Asad Ikram

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.

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.

Complex p.T88N/W130R mutation in the lysozyme gene leading to hereditary lysozyme amyloidosis with biopsy-proven cardiac involvement

Lysozyme amyloidosis (ALys) is a hereditary, autosomal dominant, non-neuropathic, systemic amyloidosis that typically begins with sicca syndrome and commonly progresses to involve the gastrointestinal organs and kidneys [1,2]. It can also present with hepatic hematoma and rupture [3]. While, eight prior mutations have been reported, cardiac involvement has not yet been described [4]. We report a complex mutation leading to familial ALys amyloidosis with biopsy-proven cardiac involvement along with the more classic renal and gastrointestinal symptoms. A 35-year-old Caucasian man of Italian, Slovakian and German descent presented with sicca syndrome, progressive abdominal symptoms and renal failure. He was initially misdiagnosed with AA-type amyloidosis at age 27 after a duodenal biopsy for the workup of nausea and abdominal pain. He subsequently developed end stage renal failure and was placed on hemodialysis. He presented with significant volume overload and diastolic heart failure and was referred for evaluation.

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