The 21st Annual Scientific Meeting • HFSA S11

Table 2. Classification of mortality in relation to serum potassium levels in CHF and data from COSMIC-HF suggest that OM produced similar findings with regard to phar-
its subcategories. (CHF: congestive heart failure, SHF: systolic heart failure, DHF: macodynamic response, cardiac function, heart rate, biomarkers, and adverse events
diastolic heart failure, SDHF: systolic and diastolic heart failure) in patients with ischemic and non-ischemic etiology of HF.

Table 3. Multivariate analysis with logistic regression of mortality among different

etiologies of heart failure with hyperkalemia and hypokalemia with reference to
normokalemia. (ACS: acute coronary syndrome, IHD: Ischemic heart disease, VHD:
valvular heart disease, HHD: hypertensive heart disease, CM: cardiomyopathy, AF:
atrial fibrillation)

021
Carpal Tunnel Syndrome and Amyloid Cardiomyopathy
Asad Ikram, Brett Sperry, Bryan Reyes, William Seitz, Mazen Hanna; Cleveland Clinic
Foundation, Cleveland, Ohio

Hypokalemia results from increased activation of Renin Angiotensin Aldosterone System.
Low serum potassium increases the transmembrane resting potential of myocardial cells
resulting in hyperpolarization and increased excitability. This increases risk of cardiac
arrhythmias. Ventricular arrhythmias are the most common cause of death in these pa-
tients. Thus, normokalemia and hyperkalemia in patients admitted with CHF has a
beneficial effect. This can be achieved by use of potassium supplements, ACE inhibi-
tors and K-sparing diuretics. Whether correction of hypokalemia during hospital stay
is beneficial or not is a matter of further studies.
020
Effect of Omecamtiv Mecarbil in Patients with Ischemic and Non-Ischemic Heart
Failure with Reduced Ejection Fraction: Results From COSMIC-HF
John R. Teerlink1, G.M. Ichael Felker2, John J.V. McMurray3, Scott D. Solomon4,
Christopher E. Kurtz5, Maria Laura Monslavo5, James Johnston5, Fady I. Malik6,
Narimon Honarpour5; 1San Francisco VAMC/UCSF, San Francisco, California; 2Duke
University School of Medicine, Durham, North Carolina; 3University of Glasgow,
Glasgow, United Kingdom; 4Brigham & Women’s Hospital, Boston, Massachusetts;
5 and one patient with AL. Conclusion: Hand surgeons, primary care providers, and car-
Amgen, Inc., Thousand Oaks, California; 6Cytokinetics, Inc, South San Francisco,
California
Introduction: Carpal tunnel syndrome (CTS) can be the initial manifestation of amy-
loidosis, often presenting years before cardiac involvement becomes apparent. Hypothesis:
We hypothesized that a significant percentage of older patients undergoing surgery for
idiopathic CTS would be diagnosed with amyloidosis through tenosynovial biopsy and
that early detection of amyloid cardiomyopathy using advanced cardiac imaging tech-
niques may be possible. Methods: This is a prospective, longitudinal study
(ClinicalTrials.gov NCT 02792790) enrolling males ≥50 and females ≥60 years of age
undergoing carpal tunnel release surgery. Patients with a known diagnosis of amyloi-
dosis or rheumatoid arthritis are excluded. A tenosynovial biopsy is taken at the time
of surgery, and each specimen is stained with Congo red to detect amyloid deposits
(Figs. 2B & 2C). Tissue positive for amyloid is subtyped by mass spectrometry and/
or immunohistochemistry. In patients with amyloidosis, physical examination, laboratory
studies, EKG, echocardiography with longitudinal strain imaging, and technetium-
99m-pyrophosphate scintigraphy are performed to evaluate for evidence of cardiac
amyloid involvement at baseline. Patients will be followed for 4 years with yearly cardiac
testing. Results: Preliminarily, 295 patients undergoing carpal tunnel decompression
were screened for eligibility (Fig. 1). Of the 183 patients who met inclusion criteria,
88 consented to participate and underwent biopsy. Nine patients (10.2%) were found
to have amyloid deposits. Tissue subtyping revealed that six patients had transthyretin
amyloidosis (ATTR), two patients had light chain amyloidosis (AL), and one could
not be subtyped due to insufficient tissue. Upon baseline cardiac workup, two pa-
tients were found to have associated amyloid cardiomyopathy: one patient with ATTR
diologists should be aware of the association between carpal tunnel syndrome and
amyloidosis. Performing a tenosynovial biopsy and staining for amyloid with Congo

Introduction: LV systolic dysfunction is a final common pathway of multiple etiolo-

gies in the pathogenesis of chronic heart failure (HF). We evaluated the influence of
HF etiology (ischemic vs. non-ischemic) on the response to the selective cardiac myosin
activator, omecamtiv mecarbil (OM), in patients with HFrEF. Hypothesis: OM would
have similar effects in patients with HFrEF regardless of HF etiology. Methods:
COSMIC-HF (NCT 01786512) was a Phase 2 multicenter, randomized, double-
blind, placebo-controlled trial in outpatients (n = 448) with a history of optimally-
treated chronic HF, LVEF ≤40%, and NT-proBNP ≥200 pg/mL (≥1200 pg/mL with atrial
fibrillation). In the expansion phase, patients were randomized 1:1:1 to receive placebo
(n = 149), OM at 25 mg BID (n = 150), or 25 mg twice daily with pharmacokinetic-
guided increases to 50 mg twice daily (n = 149; OM PK-group) for 20 weeks. Interaction
terms were used to assess for a differential effect of OM in the OM PK-group by eti-
ology on various study endpoints. Results: In COSMIC-HF, 287 (64%) had ischemic
etiology of HF and 161 (36%) had non-ischemic HF etiology. Previous COSMIC-HF
results demonstrated nominally statistically significant changes in all pre-specified sec-
ondary efficacy endpoints compared to placebo in the OM PK-group at 20 weeks. The
current analyses demonstrate similar findings of efficacy in patients regardless of HF
etiology (Table). There was no difference in the change from baseline in troponin after
20 weeks of therapy between the ischemic and non-ischemic OM PK-groups. HF eti-
ology did not modify the effectiveness of OM; there were no significant interaction
effects of treatment group with HF etiology for any of these variables (Table). Overall
and cardiac adverse events were similar between the placebo and PK-titration groups
for patients with ischemic (Subject incidence; Overall: Placebo, 58.4% vs. OM, 62.0%;
Cardiac: Placebo, 20.2% vs. OM 20.0%) or non-ischemic (Overall: Placebo, 65.0%
vs. OM, 71.7%; Cardiac: Placebo, 30.0% vs. OM 23.9%) etiologies. Conclusion: These Fig. 1. Flowchart of enrollment.