European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Clinical characteristics and prognosis of hospitalized COVID-19 patients with incident sustained tachyarrhythmias: A multicenter observational study.

INTRODUCTION: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID-19. The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. MATERIALS AND METHODS: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. RESULTS: 414 hospitalized patients with COVID-19 (66.9 ± 15.0 years, 61.1% male) were included in the present study. During a median follow-up of 28 days (IQR: 12-45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new-onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in-hospital mortality (RR: 2.55; P: .003). CONCLUSIONS: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients.

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.

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism.

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.

Incidental diagnosis of four pulmonary arteriovenous fistulas during patent foramen ovale closure: a case report.

Cryptogenic cerebral ischemia in young patients is commonly ascribed to paradoxical embolism. We report the clinical case of a young patient with cryptogenic stroke and a patent foramen ovale, undergoing percutaneous closure of atrial septal defect. Contrast transoesophageal echocardiography at the end of the procedure demonstrated massive late residual right-to-left shunt, due to the coexistence of pulmonary arteriovenous fistulas that were subsequently closed. Routinary adoption of contrast transoesophageal echocardiography at the end of patent foramen ovale closure interventions may be useful to detect early and late residual shunts. Late residual shunts may be due to pulmonary fistulas, a well-known risk factor for recurrent thromboembolic events.

Culprit plaque characteristics in younger versus older patients with acute coronary syndromes: An optical coherence tomography study from the FORMIDABLE registry.

OBJECTIVES: Culprit plaque characteristics in young patients who experience an Acute Coronary Syndrome (ACS) evaluated by OCT (Optical Coherence Tomography) have to be defined. The OCT-FORMIDABLE is a multicentre retrospective registry enrolling consecutive patients with ACS who performed OCT in 9 European centres. METHODS: Patients were divided in two groups according to age at presentation: juvenile-ACS (age ≤ 50 years) and not juvenile-ACS (age > 50 years). Primary end-point was the prevalence of plaque rupture (PR). Secondary end point was the prevalence of thin cap fibro atheroma (TCFA), fibrocalcific and fibrotic plaque. RESULTS: 285 patients were included, 71 (24.9%) in juvenile-ACS group and 215 (75.1%) in not juvenile-ACS group. Younger patients showed a trend for a higher prevalence of TCFA (70 vs. 58%, P = 0.06) and thrombus presence (62 vs. 51%, P = 0.1), while no statistical difference concerning PR (70 vs. 64%, P = 0.29). Of interest patients younger that 35 years showed a higher prevalence of PR compared to patients aged between 35 and 45 or 45 and 50 years (100 vs. 72 vs. 55%, P = 0.03). Culprit plaque in juvenile-ACS group showed more frequently a reduced mean cap thickness (119 ± 66 vs. 155 ± 95 nm, P = 0.05) and less frequently fibrotic (32 vs. 57%, P < 0.001) or fibrocalcific (17 vs. 36%, P = 0.003) characteristics. CONCLUSION: young patients with ACS show a trend for a higher prevalence of culprit PR, a thinner cap and less fibrotic or fibrocalcific components.

Angiography vs transesophageal echocardiography-guided patent foramen ovale closure: A propensity score matched analysis of a two-center registry.

OBJECTIVES: The purpose of this study is to compare the long-term outcomes of patent foramen ovale (PFO) closure using angiography or transesophageal echocardiography as procedural guidance. BACKGROUND: The interventional treatment is emerging as a safe and efficient option for patients with high likelihood of PFO-related cryptogenic stroke and high risk of recurrence. The "gold-standard" guidance technique remains an issue. METHODS: Two cohorts of patients undergoing PFO closure for cryptogenic stroke in two catheterization laboratories of the same institution, using similar inclusion criteria but different guidance, were compared with propensity score matching. RESULTS: A total of 374 patients were enrolled, 161 in Angio-group and 213 in Echo-group. No difference was detected in the procedural complication rate. In Angio-group, radiological exposure (P = .001) and 6-month residual shunt (16.8% vs 8.0%, P = .015) were higher. After a mean follow-up of 41 ± 30 months, 28 patients (7.5%) presented any adverse event (death, recurrent cerebral ischemia, device-related complications, reintervention), with a higher rate in Angio-group (13.0% vs 3.3%, P = .001), mainly due to repeated percutaneous intervention (10.6% vs 1.4%, P = .001). The results were confirmed after propensity score matching (118 patients/group). The rate of recurrent cerebral ischemia was 1.9% and was not significantly different in the two groups. Intra-procedural guidance and atrial septum aneurysm were independent predictors of the composite primary endpoint (OR 1.2, P = .016). CONCLUSIONS: The use of intra-procedural transesophageal echocardiography (TEE) guidance for PFO closure allows lower residual shunt rate, radiological exposure, and adverse events, mainly driven by a significant reduction in percutaneous reintervention.

Outcomes of patients with low-pressure aortic gradient undergoing transcatheter aortic valve implantation: A Meta-analysis.

BACKGROUND: The risk/benefit balance of transcatheter aortic valve implantation (TAVI) in patients with low-gradient aortic stenosis (LGAS) remains to be well defined. Aim of the study was to investigate the impact of LGAS in patients undergoing TAVI. METHODS: Medline, Cochrane Library, and Scopus were searched for articles reporting outcome of patients with LGAS undergoing TAVI. The primary endpoint was 12-months all-cause mortality and the secondary endpoint was 30-day all-cause mortality. Using event-rates as dependent variable, a meta-regression was performed to test for interaction between baseline clinical features (age, gender, diabetes mellitus, coronary artery disease, left ventricular ejection fraction (LVEF) and type of implanted valve) and transaortic gradient for the primary endpoint. RESULTS: Eight studies with a total of 12,589 patients were included. Almost one-third of the patients presented with LGAS (27.3%: 24.4-29.2). Median LVEF was 48% in patients with LGAS and 56% in patients with high-gradient AS. Patients with LGAS were more likely to have diabetes mellitus, previous coronary artery disease, higher mean Logistic EuroSCORE, and lower EF. At 12 (12-16.6) months, low transaortic gradient emerged as independently associated with all-cause death, both if evaluated as a dichotomous and continuous value (respectively OR 1.17; 1.11-1.23 and OR 1.02; 1-1.04, all CI 95%). Clinical variables, including EF did not affect this result. CONCLUSIONS: In a population of TAVI patients, LGAS appears to be independently related to dismal prognosis. © 2016 Wiley Periodicals, Inc.

Recurrent cerebral ischemia after patent foramen ovale percutaneous closure in older patients: A two-center registry study.

OBJECTIVES: The aim of this study is to describe the cerebral ischemia recurrence rate after percutaneous patent foramen ovale (PFO) closure in patients older than 55 years and their outcomes, compared with younger patients. BACKGROUND: The registries data and the recent randomized trials about PFO closure are focused on patients younger than 55 years. Little is known about older patients' long-term outcome. METHODS: In total, 458 patients underwent PFO closure for cryptogenic cerebral ischemia and were stratified into an "older" (≥ 55 years, 151 patients) and a "younger" (<55 years, 307 patients) group. RESULTS: Older patients had mean age of 63 ± 6 years and more atrial septum aneurysm (P = 0.05), hypertension, diabetes, and dyslipidemia (P = 0.001). Mean followup was 4.5 ± 2.8 years. Older patients had a higher rate of ischemic recurrence (0.3 vs. 4.0%, P = 0.002), after a mean time of 3.1 ± 2.6 years. The Kaplan-Meier curve confirmed higher event-free survival in the youngers (P = 0.008). None of the patients with ischemic recurrence had significant residual shunt. Age and hypertension were correlated to ischemic recurrence, but age was the only independent predictor at multivariate analysis. CONCLUSIONS: Recurrent cerebral ischemia after PFO closure is more frequent in older patients and could most likely be associated to conditions related to age (atherosclerosis, atrial fibrillation), than to paradoxical embolism. The procedure is as safe as in younger patients.

A meta-analysis of sex-related differences in outcomes after primary percutaneous intervention for ST-segment elevation myocardial infarction.

INTRODUCTION: The increasing use of primary percutaneous coronary intervention (pPCI) has improved clinical outcome in ST-segment elevation myocardial infarction (STEMI) patients, but the impact of sex on early and mid-term outcomes remains to be defined. METHODS: Medline, Cochrane Library, Biomed Central, and Google Scholar were searched for articles describing differences in baseline, periprocedural, and midterm outcomes after pPCI, by sex. The primary end point was all-cause mortality at early and mid-term follow-up. Secondary endpoints included in-hospital bleeding and stroke. RESULTS: Sixteen studies were included. Women were older, had more frequent hypertension, diabetes mellitus, and hypercholesterolemia, as well as longer ischemia time and more shock at presentation. Men were more likely to have had a previous myocardial infarction. Female sex emerged as independently associated to early mortality (OR 1.1; 95%CI, 1.02-1.18) but not to mid-term mortality (OR, 1.01; 95%CI, 0.99-1.03). The pooled analysis showed a significantly higher risk of in hospital stroke (OR, 1.69; 95%CI, 1.11-2.56) and major bleeding (OR, 2.04; 95%CI, 1.51-2.77) in women. CONCLUSIONS: As compared to men, women undergoing pPCI have more bleedings and strokes, and a worse early, but not mid-term mortality. These findings may allow a better risk stratification of pPCI patients.

Coronary Thrombosis and Type A Aortic Dissection.

A 74-year-old female had urgent surgery with replacement of the ascending aorta for acute type A dissection. Postprocedure, the electrocardiogram showed an ST-segment elevation myocardial infarction in the antero-lateral leads. Angiography revealed a thrombotic occlusion of the left anterior descending artery, treated successfully with bivalirudin administration, thrombus aspiration and a balloon angioplasty. This case involves the rare coexistence of acute type A aortic dissection and myocardial infarction due to coronary plaque thrombosis.

Iatrogenic erosion of the septum primum resulting in an atrial septal defect with left-to-right shunt: a rare pitfall of patent foramen ovale percutaneous closure.

Iatrogenic erosion of the septum primum after foramen ovale closure is an anecdotal event. We report the case of a 39-year-old woman admitted to our institution for multifocal cryptogenic cerebral ischemia and a patent foramen ovale (PFO) associated with an aneurysm of the septum primum. The patient underwent percutaneous closure of the PFO with an Amplatzer PFO Occluder device. At the 6-months follow up, the device was in the right position, but a jagged defect of the septum primum and evidence of significant left-to-right shunting was detected. The atrial septal defect was then repaired by a surgical approach. Although this event is not life-threatening, it should be considered as a therapeutic pitfall, resulting in a risk of paradoxical embolism recurrences and long-term hemodynamic impairment. © 2013 Wiley Periodicals, Inc.

A rare case of upper septal fascicular ventricular tachycardia presented in a case report.

CASE SUMMARY: A 71-year-old presented at the outpatient clinic with palpitations and NYHA II functional class. 12-lead ECG exhibited Upper septal idiopathic left ventricular tachycardia (US-ILVT). Ventricular tachycardia (VT) was interrupted with Verapamil administration, no further recurrences were documented after beta-blockers therapy was started. No coronary artery stenosis were detected. The US-ILVT was successfully treated by ablating the proximal site of the left anterior fascicle (LAF), where diastolic potential (P1) and pre-systolic potential (P2) with inverted sequence were detected during the electrophysiology study (EP) study. Cardiac magnetic resonance imaging (CMR) was performed with demonstration of intramyocardial late gadolinium enhancement (LGE) at the level of middle-basal portions of interventricular septum and basal portion of infero-lateral wall and no edema detection. A single catheter implantable cardioverter defibrillator (ICD) was implanted as secondary prevention. VT has never recurred during 3 months of follow-up with remote control of ICD. DISCUSSION: To the best of our knowledge, this is the first report in which US-ILVT was associated with ventricular septal LGE, suggestive of previous myocarditis, as substrate of re-entrant circuit. Scar-related ventricular tachycardia circuit is also suggested by the evidence of a premature ventricular complex (PVC) as trigger of recurrent VT in our case.

Use of Taurolidine in a Patient With a Cardiac Implantable Electronic Device Protrusion.

We report the successful salvage of cardiac implantable electronic device pulse generator protrusion sealed by the surrounding skin in a frail patient presenting 5 months after the last surgical revision. (Level of Difficulty: Advanced.).

Estimation of Aortic Stiffness with Bramwell-Hill Equation: A Comparative Analysis with Carotid-Femoral Pulse Wave Velocity.

Aortic stiffness is an important clinical parameter for predicting cardiovascular events. Carotid-femoral pulse wave velocity (cf-PWV) has been proposed for performing this evaluation non-invasively; however, it requires dedicated equipment and experienced operators. We explored the possibility of measuring aortic stiffness using ultrasound scans of the abdominal aorta coupled with the Bramwell-Hill equation. Healthy subjects were investigated; measurements of cf-PWV were taken by arterial tonometry and aortic systo-diastolic pressure difference was estimated using a validated model. Pulsatility of an abdominal tract of aorta was assessed by automated processing of ultrasound scans. Through a Bland-Altmann analysis, we found large biases when estimating each parameter by applying the Bramwell-Hill equation to the measured values of the other two paramters (bias, ± 1.96 SD; PWV, about 2.1 ± 2.5 m/s; pulsatility, 12 ± 14%; pressure jump, 47 ± 55 mmHg). These results indicate that the two measures are not interchangeable, and that a large part of the bias is attributable to blood pressure estimation. Further studies are needed to identify the possible sources of bias between cf-PWV and aortic pulsatility.

Inferior Vena Cava Edge Tracking Echocardiography: A Promising Tool with Applications in Multiple Clinical Settings.

Ultrasound (US)-based measurements of the inferior vena cava (IVC) diameter are widely used to estimate right atrial pressure (RAP) in a variety of clinical settings. However, the correlation with invasively measured RAP along with the reproducibility of US-based IVC measurements is modest at best. In the present manuscript, we discuss the limitations of the current technique to estimate RAP through IVC US assessment and present a new promising tool developed by our research group, the automated IVC edge-to-edge tracking system, which has the potential to improve RAP assessment by transforming the current categorical classification (low, normal, high RAP) in a continuous and precise RAP estimation technique. Finally, we critically evaluate all the clinical settings in which this new tool could improve current practice.

Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

BACKGROUND AIMS: Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. METHODS: The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. RESULTS: Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. CONCLUSIONS: Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

Percutaneous closure of patent foramen ovale in patients with anatomical and clinical high-risk characteristics: long-term efficacy and safety.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) is a widespread procedure, but no randomized study on its outcome in high-risk patients is available. Our aims were to determine the efficacy and safety of this procedure in a cohort of high-risk patients through the observation of clinical adverse events and residual shunt, to evaluate the impact of transesophageal echocardiography (TEE) guidance during the procedure, and investigate the relationship between the anatomical and clinical characteristics and the outcome. METHODS AND RESULTS: Ninety-five patients underwent PFO closure for cryptogenic cerebral ischemia; each of them presented one or more of the following risk factors: recurrent cerebral ischemia (9.5%), atrial septum aneurysm (ASA, 74.5%), prominent Eustachian valve (EV, 23.2%), severe basal shunt (9.5%), thrombophilic factors (20%), deep vein thrombosis (4.2%). The procedure was performed successfully in all patients. On median follow-up of 18 months, the neurologic recurrent events rate was 1.1% and the major adverse cardiac event (MACE) rate was 1.1%. At 6-month TEE follow-up, the residual shunt rate was 12.6% (3.1% moderate to severe). A significant correlation was found between residual shunt and prominent EV alone (P = 0.036) or in association with ASA (P = 0.021). All adverse events occurred in the first 8 months, and the event-free survival rate was 86.2%. CONCLUSIONS: Our study suggests that transcatheter PFO closure is a safe procedure even in a selected population of high-risk patients, presenting satisfactory efficacy and safety. The presence of a prominent EV alone or with ASA correlates positively with the occurrence of residual shunt.

Left atrial appendage closure device complicated by late-onset pericardial effusion and tamponade: a case report.

BACKGROUND: Late-onset complications of left atrial appendage occlusion (LAAO) device procedure are anecdotal and there are no such complications reported in literature using Cardia Ultraseal (Cardia, Inc., Eagan, MN, USA). CASE SUMMARY: We report the case of a 74-year-old Caucasian man affected by paroxysmal atrial fibrillation with significant bleeding risk (familiar thrombocytopenia, macroscopic haematuria episodes during therapy with direct oral anticoagulants, HAS-BLED risk score: 4) and ischaemic risk as well (CHADSVASC score: 3). The patient was treated with LAAO device implantation for high bleeding risk. Subsequently, after 26 days from LAAO procedure, he was admitted to the emergency department for haematic cardiac tamponade. The patient was successfully treated with subxyphoidal pericardiocentesis in the acute phase, unfortunately cardiac arrest occurred during the transfer to the referral hospital for urgent cardiac surgery. Permanent neurological damage was reported and the patient died on day 28. DISCUSSION: LAAO late-onset complications are very rare and the case presented is the first case described of late-onset pericardial effusion and tamponade secondary to the Cardia Ultraseal LAAO device implantation. We present a revision of the literature regarding the occurrence of similar adverse events and discuss the hypothetical mechanism of this major complication.

Assessment of Phasic Changes of Vascular Size by Automated Edge Tracking-State of the Art and Clinical Perspectives.

Assessment of vascular size and of its phasic changes by ultrasound is important for the management of many clinical conditions. For example, a dilated and stiff inferior vena cava reflects increased intravascular volume and identifies patients with heart failure at greater risk of an early death. However, lack of standardization and sub-optimal intra- and inter- operator reproducibility limit the use of these techniques. To overcome these limitations, we developed two image-processing algorithms that quantify phasic vascular deformation by tracking wall movements, either in long or in short axis. Prospective studies will verify the clinical applicability and utility of these methods in different settings, vessels and medical conditions.