Sodium-glucose cotransporter-2 Inhibitors in Heart Failure: An Updated Systematic Review and Meta-analysis of 13 Randomized Clinical Trials Including 14,618 Patients With Heart Failure.

ABSTRACT: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors showed benefit in patients with heart failure. In this updated meta-analysis, we evaluate the therapeutic efficacy and safety of SGLT-2 inhibitors in patients with heart failure. Different electronic databases were searched to find relevant articles. RevMan 5.4 was used for pooling data using a random/fixed-effects model, complemented by several sensitivity and subgroup analyses. A total of 13 randomized clinical trials including 14,618 patients with heart failure were included in analysis among 6797 studies screened. The overall mortality rate was 12.45% in the SGLT-2 group and 14.67% in the placebo group with 18% lower odds of overall mortality [odds ratio (OR), 0.82; confidence interval (CI), 0.75-0.91] in the SGLT-2 group. Odds of cardiovascular mortality was 18% lower (OR, 0.82; CI, 0.74-0.92) in the SGLT-2 group. The odds of hospitalization for heart failure (HHF) was 38% lower during the study period (OR, 0.62; CI, 0.56-0.68) in the SGLT-2 group. In addition, a benefit was seen for composite outcome HHF or mortality and considering subgrouping based on diabetes status, gender, and age groups. Although genital infection was significantly higher in the SGLT-2 group, the occurrence of severe adverse events, hypoglycemia, urinary tract infection, bone fracture, volume depletion, and other renal events did not differ between the 2 groups. Thus, SGLT-2 inhibitors improved cardiovascular outcomes among patients with heart failure with no significant difference in adverse events. Clinical benefit was comparable in diabetic and nondiabetic individuals, males and females, people in younger and older age groups with underlying heart failure, and HF with reduced ejection fraction.

Staged versus index procedure complete revascularization in ST-elevation myocardial infarction: A meta-analysis.

BACKGROUND: Complete revascularization of patients with ST-elevation myocardial infarction and multivessel coronary artery disease reduces adverse events compared to infarct-related artery only revascularization. Whether complete revascularization should be done as multivessel intervention during index procedure or as a staged procedure remains controversial. METHOD: We performed a meta-analysis of randomized controlled trials comparing outcomes of multivessel intervention in patients with ST-elevation myocardial infarction and multivessel coronary artery disease as staged procedure versus at the time of index procedure. Composite of death or myocardial infarction was the primary outcome. Mantel-Haenszel risk ratios were calculated using random effect model. RESULTS: Six randomized studies with a total of 1126 patients met our selection criteria. At a mean follow-up of 13 months, composite of myocardial infarction or death (7.2% vs 11.7%, RR: 1.66, 95%CI: 1.09-2.52, P = 0.02), all cause mortality (RR: 2.55, 95%CI: 1.42-4.58, P < 0.01), cardiovascular mortality (RR: 2.8, 95%CI: 1.33-5.86, P = 0.01), and short-term (<30 days) mortality (RR: 3.54, 95%CI: 1.51-8.29, P < 0.01) occurred less often in staged versus index procedure multivessel revascularization. There was no difference in major adverse cardiac events (RR: 1.14, 95%CI: 0.88-1.49, P = 0.33), repeat myocardial infarction (RR: 1.14, 95%CI: 0.68-1.92, P = 0.61), and repeat revascularization (RR: 0.92, 95%CI: 0.66-1.28, P = 0.62). CONCLUSION: In patients with ST-elevation myocardial infarction and multivessel coronary artery disease, a strategy of complete revascularization as a staged procedure compared to index procedure revascularization results in reduced mortality without an increase in repeat myocardial infarction or need for repeat revascularization.

Transcranial Doppler: Does Addition of Blood to Agitated Saline Affect Sensitivity for Detecting Cardiac Right-to-Left Shunt?

BACKGROUND: Transcranial Doppler (TCD) with agitated saline has been shown to be an alternative for the detection of right-to-left shunts (RLS) with similar diagnostic accuracies as transesophageal echocardiography (TEE). It is hypothesized that the addition of blood to agitated saline increases the sensitivity of TCD for the detection of RLS. The aim of this meta-analysis was to determine whether agitated saline with blood increases the sensitivity of TCD for the detection of RLS compared to agitated saline alone and other contrast agents. METHOD: A systematic review of Medline, Cochrane, and Embase was performed to look for all prospective studies assessing intracardiac RLS using TCD compared with TEE as the reference; both tests were performed with a contrast agent and a maneuver to provoke RLS in all studies. RESULTS: A total of 27 studies (29 comparisons) with 1,968 patients met the inclusion criteria. Of 29 comparisons, 10 (35%) used echovist contrast during TCD, 4 (14%) used a gelatin-based solution, 12 (41%) used agitated saline, and 3 (10%) utilized 2 different contrast agents. The addition of blood to agitated saline improved the sensitivity of TCD to 100% compared to agitated saline alone (96% sensitivity, P = 0.161), echovist (94% sensitivity, P = 0.044), and gelatin-based solutions (93% sensitivity, P = 0.041). CONCLUSION: The addition of blood to agitated saline improves the sensitivity of TCD for the detection of RLS to 100% when compared to other conventional contrast agents; these findings support the addition of blood to agitated saline during TCD bubble studies.

Thrombocytopaenia as a Prognostic Indicator in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Studies suggest that thrombocytopaenia is associated with a higher mortality in several diseases. Little is known about the effect of low platelet count on mortality in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to determine the prognostic value of thrombocytopaenia in these patients by assessing all-cause mortality. METHODS: A total of 1,907 patients with HFrEF, defined by left ventricular ejection fraction <40% on echocardiography, were analysed in this multi-centre retrospective study. All patients were on medical therapy with a beta-blocker and an angiotensin-converting enzyme inhibitor. Patients were categorised into two groups based on platelet count measured within one month of the diagnosis of HFrEF: normal to mild thrombocytopaenia (platelet count 100,000-450,000 per uL); and moderate to severe thrombocytopaenia (platelet count <100,000 per uL). One-year all-cause mortality was compared between the two groups. RESULTS: Mean age was 65±15 years and 62% of patients were male. Overall one-year mortality was 17.2% with higher mortality among patients with HFrEF and moderate/severe thrombocytopaenia compared to those with normal/mild thrombocytopaenia (33.0% vs. 15.4%, p <0.001). After adjusting for baseline characteristics, patients with HFrEF and moderate/severe thrombocytopaenia had a higher mortality compared to patients with normal/mild thrombocytopaenia (HR 1.84, 95% CI 1.33-2.56, p <0.001). CONCLUSION: In patients with HFrEF, higher degree of thrombocytopaenia is associated with higher all-cause mortality. These findings may support the use of platelet counts as a prognostic marker in the assessment of the patient with HFrEF.

The effect of patent foramen ovale closure in patients with platypnea-orthodeoxia syndrome.

BACKGROUND: Platypnea-orthodeoxia syndrome is a rare condition characterized by hypoxemia in the upright position that is improved in the supine position. Although several etiologies of platypnea-orthodeoxia exist, it is frequently associated with right-to-left shunting of blood at the cardiac or pulmonary level, usually via a patent foramen ovale (PFO). The aim of this study was to evaluate the incidence of platypnea-orthodeoxia syndrome in a select patient population with right-to-left shunting and to describe the outcomes after PFO closure. METHODS: Patients with platypnea-orthodeoxia were prospectively identified from a population of patients who had a PFO and were referred to UCLA from 2001 to 2012. Those patients who elected to have their PFO closed were assessed for the severity of their symptoms and interval SaO2 changes. The changes in SaO2 before and after closure were compared in the supine and upright position. Patients were classified depending on the result of PFO closure as having "improved SaO2 " or "no change." RESULTS: Of 683 patients with PFO-associated conditions, 17 (2.5%) had platypnea-orthodeoxia and elected to close their PFO. The results in 11 of 17 patients (64.8%) were classified as having "improved SaO2 "; they experienced improvement or complete resolution of their dyspnea and hypoxemia (improved SaO2 from baseline 5.2 ± 4.7% when recumbent and 15.6 ± 3.0% when upright, P = 0.03 and P < 0.0001, respectively). Patients with no change after PFO closure predominantly had a pulmonary etiology for their hypoxia, with elevated mean pulmonary pressures measured before closure (51.4 ±16.8 mmHg, P = 0.06). CONCLUSION: PFO closure may resolve symptomatic postural dyspnea and hypoxemia and is an effective method for treating platypnea-orthodeoxia, but is not effective when the primary etiology of the hypoxemia is due to a pulmonary cause.

Comparison of residual shunt rates in five devices used to treat patent foramen ovale.

OBJECTIVES: To assess the effective closure rate among devices used for transcatheter patent foramen ovale (PFO) closure, and to discuss the management of patients with large residual shunts. BACKGROUND: Several devices are used off-label for transcatheter closure of a PFO in the United States. The rate of residual shunting after PFO closure varies by device. Failure of effective closure poses risk of a recurrent cerebrovascular event, persistent migraine, or recurrent orthodeoxia. METHODS: Patients who underwent PFO closure in the Cardiac Catheterization Laboratory at UCLA between 2001 and 2013 and had baseline and adequate follow-up transcranial Doppler studies following device placement were enrolled in the study. RESULTS: Of 167 patients whose records were analyzed, effective PFO closure occurred in 90% (150/167) of patients. The highest effective closure rate was with the Amplatzer Septal Occluder (ASO; 100%), followed by the Amplatzer Cribriform (93%), Gore Helex (90%), Amplatzer PFO (86%), and CardioSEAL (86%) device. The highest rate of residual shunting was observed after placement of the 30-mm Gore Helex device (55%). Of the 17 patients with a residual shunt, three required a repeat PFO closure procedure due to a significant residual shunt associated with recurrent pulmonary emboli or profound orthodeoxia. All three patients received an ASO which successfully closed the residual shunt. CONCLUSIONS: Transcatheter PFO closure has a high success rate, but a moderate residual shunt occurs in about 10% of cases. The observed incidence of residual shunting after PFO closure is significantly larger with the 30-mm Helex device. © 2014 Wiley Periodicals, Inc.

Diagnostic accuracy of transesophageal echocardiogram for the detection of patent foramen ovale: a meta-analysis.

BACKGROUND: Patent foramen ovale (PFO) is a remnant of the fetal circulation present in 20% of the population. Right-to-left shunting (RLS) through a PFO has been linked to the pathophysiology of stroke, migraine with aura, and hypoxemia. While different imaging modalities including transcranial Doppler, intra-cardiac echo, and transthoracic echo (TTE) have often been used to detect RLS, transesophageal echo (TEE) bubble study remains the gold standard for diagnosing PFO. The aim of this study was to determine the relative accuracy of TEE in the detection of PFO. METHODS AND RESULTS: A systematic review of Medline, using a standard approach for meta-analysis, was performed for all prospective studies assessing accuracy of TEE in the detection of PFO using confirmation by autopsy, cardiac surgery, and/or catheterization as the reference. Search results revealed 3105 studies; 4 met inclusion criteria. A total of 164 patients were included. TEE had a weighted sensitivity of 89.2% (95% CI: 81.1-94.7%) and specificity of 91.4% (95% CI: 82.3-96.8%) to detect PFO. The overall positive likelihood ratio (LR+) was 5.93 (95% CI: 1.30-27.09) and the overall negative likelihood ratio (LR-) was 0.22 (95% CI: 0.08-0.56). CONCLUSION: While TEE bubble study is considered to be the gold standard modality for diagnosing PFO, some PFOs may still be missed or misdiagnosed. It is important to understand the limitations of TEE and perhaps use other highly sensitive screening tests, such as transcranial doppler (TCD), in conjunction with TEE before scheduling a patient for transcatheter PFO closure.

Accuracy of conventional transthoracic echocardiography for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies.

BACKGROUND: Paradoxical embolization through a right-to-left shunt (RLS), often from a patent foramen ovale (PFO), has been associated with cryptogenic stroke. While transesophageal echo (TEE) bubble study is the current standard reference for diagnosing PFO, transthoracic echo (TTE) remains the most commonly used screening test for RLS due to its noninvasiveness and easy availability. The aim of this meta-analysis was to determine the accuracy of TTE compared to TEE as the reference. METHODS AND RESULTS: A systematic review of Medline, Cochrane, and Embase was done to look for all the prospective studies assessing for intracardiac RLS using conventional TTE compared to TEE as the reference; both TTE and TEE were performed with a contrast agent and a maneuver to provoke RLS in all studies. A total of 13 studies with 1436 patients fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TTE were 46% and 99%, respectively. Likewise, the positive likelihood ratio and negative likelihood ratio were 20.85 and 0.57, respectively. Using different contrast agents, different microbubble cutoffs for a positive TTE/TEE, and different cardiac cycle cutoffs for a positive TTE/TEE did not affect the accuracy of TTE. In a population of patients with cryptogenic stroke, a TTE that tests positive for RLS has a 95% probability of being a true positive. CONCLUSION: Transthoracic echocardiogram has a low sensitivity and extremely high specificity, making it a poor rule out test but an excellent rule in test for the detection of intracardiac RLS.

Quadricuspid aortic valve: a case report and review of literature.

Quadricuspid aortic valve, a rare congenital cardiac defect, manifests most commonly as aortic regurgitation. Clinical presentation mainly depends on the functional status of the aortic valve, myocardium and associated cardiovascular abnormalities. Aortic valve replacement or repair is usually warranted in the 5th or 6th decade.

Dual versus triple antithrombotic therapy in patients undergoing percutaneous coronary intervention-meta-analysis and meta-regression.

BACKGROUND: Anti-thrombotic regimen in patients on long term anticoagulation requiring coronary intervention remains a clinical challenge. METHODS: We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (P2Y12 inhibitor and anticoagulant) in patients on long-term anticoagulants after percutaneous coronary intervention (PCI). Major bleeding was the primary outcome. RESULTS: Three observational studies and 3 randomized controlled trials with a total of 6654 patients met our selection criteria. At a mean follow up of 12.5 months major bleeding was lower in dual therapy cohort compared to triple therapy (2.2% vs 5.2%, RR 0.60, 95% CI 0.44-0.81, P = 0.001). No difference was observed between the two groups for major adverse cardiac events (11.8% vs 13.0%, RR 1.03, CI 0.79-1.34, P = 0.85), all-cause mortality (3.9% vs 5.6%, RR 0.94, CI 0.65-1.36, P = 0.76), myocardial infarction (3.7% vs 3.9%, RR 1.12, CI 0.83-1.50, P = 0.47), target vessel revascularization (6.8% vs 7.1%, RR 1.12, CI 0.72-1.74, P = 0.60), thromboembolic events (1.3% vs 1.6%, RR 0.95, CI 0.55-1.64, P = 0.85) and stent thrombosis (1.3% vs 1.4%, RR1.36, CI 0.84-2.21, P = 0.21). CONCLUSION: For patients undergoing PCI and requiring long term anticoagulation, a strategy of P2Y12 inhibitor plus anticoagulant confers a benefit of less major bleeding with no difference in major adverse cardiac events, mortality, myocardial infarction, target vessel revascularization, stent thrombosis or thromboembolism compared with triple therapy.

The Relationship between Carotid and Femoral Artery Intima-Media Thickness and Histopathologic Grade of Atherosclerosis in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Variability in the grade of atherosclerosis among patients with chronic kidney disease (CKD) could affect the ultrasound measurements of intima media thickness (IMT). We sought to investigate IMTs of carotid (cIMT) and femoral (fIMT) arteries in CKD patients and assess the degree of their correlation with histopathological atherosclerosis. METHODS: Eighty-nine out of 99 enrolled subjects completed this study. The subjects were divided into 3 groups: 34 patients with CKD (Case group), 31 with coronary artery disease undergoing coronary artery bypass graft (CABG, positive control group), and 24 healthy kidney donors (negative control group). For histopathological assessment of atherosclerosis, arterial tissue samples were obtained from the patients in each study group. The cIMT and fIMTs were measured by ultrasonography. RESULTS: Histopathological atherosclerosis was present in 82.3, 100, and 20.8% of CKD, CABG, and donor groups respectively (p < 0.001). CKD patients had higher values of cIMT and fIMT than the donor group (p = 0.01 and 0.004, respectively). cIMT was positively correlated with the grade of atherosclerosis in the CKD group only (p < 0.001), while fIMT was correlated with the grade of atherosclerosis in both CKD and donor groups (p < 0.001 and p = 0.009 respectively). In CKD patients, cIMT >0.65 mm and femoral values >0.57 mm predicted the presence of histopathological atherosclerosis with sensitivities of 96 and 92% respectively. CONCLUSION: Higher values of cIMT and fIMT in CKD patients are associated with higher rates and degrees of histopathological atherosclerosis. Additionally, when compared to fIMT, cIMT has a higher sensitivity for detecting atherosclerosis in CKD patients.

Meta-Analysis of Aspirin Versus Dual Antiplatelet Therapy Following Coronary Artery Bypass Grafting.

Although aspirin monotherapy is considered the standard of care after coronary artery bypass grafting (CABG), more recent evidence has suggested a benefit with dual antiplatelet therapy (DAPT) after CABG. We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of aspirin monotherapy with DAPT in patients after CABG. Subgroup analyses were conducted according to surgical technique (i.e., on vs off pump) and clinical presentation (acute coronary syndrome vs no acute coronary syndrome). Random effects overall risk ratios (RR) were calculated using the DerSimonian and Laird model. Eight randomized control trials and 9 observational studies with a total of 11,135 patients were included. At a mean follow-up of 23 months, major adverse cardiac events (10.3% vs 12.1%, RR 0.84, confidence interval [CI] 0.71 to 0.99), all-cause mortality (5.7% vs 7.0%, RR 0.67, CI 0.48 to 0.94), and graft occlusion (11.3% vs 14.2%, RR 0.79, CI 0.63 to 0.98) were less with DAPT than with aspirin monotherapy. There was no difference in myocardial infarction, stroke, or major bleeding between the 2 groups. In conclusion, DAPT appears to be associated with a reduction in graft occlusion, major adverse cardiac events, and all-cause mortality, without significantly increasing major bleeding compared with aspirin monotherapy in patients undergoing CABG.

Constrictive pericarditis from an endocardial pacemaker lead.

Constrictive pericarditis secondary to endocardial pacemaker inflammation, without associated pericardial effusion or infection, has yet to be described in the literature. We present a case of a 42-year-old man who developed recurrent ascites from regional constrictive pericarditis following pacemaker implant. Symptoms resolved after pericardiectomy.

Identification and Quantification of Patent Foramen Ovale-Mediated Shunts: Echocardiography and Transcranial Doppler.

Once deemed benign, patent foramen ovale (PFO)-mediated right-to-left shunting has now been linked to stroke, migraine, and hypoxemia. Contrast transesophageal echocardiography is considered the standard technique for identifying a PFO, allowing visualization of the atrial septal anatomy and differentiation from non-PFO right-to-left shunts. Transthoracic echocardiography is the most common method for PFO imaging, being cost-effective, but has the lowest sensitivity. Transcranial Doppler is highly sensitive but is unable to differentiate cardiac from pulmonary shunts; it is the best method to quantitate shunt severity, being more sensitive than transthoracic or transesophageal echocardiography so is our preferred screening method for PFO.

Coronary artery bypass graft pseudoaneurysm from saphenous vein graft stent fracture.

Saphenous venous graft (SVG) pseudoaneurysms are a rare complication of coronary artery bypass grafting (CABG). An 85-year-old man with CABG and a distal SVG stent presented with dyspnea. Chest computed tomography (CT) revealed a large partially thrombosed pseudoaneurysm at the distal SVG with stent fracture. Endoluminal exclusion of the distal SVG pseudoaneurysm using a covered stent was performed. Follow-up chest CT and angiography showed persistent pseudoaneurysm filling and enlargement. The SVG proximal to the pseudoaneurysm was embolized with coils to reduce rupture risk. Following embolization, the patient's left ventricular ejection fraction was moderately depressed but the patient remained stable and was discharged. .

Safety and Efficacy of Dual Versus Triple Antithrombotic Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Choosing an antithrombotic regimen after coronary intervention in patients with concomitant indication for anticoagulation is a challenge commonly encountered by clinicians. METHODS: We performed a meta-analysis of observational studies and randomized, controlled trials comparing outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (single antiplatelet therapy and anticoagulant) in patients taking long-term anticoagulants after percutaneous coronary intervention. Major bleeding was the primary outcome. Random effects overall risk ratios (RRs) were calculated using the DerSimonian and Laird model. RESULTS: Nine observational studies and 2 randomized controlled trials with a total of 7276 patients met our selection criteria. At a mean follow-up of 10.8 months major bleeding was higher in the triple therapy cohort compared with dual therapy (6.6% vs 3.8%; RR 1.54; 95% confidence interval [CI], 1.2-1.98; P <.01). No difference was observed between the 2 groups for all-cause mortality (RR 0.98; 95% CI, 0.68-1.43; P = .93), major adverse cardiac events (RR 1.03; 95% CI, 0.8-1.32; P = .83), thromboembolic events (RR 1.02; 95% CI, 0.49-2.10; P = .96), myocardial infarction (RR 0.85; 95% CI, 0.67-1.09; P = .21), stent thrombosis (RR 0.77; 95% CI, 0.46-1.3; P = .33), and target vessel revascularization (RR 0.87; 95% CI, 0.66-1.15; P = .33). CONCLUSION: In patients receiving anticoagulant therapy, a strategy of single antiplatelet therapy confers a benefit of less major bleeding with no difference in all-cause mortality, cardiovascular mortality, major adverse cardiac events, myocardial infarction, stent thrombosis, or thromboembolic event rate compared with dual antiplatelet therapy.

Renal Collecting System Anatomy in Living Kidney Donors by Computed Tomographic Urography: Protocol Accuracy Compared to Intravenous Pyelographic and Surgical Findings.

OBJECTIVES: To evaluate the accuracy of triple-bolus computed tomography urography (CTU) as a surrogate of intravenous pyelography (IVP) for determining the anatomy of the urinary collecting system in living kidney donors. MATERIALS AND METHODS: In an analytic descriptive cross-sectional study, 36 healthy kidney donors were recruited during 12 months. Preoperative IVP and CTU were utilized to evaluate kidneys' anatomy; major and minor calyces and variation were used as anatomical indices to compare the accuracy of CTU and IVP; the images were then compared to surgical findings. RESULTS: Thirty-six kidney donors (92% male; mean age: 28 ± 6 years) were enrolled in this study. The kappa coefficient value was significant and almost perfect for the CTU and IVP findings in detecting the pattern of calyces (kappa coefficient 0.92, asymptotic 95% confidence interval 0.86-0.97). Anatomic variations or anomalies of the urinary collecting system included the bifid pelvis (5.6%), duplication (8.3%), and extra-renal pelvis (2.8%). Both the sensitivity and specificity of CTU in the detection of the anatomy and variations were 100%; the sensitivity and specificity of IVP were 83.3% and 100%, respectively. CONCLUSIONS: The triple-bolus preoperative CTU can be considered an alternative to IVP for assessing the anatomy of the urinary collecting system.

Patent foramen ovale: Unanswered questions.

The foramen ovale is a remnant of the fetal circulation that remains patent in 20-25% of the adult population. Although long overlooked as a potential pathway that could produce pathologic conditions, the presence of a patent foramen ovale (PFO) has been associated with a higher than expected frequency in a variety of clinical syndromes including cryptogenic stroke, migraines, sleep apnea, platypnea-orthodeoxia, deep sea diving associated decompression illness, and high altitude pulmonary edema. A unifying hypothesis is that a chemical or particulate matter from the venous circulation crosses the PFO conduit between the right and left atria to produce a variety of clinical syndromes. Although observational studies suggest a therapeutic benefit of PFO closure compared to medical therapy alone in patients with cryptogenic stroke, 3 randomized controlled trials (RCTs) did not confirm the superiority of PFO closure for the secondary prevention of stroke. However, meta-analyses of these RCTs demonstrate a significant benefit of PFO closure over medical therapy alone. Similarly, observational studies provide support for PFO closure for symptomatic relief of migraines. But one controversial randomized study failed to replicate the results of the observational studies while another two demonstrated a partial benefit. The goal of this review is to discuss the clinical conditions associated with PFO and provide internists and primary care physicians with current data on PFO trials, and clinical insight to help guide their patients who are found to have a PFO on echocardiographic testing.