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BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated benefit in patients with heart failure, but minimal data exist concerning the use of these medications in amyloid light-chain cardiomyopathy (AL-CM). We performed a retrospective study to assess the safety and efficacy of SGLT2is in AL-CM. METHODS: We queried our institutional registry and identified 27 patients with AL-CM who received SGLT2is. The safety analysis included all 27 patients and assessed SGLT2i-associated adverse events, hospitalizations and deaths. To decrease confounding, the efficacy analysis included only a subset of patients with stable disease (on stable anti-plasma cell therapy for ≥ 2 months prior to baseline and had achieved at least a hematologic Very Good Partial Response) and compared disease-marker changes in these patients (nâ¯=â¯17) with those of a contemporaneous untreated control cohort from our registry (nâ¯=â¯21). RESULTS: The mean age of the overall population was 68.6 (standard deviation 9.4) years. Of the patients, 7 (14.6%) had diabetes, and 19 (39.6%) had chronic kidney disease. In the safety analysis, the median follow-up time was 10.9 (interquartile range 7.2) months. Two (7.4%) patients discontinued SGLT2is due to hypovolemia and genital irritation, and 6 (22.2%) additional patients temporarily held SGLT2is due to an adverse event that is commonly related to volume depletion. There were 13 hospitalizations, all considered unrelated to SGLT2i use, and no deaths occurred. In the efficacy analysis, SGLT2i-treated patients had more severe disease at baseline than controls, demonstrating significantly higher median troponin-T and loop diuretic dosage (P < 0.05). Compared with controls, SGLT2i treatment was associated with significantly greater reductions in loop diuretic dosage (P < 0.001) and NTproBNP levels (Pâ¯=â¯0.033) across 3-, 6- and 12-month follow-up timepoints. SGLT2i treatment was also associated with a significantly greater reduction in mean arterial pressure at 12 months (Pâ¯=â¯0.031) but not at other timepoints. No significant differences were observed in changes in weight, eGFR, troponin-T, proteinuria, or albumin levels. CONCLUSIONS: In this small-scale retrospective study, we demonstrate that SGLT2is are well tolerated by most patients with AL-CM, but volume depletion symptoms may limit continuous use. SGLT2is may aid management of congestion in AL-CM, as evidenced by reduced diuretic dosage and NTproBNP levels without adverse renal effects. Larger long-term studies are needed to build on our findings.
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BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly recognized. Clinical outcomes have evolved over time amid changes in the diagnostic pathway and advances in therapeutics. We sought to evaluate clinical outcomes over time of patients with ATTR-CA with access to disease-modifying therapy. METHODS AND RESULTS: This is a retrospective cohort study of 419 patients diagnosed with ATTR-CA during 2001-2021, comparing clinical characteristics across eras. The primary end point was composite all-cause mortality or orthotopic heart transplantation (OHT). Time-to-event analysis was performed using Cox proportional hazard modeling controlling for differences among cohorts. Patients diagnosed in the more recent years had higher median age (2017-2021, 78 years; 2014-2016, 75 years; 2001-2013, 74 years) and more often had wild-type ATTR (81.9% vs 82.5% vs 56.4%), but less severe phenotypes as evidenced by more individuals with Columbia stage I disease (47.6% vs 35.9% vs 22.4%), owing to lower biomarkers, more patients in New York Heart Association functional classes I and II (68.9% vs 47.6% vs 43.6%), and lower use of loop diuretics (67.0% vs 78.6% vs 89.1%). Over time, patients were treated more frequently with tafamidis (74% vs 37% vs 32%). On multivariable analysis, greater Columbia score (hazard ratio 1.42, 95% confidence interval 1.30-1.54, P < .001) was predictive of death or OHT, whereas tafamidis (hazard ratio 0.31, 95% confidence interval 0.22-0.44, P < .001) was associated with greater survival and freedom from OHT. CONCLUSIONS: Patients recently diagnosed with ATTR-CA have earlier stage disease and substantially lower mortality. Tafamidis is associated with significantly improved survival and freedom from OHT.
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INTRODUCTION: Technetium-labeled bone-avid radiotracers can be used to diagnose transthyretin cardiac amyloidosis (ATTR-CA). Extracardiac uptake of technetium pyrophosphate (Tc-99m PYP) in this context has not been extensively explored and its significance is not well characterized. We assessed extracardiac Tc-99m PYP uptake in individuals undergoing nuclear scintigraphy and the extent of clinically actionable findings. METHODS: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study utilizes Tc-99m PYP imaging to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥ 60 years old with heart failure. We characterized the distribution of extracardiac uptake, including stratification of findings by timing of scan (1 hour vs 3 hours after Tc-99m PYP administration) and noted any additional testing in these subjects. RESULTS: Of 379 participants, 195 (51%) were male, 306 (81%) Black race, and 120 (32%) Hispanic ethnicity; mean age was 73 years. Extracardiac Tc-99m PYP uptake was found in 42 subjects (11.1%): 21 with renal uptake only, 14 with bone uptake only, 4 with both renal and bone uptake, 2 with breast uptake, and 1 with thyroid uptake. Extracardiac uptake was more common in subjects with Tc-99m PYP scans at 1 hour (23.8%) than at 3 hours (6.2%). Overall, four individuals (1.1%) had clinically actionable findings. CONCLUSION: Extracardiac Tc-99m PYP uptake manifested in about 1 in 9 SCAN-MP subjects but was clinically actionable in only 1.1% of cases.
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Amiloidose , Cardiomiopatias , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Feminino , Difosfatos , Tecnécio , Pirofosfato de Tecnécio Tc 99m , Prevalência , Tomografia Computadorizada por Raios X , Compostos Radiofarmacêuticos , Pré-AlbuminaRESUMO
Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.
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Neuropatias Amiloides Familiares , Amiloidose , Cardiomiopatias , Transplante de Coração , Neuropatias Amiloides Familiares/cirurgia , Cardiomiopatias/etiologia , Humanos , Pré-Albumina , Prognóstico , Taxa de SobrevidaRESUMO
AIMS: Despite their potential, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been well-studied in transthyretin amyloid cardiomyopathy (ATTR-CM) as randomized trials have excluded patients with this morbid disease. We performed a retrospective study assessing the short-term efficacy and safety of SGLT2i in ATTR-CM. METHODS AND RESULTS: We screened consecutive patients seen at a tertiary care centre and identified 87 ATTR-CM patients treated with SGLT2i and 95 untreated control patients. Endpoints included changes in weight, loop diuretic dose, and cardiac/renal biomarkers. The median age of the overall population was 79 (interquartile range [IQR] 11) years. Nearly 90% of patients were male, and 93% were on a transthyretin stabilizer. Control patients demonstrated generally less severe disease at baseline compared to SGLT2i-treated patients, with lower median Columbia risk score (p < 0.001). Median follow-up time was 5.6 (IQR 5.2) and 8.4 (IQR 2.1) months in the SGLT2i and control cohorts, respectively. Compared with controls, SGLT2i treatment was associated with significantly greater reductions from baseline in weight, loop diuretic dose, and uric acid during follow-up (p < 0.001). While no significant between-group differences were observed on cardiac biomarkers, estimated glomerular filtration rate was significantly reduced versus controls 1 month after SGLT2i initiation (p = 0.002), but no significant differences were observed at later timepoints. Results were similar in a propensity score-matched analysis (n = 42 per cohort). A total of 10 (11.5%) patients discontinued SGLT2i, most commonly due to genitourinary symptoms. CONCLUSION: Sodium-glucose cotransporter 2 inhibitors were well tolerated by most patients with ATTR-CM and appeared to improve volume status and combat diuretic resistance. Randomized studies are needed to confirm these findings.