Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry.

BACKGROUND: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients. METHODS: Using data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype. RESULTS: Our study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course. CONCLUSIONS: Lymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.

Mitochondrial diaphorases as NAD⁺ donors to segments of the citric acid cycle that support substrate-level phosphorylation yielding ATP during respiratory inhibition.

Substrate-level phosphorylation mediated by succinyl-CoA ligase in the mitochondrial matrix produces high-energy phosphates in the absence of oxidative phosphorylation. Furthermore, when the electron transport chain is dysfunctional, provision of succinyl-CoA by the α-ketoglutarate dehydrogenase complex (KGDHC) is crucial for maintaining the function of succinyl-CoA ligase yielding ATP, preventing the adenine nucleotide translocase from reversing. We addressed the source of the NAD(+) supply for KGDHC under anoxic conditions and inhibition of complex I. Using pharmacologic tools and specific substrates and by examining tissues from pigeon liver exhibiting no diaphorase activity, we showed that mitochondrial diaphorases in the mouse liver contribute up to 81% to the NAD(+) pool during respiratory inhibition. Under these conditions, KGDHC's function, essential for the provision of succinyl-CoA to succinyl-CoA ligase, is supported by NAD(+) derived from diaphorases. Through this process, diaphorases contribute to the maintenance of substrate-level phosphorylation during respiratory inhibition, which is manifested in the forward operation of adenine nucleotide translocase. Finally, we show that reoxidation of the reducible substrates for the diaphorases is mediated by complex III of the respiratory chain.

Pretreatment identification of 90-day readmission among heart failure patients receiving aquapheresis treatment.

BACKGROUND: The use of traditional models to predict heart failure (HF) has limitations in preventing HF hospitalizations. Artificial intelligence (AI) and machine learning (ML) in cardiovascular medicine only have limited data published regarding HF populations, with none assessing the favorability of decongestive therapy aquapheresis (AQ). AI and ML can be leveraged to design non-traditional models to identify those who are at high risk of HF readmissions. OBJECTIVES: This study aimed to develop a model for pretreatment identification of risk for 90-day HF events among HF patients who have undergone AQ. METHODS: Using data from the AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial, we designed a ML-based predictive model that can be used before initiating AQ to anticipate who will respond well to AQ and who will be at high risk of future HF events. RESULTS: Using ML we identified the top ten predictors for 90-day HF events. Interestingly, the variable for 'intimate relationships with loved ones' strongly predicted response to therapy. This ML-model was more successful in predicting the outcome in HF patients who were treated with AQ. In the original AVOID-HF trial, the overall 90-day HF event rate in the AQ arm was 32%. Our proposed predictive model was accurate in anticipating 90-day HF events with better statistical accuracy (area under curve 0.88, sensitivity 80%, specificity 75%, negative predictive value 90%, and positive predictive value 57%). CONCLUSIONS: ML can help identify HF patients who will respond to AQ therapy. Our model can identify super-respondents to AQ therapy and predict 90-day HF events better than currently existing traditional models. CONDENSED ABSTRACT: Utilizing data from the AVOID-HF trial, we designed a ML-predictive model that can be used before initiating AQ to anticipate who will respond well to AQ and who will be at high risk of future HF events. Using ML, we identified the top 10 predictors for 90-day HF events. Our model can identify super-respondents to ultrafiltration therapy and predict 90-day HF events better than currently existing traditional models.

Novel Cardiovascular and Pulmonary Findings in the Noninvasive Ischemic Assessment of Patients With Coronavirus 2019 (COVID-19).

In the past several years, the coronavirus pandemic has introduced multiple medical disciplines to various new forms of disease previously unknown and has shown us a unique presentation of already existing diseases. We continue to understand the long-term effects of the pandemic on the population's health and continue to find new unique features previously unknown. This paper presents the unique feature of lung uptake abnormalities discovered on nuclear stress testing for cardiac perfusion defects, a consistent finding in multiple individuals with recent COVID-19 or ongoing infection.

The Roles of Coronary Computed Tomography Angiography in Characterizing Coronary Plaque: Screening, Treatment, and Prevention.

One of the major risk factors for coronary atherosclerosis is the gradual formation and maturation of coronary atherosclerotic plaque (CAP) [...].

Primary Cardiac Sarcoma: Angiosarcoma Compressing the Right Coronary Artery.

Cardiac tumors are uncommon and can be classified as either primary benign, primary malignant, or metastatic. Cardiac tumors have a wide range of presentations, which can lead to delays in diagnosis and treatment. Primary cardiac tumors can also affect nearby structures, and there have been a few reported cases of coronary artery involvement with various underlying causes. In this case report, we describe a patient with a primary cardiac sarcoma (angiosarcoma) that had spread to other parts of the body and caused occlusion of the right coronary artery.

Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy resulting from a mutation in one of several cardiac sarcomeric proteins [...].

Novel Device Therapies for Heart Failure.

Heart failure (HF) therapeutics have advanced significantly over the past few years [...].

Beyond Ejection Fraction: Novel Clinical Approaches Towards Sudden Cardiac Death Risk Stratification in Patients with Dilated Cardiomyopathy.

Implantable Cardioverter-Defibrillator (ICD) therapy is indicated for patients at risk for sudden cardiac death due to ventricular tachyarrhythmia. The most commonly used risk stratification algorithms use Left Ventricular Ejection Fraction (LVEF) to determine which patients qualify for ICD therapy, even though LVEF is a better marker of total mortality than ventricular tachyarrhythmias mortality. This review evaluates imaging tools and novel biomarkers proposed for better risk stratifying arrhythmic substrate, thereby identifying optimal ICD therapy candidates.

A Review of Cardiac Amyloidosis: Presentation, Diagnosis, and Treatment.

Amyloidosis is a group of disorders that can affect almost any organ due to the misfolding of proteins with their subsequent deposition in various tissues, leading to various disease manifestations based on the location. When the heart is involved, amyloidosis can manifest with a multitude of presentations such as heart failure, arrhythmias, orthostatic hypotension, syncope, and pre-syncope. Diagnosis of cardiac amyloidosis can be difficult due to the non-specific nature of symptoms and the relative rarity of the disease. Amyloidosis can remain undiagnosed for years, leading to its high morbidity and mortality due to this delay in diagnosis. Newer imaging modalities, such as cardiac magnetic resonance imaging, advanced echocardiography, and biomarkers, make a timely cardiac amyloidosis diagnosis more feasible. Many treatment options are available, which have provided new hope for this patient population. This manuscript will review the pathology, diagnosis, and treatment options available for cardiac amyloidosis and provide a comprehensive overview of this complicated disease process.

Barth Syndrome: Psychosocial Impact and Quality of Life Assessment.

BACKGROUND: Barth syndrome (BTHS) is a rare X-linked genetic disease that affects multiple systems and leads to complex clinical manifestations. Although a considerable amount of research has focused on the physical aspects of the disease, less has focused on the psychosocial impact and quality of life (QoL) in BTHS. METHODS: The current study investigated caregiver- (n = 10) and self-reported (n = 16) psychological well-being and QoL in a cohort of BTHS-affected patients and families. Participants completed the depression and anxiety components of the Patient-Reported Outcomes Information System (PROMIS) Short Form 8A and Health-related quality of life (HRQoL) surveys at enrollment and again during a follow-up period ranging from 6 to 36 months after baseline. RESULTS: Quality of life changed significantly over time and the various domains with some improvement and some decline. Among the available caregiver-patient dyad data, there was a trend toward discordance between caregiver and self-reported outcomes. Most notably, patients reported improvement in HRQoL, while caregivers reported declines. This suggests that there may be differences in perceived quality of life between the patients and parents, though our study is limited by small sample size. CONCLUSION: Our study provides valuable insights into the impacts of psychosocial and mental health aspects of BTHS. Implications of these findings include incorporating longitudinal assessment of QoL and screening for psychological symptoms in BTHS care to identify interventions that may drastically impact health status and the course of the disease.

Invasive Strategies for the Treatment of Pulmonary Embolism. Where Are We in 2020?

Pulmonary Embolism (PE) is the third most common cause of cardiovascular mortality in the United States, with 60,000-100,000 deaths per year following myocardial infarction and stroke. During the past 5 years, there has been an introduction of novel interventions as a result of a renewed interest in optimizing PE management, particularly among those individuals with more severe disease of hemodynamic significance. The cornerstone treatment for PE is anticoagulation. More aggressive alternatives have been considered for patients with intermediate and high-risk PE. In general, these options can be grouped into 3 different categories: systemic thrombolysis, catheter-directed interventions, and surgical embolectomy. Systemic thrombolysis has shown statistical benefit in several randomized trials for intermediate- and high-risk PE, however, this benefit has been offset by an elevated risk of major bleeding and intracerebral hemorrhage, limiting their use in clinical practice. Catheter-directed thrombolysis refers to catheter-directed injection of a thrombolytic drug directly into the pulmonary artery. Three interventional devices (EKOSonic endovascular system, FlowTriever embolectomy device and the Indigo thrombectomy system) have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. As of today, catheter-based interventions are limited to small randomized trials and single arm-prospective studies focused on short-term surrogate endpoints. Although single arm studies carry some value establishing the preliminary safety and effectiveness of these devices, they are not sufficient to stratify risk and guide clinical practice. Furthermore, no trials have been performed with enough power to assess potential mortality benefit with the use of catheter-directed thrombolysis or catheter-based embolectomy devices, hence treatment decisions continue to be influenced by individual risk of bleeding, the location of thrombus and operator expertise until additional evidence becomes available.

Emerging Technologies in Cardiac Pacing From Leadless Pacers to Stem Cells.

Modern pacemakers can sense and pace multiple chambers of the heart. These pacemakers have different modes and features to optimize atrioventricular synchrony and promote intrinsic conduction. Despite recent advancements, current pacemakers have several drawbacks that limit their feasibility. In this review article, we discuss several of these limitations and detail several emerging technologies in cardiac pacing aimed to solve some of these limitations. We present several technological advancements in cardiac pacing, including the use of leadless pacemakers, physiologic pacing, battery improvements, and bioartificial pacemakers. More research still needs to be done in testing the safety and efficacy of these new developments.

Correlation Between Aortic Angulation and Outcomes of Transcatheter Aortic Valve Replacement With New-Generation Valves.

The aim of this study was to assess the correlation of aortic angulation (AA) on immediate postprocedural and long-term outcomes following transcatheter aortic valve replacement (TAVR) with new-generation valves. There is limited and conflicting data on the impact of AA on short- and long-term outcomes in patients undergoing TAVR. Available studies to date were done with first-generation valves. We assessed 179 patients who underwent TAVR with either a balloon-expandable or self-expandable valve at our institute from May 2014 to June 2017 and had multislice computed tomography scans available for AA evaluation. All included patients received a second- or third-generation valve. TAVR endpoints, device success, and adverse events were defined according to the Valve Academic Research Consortium-2 criteria. The mean AA of the study population was 49.05 ± 10.07. Patients were divided into 2 groups: AA <49 and AA ≥49, and then further subdivided by valve type. There were no difference in mean age, The Society for Thoracic Surgery (STS) score, or race distribution between the AA <49 and AA ≥49 groups. The preimplantation balloon valvuloplasty rate was higher in patients with AA ≥ 49 compared to patients with AA <49, (70% vs 55.1%, P = 0.04). There was no difference in re-hospitalization, pacemaker implantation, postprocedural aortic regurgitation or mortality between patients with AA <49 and AA ≥49 irrespective of valve type (P < 0.05). AA does not significantly affect short- or long-term outcomes in patients who undergo TAVR with new-generation balloon-expandable or self-expandable valves.

Review of Hypothermia Protocol and Timing of the Echocardiogram.

Targeted temperature management, also known as therapeutic hypothermia (TH), is recommended for out-of-hospital cardiac arrest (OHCA). Both internal or external methods of cooling can be applied. Individuals resuscitated from OHCA frequently develop postarrest myocardial dysfunction resulting in decreased cardiac output and left ventricular systolic function. This dysfunction is usually transient and improves with spontaneous recovery over time. Echocardiogram (ECHO) can be a vital tool for the assessment and management of these patients. This manuscript reviewed methods available for TH after OHCA and reviews role of ECHO in the diagnosis and prognosis in this setting.

Levamisole-induced Vasculitis in a Hepatitis C Patient: A General Medicine Ward Perspective on Diagnosis and Management.

Purpura in hepatitis C patients has a wide range of possible etiologies, some of which include mixed cryoglobulinemia and idiopathic thrombocytopenic purpura. Levamisole is a common chemical used as a lacing agent for cocaine. It is believed to enhance the addictive properties of cocaine, but it has been associated with a vasculitis syndrome that most commonly presents with purpura and leukopenia. We report a case of a patient with hepatitis C and cocaine abuse who presented with vasculitis, thrombocytopenia, and bloody sputum. A punch biopsy was performed, which confirmed the diagnosis of levamisole-induced vasculitis. A comprehensive rheumatology workup could result in variable serology and does not provide a definitive diagnosis. We suggest performing a punch biopsy as part of the initial workup for these patients, as it can provide rapid diagnosis and is associated with a lower cost.

Is early invasive management as ST elevation myocardial infarction warranted in de Winter's sign?-a "peak" into the widow-maker.

de Winter's sign was first described by de Winter et al. in 2008 as a new electrocardiographic (EKG) pattern of acute proximal left anterior descending coronary artery (LAD) occlusion. Instead of the normal presentation of ST elevation, it is described as depression of ST segment at the J point in the precordial leads V1-V6, which are upsloping leading to hyper-acute T waves, with ST elevation in aVR. The initial retrospective systematic analysis proved this sign to be present in about 2% of anterior myocardial infarction. This review aims to address the important question of mode and urgency of intervention, on detection of de Winter's sign. In this review, we take a look at the de Winter's sign EKG characteristics, accuracy in diagnosis, typical patient presentation, and the outcomes of early intervention. We conducted a Medline search using various combinations of "de Winter's sign," "STEMI equivalent," "cardiac catheterization," and "thrombolysis" to identify pivotal research articles published before June 1, 2019, for inclusion in this review. Concurrently, major practice guidelines, trial bibliographies, and pertinent reviews were examined to ensure inclusion of relevant trials. A consensus among the authors was used to choose items for narrative inclusion. The following section reviews data from pivotal trials to determine the need for early invasive management in de Winter's sign. Research articles reviewed evaluating cardiac catheterization in de Winter's sign. de Winter's sign, although rare (~2%), should be promptly recognized, as it reveals underlying severe coronary artery pathology, frequently involving the LAD which is associated with a high rate of mortality. This systematic review emphasizes awareness and strong consideration of early activation of the cardiac catheterization lab with PPCI; which may yield better treatment outcomes. The evidence suggests that de Winter's sign, presenting with ST depression and T wave elevation, should indeed be treated as ST-elevation myocardial infarction (STEMI) equivalent, with prompt recognition and early intervention.

CardioMEMS: where we are and where can we go?

The prevalence of heart failure (HF) has been on the rise with associated increase in hospitalizations, morbidity and mortality. These hospitalizations have led to increasingly more cost on and decreased quality of life for patients. CardioMEMS is one of the newer devices designed to help tackle this issue by allowing for better monitoring of HF patients. This device also allows for accurate recording of pulmonary artery pressures (PAPs) and has also been applied in various other areas, such as aneurysmal tears, for monitoring pressures. In this manuscript we will review the current state of CardioMEMS HF system and investigate some of the other areas for its promising use in the field.

Apple Watch, Wearables, and Heart Rhythm: where do we stand?

Atrial fibrillation (AF) poses a major health concern in the United States by affecting over 5 million people accounting for at least 15% to 25% of strokes. It can be asymptomatic or subclinical with its first presentation being stroke in 18%, and AF being only detected at the time of stroke. With evidence of subclinical AF associated with increased risk of ischemic stroke, recent developments indeed point towards wearables, especially smart watches, being quite effective and representing a novel method for screening for silent AF in the general population, and thereby reducing mortality and morbidity associated with it. This manuscript aims to review whether the photoplethysmography (PPG) technology, employed in the wearables to monitor heart rate, is accurate enough to aid in the diagnosis of AF that may remain asymptomatic or paroxysmal. It also explores the option of actually employing this method in the general population, the feasibility of this mode of diagnosis, sensitivity and specificity of this method compared to the conventional electrocardiogram (EKG), and the actual follow up with a practitioner and subsequent treatment of AF, if diagnosed. We conducted a Medline search using various combinations of "smart watch" "atrial fibrillation" "wearables", and "Kardia" to identify pivotal randomized trials published before June 1, 2019, for inclusion in this review. Concurrently, major practice guidelines, trial bibliographies, and pertinent reviews were examined to ensure inclusion of relevant trials. A consensus among the authors was used to choose items for narrative inclusion. The following section reviews data from pivotal trials to determine the effectiveness of smart watch technology in detecting AF in the general population. Trials reviewed evaluated apple watch, Kardia, Samsung wearables in diagnosis of AF. The fact that there is an increase in consumer use of wearables, smart devices, which can serve as health monitoring devices that can be used as a non-invasive, ambulatory assessment of heart rate and rhythm, is definitely novel. Intermittent short EKG recordings repeated over a longer-term period produced significantly better sensitivity for AF detection, with 4 times as many cases diagnosed compared with a single time-point measurement. Since there are limitations and further research into this new field is required, the wearable technology may not serve as the ultimate tool for diagnosis of AF, rather a nidus for the general population to seek medical advice for confirmation on being notified of having an irregular rhythm leading to prevention of morbidity and mortality associated with it.

Transcatheter aortic valve replacement with a focus on transcarotid: a review of the current literature.

Valve replacement in high-risk patients with severe aortic stenosis has undergone a huge paradigm shift in the recent years in terms of procedural details and vascular access site for patients who have poor peripheral access. Carotid artery is one of the more promising access sites which has been proven to provide a good alternative site with comparable outcomes to transfemoral approach. In this manuscript, we will provide a review of the current literature on transaortic, transapical, transaxillary and transcarotid approaches to transcatheter aortic valve replacement (TAVR) while focusing on the transcarotid approach.