Some Practical Points About Patent Foramen Ovale Conditions that May Not Be Covered in the Rest of the Book.

This introductory article provides many key lessons that I have learned in my 23 years of studying patent foramen ovale (PFO). It discusses issues related to the diagnosis, clinical presentation, and treatment of PFO.

Patent Foramen Ovale and Acute Mountain Sickness.

Acute mountain sickness (AMS) commonly plagues people who travel to high altitude and can be life threatening. Clinically, AMS is defined by a constellation of symptoms as outlined in the Lake Louise Criteria. The underlying etiology is thought to be related to a decrease in partial pressure of oxygen leading to tissue hypoxia. Patent foramen ovale (PFO) has been postulated to play a role in AMS through right-to-left shunt, which can worsen hypoxemia. Recent data demonstrate a higher prevalence of PFO in hikers with AMS. Future studies are needed to further elucidate the relationship between PFO and AMS.

Patent Foramen Ovale and Coronary Artery Spasm: A New Patent Foramen Ovale-associated Condition that May Explain the Mechanism of Vasospastic Angina.

Patent foramen ovale (PFO) may be an underlying factor in the pathogenesis of migraine, vasospastic angina, and Takotsubo cardiomyopathy. This article reviews the role that PFO may play in each of these clinical entities and discusses potential interventions. It also proposes a novel clinical syndrome wherein PFO may be the unifying link among migraine, coronary vasospasm, and Takotsubo cardiomyopathy in predisposed individuals.

Incidence of Atrial Fibrillation or Arrhythmias After Patent Foramen Ovale Closure.

Background: Patients with a patent foramen ovale (PFO) who undergo percutaneous PFO closure are at a greater risk of developing atrial fibrillation (AF) compared with patients whose PFOs are managed medically. Postclosure AF appears to be well tolerated if treated but may increase the risk for stroke. Postclosure AF is reported to occur in 3.7% to 7.4% of patients; however, incidence across devices remains uncertain. This study aims to evaluate the frequency of postclosure AF, atrial flutter, and arrhythmias in 6 PFO closure devices. Methods: Four hundred forty-five patients underwent percutaneous PFO closure with appropriate follow-up between 2001 and 2021. The procedure was performed using Abbott Amplatzer PFO, Amplatzer ASD, Amplatzer Cribriform, NMT CardioSEAL, Gore Helex, or Gore Cardioform devices. Incidence of AF, atrial flutter, and arrhythmias were assessed by electrocardiogram within 6 months from closure. Multivariate logistic regression evaluated potential predictors of postclosure AF or atrial flutter. Results: Postclosure AF or atrial flutter occurred in 30 patients (6.7%) within 6 months, and its incidence was significantly different across devices. Gore Cardioform had the greatest frequency of postclosure AF or atrial flutter events (16.8%) compared with other devices. The Gore Cardioform device, larger device sizes, and male sex were associated with greater risk of postclosure AF or atrial flutter. Conclusions: Postclosure AF or atrial flutter was more likely to occur in the Gore Cardioform device, in males, and in patients who underwent PFO closure with larger devices. Although it is more effective for complete closure, the Gore Cardioform device was shown to be an independent predictor of postclosure AF or atrial flutter.

Right-to-Left Shunt in Divers with Neurological Decompression Sickness: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to assess the association between the presence of a right-to-left shunt (RLS) and neurological decompression sickness (NDCS) and asymptomatic brain lesions among otherwise healthy divers. BACKGROUND: Next to drowning, NDCS is the most severe phenotype of diving-related disease and may cause permanent damage to the brain and spinal cord. Several observational reports have described the presence of an RLS as a significant risk factor for neurological complications in divers, ranging from asymptomatic brain lesions to NDCS. METHODS: We systematically reviewed the MEDLINE, Embase, and CENTRAL databases from inception until November 2021. A random-effects model was used to compute odds ratios. RESULTS: Nine observational studies consisting of 1830 divers (neurological DCS: 954; healthy divers: 876) were included. RLS was significantly more prevalent in divers with NDCS compared to those without (62.6% vs. 27.3%; odds ratio (OR): 3.83; 95% CI: 2.79-5.27). Regarding RLS size, high-grade RLS was more prevalent in the NDCS group than the no NDCS group (57.8% versus 18.4%; OR: 4.98; 95% CI: 2.86-8.67). Further subgroup analysis revealed a stronger association with the inner ear (OR: 12.13; 95% CI: 8.10-18.17) compared to cerebral (OR: 4.96; 95% CI: 2.43-10.12) and spinal cord (OR: 2.47; 95% CI: 2.74-7.42) DCS. RLS was more prevalent in divers with asymptomatic ischemic brain lesions than those without any lesions (46.0% vs. 38.0%); however, this was not statistically significant (OR: 1.53; 95% CI: 0.80-2.91). CONCLUSIONS: RLS, particularly high-grade RLS, is associated with greater risk of NDCS. No statistically significant association between RLS and asymptomatic brain lesions was found.

Patent Foramen Ovale Closure for Nonstroke Indications.

The patent foramen ovale (PFO) is a flap or tunnel-like communication in the atrial septum present in 20% to 34% of the adult population. In most cases, it is a benign finding and poses no health risk. However, some PFOs may provide a conduit for bloodborne materials, such as thrombi, vasoactive substances, or air to pass into the systemic circulation causing a paradoxical embolus. PFOs have been linked with several clinical disease states including cryptogenic stroke, migraine headache, platypnea-orthodeoxia, and decompression illness. Percutaneous PFO closure provides a practical solution to the problem of PFO in carefully selected populations. Recent randomized control trials have demonstrated that PFO closure in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke compared with medical therapy. This translated into a dramatic increase in the number of PFO closure procedures worldwide, primarily for the indication of cryptogenic stroke, with high procedural success and low complication rates. However, there are no randomized clinical trials available to support PFO closure in other clinical conditions. This article reviews potential indications, existing data, and management approaches for PFO closure in disorders other than cryptogenic stroke.

A New Syndrome of Patent Foramen Ovale Inducing Vasospastic Angina and Migraine.

Patent foramen ovale (PFO) is the most common congenital cardiac abnormality and is usually considered a benign finding. This case series suggests a potential link between PFO and vasospastic angina. It also demonstrates PFO closure as a potential therapeutic intervention for individuals with PFO who suffer from refractory vasospastic angina.

Invasive Coronary Imaging Assessment for Cardiac Allograft Vasculopathy: State-of-the-Art Review.

Heart transplantation is the standard of care treatment for end-stage heart failure. Therapeutic advances including enhanced immunosuppression and aggressive infectious prophylaxis have led to increased life-expectancy following transplantation; however, cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality. Although coronary angiography is the current guideline-recommended diagnostic modality for invasive CAV screening, it is limited in its ability to detect early and/or diffuse disease. Efforts to improve outcomes for heart transplant recipients with CAV have focused on developing diagnostic tools with greater sensitivity to capture early CAV in order to better understand the pathobiology and implement treatment to slow disease progression sooner after transplant. The contemporary invasive imaging armamentarium for CAV surveillance includes coronary angiography, intravascular ultrasound, and newer technologies including optical coherence tomography and near-infrared spectroscopy. The present review outlines the use of and data in support of these imaging platforms in the CAV arena and highlights the potential advantages and limitations of each of these modalities.

SCAI Guidelines for the Management of Patent Foramen Ovale.

Background: Patent foramen ovale (PFO) is a vestigial congenital cardiovascular structure present in around 25% of adults. In most cases, PFO is entirely benign and requires no treatment. However, it may cause serious complications under certain circumstances. Objective: These evidence-based guidelines from the Society for Cardiovascular Angiography and Interventions (SCAI) aim to support patients, clinicians, and other stakeholders in decisions about management of PFO. Methods: SCAI convened a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The Evidence Foundation, a registered 501(c)(3) nonprofit organization, provided methodological support for the guideline-development process. Following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the guideline panel formulated and prioritized clinical questions in population, intervention, comparison, outcome (PICO) format. A separate technical review team of clinical and methodological experts conducted systematic reviews of the evidence, synthesized data, and graded the certainty of the evidence across outcomes. The guideline panel then reconvened to formulate recommendations and supporting remarks informed by the results of the technical review and additional contextual factors described in the GRADE evidence-to-decision framework. Results: The panel agreed on 13 recommendations to address variations on 5 clinical scenarios. Conclusions: Key recommendations address patient selection for PFO closure in the prevention of recurrent PFO-associated stroke, including populations not commonly included in randomized studies, and scenarios where the PFO closure might serve a role in the prevention of other outcomes such as migraine headaches and decompression illness. The panel has also identified future research priorities to advance the field.

Pathophysiology of Takotsubo Cardiomyopathy: Reopened Debate.

Takotsubo cardiomyopathy (TTC), a persistently obscure dysfunctional condition of the left ventricle, is uniquely transient but nevertheless dangerous. It features variable ventricular patterns and is predominant in women. For 30 years, pathophysiologic investigations have progressed only slowly and with inadequate focus. It was initially proposed that sudden-onset spastic obliteration of coronary flow induced myocardial ischemia with residual stunning and thus TTC. Later, it was generally accepted without proof that, in the presence of pain or emotional stress, the dominant mechanism for TTC onset was a catecholamine surge that had a direct, toxic myocardial effect. We think that the manifestations of TTC are more dynamic and complex than can be assumed from catecholamine effects alone. In addition, after reviewing the recent medical literature and considering our own clinical observations, especially on spasm, we theorize that atherosclerotic coronary artery disease modulates and physically opposes obstruction during spasm. This phenomenon may explain the midventricular variant of TTC and the lower incidence of TTC in men. We continue to recommend and perform acetylcholine testing to reproduce TTC and to confirm our theory that coronary spasm is its initial pathophysiologic factor. An improved understanding of TTC is especially important because of the condition's markedly increased incidence during the ongoing COVID-19 pandemic.

Pooled Analysis of PFO Occluder Device Trials in Patients With PFO and Migraine.

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 ≥50% 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.

Left atrial thrombus mimicking myxoma in a patient with hereditary hemorrhagic telangiectasia: Diagnostic and therapeutic dilemmas.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of arteriovenous malformations. The arteriovenous shunts may result in high output heart failure, which predisposes to atrial dilatation and atrial fibrillation. Due to recurrent bleeding from epistaxis or the gastrointestinal tract, patients with HHT and atrial fibrillation are at high risk of bleeding if anticoagulated for stroke prevention. In this report, we present a case of a 74-year-old woman with a history of HHT and atrial fibrillation who developed a large left atrial thrombus that initially was thought to represent an atrial myxoma. The diagnosis was confirmed with cardiac magnetic resonance imaging, and the patient underwent surgical resection of the thrombus. This case demonstrates the role of different imaging modalities in the assessment of left atrial masses and presents an opportunity to review the data on safety of anticoagulation in patients with HHT.