Primary Outcomes

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6

Time: Week 6

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Secondary Outcomes

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12

Time: Month 6, Month 12

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Other Outcomes

Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)

Time: Baseline up to 30 days after the last dose

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Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. On the basis of intensity, grade 3 was referred as severe, grade 4 as life-threatening and grade 5 as death.

Measure: Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs

Time: Baseline up to 30 days after the last dose

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Description: ECHO:investigator assessed test to assess cardiac function.ECHO abnormality criteria:any/valvular abnormality,pericardial effusion,abnormal regional wall motion,inferior vena cava respiratory variation,posterior left ventricular wall/septal thickness>=13 millimeter(mm),right ventricular thickness>=7mm,ejection fraction <50%, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A)>=2, ratio of 'E'to lateral/septal mitral annular velocity (e') (E/e'prime lateral>15, E/e'prime septal>15), E deceleration time<=150 millisecond(msec),Isovolumic relaxation time<=70msec.

Measure: Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings

Time: Baseline up to Month 12

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Measure: Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs)

Time: Baseline up to Month 12

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Description: Echocardiography was used to measure interventricular septal thickness (IVST), posterior left ventricular wall thickness (PLVWT), right ventricular wall thickness (RVWT), left atrial diameter (LAD): anterior-posterior (ant-post), medio-lateral, superior-inferior (sup-inf) and left ventricular end diastolic diameter (LVEDD).

Measure: Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: LVM was defined as increase in the mass of left ventricle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.

Measure: Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Left ventricular ejection fraction (LVEF) was the fraction of the end-diastolic volume (EDV) that is ejected out of left ventricle with each contraction, estimated by echocardiography. EDV is the volume of blood within a ventricle immediately before a contraction.

Measure: Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Ratio of early (E) diastolic transmitral flow velocity and atrial (A) contraction velocity (E/A) and ratio of the early (E) diastolic transmitral flow velocity to the mitral annular velocity (e') (E/e') were estimated.

Measure: Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. The mitral deceleration time was the time taken from the maximum E wave to baseline. E wave arises due to early diastolic filling.

Measure: Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Tissue Doppler used doppler principles to measure the annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity.

Measure: Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Pericardial effusion was the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography.

Measure: Change From Baseline in Pericardial Effusion at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Valvular abnormalities were those abnormalities (thickening or regurgitation) that involved one or more valves of the heart, determined by echocardiography.

Measure: Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac Magnetic Resonance Imaging (MRI) was done to measure the thickness of left ventricular anteroseptal (LVAS) wall, left ventricular inferolateral (LVIL) wall and right ventricular end diastolic free (RVEDF) wall.

Measure: Change From Baseline in Left Ventricular Anteroseptal, Left Ventricular Inferolateral Wall Thickness and Right Ventricular End Diastolic Free Wall Thickness at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure LVM, mass of left ventricular (LV) myocardium with amyloidosis, mass of LV myocardium with fibrosis/scar and right ventricular end diastolic mass (RVEDM).

Measure: Change From Baseline in Left Ventricular Mass, Mass of Left Ventricular Myocardium With Amyloidosis, Mass of Left Ventricular Myocardium With Fibrosis/Scar and Right Ventricular End Diastolic Mass at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure left ventricle end diastolic volume (LVEDV), left ventricle end systolic volume (LVESV), left ventricle stroke volume (LVSV), right ventricle end diastolic volume (RVEDV), right ventricle end systolic volume (RVESV) and right ventricle stroke volume (RVSV).

Measure: Change From Baseline in Left Ventricle End Diastolic Volume, Left Ventricle End Systolic Volume, Left Ventricle Stroke Volume, Right Ventricle End Diastolic Volume, Right Ventricle End Systolic Volume, Right Ventricle Stroke Volume at Month 6 and 12.

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure: left ventricular ejection fraction (LVEF) was the fraction of the EDV that is ejected out of left ventricle with each contraction and right ventricular ejection fraction (RVEF) was the fraction of the EDV that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction.

Measure: Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure cardiac output, which was the volume of blood being pumped by the heart, in particular by the left or right ventricle in the time interval of one minute.

Measure: Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure percentage of LV myocardial mass with amyloidosis and LV myocardial mass with fibrosis/scar. LV myocardial mass with amyloidosis or fibrosis/scar was calculated from the product of the myocardial volume and specific gravity of heart muscle, in participants with amyloidosis or fibrosis/scar, respectively.

Measure: Change From Baseline in Percentage of Left Ventricular Myocardial Mass With Amyloidosis and Left Ventricular Myocardial Mass With Fibrosis/Scar at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure interatrial septal thickness in the 4 chamber view.

Measure: Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Cardiac MRI was done to measure the left and right atrial dimensions which have diagnostic and prognostic significance in cardiology, in the 4 chamber view.

Measure: Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Holter monitor was a machine that recorded the heart rhythms. Holter monitoring abnormalities of atrial fibrillation/flutter (rapid, irregular heart rhythm), atrial tachycardia (rapid cardiac rate), non-sustained ventricular tachycardia (NSVT)<30 beats, sustained ventricular tachycardia (SVT) >=30 beats and sinus pause (transient interruption in the sinus rhythm) were recorded.

Measure: Number of Participants With Atrial Fibrillation/Flutter, Atrial Tachycardia, Non-Sustained Ventricular Tachycardia (NSVT) Beats), Sustained Ventricular Tachycardia (SVT), Sinus Pause at Month 6 and 12

Time: Baseline, Month 6, Month 12

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Description: Holter monitor was a machine that recorded the heart rhythms. 24-hour average heart rate and maximium/minimum heart rate was recorded using Holter monitoring.

Measure: 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate

Time: Baseline, Month 6, Month 12

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Description: Complete heart block is the third-degree atrioventricular block in which the impulse generated in the sinoatrial node in the atrium does not propagate to the ventricles.

Measure: Number of Participants With Complete Heart Block

Time: Baseline, Month 6, Month 12

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Description: Holter monitor was a machine that recorded the heart rhythms. HRV time-domain indices were summarized for root-mean-square of successive differences [RMS SD] of the R-R intervals (R-R is the interval between successive Rs in the ECG wave) between normal beats (NN), magid standard deviation (Magid SD) of normal to normal R-R intervals and Kleiger standard deviation of normal to normal R-R intervals (Kleiger SD). The term 'NN' is used in place of 'R-R' when the processed beats are normal beats.

Measure: Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters

Time: Baseline, Month 6, Month 12

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Description: Holter monitor was a machine that recorded the heart rhythms. The term 'NN' was used in place of 'R-R' when the processed beats are normal beats. The percentage of successive R-R intervals with greater than 50 msec difference between normal beats was derived by dividing NN50 by the total number of NN intervals (pNN50), where NN50 was the number of interval differences of successive NN intervals greater than 50 msec.

Measure: Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50)

Time: Baseline, Month 6, Month 12

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Description: NYHA: classified as 'class I' (participants with cardiac disease but without resulting limitations of physical activity), 'class II' (participants with cardiac disease resulting in slight limitation of physical activity), 'class III' (participants with cardiac disease resulting in marked limitation of physical activity), 'class IV' (participants with cardiac disease resulting in inability to carry on any physical activity without discomfort). Participants with change from baseline were classified as 'improved' (positive change), 'no change' or 'worsened' (negative change).

Measure: Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12

Time: Baseline, Week 6, Month 3, Month 6, Month 12

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Description: Cardiothoracic ratio was defined as the transverse diameter of the heart, compared with that of the thoracic cage, used to help determine enlargement of the heart.

Measure: Cardiothoracic (CT) Ratio

Time: Baseline, Month 6, Month 12

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Description: Chest x-ray was done to record the presence of increased interstitial markings (a large number of interstitial markings was indicative of abnormality in the lung) and pleural effusion, which was defined as accumulation of fluid between the layers of tissue that line the lungs and chest cavity.

Measure: Number of Participants With Increased Interstitial Markings and Pleural Effusions

Time: Baseline, Month 6, Month 12

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Description: Participant's overall quality of life was measured by the PtGA. At baseline participants answered to question: "in general, how do you feel today?" - on a 5-point scale from '1' (excellent) to '5' (poor). At each follow-up visit, participant's answered to question: "How do you feel today as compared to when we talked with you at your last clinic visit for this study?" on a 7-point scale- '1' markedly improved, '2' moderately improved, '3' mildly improved, '4' unchanged, '5' mildly worsened, '6' moderately worsened, '7' markedly worsened.

Measure: Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12

Time: Baseline, Month 3, Month 6, Month 12

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Description: KCCQ was a 23-item heart failure specific questionnaire quantified in to following 10 summary scores: physical limitation, symptom frequency, symptom severity, and symptom stability, total symptoms, quality of life, social interference, self-efficacy, overall summary and clinical summary. Total score ranged from 0 to 100, where higher scores indicated better functioning, fewer symptoms, and better disease specific quality of life. Summary scores were scaled to range from 0 to 100, with higher scores representing greater disability.

Measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12

Time: Baseline, Month 3, Month 6, Month 12

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Description: SF-36 was standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Scores for the 8 domains range from 0-100, where higher scores were better (100=highest level of functioning) and reported as 2 summary scores; Mental Component Score (MCS) and Physical Component Score (PCS). The score for a section was an average of the individual question scores, which were scaled 0-100, where higher scores were better.

Measure: Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12

Time: Baseline, Month 3, Month 6, Month 12

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Description: Troponin I and troponin T were the cardiac markers. Troponin I and troponin T were part of the troponin complex, where troponin I was bound to actin in thin myofilaments and troponin T was bound to tropomyosin. Higher level of these markers was indicative of heart damage.

Measure: Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12

Time: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12

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Description: NT-proBNP was a cardiac marker which had the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.

Measure: Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12

Time: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12

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Description: 6MWT was used to assess the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.. The distance walked in 6 minutes was categorized as: Level 1: <300 meter, Level 2: 300-374.9 meter, Level 3: 375-449.9 meter, Level 4: >=450 meter.

Measure: Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12

Time: Baseline, Month 3, Month 6, Month 12

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Primary Outcomes

Description: PND Scores: Stage 0=No symptoms, Stage 1=Sensory disturbances but preserved walking capability, Stage 2=Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B=Walking with the help of 1 or 2 sticks or crutches, Stage 4=confined to wheel chair or bedridden.

Measure: Percentage of Participants with Stable or Improved Polyneuropathy Disability (PND) Score at 12 Months Relative to Baseline

Time: Baseline, Month 12

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Primary Outcomes

Description: The prevalence of ATTR CA will be defined by the number of cases with significant myocardial retention of Tc-99 PYP including both ATTRwt and ATTRm CA as a percentage of total enrollment.

Measure: Prevalence of Transthyretin Cardiac Amyloidosis in Caribbean Hispanics and Blacks with heart failure (HF)

Time: 5 years

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Secondary Outcomes

Description: Among subjects with ATTR-CA we will determine the prevalence of ATTRwt and ATTRm from the Val122Ile mutation in Blacks and Caribbean Hispanics

Measure: Prevalence of ATTRwt and ATTRm in Blacks and Caribbean Hispanics

Time: 5 years

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Description: The prevalence of ATTR cardiac amyloidosis will be calculated among men and women enrolled in this study

Measure: Sex distribution of ATTR cardiac amyloidosis

Time: 5 years

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Description: In the ATTR CA group alone, a composite time-to-first-event endpoint at 1-year of death, heart failure hospitalization, or 30% decline in 6-minute hall walk will be compared between ATTRwt and ATTRm subjects.

Measure: Disease progression in ATTRwt compared to ATTRm

Time: 5 years

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Description: Retinol binding protein 4 (RBB4) will be measured in urine.

Measure: RBP4 in Urine

Time: 5 years

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