Predictors of recurrent cerebral ischemia after patent foramen ovale closure: A single center observational study.

OBJECTIVES: Transcatheter patent foramen ovale closure lowers recurrent stroke in patients with cryptogenic stroke or transient ischemic attack with an indication for closure. However, the incidence of recurrent stroke is not negligible and underlying pathophysiology remains largely unknown. We sought to evaluate the prevalence of recurrent ischemic neurological events and to assess its predictors after transcatheter patent foramen ovale closure. METHODS: We enrolled consecutive patients who underwent patent foramen ovale closure for secondary prevention of neurological ischemic events at the University Hospital of Parma between 2006 and 2021. Clinical and procedure-related features were collected for each patient. The incidence of recurrent ischemic neurological events was assessed at follow-up. RESULTS: We enrolled a total of 169 patients with mean Risk of Paradoxical Embolism score at hospital admission of 6.4 ± 1.5. The primary indication was previous cryptogenic stroke (94 [55.6 %] subjects), followed by transient ischemic attack (75 [44.4 %]). Among patients with complete outcome data (n= 154), after a median follow-up of 112 months, recurrent cerebral ischemia occurred in 13 [8.4 %], with an annualized rate of 0.92/100 patients. The presence of obesity [OR 5.268, p = 0.018], Risk of Paradoxical Embolism score < 7 [OR 5.991, p = 0.035] and migraine [OR = 5.932 p = 0.012] were independent positive predictors of recurrent stroke/ transient ischemic attack after patent foramen ovale closure. CONCLUSIONS: The presence of obesity, Risk of Paradoxical Embolism score < 7 and migraine were independent positive predictors of recurrent ischemic neurological events after patent foramen ovale closure.

A giant left atrial appendage: a case report on the feasibility of closure with a custom-made device.

Background: Transcatheter left atrial appendage occlusion (LAAO) is a valuable therapeutic option for stroke prevention in patients with atrial fibrillation (AF) at high bleeding risk. However, complex LAA anatomies sometimes preclude the adoption of commercially available LAAO devices. The design of a custom-made LAAO device is a promising strategy in these cases. However, few examples of custom-made devices in case of giant LAAs have been reported. Case summary: An 85-year-old man with permanent AF with CHA2DS2-VASc 4 and recurrent active gastrointestinal major bleedings was referred for transcatheter LAAO at Parma University Hospital after multidisciplinary team evaluation. Pre-procedural coronary computed tomography angiography revealed a giant windsock LAA, with a maximum ostium diameter of 44 mm, a landing zone diameter of 34 mm, and maximal length of 49 mm. Patient's management was particularly challenging given that available LAAO devices were too small to completely exclude the LAA. In accordance with the manufacturer, a custom-made LAmbre™ Closure System (Lifetech Scientific, Shenzhen, China), which specifically fitted with patient's LAA anatomy, was designed and successfully deployed under transoesophageal echocardiography (TEE) and fluoroscopic guidance. Periprocedural TEE confirmed the appropriate position of the device and the absence of peri-device leaks. No adverse ischaemic and haemorrhagic events were reported at 3-months follow-up. Discussion: We present a case of a successful transcatheter LAAO procedure by deploying a custom-made LAmbre device 38/46 mm to mechanically exclude a giant windsock LAA. This case illustrates the effectiveness of a custom-made device strategy, which potentially enables the closure of all complex LAA anatomies.

Dual Antiplatelet Therapy or Antiplatelet Plus Anticoagulant Therapy in Patients with Peripheral and Chronic Coronary Artery Disease: An Updated Review.

Despite evidence-based therapies, patients presenting with atherosclerosis involving more than one vascular bed, such as those with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), constitute a particularly vulnerable group characterized by enhanced residual long-term risk for major adverse cardiac events (MACE), as well as major adverse limb events (MALE). The latter are progressively emerging as a difficult outcome to target, being correlated with increased mortality. Antithrombotic therapy is the mainstay of secondary prevention in both patients with PAD or CAD; however, the optimal intensity of such therapy is still a topic of debate, particularly in the post-acute and long-term setting. Recent well-powered randomized clinical trials (RCTs) have provided data in favor of a more intense antithrombotic therapy, such as prolonged dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor or a therapy with aspirin combined with an anticoagulant drug. Both approaches increase bleeding and selection of patients is a key issue. The aim of this review is, therefore, to discuss and summarize the most up-to-date available evidence for different strategies of anti-thrombotic therapies in patients with chronic PAD and CAD, particularly focusing on studies enrolling patients with both types of atherosclerotic disease and comparing a higher- versus a lower-intensity antithrombotic strategy. The final objective is to identify the optimal tailored approach in this setting, to achieve the greatest cardiovascular benefit and improve precision medicine.

Looking for optimal antithrombotic strategy after transcatheter left atrial appendage occlusion: a real-world comparison of different antiplatelet regimens.

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an effective procedure for the prevention of thromboembolic events in non-valvular atrial fibrillation (AF) patients with contraindications to oral anticoagulation. After the procedure, different antithrombotic regimens have been used, in order to prevent device-related thrombus and trying to minimize bleedings. The search for the optimal antithrombotic strategy is still ongoing. We sought to assess efficacy and safety of different antiplatelet therapy (APT) regimens. METHODS: We enrolled non-randomized consecutive patients who underwent LAAO at the University Hospital of Parma between 2010 and 2021. Three study groups were identified according to post-procedural APT: long (>1, ≤12 months)-dual APT (DAPT), short (≤ 1 month)-DAPT, lifelong single APT (SAPT). The choice of the APT was left to multidisciplinary team evaluation. The incidence of the primary outcome, a composite of any ischemic or hemorrhagic event, was assessed at follow-up. RESULTS: We enrolled a total of 130 patients. Technical success was achieved in 123 (94.6%) patients. After LAAO, 39 [31.7%] patients were discharged on short-DAPT, 35 [28.5%] on long-DAPT and 49 [39.8%] on SAPT. After a median follow-up of 32 months, short-DAPT group had a significantly lower occurrence of the primary outcome (3 [7.7%] vs. 7 [20.0%] in long-DAPT vs. 14 [28.6%] in SAPT, p = 0.049], mainly driven by a lower occurrence of the bleeding endpoint (0 vs. 4 [11.4%] in long-DAPT vs. 9 [18.4%] in SAPT, p = 0.020). Finally, comparison of the Kaplan-Meier curves showed that short-DAPT group had a higher primary endpoint-free survival [p = 0.015] compared to the other groups. CONCLUSION: Post-procedural short-DAPT strategy was associated with better outcomes, mainly driven by reduction of major bleedings.

Severe hypertrophic cardiomyopathy in a patient with a homozygous MYH7 gene variant.

Background: Hypertrophic cardiomyopathy is an autosomal dominant disease. The main feature of this disorder is its occurrence in patients who present a left ventricular hypertrophy, unexplained by the loading conditions, usually asymmetric with greatest involvement most commonly of the interventricular septum.Case presentation During a sports medicine control, a ultrasound scan in a 17 years old patient has shown a concentric left ventricular parietal hypertrophy associated with a 23 mm mid- basal interventricular septum thickness. After genetic counselling, a positive family history for hypertrophic cardiac disease and parents' consanguineity was found. The genetic basis of the hypertrophic cardiomyopathy was investigated through a dedicated gene panel. The genetic test has revealed the presence of the variant c.3424G>A (p.Glu1142Lys) in the MYH7 gene in a homozygous state. Genotyping of the parents and of the two brothers revealed the presence of the MYH7 variant in heterozygosity in both parents and in the younger brother. In all of them, variable signs of hypertrophic cardiomyopathy were found. Conclusions: Our findings report the presence of a homozygous variant in a sarcomeric gene (MYH7) which gave rise to early HCM, whereas the variant in a heterozygous state was associated to much milder cardiac phenotypes in the affected relatives. The onset and the progression of the hypertrophic cardiomyopathy in the reported family is to be referred to the presence of the variant in hetero- or homo-zygosity in a gene dosage manner.

Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease (MINOCA).

BACKGROUND: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting. METHODS: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalisation for coronary revascularisation. RESULTS: MINOCA occurred in 317 patients (15.9%) and, during the follow-up, there was no significant difference in MACE rates between them and the patients with obstructive coronary artery disease (MICAD: 27.8% vs 37.5%; adjusted hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.09;p = 0.15). The CV death rate was lower in the MINOCA group (4.2% vs 8.4%, HR 0.26, 95%CI 0.08-0.86;p = 0.03), whereas the rates of non-fatal reinfarction (17.3% vs 25.4%; HR 0.76, 95%CI 0.52-1.13;p = 0.18), non-fatal ischemic stroke (9.5% vs 3.7%; HR 1.79, 95%CI 0.87-3.70;p = 0.12), and all-cause mortality (14.1% vs 20.7%, HR 0.73, 95%CI 0.43-1.25;p = 0.26) were not significantly different in the two groups. The rate of rehospitalisation for coronary revascularisation was lower among the MINOCA patients (6.7% vs 27.7%; HR 0.27, 95% CI 0.15-0.47;p < 0.001). CONCLUSIONS: MINOCA is frequent and not benign in patients with early-onset MI. Although there is a lower likelihood of CV death,the long-term risk of MACE and overall mortality is not significantly different from that of MICAD patients.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Left atrial appendage occlusion in patients with atrial fibrillation and large prevalence of prior intracranial bleeding.

BACKGROUND: Left atrial appendage occlusion (LAAO) represents an alternative approach for the prevention of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF) and contraindication for oral anticoagulation (OAC). The aim of our study was to analyse the outcomes in patients treated with LAAO, with a focus on cases with previous intracranial bleeding. METHODS: Sixty patients with NVAF underwent LAAO (75.4 ±â€Š9 years); mean CHA2DS2-VASc was 4.4 ±â€Š1.7, mean HAS-BLED 3.2 ±â€Š0.9. Thirty-two patients (53.3%) reported previous intracranial bleeding. Ischaemic and bleeding events recorded during follow-up were compared with expected event rates according to CHA2DS2-VASc and HAS-BLED scores. RESULTS: Device implantation was successful in 58 patients (96.7%). The antiplatelet therapy was tailored according to patients' bleeding risk. During follow-up (2.32 ±â€Š1.5 years) 3 ischaemic strokes and 1 transient ischaemic attack occurred, versus 13 total expected thromboembolic events (P = 0.033); 5 major bleedings were observed, versus 7 expected ones, if the patients were under OAC. Considering the combined endpoint (thromboembolic and major bleeding events) 9 events were observed versus 20 expected major events (P = 0.031). In the prespecified subgroup of patients with previous intracranial bleeding, two ischaemic strokes and one transient ischaemic attack were observed during follow-up versus six total expected thromboembolic events; no intracranial bleeding recurrence was recorded. Regarding the combined endpoint four major events were recorded versus nine expected ones. CONCLUSION: LAAO is an efficient and safe option for the prevention of cardioembolic stroke in patients with NVAF, high thromboembolic risk and contraindication to OAC, particularly in patients with previous intracranial bleeding.