International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review.

Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure.

Blood Levels of Angiotensinogen and Hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Angiotensinogen is the proximal precursor of the angiotensin peptide hormones of the renin-angiotensin-aldosterone system (RAAS). Clinical trials are ongoing targeting angiotensinogen for the treatment of hypertension and heart failure. The epidemiology of angiotensinogen is not well defined, particularly its relationship to ethnicity, sex, and blood pressure (BP)/hypertension.

Impact of transitioning patients to oral diuretics 24 hours before discharge from heart failure hospitalization on 30 day outcomes.

Background: Patients hospitalized for heart failure (HF) are at high risk for post-discharge events. Although transition from intravenous to oral diuretics for ≥24 h is commonly practiced to reduce post-discharge risk, evidence supporting this strategy is limited. We investigated the impact of this practice on 30 day post-discharge outcomes following HF hospitalization at our institution.

Myocardial Strain and Association With Clinical Outcomes in Danon Disease: A Model for Monitoring Progression of Genetic Cardiomyopathies.

Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X-linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD.

Cardiac Transplantation in Danon Disease.

Background: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation.

Methods: The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers.

Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.

Background: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs.

Methods: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111).

Results: A total of 524 patients (age 52 years ±12, 84.

Biventricular Intravascular Microaxial Blood Pumps and Immunosuppression as a Bridge to Recovery in Giant Cell Myocarditis.

We report a case of giant cell myocarditis in a 76-year-old patient managed with combined immunosuppression and biventricular intravascular microaxial blood pumps. This case highlights a feasible approach for managing such patients who are not candidates for transplantation or durable ventricular assist devices. ().

Improved Time in Therapeutic Range with International Normalized Ratio Remote Monitoring for Patients with Left Ventricular Assist Devices.

Despite advances in therapy, bleeding and thromboembolic events are frequent complications in patients with left ventricular assist device (LVAD) support. Maintaining warfarin in therapeutic range has been shown to be more challenging in this patient population compared to other indications. Patients with LVADs on warfarin typically are within goal international normalized ratio (INR) range 36-57% of the time, compared to about 65% for other indications.

Antisense Inhibition of Angiotensinogen With IONIS-AGT-L: Results of Phase 1 and Phase 2 Studies.

Targeting angiotensinogen (AGT) may provide a novel approach to more optimally inhibit the renin-angiotensin-aldosterone system pathway. Double-blind, placebo-controlled clinical trials were performed in subjects with hypertension as monotherapy or as an add-on to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with IONIS-AGT-L versus placebo up to 2 months. IONIS-AGT-L was well tolerated with no significant changes in platelet count, potassium levels, or liver and renal function.

Post-discharge arrhythmic risk stratification of patients with acute myocarditis and life-threatening ventricular tachyarrhythmias.

Aims: The outcomes of patients presenting with acute myocarditis and life-threatening ventricular arrhythmias (LT-VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population.

Methods And Results: We retrospectively analysed 156 patients (median age 44 years; 77% male) discharged with a diagnosis of acute myocarditis and LT-VA from 16 hospitals worldwide.

Kidney Function Following Left Ventricular Assist Device Implantation: An Observational Cohort Study.

Rationale & Objective: Nearly half the patients with heart failure have chronic kidney disease. Implantation of a left ventricular assist device (LVAD) improves kidney function in some but not all patients, and lack of improvement is associated with worse outcomes. Preimplantation factors that predict change in kidney function after LVAD placement are not well described.

Fasciculoventricular and atrioventricular accessory pathways in patients with Danon disease and preexcitation: A multicenter experience.

Background: Studies have suggested that a fasciculoventricular pathway (FVP) may be the cause of preexcitation in patients with Danon disease, a rare X-linked dominant genetic disorder of hypertrophic cardiomyopathy.

Objective: The purpose of this study was to describe the prevalence of ventricular preexcitation on resting 12-lead electrocardiogram (ECG) in patients with Danon disease and the electrophysiological study (EPS) results of those with preexcitation.

Methods: Patients with confirmed Danon disease diagnosed with preexcitation (PR ≤120 ms, delta wave, QRS >110 ms) on ECG were included from a multicenter registry.

Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices.

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV).

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

Background: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown.

Methods: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.

Systemic AAV9.LAMP2B injection reverses metabolic and physiologic multiorgan dysfunction in a murine model of Danon disease.

Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy associated with multiorgan dysfunction, including the heart, skeletal muscle, and liver. There are no specific treatments, and most male patients die from advanced heart failure during the second or third decade of life. DD is caused by mutations in the lysosomal-associated membrane protein 2 () gene, a key mediator of autophagy.

Ventricular arrhythmias in patients with biventricular assist devices.

Purpose: Ventricular arrhythmias (VAs) are common in patients after left ventricular assist device (LVAD) implant and are associated with worse outcomes. However, the prevalence and impact of VA in patients with durable biventricular assist device (BIVAD) is unknown. We performed a retrospective cohort study of patients with BIVADs to evaluate the prevalence of VA and their clinical outcomes.

The impact of using hepatitis c virus nucleic acid test-positive donor hearts on heart transplant waitlist time and transplant rate.

Background: Previous studies suggest that direct-acting anti-virals (DAAs) for the treatment of hepatitis C virus (HCV) infection permits the transplantation of HCV-viremic donor organs in uninfected recipients. This opportunity may expand the donor pool. We assessed the impact of using HCV nucleic acid test-positive (NAT+) donor hearts on heart transplant (HTx) waitlist time and transplant rate.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.

Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists.