Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure: JACC State-of-the-Art Review.

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF.

Acute COVID-19 Pneumonia Unmasking a Large Left Atrial Myxoma.

This is a case of acute coronavirus disease 2019 pneumonia that revealed an incidental large atrial myxoma with obstructive physiology that ultimately required emergent treatment with a definitive atriotomy and resection of the underlying myxoma.

Who needs their descending thoracic aorta anyway? Extra-anatomic bypass for aorto-bronchial fistula after TEVAR.

BACKGROUND: Aortobronchial fistula after TEVAR remains a vexing clinical problem associated with high mortality. Although a combination of endovascular and open surgical strategies have been reported in managing this pathology, there is as yet no definitive treatment algorithm that can be used for all patients. We discuss our approach to an aortobronchial fistula associated with an overtly infected aortic endograft. CASE PRESENTATION: A 49-year-old female sustained a traumatic aortic transection 14 years prior, managed by an endovascular stent-graft. Due to persistent endoleak, she underwent open replacement of her descending thoracic aorta 4 years later. Ten years after her open aortic surgery, the patient presented with hemoptysis, and a pseudoaneurysm at her distal aortic suture line was identified on computed tomography, whereupon she underwent placement of an endograft. Eight weeks later, she presented with dyspnea, recurrent hemoptysis, malaise and fever, with clinical and radiographic evidence of an aortobronchial communication and an infected aortic stent-graft. The patient underwent management via a two-stage open surgical approach, constituting an extra-anatomic bypass from her ascending aorta to distal descending aorta and subsequent radical excision of her descending aorta with all associated infected prosthetic material and repair of the airway. CONCLUSION: Aortobronchial fistula after TEVAR represents a challenging complex clinical scenario. Extra-anatomic aortic bypass followed by radical debridement of all contaminated tissue may provide the best option for durable longer-term outcomes.

Fibrinolytic Status and Risk of Death After Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is a heterogeneous disease process with variable presentation and outcomes. The endogenous fibrinolytic system is a complex framework of regulatory pathways that maintains homeostasis by dissolving overabundant thrombi. We sought to investigate phenotypic profiles of the endogenous fibrinolytic system among patients presenting with acute PE and their impact on mortality. METHODS: We enrolled all consecutive patients with acute PE in our institutional Pulmonary Embolism Response Team registry. We collected blood samples at the time of PE diagnosis and analyzed concentrations of plasminogen activator inhibitor 1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and alpha-2-antiplasmin (A2A). We assessed the association of concentration of fibrinolytic inhibitors and 1-year all-cause mortality and various echocardiographic markers of right ventricular (RV) dysfunction. RESULTS: There is significant variability of PAI-1, A2A, and TAFI concentrations across the spectrum of PE risk profiles with high PAI-1, low TAFI, and low A2A (herein referred to as a high-risk biomarker profile) correlating with worse PE severity. High-risk biomarker profile correlated with high-risk echocardiographic features of RV dysfunction, including increased RV/left ventricular (LV) ratio, low tricuspid annular plane systolic excursion, and low right ventricular outflow tract velocity time integral. Higher-risk biomarker profile was able to discriminate and independently identify patients at high risk of all-cause mortality (Group 2 HR 6 95% CI 1.3-27.8, Group 3 HR 12, 95% CI 1.7-86). CONCLUSIONS: Further studies are needed to assess the exact pathophysiological link between fibrinolytic status and poor outcome after acute PE and to ascertain the impact of anti-inhibitors of the fibrinolytic system on response to therapy and outcomes after acute PE.

Evaluation of cell-free DNA approaches for multi-cancer early detection.

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test.

Massive Embolism: Knife versus PCI.

Pulmonary embolism is the third most common cardiovascular syndrome with an estimated up to 25% of patients presenting with sudden death. For those who survive, a mainstay of management for patients with hemodynamic stability is anticoagulation; however, recommendations and options are rapidly changing for patients with submassive or massive pulmonary embolism with hemodynamic instability. Catheter-based and surgical approaches offer efficacious management options for unstable patients or patients with contraindications to anticoagulation; however, both approaches have inherent benefits and risk. This article seeks to offer a brief review on the recommendations and options for management of pulmonary embolism from both surgical and catheter-based perspectives.

Post-transplant diabetes mellitus following heart transplantation.

Post-transplant diabetes mellitus (PTDM) is common following heart transplant, impacting greater than 20% of patients with most cases occurring in the first year after transplant. PTDM is associated with multiple negative sequelae including increased post-operative infections, a higher rate of renal failure, and increased mortality. Compared with pre-transplant diabetes mellitus, PTDM has several unique risk factors and immunosuppressive medications play an important role in disease pathophysiology. Newer treatments for hyperglycemia, including glucagon like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, may counter the mechanisms of immunosuppression-related hyperglycemia making them an appealing treatment option for patients with PTDM. Here, we review the definitions, incidence, risk factors, pathophysiology, clinical outcomes, treatment options, pharmacologic considerations, and future directions in PTDM.

Upregulation of Inflammatory Cytokines in Pulmonary Embolism Using Biochip-Array Profiling.

The complex pathophysiology of pulmonary embolism (PE) involves hemostatic activation, inflammatory processes, cellular dysfunction, and hemodynamic derangements. Due to the heterogeneity of this disease, risk stratification and diagnosis remains challenging. Biochip-array technology provides an integrated high throughput method for analyzing blood plasma samples for the simultaneous measurement of multiple biomarkers for potential risk stratification. Using biochip-array method, this study aimed to quantify the inflammatory biomarkers such as interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor (EGF) in 109 clinically confirmed PE patients in comparison to the control group comprised of plasma samples collected from 48 healthy subjects. Cytokines IL-4, IL-6, IL-8, IL-10, IL-1ß, and MCP-1 demonstrated varying level of significant increase (P < 0.05) in massive-risk PE patients compared to submassive- and low-risk PE patients. The upregulation of inflammatory cytokines in PE patients observed in this study suggest that inflammation plays an important role in the overall pathophysiology of this disease. The application of biochip-array technology may provide a useful approach to evaluate these biomarkers to understand the pathogenesis and risk stratification of PE patients.

Angiopoietin-2 correlates with pulmonary embolism severity, right ventricular dysfunction, and intensive care unit admission.

Risk stratification of acute pulmonary embolism (PE) is important to identify patients at risk for hemodynamic collapse who would benefit from more aggressive therapies. Angiopoietin-2 (Ang-2) is a signaling molecule involved in angiogenesis and is upregulated in response to tissue hypoxia. We aimed to assess the association of Ang-2 with (1) PE severity, (2) echocardiographic and invasive hemodynamic markers of right ventricular (RV) dysfunction, and (3) need for intensive treatment. Patients presenting to our institution with acute PE were included in a prospective database and blood samples were collected and stored for later analysis. A total of 65 patients were included in the study. Ang-2 correlated with PE risk stratification and echocardiographic and invasive hemodynamic markers of RV dysfunction and pulmonary hypertension. An Ang-2 level of > 4101 pg/mL had an odds ratio of 7.4 (95% CI: 1.53-12.5, p < 0.01) for intensive care unit (ICU) admission. In conclusion, Ang-2 correlates with PE severity, RV dysfunction, and need for ICU admission. Ang-2 holds promise as a novel marker that can aid in risk stratification for this patient population.

Preoperative Right Heart Dysfunction and Gastrointestinal Bleeding in Patients with Left Ventricular Assist Devices.

Gastrointestinal bleeding (GIB) is a common cause of morbidity among patients supported by left ventricular assist devices (LVADs). The aim of this study was to identify if pre-LVAD right ventricular (RV) dysfunction is associated with risk of GIB after LVAD implantation. Of 398 patients implanted with LVADs between July 2008 and July 2016, 130 (33%) developed GIB at a median of 2.6 months following LVAD implantation. Arteriovenous malformations (AVMs) were found in 42 (34%) GIB patients. Patients with GIB were older and more likely to have hypertension, diabetes, and ischemic cardiomyopathy. On pre-LVAD echocardiography, GIB patients had increased RV diastolic dimension (4.7 ± 0.8 vs. 4.4 ± 0.9 cm, p = 0.02), a higher rate of greater than mild tricuspid valve (TV) regurgitation (73 [60%] vs. 120 [47%], p = 0.006), and underwent TV repair more often (38 [30%] vs. 43 [16%], p = 0.0006) during LVAD implantation. After multivariable adjustment, preoperative greater than mild RV enlargement (hazard ratio [HR] 2.32, 95% CI 1.12-5.03; p = 0.03), TV regurgitation (HR 1.83, CI 1.02-3.44; p = 0.01), and TV repair (HR 3.76, confidence interval [CI] 1.02-4.44; p = 0.01) remained associated with risk of GIB. This finding was driven by the AVM-GIB subgroup. Preoperative RV enlargement and TV regurgitation are associated with post-LVAD AVM-related GIB.

Degenerative Pulmonary Valve Insufficiency in a Patient With a Prior Bentall Procedure.

Adult pulmonary valve regurgitation most commonly presents after congenital cardiac surgery, with limited reports of pure degenerative valvular disease. We present a patient who underwent a Bentall procedure for annuloaortic ectasia with severe aortic insufficiency 14 years prior now presenting with degenerative, severe, symptomatic pulmonary valve regurgitation and normal pulmonary pressures. The patient underwent successful valve replacement with a bovine prosthesis. Recovery was unremarkable, and he continues to do well without further cardiac surgical requirements.

Uniportal VATS Lobectomy and Decortication: Not an Everyday Occurrence.

Management of trapped lung with an underlying lung lesion and hydropneumothorax remains controversial. Furthermore, Aspergillus empyema and aspergilloma are rare pathologies for which uniportal video-assisted thoracoscopic (VATS) surgical management remains controversial. We present a young patient referred to our service after recent hospitalization for pneumonia. The patient was found to have a chronic effusion with a right lower lobe cystic parenchymal lesion and was taken to the operating room. The patient underwent right uniportal VATS surgery with evacuation of empyema, total pulmonary decortication, and right lower lobectomy. His postoperative course was unremarkable, and he was discharged home. Postoperative workup demonstrated lymphocyte variant hypereosinophilia. He continues to follow with thoracic surgery at the time of this report and remains asymptomatic. We conclude that uniportal VATS is a most minimally invasive, safe, and efficient approach for management of complex intrathoracic pathology including total pulmonary decortication and lobectomy.

Protein C Pathway, Inflammation, and Pump Thrombosis in Patients With Left Ventricular Assist Devices.

Use of left ventricular assist devices (LVADs) for management of advanced heart failure is becoming increasingly common; however, device associated thrombosis remains an important cause of mortality in this patient population. We hypothesize that inflammation in LVAD implanted patients dysregulates the protein C pathway, creating a hypercoagulable state leading to thrombosis. Plasma samples from 22 patients implanted with the Thoratec HeartMate II LVAD were analyzed by commercial ELISAs. Retrospective sample selection included those collected 1-3 months prior to and within 1 month after a thrombotic or bleeding event. Unrelated to warfarin dosing, total protein S and free protein S (p = 0.033) levels were 20% lower in patients with LVAD-thrombosis than in patients with LVAD-bleeding. Levels of protein C, soluble endothelial cell protein C receptor, and soluble thrombomodulin were similar in both groups before and after the event. Compared to normal, C-reactive protein levels were 25-fold elevated in LVAD-thrombosis patients but only 9-fold elevated in LVAD-bleeding patients. This study suggests that protein S, influenced by the inflammatory state, is a gatekeeper for the function of protein C in patients with LVAD-associated thrombosis.

Intermediate oncologic outcomes after uniportal video-assisted thoracoscopic thymectomy for early-stage thymoma.

BACKGROUND: Recent years have seen a trend towards utilizing a video-assisted thoracic surgery (VATS) approach for treatment of thymoma. Although increasing in practice, intermediate- and long-term oncologic outcome data is lacking for the VATS approach. There is no oncologic data for the uniportal VATS approach. We sought to evaluate the feasibility and impact on patient survival of uniportal VATS thymectomy for early-stage thymoma. METHOD: The clinical outcomes for 17 patients with Masaoka stage I to II thymomas treated between January of 2009 and July of 2014 at a single institution were collected retrospectively. Primary endpoint was overall survival (OS) and secondary endpoint was recurrence-free survival (RFS). RESULTS: Ten women and seven men underwent uniportal VATS thymectomy; eleven had stage I thymoma and six had stage II thymoma. There were no conversions to open surgery. Operative mortality was zero. Mean tumor size was 3.8±1.0 centimeters, with a range of 1.9 to 6.0 centimeters. All patients underwent a R0 resection. Five-year survival was 100%, and the estimated RFS was 100%. CONCLUSIONS: Our findings suggest that uniportal VATS thymectomy for early-stage thymoma is feasible, and the intermediate-term oncologic outcomes are comparable to historic standards for open and multi-incision VATS thymectomy. However, additional follow-up is required to evaluate for long-term oncologic outcomes.

Treatment Complications of Atrial Fibrillation and Their Management.

Atrial fibrillation (AF) is a rhythm disturbance defined by irregular, rapid electrical, and mechanical activation of the atria, which causes unsynchronized atrial contraction and promotes thromboembolism. AF is the most common sustained arrhythmia. Its prevalence and incidence are increasing due to aging and improved survival from acute heart diseases. This article is a review on AF management from both a surgical and catheter-based perspective. While both treatment approaches to AF have been shown to be successful in the management of AF, they are not without their own inherent complications. This article seeks to review some of these complications and help to guide treatment.