Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis.

BACKGROUND: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. METHODS: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses. RESULTS: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39). CONCLUSIONS: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.

Outcomes during the first year following spontaneous coronary artery dissection: A systematic timeframe pooled analysis.

OBJECTIVES: We aimed to compare the incidence and timing of major adverse cardiovascular events (MACE) within the first year after spontaneous coronary artery dissection (SCAD) according to the management strategy: conservative versus invasive. BACKGROUND: Treatment of SCAD remains controversial. METHODS: A pooled analysis of studies providing separate individual clinical outcomes for conservative and invasive treatment strategies within 1 year after SCAD was performed. The primary outcome measure was MACE incidence within three predefined study periods after SCAD, namely "in-hospital", "discharge-to-6-months" and "6-to-12-months". MACE was defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, heart failure and SCAD recurrence. RESULTS: A total of 16 studies (444 patients) were included; 277 (62%) patients were treated conservatively and 167 (38%) invasively. Within 1-year follow-up, 39 (67%) MACE occurred during the in-hospital period compared to 10 (17%) in the "discharge-to-6 months" period and 9 (16%) in the "6-to-12-months" period (p < 0.0001 for the overall comparison). MACE incidence was also significantly different between the three study periods in the conservatively-treated group (23 [78%] vs. 7 [23%] vs. 0 [0%], respectively; p < 0.0001) and the invasively-treated group (12 [66%] vs. 3 [17%] vs. 3 [17%], respectively; p < 0.0001), although no significant difference was found regarding MACE incidence in the intra-period comparisons between conservative and invasive treatment strategies. CONCLUSIONS: This pooled analysis showed that most MACE following SCAD occurred during the in-hospital period compared to the following two semesters, regardless of the treatment strategy. No difference regarding MACE incidence was found between conservative and invasive strategies in each study period.

Atrial fibrillation and coronary artery disease: a review on the optimal use of oral anticoagulants.

Atrial fibrillation (AF) represents the most prevalent supraventricular arrhythmia in adults population and up to 15% of AF patients undergo percutaneous coronary intervention (PCI) for coronary artery disease (CAD) during their life. While oral anticoagulants (OACs) exert a protective effect in the setting of stroke prevention and systemic embolization in AF patients, patients undergoing PCI are recommended to receive dual antiplatelet therapy (DAPT) to reduce the risk of cardiovascular death, recurrent myocardial infarction and stent thrombosis. When these two scenarios coexist, as all antithrombotic regimens are burdened by an increase in bleeding risk, antithrombotic regimen and therapy duration must be cautiously tailored on individual patients' characteristics after attentive assessment of ischemic and bleeding risks. Non-vitamin K oral anticoagulants (NOACs), directly inhibiting either thrombin or factor Xa of the coagulation cascade, have progressively replaced warfarin as first choice OACs in several scenarios; recently, randomized controlled trials have compared antithrombotic regimens including NOAC molecules vs vitamin K antagonists in AF patients undergoing PCI to explore the efficacy and safety of NOACs in this setting. These studies have provided a deeper understanding of antithrombotic therapy after PCI in AF patients and have been promptly implemented by the most recent guidelines on AF and CAD management. The aim of the present review was to summarize the current available literature on the perils and benefits of individual OAC molecules in AF patients with acute and/or chronic coronary syndromes in order to provide guidance on the optimal use of OACs in these complex scenarios.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Comparison of antithrombotic strategies in patients with cryptogenic stroke and patent foramen ovale: an updated meta-analysis.

PURPOSE: Patients with patent foramen ovale (PFO) and cryptogenic ischemic stroke (CS) are at risk for stroke recurrence. The optimal antithrombotic strategy in patients who undergo medical management is still debated. METHODS: We systematically searched the literature for studies that reported on cerebrovascular event recurrences and/or death in patients with PFO treated with oral anticoagulation (OAC) or antiplatelet therapy (APT) for secondary prevention of CS. The efficacy endpoints were stroke recurrence and the composite of stroke, transient ischemic attack or all-cause death. Major bleedings represented the safety endpoint. RESULTS: A total of 16 studies with 3953 patients (OAC = 1527, APT = 2426) were included. Weighted mean follow-up was 2.9 years. OAC was associated with a significant reduction in the risk of stroke compared with APT (RR 0.65; 95% CI 0.44-0.95; ARR 2%, NNT 49), while no difference was found regarding the composite outcome (RR 0.78; 95% CI 0.57-1.07) and the safety outcome (RR 1.57; 95% CI 0.85-2.90; p = 0.15). CONCLUSIONS: OAC was more effective than APT in reducing the risk of stroke recurrence in patients with PFO and CS, without a significant increase in the risk of major bleedings. Our findings support the need for further randomized data focused on the comparison of antithrombotic strategies in this setting.

New anti-diabetic agents: major advances with unanswered questions.

No abstract present.

Anticoagulant and anti-thrombotic therapy in acute type B aortic dissection: when real-life scenarios face the shadows of the evidence-based medicine.

BACKGROUND: Evidence-based recommendations about anticoagulation in acute type B aortic dissection (TBAD) are completely missing, but there is a diffuse conviction that it could prevent the healing process of the dissected aorta's false lumen. However, several clinical conditions may lead to the necessity to start anticoagulant therapy among patients with acute type B aortic dissection, ranging from atrial fibrillation to more complicated clinical scenarios and the correct management in this kind of patients is still an open issue. CASE PRESENTATION: We are presenting a 51-years-old man with multi-infarct encephalopathy referred to us for an acute TBAD and a first diagnosis of ischemic cardiomyopathy complicated by left ventricular (LV) thrombus formation. Coronary angiography revealed a critical stenosis of left anterior descending artery (LAD) treated with drug-eluting stent deployment. The patient was addressed to triple antithrombotic therapy with acetylsalicylic acid, clopidogrel and warfarin with target INR 2.0-2.5. After 6 months, computed tomography angiography revealed the stability of the dissection flap. Cardiac magnetic resonance imaging, however, confirmed the persistence of a small thrombotic formation in LV apex, thus double antithrombotic therapy with warfarin and clopidogrel was instituted. The patient remained asymptomatic during the follow-up period but was advised to suspend his job and physical activities. CONCLUSION: Current guidelines do not discuss anticoagulant therapy in the setting of TBAD and large randomized trials are lacking. Despite it is generally considered unsafe to administer anticoagulants in patients with TBAD, we present a case in which triple antithrombotic therapy was well tolerated and did not lead to progression of the intimal flap after 6 months.

Subclinical and Asymptomatic Atrial Fibrillation: Current Evidence and Unsolved Questions in Clinical Practice.

Atrial Fibrillation (AF) may be diagnosed due to symptoms, or it may be found as an incidental electrocardiogram (ECG) finding, or by implanted devices recordings in asymptomatic patients. While anticoagulation, according to individual risk profile, has proven definitely beneficial in terms of prognosis, rhythm control strategies only demonstrated consistent benefits in terms of quality of life. In fact, evidence collected by observational data showed significant benefits in terms of mortality, stroke incidence, and prevention of cognitive impairment for patients referred to AF catheter ablation compared to those medically treated, however randomized trials failed to confirm such results. The aims of this review are to summarize current evidence regarding the treatment specifically of subclinical and asymptomatic AF, to discuss potential benefits of rhythm control therapy, and to highlight unclear areas.

Autonomic Tone Activity Before the Onset of Atrial Fibrillation.

INTRODUCTION: The autonomic nervous system has been proven to play a major role in the onset of atrial fibrillation (AF), along with a predisposing substrate and a specific trigger event usually consisting of a premature supraventricular ectopic beat (SVEB). By means of heart rate variability (HRV) analysis, we investigated the activity of the autonomic nervous system before SVEBs nontriggering and triggering AF. METHODS AND RESULTS: We evaluated 28 patients with at least 1 episode of sustained AF (>30 seconds) recorded during 24-hour Holter monitorings. We performed HRV analysis during the hour preceding 35 AF onsets and compared these results with the HRV values before nontriggering SVEBs with similar prematurity. According to the low frequency (LF)/high frequency (HF) ratio in the 5 minutes before the onset, AF episodes were classified as either vagal (LF/HF ratio <1.5) or adrenergic (LF/HF ratio ≥1.5).Vagal episodes (16) showed a decrease in LF (from 50.81 ± 1.67 to 32.73 ± 3.54) and an increase in HF (from 36.00 ± 2.30 to 54.7 ± 3.69) throughout the hour preceding the onset. Adrenergic episodes (19) had opposite changes in LF (from 55.4 ± 4.95 to 67.51 ± 5.24) and HF (from 33.78 ± 5.82 to 27.96 ± 3.51) during the same period. No similar trends were observed before the selected nontriggering SVEBs. CONCLUSION: Only SVEBs occurring during a phase of hyperactivity of one of the 2 branches of the autonomic nervous system are able to trigger episodes of AF.

Organ perfusion pressure at admission and clinical outcomes in patients hospitalized for acute heart failure.

AIMS: Hypoperfusion portends adverse outcomes in acute heart failure (AHF). The gradient between end-organ inflow and outflow pressures may more closely reflect hypoperfusion than mean arterial pressure (MAP) alone. The aim of this study was to investigate organ perfusion pressure (OPP), calculated as MAP minus central venous pressure (CVP), as a prognostic marker in AHF. METHODS AND RESULTS: The Sodium NItroPrusside Treatment in Acute Heart Failure (SNIP)-AHF study was a multicentre retrospective cohort study of 200 consecutive patients hospitalized for AHF treated with sodium nitroprusside. Only patients with both MAP and invasive CVP data available from the SNIP-AHF cohort were included in this analysis. The primary endpoint was to assess OPP as a predictor of worsening heart failure (WHF), defined as the worsening of signs and symptoms of heart failure leading to intensification of therapy at 48 h. One hundred and forty-six patients fulfilling the inclusion criteria were included [mean age: 61.1 ± 13.5 years, 32 (21.9%) females; mean body mass index: 26.2 ± 11.7 kg/m2; mean left ventricular ejection fraction: 23.8%±11.4%, mean MAP: 80.2 ± 13.2 mmHg, and mean CVP: 14.0 ± 6.1 mmHg]. WHF occurred in 14 (9.6%) patients. At multivariable models including hemodynamic variables (OPP, shock index, and CVP), OPP at admission was the best predictor of WHF at 48 h [OR 0.91 (95% confidence interval 0.86-0.96), P-value = 0.001] with an optimal cut-off value of 67.5 mmHg (specificity 47.3%, sensitivity 100%, and AUC 0.784 ± 0.054). In multivariable models, including univariable significant parameters available at first bedside assessment, namely New York Heart Association functional class, OPP, shock index, CVP, and left ventricular end-diastolic diameter, OPP consistently and significantly predicted WHF at 48 h. CONCLUSION: In this retrospective analysis on patients hospitalized for AHF treated with sodium nitroprusside, on-admission OPP significantly predicted WHF at 48 h with high sensitivity.

Comprehensive non-invasive Hemodynamic Assessment in Acute Decompensated Heart Failure-Related Cardiogenic Shock. A step towards echodynamics.

BACKGROUND: Hemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of hemodynamics in acute decompensated heart failure-related CS (ADHF-CS). METHODS: All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 minutes before RHC. The evaluated hemodynamic parameters and their echocardiographic estimates ("e") comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). RESULTS: 101 ADHF-CS patients (56±11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29±5%) were included. Good correlation was found for CI, systolic PAP, RAP and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r=0.67) and PVR (r=0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 l/min/m2) were 0.97 and 0.73 respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO<0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, p<0.001). CONCLUSIONS: Echocardiographic estimation of hemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation.

De-escalation of dual antiplatelet therapy for patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis.

OBJECTIVES: To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). DESIGN: We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed. SETTING AND PARTICIPANTS: Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT. SEARCH METHODS: A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials. INTERVENTIONS: Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1-3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3-6 months. MAIN OUTCOME MEASURES: Primary outcome: Cardiovascular mortality. SECONDARY OUTCOMES: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE). RESULTS: 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3-6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89). CONCLUSIONS: DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3-6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not.

Pickering syndrome in a patient with Takayasu's arteritis.

Takayasu arteritis (TA) is a chronic granulomatous large vessel arteritis. The renal arteries are affected in up to 60% of patients with TA, with renal artery stenosis (RAS) potentially leading to ischemic nephropathy, severe arterial hypertension, and heart failure. Bilateral RAS may rarely present with recurrent flash pulmonary edema, a life-threatening association which has been termed Pickering syndrome. In this report, we describe a 55-year-old woman with severe refractory arterial hypertension admitted for acute pulmonary edema, initially treated unsuccessfully with medical therapy with vasodilators and diuretics. Given the instrumental findings of bilateral RAS and suggestive signs and symptoms, the diagnosis of TA was made, resulting as the first described case of Pickering syndrome being the clinical presentation of TA. Interventional therapy with renal artery angioplasty procedure was performed with stenting of both right and left renal arteries, leading to the resolution of the clinical scenario and the successful discharge of the patient. At the 1 year follow-up visit the patient was asymptomatic and in good clinical conditions; a significant reduction in antihypertensive therapy was achieved while immunosuppressive therapy was continued. This case highlights that secondary causes of TA should always be sought in patients with refractory hypertension who do not respond to standard treatment; also, TA should be suspected in young patients with bilateral RAS, especially when other typical signs of TA are present; lastly, a thorough investigation is essential in complicated cases, as rare diseases like TA may manifest in unusual ways.

Prevalence and predictors of left atrial thrombosis in atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants.

BACKGROUND: Few data are available regarding the prevalence of left atrium (LA) thrombi in atrial fibrillation (AF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods: We evaluated the prevalence and predictors of LA/LA appendage (LAA) thrombi in non-valvular AF patients treated with NOACs referring to a single centre for a scheduled electrical cardioversion (ECV) or catheter ablation (CA). Transesophageal echocardiography (TEE) was performed within 12 h prior to the index procedure. RESULTS: A total of 352 consecutive patients with non-valvular AF treated with NOACs were included in this analysis (ECV group n = 176 and CA group n = 176) between 2013 and 2018. 85 patients (24.2%) were on dabigatran, 150 (42.7%) on rivaroxaban, 104 (29.6%) on apixaban and 13 (3.7%) on edoxaban. A LA/LAA thrombus was detected by TEE in 27 (7.7%) patients, 18 in the ECV group and nine in the ablation group; 18 (5.1%) patients presented dense LA/LAA spontaneous echo contrast (SEC). Predictors of LA/LAA thrombi were a CHA2DS2-VASc score > 3 (OR 4.54, 95% CI 1.50 - 13.70, p value = .007) and obesity (OR 6.01, 95% CI 1.95 - 18.50, p value = .001). CONCLUSIONS: Among real-world patients with non-valvular AF treated with NOACs, we found a high incidence of LA/LAA thrombi compared to previous reports. The main predictors of LA/LAA thrombosis were a CHA2DS2-VASc score > 3 and obesity.

Risk of cardioembolic ischemic events and relation to atrial fibrillation/flutter in patients with arrhythmogenic cardiomyopathy during a long-term follow-up.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by fibro-fatty replacement of myocardium. Limited data is available concerning cardioembolic stroke. This study sought to determine the occurrence of cardioembolic ischemic events (CIEs) in ACM patients and to identify clinical and imaging predictors of CIEs. METHODS: Every consecutive ACM patient was enrolled. ECG, Holter monitoring or implantable cardiac devices were used to detect atrial arrhythmias (AAs). CIEs were defined according to TOAST classification. RESULTS: In our cohort of 111 patients, CIEs were observed in eleven (10%) over a 12.9-year median follow-up, with an incidence of 7.9 event/1000 patient-year (HR 4.12 compared to general population). Mean age at the event was 42 ± 9 years. Female sex (p = 0.03), T-wave inversion (p = 0.03), RVOT dilatation (p = 0.006) and lower LVEF (p = 0.006) were associated with CIEs. Among patients with AAs (23/111, 20.7%), 5 (21.7%) experienced CIEs. CHA2DS2-VASc did not prove useful to define patients at higher risk of CIEs (p = 0.098). 60% of stroke suffering patients had a pre-event score between 0 and 1 (if female). CONCLUSIONS: In ACM patients, CIEs are much more common than in general population and present a high burden at younger age. AAs relate to less than half of these events. In AAs patients, CHA2DS2-VASc is not useful to stratify those requiring oral anticoagulation. As a hypothesis-generating study, our research proposes the role of atrial myopathy, irrespective of AAs, as a pivotal factor in thrombogenesis risk, pointing out a definite unmet need in ACM therapeutic algorithm.