to summarize the current state of knowledge regarding the effect of adenosine administration on reperfusion myocardial injury in patients with myocardial infarction. Although some preclinical and clinical studies point towards the beneficial role of adenosine in the prevention and treatment of no-reflow phenomenon in myocardial infarction, many unanswered questions still remain, including the optimal clinical indication, mode, dosage, duration and timing of application, and the exact mechanisms leading to potential benefits. Clarifying these issues will depend on further properly designed, adequately powered and well conducted clinical trials, which will probably provide us with the definite answers.

Tough balloon with a vulnerable shaft: an unexpected device failure.

A 73-year-old man, with a previous long drug-eluting stent (DES) from the mid-portion of the left main stem artery (LMS) to proximal left anterior descending artery (LAD), underwent elective coronary angiogram due to worsening anginal symptoms and an abnormal myocardial perfusion single photon emission computed tomography (SPECT) showing ischemia in the LAD territory.

Funny coronary arteriole perforation causes tamponade post-primary percutaneous coronary intervention.

An emergency transradial coronary angiography in a 68-year-old woman demonstrated sub-total occlusion of the proximal left anterior descending artery.

Therapeutic Potential of Sodium-glucose Co-transporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists for Patients with Acute Coronary Syndrome: A Review of Clinical Evidence.

Atherosclerotic Cardiovascular Disease (ASCVD) is still one of the leading causes of death globally, with Coronary Artery Disease (CAD) being the most prevalent form of ASCVD. Patients with type 2 Diabetes Mellitus (DM) experience an increased risk for ASCVD during the disease course, with CAD being the most common cause of death among affected individuals, resulting in shorter life expectancy and increased morbidity among survivors. Recently, 2 novel classes of anti-diabetic drugs, namely Sodium-Glucose Co-Transporter- 2 (SGLT-2) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists, have shown impressive cardio-renal benefits for patients with type 2 DM, while they might decrease cardio-renal risk even in the absence of baseline DM. However, there is no evidence to date regarding their safety and efficacy in the setting of an acute coronary syndrome (ACS) event, regardless of concomitant DM. This study aims to provide a detailed, updated presentation of currently available clinical evidence concerning the potential role of SGLT-2 inhibitors and GLP-1 receptor agonists in the setting of an ACS, and to highlight whether those drug classes could be utilized as adjuncts to standard-of-care treatment in this specific patient population, along with a presentation of the potential short- and long-term cardiovascular benefits.

Effects of Glucagon-Like Peptide 1 Receptor Agonists on Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Meta-analysis.

INTRODUCTION: Despite the technological advancements in catheter ablation strategies, the recurrence of atrial fibrillation (AF) post-ablation remains a concern that requires further investigation. Glucagon-like peptide 1 (GLP-1) receptor agonists have shown a significant effect on weight reduction, which in turn is associated with freedom from AF recurrence in both patients who are obese and not obese undergoing ablation. Therefore, we aimed to summarize the available evidence on the efficacy of GLP-1 receptor agonists in maintaining sinus rhythm post-ablation. METHODS: Medline, Cochrane Library, and Scopus were searched until June 9, 2024. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled using DerSimonian-Laird random effects meta-analysis. RESULTS: Three propensity score-matched studies (n = 6031 participants) were analyzed. Over a 12-months follow-up, the use of GLP-1 receptor agonists was associated with a significant reduction in AF recurrence compared to controls, hazard ratio (HR) = 0.549, 95% confidence interval (CI) = [0.315, 0.956], P = 0.034; I2 = 57%. No significant heterogeneity was observed (Q statistic = 4.6, heterogeneity P = 0.1). CONCLUSION: The use of GLP-1 receptor agonists is associated with a lower risk of AF recurrence in patients receiving AF ablation therapy. Further large-scale randomized trials are necessary to explore the efficacy of GLP-1 receptor agonists in maintaining ablation outcomes over the long term.