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Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis.

Damy T, Judge DP, Kristen AV, Berthet K, Li H, Aarts J - J Cardiovasc Transl Res (2015)

Bottom Line: Cardiac biomarkers remained stable.Although four patients had increases in interventricular septal thickness ≥ 2 mm, the remainder had stable septal wall thickness.There were no clinically relevant changes in mean echocardiographic/electrocardiographic variables and no safety concerns.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, University Hospital Henri Mondor, Amyloidosis Mondor Network, DHU ATVB, Créteil, France, thibaud.damy@hmn.aphp.fr.

ABSTRACT
A phase 2, open-label study in 21 patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis showed that tafamidis (20 mg daily for 12 months) stabilized these transthyretin variants. We assessed cardiac amyloid infiltration and cardiac abnormalities in this same study population. At baseline, median age was 64.3 years, 11 patients were in NYHA class II, 13 had conduction abnormalities, 14 N-terminal pro-hormone brain natriuretic peptide concentrations >300 pg/ml, and 17 interventricular septal thickness >12 mm. Mean (SD) left ventricular ejection fraction was 60.3% (9.96). Patients with normal heart rate variability increased from 4/19 at baseline to 8/19 at month 12 (p < 0.05). Cardiac biomarkers remained stable. Although four patients had increases in interventricular septal thickness ≥ 2 mm, the remainder had stable septal wall thickness. There were no clinically relevant changes in mean echocardiographic/electrocardiographic variables and no safety concerns.

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Changes in cardiac amyloid infiltration, systolic function, and LV filling pressure from baseline within individual patients. a LV mass, as a measure of cardiac amyloid infiltration, was maintained or improved (<10 % increase) in 8/14 (57.1 %) from baseline to month 12. b LVEF as a measure of systolic function was maintained or improved (<10 % decrease) in 16/18 (88.9 %) from baseline to month 12. c Lateral E/e′ as an estimate of LV filling pressure was normal (E/e′ <8), undetermined (8 ≤ E/e′ ≤ 15), or elevated (E/e′ > 15) in 6/16 (37.5 %), 5/16 (31.3 %), and 5/16 (31.3 %) at baseline and in 3/11 (27.3 %), 5/11 (45.5 %), and 3/11 (27.3 %) at month 12, respectively. LV left ventricular, LVEF LV ejection fraction, E/e′ ratio of peak mitral inflow velocity of early filling to early diastolic mitral annular velocity
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Fig4: Changes in cardiac amyloid infiltration, systolic function, and LV filling pressure from baseline within individual patients. a LV mass, as a measure of cardiac amyloid infiltration, was maintained or improved (<10 % increase) in 8/14 (57.1 %) from baseline to month 12. b LVEF as a measure of systolic function was maintained or improved (<10 % decrease) in 16/18 (88.9 %) from baseline to month 12. c Lateral E/e′ as an estimate of LV filling pressure was normal (E/e′ <8), undetermined (8 ≤ E/e′ ≤ 15), or elevated (E/e′ > 15) in 6/16 (37.5 %), 5/16 (31.3 %), and 5/16 (31.3 %) at baseline and in 3/11 (27.3 %), 5/11 (45.5 %), and 3/11 (27.3 %) at month 12, respectively. LV left ventricular, LVEF LV ejection fraction, E/e′ ratio of peak mitral inflow velocity of early filling to early diastolic mitral annular velocity

Mentions: At baseline, 17 of 19 patients with an evaluable assessment (89.5 %) had left ventricular wall thickening with IVS and LVPW of >12 mm, demonstrating amyloid infiltration of the myocardium. At the end of the study, left ventricular wall thickness measures remained below >12 mm threshold in the two patients with normal IVS at baseline. As previously reported [23], 4 of the 12 patients (33.3 %) with evidence of cardiac amyloid at baseline and a valid assessment at month 12 demonstrated ≥2 mm increases in IVS thickness (range, 2–6 mm), indicative of modest disease progression during the 12-month treatment period. Moreover, of the 14 patients with available measurements, six (42.9 %) had a ≥10 % increase in LV mass at month 12 whereas LV mass was stable in seven (50.0 %) and decreased by >10 % from 228 to 201 g in the 14th patient (Fig. 4).Fig. 4


Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis.

Damy T, Judge DP, Kristen AV, Berthet K, Li H, Aarts J - J Cardiovasc Transl Res (2015)

Changes in cardiac amyloid infiltration, systolic function, and LV filling pressure from baseline within individual patients. a LV mass, as a measure of cardiac amyloid infiltration, was maintained or improved (<10 % increase) in 8/14 (57.1 %) from baseline to month 12. b LVEF as a measure of systolic function was maintained or improved (<10 % decrease) in 16/18 (88.9 %) from baseline to month 12. c Lateral E/e′ as an estimate of LV filling pressure was normal (E/e′ <8), undetermined (8 ≤ E/e′ ≤ 15), or elevated (E/e′ > 15) in 6/16 (37.5 %), 5/16 (31.3 %), and 5/16 (31.3 %) at baseline and in 3/11 (27.3 %), 5/11 (45.5 %), and 3/11 (27.3 %) at month 12, respectively. LV left ventricular, LVEF LV ejection fraction, E/e′ ratio of peak mitral inflow velocity of early filling to early diastolic mitral annular velocity
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Related In: Results  -  Collection

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Fig4: Changes in cardiac amyloid infiltration, systolic function, and LV filling pressure from baseline within individual patients. a LV mass, as a measure of cardiac amyloid infiltration, was maintained or improved (<10 % increase) in 8/14 (57.1 %) from baseline to month 12. b LVEF as a measure of systolic function was maintained or improved (<10 % decrease) in 16/18 (88.9 %) from baseline to month 12. c Lateral E/e′ as an estimate of LV filling pressure was normal (E/e′ <8), undetermined (8 ≤ E/e′ ≤ 15), or elevated (E/e′ > 15) in 6/16 (37.5 %), 5/16 (31.3 %), and 5/16 (31.3 %) at baseline and in 3/11 (27.3 %), 5/11 (45.5 %), and 3/11 (27.3 %) at month 12, respectively. LV left ventricular, LVEF LV ejection fraction, E/e′ ratio of peak mitral inflow velocity of early filling to early diastolic mitral annular velocity
Mentions: At baseline, 17 of 19 patients with an evaluable assessment (89.5 %) had left ventricular wall thickening with IVS and LVPW of >12 mm, demonstrating amyloid infiltration of the myocardium. At the end of the study, left ventricular wall thickness measures remained below >12 mm threshold in the two patients with normal IVS at baseline. As previously reported [23], 4 of the 12 patients (33.3 %) with evidence of cardiac amyloid at baseline and a valid assessment at month 12 demonstrated ≥2 mm increases in IVS thickness (range, 2–6 mm), indicative of modest disease progression during the 12-month treatment period. Moreover, of the 14 patients with available measurements, six (42.9 %) had a ≥10 % increase in LV mass at month 12 whereas LV mass was stable in seven (50.0 %) and decreased by >10 % from 228 to 201 g in the 14th patient (Fig. 4).Fig. 4

Bottom Line: Cardiac biomarkers remained stable.Although four patients had increases in interventricular septal thickness ≥ 2 mm, the remainder had stable septal wall thickness.There were no clinically relevant changes in mean echocardiographic/electrocardiographic variables and no safety concerns.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, University Hospital Henri Mondor, Amyloidosis Mondor Network, DHU ATVB, Créteil, France, thibaud.damy@hmn.aphp.fr.

ABSTRACT
A phase 2, open-label study in 21 patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis showed that tafamidis (20 mg daily for 12 months) stabilized these transthyretin variants. We assessed cardiac amyloid infiltration and cardiac abnormalities in this same study population. At baseline, median age was 64.3 years, 11 patients were in NYHA class II, 13 had conduction abnormalities, 14 N-terminal pro-hormone brain natriuretic peptide concentrations >300 pg/ml, and 17 interventricular septal thickness >12 mm. Mean (SD) left ventricular ejection fraction was 60.3% (9.96). Patients with normal heart rate variability increased from 4/19 at baseline to 8/19 at month 12 (p < 0.05). Cardiac biomarkers remained stable. Although four patients had increases in interventricular septal thickness ≥ 2 mm, the remainder had stable septal wall thickness. There were no clinically relevant changes in mean echocardiographic/electrocardiographic variables and no safety concerns.

Show MeSH
Related in: MedlinePlus