Michael N. Vranian

Subtype‐Specific Interactions and Prognosis in Cardiac Amyloidosis

Background Light chain (AL) and transthyretin (ATTR) amyloidosis have a similar effect on myocardial function but very different disease trajectories and survival. However, limited data are available evaluating subtype‐specific predictors of outcomes in a large contemporary cohort. Methods and Results We retrospectively investigated 360 patients at the time of initial diagnosis of cardiac amyloidosis (191 AL and 169 ATTR) from 2002 to 2014. Clinical, laboratory, electrical, and morphologic covariates were evaluated based upon amyloid subtype. ATTR etiology was associated with older age, more chronic medical conditions, and the use of standard heart failure medical therapy. Left ventricular mass index and electrocardiographic voltage were higher in ATTR, while there was no difference in ejection fraction or markers of diastology between subtypes. A multivariable Cox model was generated using previously identified predictors of negative outcomes in cardiac amyloidosis and analyzed after stratification for subsequent amyloid‐specific treatment. An AL etiology was the most predictive variable (hazard ratio 3.143, P<0.001) of 3‐year all‐cause mortality. The only covariate that showed a significantly greater magnitude of effect on mortality in 1 amyloid subtype versus the other was amyloid‐specific treatment in AL (P=0.015). The magnitude of effect of other variables on mortality did not significantly differ between subtypes. Conclusions Clinical, morphological, electrical, and biomarker data do not significantly interact with amyloid subtype in its association with mortality, despite the fact that the prognosis in each subtype differs greatly. This suggests an additional factor or factors (such as light chain toxicity) contributing to poorer outcomes in AL amyloid.

Emerging Advances in the Management of Cardiac Amyloidosis

Amyloidosis is a disease in which proteins misfold, aggregate into fibrils, and deposit extracellularly disrupting organ architecture and function. There are two main types which affect the heart: light chain (AL) amyloidosis and transthyretin cardiac amyloidosis (ATTR). There is a misconception that cardiac amyloidosis has no effective treatment options. However, over the past decade, there has been extensive research and drug development. Outcomes are improving in AL amyloidosis with evolving chemotherapeutic regimens and novel monoclonal antibodies. In ATTR, therapies that decrease protein production, prevent dissociation, and promote clearance have the potential to slow or even halt a disease which is uniformly fatal. Selected patients may be candidates for heart and/or stem cell transplant and should be promptly referred to an experienced amyloid program. Herein, we discuss the emerging advances for the treatment of cardiac amyloidosis.

Recognizing Transthyretin Cardiac Amyloidosis in Patients With Aortic Stenosis: Impact on Prognosis

Cardiac amyloidosis is an under recognized and underdiagnosed heart failure etiology characterized by protein misfolding, myocardial deposition, and restrictive cardiomyopathy. Cardiac involvement in elderly patients most commonly results from the transthyretin protein (ATTR) and carries a poor

Are classic predictors of voltage valid in cardiac amyloidosis? A contemporary analysis of electrocardiographic findings

BACKGROUND Low voltage electrocardiography (ECG) coupled with increased ventricular wall thickness is the hallmark of cardiac amyloidosis. However, patient characteristics influencing voltage in the general population, including bundle branch block, have not been evaluated in amyloid heart disease. METHODS A retrospective analysis was performed of patients with newly diagnosed cardiac amyloidosis from 2002 to 2014. ECG voltage was calculated using limb (sum of QRS complex in leads I, II and III) and precordial (Sokolow: S in V1 plus R in V5-V6) criteria. The associations between voltage and clinical variables were tested using multivariable linear regression. A Cox model assessed the association of voltage with mortality. RESULTS In 389 subjects (transthyretin ATTR 186, light chain AL 203), 30% had conduction delay (QRS >120ms). In those with narrow QRS, 68% met low limb, 72% low Sokolow and 57% both criteria, with lower voltages found in AL vs ATTR. LV mass index as well as other typical factors that impact voltage (age, sex, race, hypertension, BSA, and smoking) in the general population were not associated with voltage in this cardiac amyloidosis cohort. Patients with LBBB and IVCD had similar voltages when compared to those with narrow QRS. Voltage was significantly associated with mortality (p<0.001 for both criteria) after multivariable adjustment. CONCLUSION Classic predictors of ECG voltage in the general population are not valid in cardiac amyloidosis. In this cohort, the prevalence estimates of ventricular conduction delay and low voltage are higher than previously reported. Voltage predicts mortality after multivariable adjustment.

PROGNOSTIC VALUE OF TECHNETIUM PYROPHOSPHATE UPTAKE INTENSITY BY NUCLEAR SCINTIGRAPHY IN TRANSTHYRETIN AMYLOIDOSIS

In transthyretin cardiac amyloidosis (ATTR), nuclear scintigraphy using Technetium 99m-pyrophosphate (TcPYP) manifests as diffuse myocardial uptake and is sensitive and specific for this diagnosis. We examined the prognostic ability of TcPYP uptake intensity and its relationship with

Management of life-threatening flecainide overdose: A case report and review of the literature

Introduction Anti-arrhythmic drug therapy carries an understood risk for toxic side effects, even at therapeutic doses. In cases of high dose ingestion these toxic effects can present rapidly with extra-cardiac symptoms, malignant arrhythmias and lifethreatening hemodynamic deterioration. Prescribing clinicians should maintain familiarity with the mechanisms and kinetics of the anti-arrhythmic drugs they prescribe, as well as the clinical manifestations of anti-arrhythmic drug toxicity. Here we present a case of intentional flecainide overdose complicated by amphetamine co-ingestion. We hope this case illustrates the importance of prompt symptom recognition, mechanism-directed medical management and the utility of short term mechanical hemodynamic support in the management of anti-arrhythmic drug toxicity.

SERUM FREE LIGHT CHAIN DIFFERENCE AND MARKERS OF HEART FAILURE SEVERITY ARE CORRELATED WITH ONE YEAR MORTALITY, VENTRICULAR ASSIST DEVICE IMPLANTATION OR HEART TRANSPLANTATION IN NEWLY DIAGNOSED PATIENTS WITH CARDIAC LIGHT CHAIN AMYLOIDOSIS

Serum free light chain difference (FLC-diff) and cardiac specific factors are validated diagnostic and prognostic tools in evaluating prognosis in patients with amyloidosis. However, their utility in those newly diagnosed with cardiac light chain (AL) amyloidosis has not yet been tested. We