Although the most common clinical manifestations of a patent foramen ovale (PFO) are cryptogenic stroke and migraine with aura, PFO is also associated with platypnea-orthodeoxia syndrome, obstructive sleep apnea, and chronic obstructive pulmonary disease with hypoxemia out of proportion to the extent of pulmonary disease. This article will discuss these conditions and summarize the related literature.

Calcific mitral stenosis, commonly seen in the elderly in developed countries, occurs primarily due to mitral annular calcification, and its prevalence is increasing secondary to an aging population. Mitral regurgitation, commonly seen across all age groups, occurs primarily due to anatomical or functional impairment of one or more components of the mitral apparatus or the left ventricle that are necessary for normal valve function, and its prevalence is increasing secondary to an increasing number of patients with heart failure. The current review discusses the diagnosis of and treatment options (medical, surgical, and transcatheter) for mitral valve disease, including the associated challenges, specifically in the elderly.

Contrary to old belief, even asymptomatic severe calcific aortic stenosis (AS) is not a benign condition. For example, Rosenhek et al.1 reported that among patients with asymptomatic severe AS associated with moderate to severe aortic valve (AV) calcification (n = 101), the 1-, 2-, and 4-year event-free survival rates were 60% ± 6%, 47% ± 6%, and 20% ± 5%, respectively. Similarly, Zilberszac et al.2 showed that among patients >70 years of age with asymptomatic severe AS associated with moderate to severe AV calcification (n = 103), the 1-, 2-, 3-, and 4-year event-free survival rates were 73%, 43%, 23%, and 16%, respectively.

Background Atrioventricular valve regurgitation (AVVR) is present in up to 75% of Fontan patients, and it is associated with an increased risk of Fontan circulation failure, morbidity, and mortality. Traditional treatment options include surgical repair vs. surgical replacement. We present, to the best of our knowledge, one of the first cases of successful trans-catheter repair of severe common AVVR using the MitraClip device. Case summary A 20-year-old male with a history of double-outlet right ventricle (DORV) with unbalanced common atrioventricular canal to the right ventricle, severely hypoplastic left ventricle, and total anomalous pulmonary venous return status post-Fontan procedure presented with progressively worsening dyspnoea on exertion. Transoesophageal echocardiogram demonstrated severe common AVVR. After discussion of the case during the adult congenital heart disease multidisciplinary conference, patient underwent successful placement of two MitraClip devices, reducing the regurgitation from torrential to moderate. Discussion MitraClip therapy can be used to alleviate symptoms in patients deemed as high risk for surgery. However, careful attention must be paid to haemodynamics before and after clip placement, which may predict short-term clinical outcomes.

Background Perivascular epithelioid cell tumours (PEComas) are rare soft tissue neoplasms that commonly occur in the uterus, skin, and liver and less commonly in the retroperitoneum, colon, and mediastinum.Case summary A 36-year-old male patient with a history of mediastinal PEComa status post resection, essential hypertension, and atrial fibrillation status post appendage ligation currently not on anticoagulation presented with a 1-week history of fevers, chills, productive cough, chest pain, dyspnoea on exertion, loss of appetite, and general weakness. Vital signs, physical exam, laboratory data, electrocardiogram, and chest radiograph were grossly unremarkable. A multimodality imaging approach utilizing transthoracic echocardiogram, transoesophageal echocardiogram (TEE), cardiac magnetic resonance imaging (cMRI), and computed tomography angiography of the chest, abdomen, and pelvis revealed a local 40 mm x 53 mm globular bilobed vascularized scar-free posterior mediastinal mass arising from the roof of the left and right atria and extending superiorly to the main pulmonary artery and inferiorly to the inferior vena cava. Based on the mass' size and proximity to vital structures and tumour recurrence, the case was presented during tumour board rounds, and the outcome was to surgically resect the mass and then have the patient follow up with medical oncology and radiation oncology for possible chemotherapy and radiation, respectively.Discussion Perivascular epithelioid cell tumours are rare, and mediastinal PEComas are even rarer, warranting a multimodality imaging approach involving TEE and cMRI and a multidisciplinary approach involving anaesthesiologists, cardiologists, cardiothoracic surgeons, medical oncologists, pathologists, radiologists, and radiation oncologists.

Heart failure is a common cardiac condition that carries a substantial risk of morbidity and mortality despite advances in management. Echocardiography plays a central role in its diagnosis, elucidation of mechanisms, and detailed hemodynamic analysis. In this E-Challenge, the authors review a few transthoracic echocardiographic findings that yield insights into the hemodynamics.

This study examines in-hospital mortality and complicated COVID-19 infection among adult congenital heart disease (ACHD) patients admitted with COVID-19, using the National Inpatient Sample (NIS). A total of 4219 COVID-19 patients with ACHD were included. We demonstrated that COVID-19 patients with ACHD were more likely to experience in-hospital mortality (OR 1.04, 95% CI 1.04-1.04, P<0.01) and complicated COVID-19 infection (OR: 1.30, 95% CI: 1.11-1.53, P<0.01). In our sub-group analysis, COVID-19 patients with tetralogy of Fallot (TOF) had higher mortality and COVID-19 patients with atrial septal defects (ASD) had a higher incidence of complicated infection when compared to COVID-19 patients with all other ACHDs. Risk factors for mortality among COVID-19 patients with ACHD include advanced age, lower income, unrepaired ACHD, malnutrition, and chronic liver disease. Accordingly, we recommend aggressive preventive care with vaccination and non-pharmacologic measures in order to improve survival for ACHD patients.

Background Isolated membranous ventricular septal aneurysms are infrequent in clinical practice. Furthermore, current guidelines do not dictate how to diagnose or manage such lesions. Case summary A 54-year-old male patient with a history of essential hypertension and tobacco use presented with chest pain associated with dyspnoea and nausea. Electrocardiogram was unrevealing. Physical exam was significant for a diastolic murmur heard best in the apex. Computed tomography angiography of the chest revealed an aneurysm measuring 5 cm in diameter along the ascending aorta. Transoesophageal echocardiography showed that the aneurysm originated from the membranous ventricular septum, coursed along the ascending aorta, and ended anteriorly to the surface of the right ventricle and ascending aorta. Cardiac magnetic resonance imaging confirmed these findings and demonstrated that the aneurysm comprised of two loculations. Given the size of the aneurysm and its proximal location to major cardiovascular structures, percutaneous repair was considered unsafe. Following a multidisciplinary meeting, the lesion was successfully resected via a transaneurysmal approach. Discussion Isolated membranous ventricular septal aneurysms are best imaged via a combination of transoesophageal echocardiogram and cardiac magnetic resonance imaging and best managed via a multidisciplinary approach for optimal outcomes.

Background-Previous studies on coronavirus disease 2019 (COVID-19) were limited to specific geographical locations and small sample sizes. Therefore, we used the National Inpatient Sample (NIS) 2020 database to determine the risk factors for severe outcomes and mortality in COVID-19. Methods-We included adult patients with COVID-19. Univariate and multivariate logistic regression was performed to determine the predictors of severe outcomes and mortality in COVID-19. Results-1,608,980 (95% CI 1,570,803–1,647,156) hospitalizations with COVID-19 were included. Severe complications occurred in 78.3% of COVID-19 acute respiratory distress syndrome (ARDS) and 25% of COVID-19 pneumonia patients. The mortality rate for COVID-19 ARDS was 54% and for COVID-19 pneumonia was 16.6%. On multivariate analysis, age > 65 years, male sex, government insurance or no insurance, residence in low-income areas, non-white races, stroke, chronic kidney disease, heart failure, malnutrition, primary immunodeficiency, long-term steroid/immunomodulatory use, complicated diabetes mellitus, and liver disease were associated with COVID-19 related complications and mortality. Cardiac arrest, septic shock, and intubation had the highest odds of mortality. Conclusions-Socioeconomic disparities and medical comorbidities were significant determinants of mortality in the US in the pre-vaccine era. Therefore, aggressive vaccination of high-risk patients and healthcare policies to address socioeconomic disparities are necessary to reduce death rates in future pandemics.

Fractional flow reserve (FFR) determines the functional significance of epicardial stenoses assuming negligible venous pressure (Pv) and microvascular resistance. However, these assumptions may be invalid in end-stage liver disease (ESLD) because of fluctuating Pv and vasodilation. Accordingly, all patients with ESLD who underwent right-sided cardiac catheterization and coronary angiography with FFR as part of their orthotopic liver transplantation evaluation between 2013 and 2018 were included in the present study. Resting mean distal coronary pressure (Pd)/mean aortic pressure (Pa), FFR, and Pv were measured. FFR accounting for Pv (FFR - Pv) was defined as (Pd - Pv)/(Pa - Pv). The hyperemic effect of adenosine was defined as resting Pd/Pa - FFR. The primary outcome was all-cause mortality at 1 year. In 42 patients with ESLD, 49 stenoses were interrogated by FFR (90% were <70% diameter stenosis). Overall, the median model for ESLD score was 16.5 (10.8 to 25.5), FFR was 0.87 (0.81 to 0.94), Pv was 8 mm Hg (4 to 14), FFR-Pv was 0.86 (0.80 to 0.94), and hyperemic effect of adenosine was 0.06 (0.02 to 0.08). FFR-Pv led to the reclassification of 1 stenosis as functionally significant. There was no significant correlation between the median model for ESLD score and the hyperemic effect of adenosine (R = 0.10). At 1 year, 13 patients had died (92% noncardiac in etiology), and patients with FFR ≤0.80 had significantly higher all-cause mortality (73% vs 17%, p = 0.001. In conclusion, in patients with ESLD who underwent orthotopic liver transplantation evaluation, Pv has minimal impact on FFR, and the hyperemic effect of adenosine is preserved. Furthermore, even in patients with the predominantly angiographically-intermediate disease, FFR ≤0.80 was an independent predictor of all-cause mortality.

BACKGROUND Although observational studies have shown percutaneous patent foramen ovale (PFO) closure to be a safe means of reducing the frequency and duration of migraine, randomized clinical trials have not met their primary efficacy endpoints. OBJECTIVES The authors report the results of a pooled analysis of individual participant data from the 2 randomized trials using the Amplatzer PFO Occluder to assess the efficacy and safety of percutaneous device closure as a therapy for episodic migraine with or without aura. METHODS The authors analyzed individual patient-level data from 2 randomized migraine trials (the PRIMA [Percutaneous Closure of Patent Foramen Ovale in Migraine With Aura] and PREMIUM [Prospective Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects with Migraine and PFO Using the Amplatzer PFO Occluder Compared to Medical Management] studies). Efficacy endpoints were mean reduction in monthly migraine days, responder rate (defined as >= 0% reduction in monthly migraine attacks), mean reduction in monthly migraine attacks, and percentage of patients who experienced complete cessation of migraine. The safety endpoint was major procedure- and device-related adverse events. RESULTS Among 337 subjects, 176 were randomized by blocks to device closure and 161 to medical treatment only. At 12-month follow-up, the analysis met 3 of the 4 efficacy endpoints: mean reduction of monthly migraine days (-3.1 days vs. -1.9 days; p = 0.02), mean reduction of monthly migraine attacks (-2.0 vs. -1.4; p = 0.01), and number of subjects who experienced complete cessation of migraine (14 [9%] vs. 1 [0.7%]; p < 0.001). For the safety analysis, 9 procedure-related and 4 device-related adverse events occurred in 245 subjects who eventually received devices. All events were transient and resolved. CONCLUSIONS This pooled analysis of patient-level data demonstrates that PFO closure was safe and significantly reduced the mean number of monthly migraine days and monthly migraine attacks, and resulted in a greater number of subjects who experienced complete migraine cessation. (c) 2021 by the American College of Cardiology Foundation.

Based on observational studies, there was a 2–3 times increased frequency of patent foramen ovale (PFO) in patients with cryptogenic stroke, which suggested that PFO could be the pathway for a paradoxical embolus as the mechanism of these strokes. A meta-analysis of 48 observational studies showed that patients with cerebrovascular events who received only medical therapy in the presence of a PFO had a 6.3-fold increased rate of recurrent neurological events compared with patients who underwent percutaneous PFO closure. The release of these reports preceded the publication of randomized clinical trials that attempted to determine the efficacy and safety of PFO closure versus standard of care medical therapy for secondary prevention of PFO-associated stroke. CLOSURE I, PC, and the early follow-up data from RESPECT (patients were followed for a median of 2.1 years), the first 3 randomized trials, could not demonstrate a statistically significant benefit of PFO closure for secondary stroke prevention in an intention-to-treat analysis. Subsequent meta-analyses of these trials, and the long-term follow-up data from RESPECT, enhanced the individual results of these early studies and confirmed that PFO closure decreases the risk of recurrent stroke over medical therapy alone. This chapter describes the first 3 randomized trials of PFO closure for stroke along with their meta-analyses, and discusses how the Food and Drug Administration utilized these data to assess the role of percutaneous PFO device closure for secondary stroke prevention.

A patent foramen ovale (PFO) is a congenital remnant of the fetal circulation that persists in 25% of adults. Once considered a mostly benign congenital heart defect, the presence of PFO-mediated right-to-left shunt has been associated with several clinical conditions, including cryptogenic stroke, migraine with aura, myocardial infarction, peripheral embolism, symptomatic arterial desaturation, exacerbation of obstructive sleep apnea, hypoxemia out of proportion to the extent of lung disease, decompression sickness, altitude illness, and coronary artery spasm. This review paper will discuss the various PFO-associated conditions, relevant observational and prospective randomized trials, as well as preferred methods to make the diagnosis of a PFO.

Importance Recent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Observations Randomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents. Conclusions and Relevance These new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use.