136 results on '"Claggett, B"'
Search Results
2. Effect of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction treated with beta-blockers: the DELIVER trial
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Peikert, A, primary, Bart, B A, additional, Vardeny, O, additional, Vaduganathan, M, additional, Claggett, B L, additional, Desai, A S, additional, Jhund, P S, additional, Kosiborod, M N, additional, Lam, C S P, additional, Martinez, F A, additional, De Boer, R A, additional, Hernandez, A F, additional, Shah, S J, additional, Mc Murray, J J V, additional, and Solomon, S D, additional
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- 2023
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3. Effect of dapagliflozin on outpatient worsening heart failure in patients with mildly reduced or preserved ejection fraction: the DELIVER trial
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Chatur, S, primary, Vaduganathan, M, additional, Claggett, B L, additional, Desai, A S, additional, Docherty, K F, additional, Jhund, P S, additional, De Boer, R A, additional, Hernandez, A F, additional, Inzucchi, S E, additional, Kosiborod, M N, additional, Lam, C S P, additional, Martinez, F A, additional, Shah, S J, additional, Mcmurray, J V, additional, and Solomon, S D, additional
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- 2023
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4. Predicting heart failure readmission and all-cause mortality in patients with acute heart failure: a simple predischarge risk score
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Espersen, C, primary, Campbell, R, additional, Claggett, B, additional, Lewis, E, additional, Docherty, K, additional, Lee, M, additional, Lindner, M, additional, Brainin, P, additional, Biering-Soerensen, T, additional, Solomon, S, additional, McMurray, J, additional, and Platz, E, additional
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- 2023
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5. Effect of dapagliflozin in patients in Asia with heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER
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Wang, X, primary, Lam, C S P, additional, Claggett, B, additional, Miao, M, additional, Shah, S J, additional, Jhund, P S, additional, Desai, A S, additional, Chiang, C, additional, Pham, V N, additional, Han, Y, additional, Kitakaze, M, additional, Langkilde, A M, additional, Mcmurray, J J V, additional, Solomon, S D, additional, and Vaduganathan, M, additional
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- 2023
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6. Standardized longitudinal strain curves stratified by age and sex in healthy individuals: The Copenhagen City Heart Study
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Christensen, J, primary, Simonsen, J O, additional, Modin, D, additional, Skaarup, K, additional, Lassen, M C H, additional, Johansen, N D, additional, Sanchez-Martinez, S, additional, Claggett, B L, additional, Marott, J L, additional, Jensen, G B, additional, Schnohr, P, additional, Moegelvang, R, additional, and Biering-Soerensen, T, additional
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- 2023
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7. Echocardiographic characterization of patients with supranormal ejection fraction: pooled core laboratory analysis of the TOPCAT and PARAGON-HF trials
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Wang, X, primary, Chatur, S, additional, Lu, H, additional, Claggett, B, additional, Skali, H, additional, Vaduganathan, M, additional, Minamisawa, M, additional, Inciardi, R M, additional, Shah, A M, additional, Packer, M, additional, Pitt, B, additional, Rouleau, J, additional, Pfeffer, M A, additional, Mcmurray, J J V, additional, and Solomon, S D, additional
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- 2023
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8. Increased circumferential deformation predicts cardiac events when left ventricular ejection fraction is normal
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Skaarup, K G, primary, Lassen, M C H, additional, Johansen, N D, additional, Olsen, F J, additional, Jensen, G B, additional, Schnohr, P, additional, Shah, A, additional, Claggett, B L, additional, Solomon, S D, additional, Mogelvang, R, additional, and Biering-Sorensen, T, additional
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- 2022
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9. Prognostic importance of NT-proBNP following high-risk myocardial infarction in the PARADISE-MI Trial
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Jering, K, primary, Claggett, B, additional, Pfeffer, M A, additional, Granger, C, additional, Kober, L, additional, Lewis, E F, additional, Maggioni, A P, additional, Mann, D L, additional, McMurray, J J V, additional, Prescott, M F, additional, Rouleau, J L, additional, Solomon, S D, additional, Steg, P G, additional, Von Lewinski, D, additional, and Braunwald, E, additional
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- 2022
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10. Atrial fibrillation in patients with high-risk acute myocardial infarction – the PARADISE-MI trial
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Cikes, M, primary, Jering, K, additional, Claggett, B, additional, Amir, O, additional, Cadena Bonfanti, A J, additional, Cho, M C, additional, Granger, C, additional, Gullestad, L M, additional, Kao, H L, additional, Morais, J, additional, Tanguay, J F, additional, Tokmakova, M, additional, Widimsky, P, additional, and Solomon, S D, additional
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- 2022
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11. Sacubitril/valsartan compared to ramipril in high risk post myocardial infarction patients stratified according use of mineralocorticoid receptor antagonists: insight from PARADISE MI trial
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Schou, M, primary, Claggett, B, additional, Fernandez, A, additional, Filippatos, G, additional, Granger, C, additional, Jering, K, additional, Maggioni, A, additional, McCausland, F, additional, Nunez Villota, J, additional, Rouleau, J L, additional, Mody, F G, additional, Van Der Meer, P, additional, Vinereanu, D, additional, Zhou, Y, additional, and Kober, L, additional
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- 2022
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12. PARADISE-MI – event rates and treatment effect of sacubitril/valsartan v ramipril by the presence or absence of transient pulmonary congestion and/or LVEF less or greater than 40
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Petrie, M, primary, Solomon, S, additional, Claggett, B L, additional, Jering, K, additional, Steg, G, additional, Granger, C, additional, Lewis, E, additional, Kober, L, additional, Mann, D, additional, Rouleau, J L, additional, McMurray, J J, additional, Maggioni, A, additional, Braunwald, E, additional, and Pfeffer, M A, additional
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- 2022
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13. Risk of acute myocardial infarction, stroke and thromboembolism following COVID-19 vaccination compared to testing positive for COVID-19 infection: a nationwide cohort study of 4.6 mio individuals
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Lassen, M H, primary, Modin, D, additional, Skaarup, K G, additional, Claggett, B, additional, Solomon, S D, additional, Fralick, M, additional, Staehr-Jensen, J U, additional, Sivapalan, P, additional, Schou, M, additional, Krause, T G, additional, Hviid, A, additional, Koeber, L, additional, Torp-Pedersen, C, additional, Gislason, G, additional, and Biering-Soerensen, T, additional
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- 2022
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14. Proteomic biomarkers associated with incident heart failure and frailty in late life
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Ramonfaur, D R, primary, Buckley, L B, additional, Arthur, V A, additional, Claggett, B C, additional, Ndumele, C N, additional, Walker, K A W, additional, Kitzman, D K, additional, Konety, S K, additional, Schrack, J S, additional, Liu, F L, additional, Windham, B G W, additional, Palta, P P, additional, Coresh, J C, additional, Yu, B Y, additional, and Shah, A M S, additional
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- 2022
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15. A comprehensive study of the incremental prognostic value of novel biomarkers in PARADIGM-HF (Bio-PREDICT-HF)
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McDowell, K, primary, Simpson, J, additional, Jhund, P S, additional, Abraham, W T, additional, Claggett, B, additional, Cunningham, J, additional, Desai, A S, additional, Kober, L, additional, Prescott, M, additional, Rouleau, J L, additional, Swedberg, K, additional, Zile, M R, additional, Solomon, S D, additional, Packer, M, additional, and McMurray, J J V, additional
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- 2022
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16. Trajectory of pulmonary congestion by lung ultrasound in patients with acute myocardial infarction and association with cardiac structure and function
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Platz, E, primary, Claggett, B, additional, Jering, K S, additional, Kovacs, A, additional, Cikes, M, additional, Winzer, E B, additional, Rad, A, additional, Lefkowitz, M, additional, Gong, J, additional, Kober, L, additional, McMurray, J J V, additional, Solomon, S D, additional, and Shah, A, additional
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- 2022
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17. Differing approaches to analyse on-treatment cardiovascular events comparing daprodustat with darbepoetin: results from the ASCEND-ND trial
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McCausland, F, primary, Singh, A, additional, Claggett, B, additional, Carroll, K, additional, Wittes, J, additional, McMurray, J J V, additional, Perkovic, V, additional, Snappin, S, additional, Lopes, R, additional, and Solomon, S, additional
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- 2022
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18. Sex disaggregated analysis of risk factors for adverse outcomes in hypertrophic cardiomyopathy
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Butters, A, primary, Arnott, C, additional, Sweeting, J, additional, Claggett, B, additional, Atherton, J, additional, Semsarian, C, additional, Lakdawala, N K, additional, Ho, C Y, additional, and Ingles, J, additional
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- 2022
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19. Prognostic implications of NYHA class and NT-proBNP levels in mild heart failure: a PARADIGM-HF analysis
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Rohde, L E, primary, Zimerman, A, additional, Claggett, B, additional, Packer, M, additional, Desai, A S, additional, Zile, M, additional, Rouleau, J, additional, Swedberg, K, additional, Lefkowitz, M, additional, Shi, V, additional, McMurray, J, additional, Vaduganathan, M, additional, and Solomon, S D, additional
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- 2022
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20. Aptamer proteomics for biomarker discovery in heart failure with reduced ejection fraction
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Cunningham, J, primary, Zhang, L, additional, Claggett, B, additional, Abraham, W, additional, Jhund, P, additional, Kober, L, additional, Packer, M, additional, Rouleau, J, additional, Zile, M, additional, Prescott, M, additional, Mendelson, M, additional, Lefkowitz, M, additional, McMurray, J, additional, Solomon, S, additional, and Chutkow, W, additional
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- 2022
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21. Influence of glycaemic status on the risk of cardiovascular events after a myocardial infarction
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Zhou, Y., Wijkman, M., Claggett, B., Jering, K., Yilmaz, M., Claeys, M., De Pasquale, C., Kerkar, P., Moccetti, T., Ntsekhe, M., Sim, D., Studencan, M., Tokmakova, M., Zaman, A., and Lewis, E.
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- 2022
22. Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial
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Cikes M., Planinc I., Claggett B., Cunningham J., Milicic D., Sweitzer N., Senni M., Gori M., Linssen G., Shah S. J., Packer M., Pfeffer M., Zile M. R., Anand I., Chiang L. -M., Lam C. S. P., Redfield M., Desai A. S., McMurray J. J. V., Solomon S. D., Cikes, M, Planinc, I, Claggett, B, Cunningham, J, Milicic, D, Sweitzer, N, Senni, M, Gori, M, Linssen, G, Shah, S, Packer, M, Pfeffer, M, Zile, M, Anand, I, Chiang, L, Lam, C, Redfield, M, Desai, A, Mcmurray, J, and Solomon, S
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heart failure with preserved ejection fraction ,heart failure outcome ,sacubitril/valsartan ,echocardiography ,atrial fibrillation - Abstract
Objectives: In this study, the authors sought to assess the relationship between AFF and outcomes, the treatment response to sacubitril/valsartan and first-detected AFF in patients with HFpEF enrolled in the PARAGON-HF trial. Background: Atrial fibrillation and flutter (AFF) are common in heart failure with preserved ejection fraction (HFpEF) and increase the risk of adverse outcomes. Methods: A total of 4,776 patients formed 3 groups: those with AFF according to electrocardiography (ECG) at enrollment (n = 1,552; 33%), those with history of AFF but without AFF on ECG at enrollment (n = 1,005; 21%), and those without history of AFF or AFF on ECG at enrollment (n = 2,219, 46%). We assessed outcomes, treatment response to sacubitril/valsartan in each group, and the risk associated with first-detected AFF in patients without any known AFF. The primary outcome was a composite of total heart failure hospitalizations and cardiovascular death. Results: History of AFF and AFF at enrollment were associated with higher risk of the primary outcome (risk ratio [RR]: 1.36 [95% CI: 1.12-1.65] and RR: 1.31 [1.11-1.54], respectively), than no AFF. Neither history of AFF nor AFF at enrollment modified the treatment effect of sacubitril/valsartan. Post randomization AFF occurred in 12% of patients without previous AFF and was associated with 2.8-fold higher risk of the primary outcome, but it was not influenced by sacubitril/valsartan. Conclusions: History of AFF and AFF on ECG at enrollment were associated with a higher risk of the primary outcome. First-detected AFF was not influenced by sacubitril/valsartan, yet it was associated with increased risk of all subsequent outcomes and may represent a potential target for future HFpEF trials. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)
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- 2022
23. Deep Learning-Based Automated Workflow for the Interpretation of the Echocardiogram for the Presence of LV Dysfunction and Probability of Pulmonary Hypertension
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Tromp, J., primary, Claggett, B., additional, Frost, M., additional, Iversen, M., additional, Prasad, N., additional, Petrie, M., additional, Ezekowitz, J., additional, and Solomon, S., additional
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- 2022
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24. Sex Disaggregated Analysis of Risk Factors for Adverse Outcomes in Hypertrophic Cardiomyopathy
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Butters, A., primary, Arnott, C., additional, Sweeting, J., additional, Claggett, B., additional, Ashley, E., additional, Parikh, V., additional, Colan, S., additional, Day, S., additional, Owens, A., additional, Helms, A., additional, Saberi, S., additional, Jacoby, D., additional, Michels, M., additional, Olivotto, I., additional, Pereira, A., additional, Rossano, J., additional, Wittekind, S., additional, Ware, J., additional, Atherton, J., additional, Semsarian, C., additional, Lakdawala, N., additional, Ho, C., additional, and Ingles, J., additional
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- 2022
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25. Lung ultrasound in acute heart failure: association between quality of life, symptoms and B-lines
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Lee, M, primary, Campbell, R T, additional, Claggett, B L, additional, Lewis, E F, additional, Groarke, J D, additional, Docherty, K F, additional, Lindner, M, additional, Liu, J, additional, Solomon, S D, additional, McMurray, J J V, additional, and Platz, E, additional
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- 2021
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26. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.
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Pfeffer, M. A., Claggett, B., Lewis, E. F., Granger, C. B., Kober, L., Maggioni, A. P., Mann, D. L., McMurray, J. J. V., Rouleau, J.-L., Solomon, S. D., Steg, P. G., Berwanger, O., Cikes, M., De Pasquale, C. G., East, C., Fernandez, A., Jering, K., Landmesser, U., Mehran, R., and Merkely, B.
- Abstract
BACKGROUND In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicaITrials.gov number, NCT02924727.). [ABSTRACT FROM AUTHOR]
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- 2021
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27. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.
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Solomon, S. D., McMurray, J. J. V., Claggett, B., de Boer, R. A., DeMets, D., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S. P., Martinez, F., Shah, S. J., Desai, A. S., Jhund, P. S., Belohlavek, J., Chiang, C.-E., Borleffs, C. J. W., Comin-Colet, J., Dobreanu, D., Drozdz, J., and Fang, J. C.
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HEART failure , *VENTRICULAR ejection fraction , *HEART failure patients , *DAPAGLIFLOZIN , *SODIUM-glucose cotransporter 2 inhibitors ,CARDIOVASCULAR disease related mortality - Abstract
BACKGROUND Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitaliza-tion for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovas. cular death, as assessed in a time-to-event analysis. RESULTS Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.) [ABSTRACT FROM AUTHOR]
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- 2022
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28. Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.
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Maron, M. S., Masri, A., Nassif, M. E., Barriales-Villa, R., Arad, M., Cardim, N., Choudhury, L., Claggett, B., Coats, CJ, DOngen, H.-D., Garcia-Pavia, P., Hagtge, A. A., Januzzi, J. L., Lee, M. M. Y., Lewis, G. D., Ma, C.-S., Michels, M., Olivotto, Oreziak, A., and Owens, A. T.
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HYPERTROPHIC cardiomyopathy , *VENTRICULAR outflow obstruction , *EXERCISE tests , *VALSALVA'S maneuver , *VENTRICULAR ejection fraction - Abstract
BACKGROUND One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.) [ABSTRACT FROM AUTHOR]
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- 2024
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29. Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial
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Otavio Berwanger, Ivo Petrov, Eugene Braunwald, Douglas L. Mann, Morten Schou, Yinong Zhou, Alberto Fernandez, Venugopal Menon, Gerasimos Filippatos, Ulf Landmesser, Lars Køber, Aldo P. Maggioni, Karola S. Jering, Christopher B. Granger, Eldrin F. Lewis, Jean-Lucien Rouleau, Marc A. Pfeffer, B Merkely, Brian Claggett, Peter van der Meer, David Sim, Martin Lefkowitz, Carmine G. De Pasquale, John J.V. McMurray, Mark C. Petrie, Philippe Gabriel Steg, Yi Wang, Michele Senni, Scott D. Solomon, Maja Čikeš, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Pfeffer, M, Claggett, B, Lewis, E, Granger, C, Kober, L, Maggioni, A, Mann, D, Mcmurray, J, Rouleau, J, Solomon, S, Steg, P, Berwanger, O, Cikes, M, De Pasquale, C, Fernandez, A, Filippatos, G, Jering, K, Landmesser, U, Menon, V, Merkely, B, Petrie, M, Petrov, I, Schou, M, Senni, M, Sim, D, van der Meer, P, Lefkowitz, M, Zhou, Y, Wang, Y, and Braunwald, E
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Ramipril ,medicine.medical_specialty ,business.industry ,Aminobutyrates ,Biphenyl Compounds ,heart failure ,ramipril ,medicine.disease ,Article ,Drug Combinations ,myocardial infarction ,Physiology (medical) ,Heart failure ,Internal medicine ,sacubitril/valsartan ,medicine ,Cardiology ,Humans ,Valsartan ,Cardiology and Cardiovascular Medicine ,business ,Antihypertensive Agents ,Sacubitril, Valsartan ,medicine.drug - Abstract
Ovo istraživačko pismo prikazuje detaljniju analizu kliničkih ishoda u kliničkom ispitivanju PARADISE- MI.
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- 2022
30. Impact of chronic obstructive pulmonary disease in patients with heart failure with preserved ejection fraction: Insights from PARAGON‐HF
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Masatoshi Minamisawa, Pardeep S. Jhund, John J.V. McMurray, Muthiah Vaduganathan, Dirk J. van Veldhuisen, Marc A. Pfeffer, Margaret M. Redfield, Aldo P. Maggioni, Michael R. Zile, Martin Lefkowitz, Akshay S. Desai, Nathaniel M. Hawkins, Michele Senni, Amil M. Shah, Brian Claggett, Jean L. Rouleau, Scott D. Solomon, Inder S. Anand, Leanne Mooney, Cardiovascular Centre (CVC), Mooney, L, Hawkins, N, Jhund, P, Redfield, M, Vaduganathan, M, Desai, A, Rouleau, J, Minamisawa, M, Shah, A, Lefkowitz, M, Zile, M, Van Veldhuisen, D, Pfeffer, M, Anand, I, Maggioni, A, Senni, M, Claggett, B, Solomon, S, and Mcmurray, J
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Male ,medicine.medical_specialty ,Rate ratio ,Pulmonary Disease, Chronic Obstructive ,chemistry.chemical_compound ,Internal medicine ,Humans ,Medicine ,Diseases of the circulatory (Cardiovascular) system ,Prospective Studies ,Sacubitril/valsartan ,Heart Failure ,COPD ,Creatinine ,business.industry ,Chronic obstructive pulmonary disease ,Hazard ratio ,Stroke Volume ,medicine.disease ,Hospitalization ,Treatment Outcome ,Heart failure with preserved ejection fraction ,chemistry ,Heart failure ,Concomitant ,RC666-701 ,Cardiology ,Right ventricle ,Female ,Cardiology and Cardiovascular Medicine ,business ,Sacubitril, Valsartan - Abstract
Background Little is known about the impact of chronic obstructive pulmonary disease (COPD) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We examined outcomes in patients with heart failure with preserved ejection fraction, according to COPD status, in the PARAGON‐HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and cardiovascular death. Of 4791 patients, 670 (14%) had COPD. Patients with COPD were more likely to be men (58% versus 47%; P P P Conclusions Approximately 1 in 7 patients with heart failure with preserved ejection fraction had concomitant COPD, which was associated with greater functional limitation and a higher risk of heart failure hospitalization and death. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920711 .
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- 2021
31. Angiotensin-neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure
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Finnian R. Mc Causland, Martin P. Lefkowitz, Brian Claggett, Milton Packer, Michele Senni, Mauro Gori, Pardeep S. Jhund, Martina M. McGrath, Jean L. Rouleau, Victor Shi, Karl Swedberg, Muthiah Vaduganathan, Faiez Zannad, Marc A. Pfeffer, Michael Zile, John J.V. McMurray, Scott D. Solomon, Mc Causland, F, Lefkowitz, M, Claggett, B, Packer, M, Senni, M, Gori, M, Jhund, P, Mcgrath, M, Rouleau, J, Shi, V, Swedberg, K, Vaduganathan, M, Zannad, F, Pfeffer, M, Zile, M, Mcmurray, J, and Solomon, S
- Subjects
Heart Failure ,Angiotensins ,Aminobutyrates ,Biphenyl Compounds ,Tetrazoles ,Angiotensin-Converting Enzyme Inhibitors ,Stroke Volume ,Kidney ,Angiotensin Receptor Antagonists ,Drug Combinations ,Enalapril ,Chronic kidney disease ,Humans ,Kidney Failure, Chronic ,Valsartan ,Neprilysin ,Renal outcome ,Cardiology and Cardiovascular Medicine - Abstract
Aims: Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin–neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and results: We combined data from PARADIGM-HF (EF ≤40%; n = 8399) and PARAGON-HF (EF ≥45%; n = 4796) in a pre-specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 ± 20 ml/min/1.73 m2 in PARADIGM-HF and 63 ± 19 ml/min/1.73 m2 in PARAGON-HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42–0.75; p < 0.001). The mean eGFR change was −1.8 (95% CI −1.9 to −1.7) ml/min/1.73 m2/year for the sacubitril/valsartan group, compared with −2.4 (95% CI −2.5 to −2.2) ml/min/1.73 m2/year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (p-interaction = 0.64), but was most pronounced in those with baseline EF between 30% and 60% (p-interaction = 0.001). Conclusions: In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.
- Published
- 2021
32. Recurrent venous thromboembolism and vaginal estradiol in women with prior venous thromboembolism: A nested case-control study.
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Eckert-Lind C, Meaidi A, Claggett B, Johansen ND, Lassen MCH, Skaarup KG, Fralick M, Pareek M, Jensen JUS, Torp-Pedersen C, Gislason G, Biering-Sørensen T, and Modin D
- Abstract
Objectives: Whether vaginal estradiol use is associated with an increased risk of recurrent venous thromboembolism (VTE) in women with prior VTE is unknown. We sought to evaluate the association between vaginal estradiol use and recurrent VTE in women with prior VTE., Methods: We performed a nationwide nested case-control study among 44 024 women aged ≥45 years who developed a first VTE without a history of vaginal estrogen use prior to VTE diagnosis. Cases with recurrent VTE were matched 1:2 on birth year with controls using incidence density sampling. Exposure to vaginal estradiol tablets was categorized into current use (0-2 months before index), prior use (2-24 months before index) and past use (more than 24 months prior to index)., Results: We identified 5066 cases and 10 127 age-matched controls. In fully adjusted analysis vaginal estrogen was not associated with recurrent VTE with a hazard ratio of 0.75, p = .07 for current use, 0.83, p = .13 for prior use, and 1.24, p = .06 for past use., Conclusion: Use of vaginal estradiol tablets in women with prior VTE was not associated with an increased rate of recurrent VTE. Our study indicates that vaginal estradiol therapy is unlikely to increase risk of recurrent VTE in women with prior VTE., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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33. Response by Chatur et al to Letter Regarding Article, "Outpatient Worsening Among Patients With Mildly Reduced and Preserved Ejection Fraction Heart Failure in the DELIVER Trial".
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Chatur S, Vaduganathan M, Claggett B, and Solomon SD
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- Humans, Disease Progression, Outpatients, Heart Failure physiopathology, Heart Failure therapy, Stroke Volume
- Abstract
Competing Interests: S.C. is supported by the Canadian Arthur J.E. Child’s Cardiology Fellowship. M.V. has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer Aktiengesellschaft, Occlutech, and Impulse Dynamics. B.L.C. has consulted for Amgen, AO Biome, Biogen, Boehringer Ingelheim, Corvia, Gilead, Myokardia, Cardurion, and Novartis. S.D.S. has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Heatlh/National Heart Lung and Blood Institute, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health.
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- 2024
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34. Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.
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Coats CJ, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, Choudhury L, Claggett B, Düngen HD, Garcia-Pavia P, Hagège AA, Januzzi JL, Lee MMY, Lewis GD, Ma CS, Maron MS, Miao ZM, Michels M, Olivotto I, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins H, Jacoby DL, German P, Heitner SB, Kupfer S, Lutz JD, Malik FI, Meng L, Wohltman A, and Abraham TP
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- Humans, Male, Female, Middle Aged, Aged, Treatment Outcome, Double-Blind Method, Dose-Response Relationship, Drug, Adult, Atrial Fibrillation drug therapy, Atrial Fibrillation diagnosis, Atrial Fibrillation physiopathology, Benzylamines, Uracil analogs & derivatives, Cardiomyopathy, Hypertrophic physiopathology, Cardiomyopathy, Hypertrophic drug therapy, Cardiomyopathy, Hypertrophic diagnosis, Ventricular Function, Left drug effects, Stroke Volume drug effects
- Abstract
Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM)., Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5-20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site-interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8-24), and washout (weeks 24-28), and included major adverse cardiac events, new-onset atrial fibrillation, implantable cardioverter-defibrillator discharges, LVEF <50%, and treatment-emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5-, 10-, 15-, and 20-mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by -0.9% (95% CI, -1.3 to -0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per-protocol dose reduction for site-interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment-emergent adverse events were similar between treatment groups, including atrial fibrillation., Conclusions: A site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05186818.
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- 2024
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35. Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.
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Ireland CG, Burstein DS, Day SM, Axelsson Raja A, Russell MW, Zahka KG, Pereira A, Canter CE, Bach RG, Wheeler MT, Rossano JW, Owens AT, Bundgaard H, Mestroni L, Taylor MRG, Patel AR, Wilmot I, Soslow JH, Becker JR, Giverts I, Orav EJ, Claggett B, Lin KY, and Ho CY
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- Humans, Female, Male, Adolescent, Young Adult, Adult, Child, Angiotensin II Type 1 Receptor Blockers therapeutic use, Treatment Outcome, Quality of Life, Cardiomyopathy, Hypertrophic physiopathology, Cardiomyopathy, Hypertrophic drug therapy, Exercise Tolerance drug effects, Exercise Test, Valsartan therapeutic use
- Abstract
Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being., Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort., Results: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P =0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P =0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P =0.01) but did not significantly impact CPET performance., Conclusions: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534., Competing Interests: Dr Day is involved in consulting for Lexicon Pharmaceuticals; is on the Data Monitoring Committee of Cytokinetics; and receives funding from Lexicon Pharmaceuticals and Bristol Myers Squibb. Dr Canter is a consultant for Bristol Myers Squibb and receives research support from Tenaya, Merck, and Novartis (none relevant). Dr Bach receives research support (institutional only) from MyoKardia, Bristol Myers Squibb, and Cytokinetics, outside of the submitted work. Dr Wheeler receives research support and in-kind support from MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb, and research support from Cytokinetics Inc and Novartis Inc, all outside of the submitted work. Dr Rossano is a consultant for AskBio, American Regent, Bayer, BioMarin, Bristol Myers Squibb, Enzyvant, and Merck. Dr Owens has been consulting for Bristol Myers Squibb, Cytokinetics, Pfizer, Tenaya, BioMarin, Lexicon, Lexeo, Edgewise, and Stealth Therapeutics and receives research support from Bristol Myers Squibb. Dr Mestroni receives research funding from Bristol Myers Squibb, Tenaya Therapeutics, Pfizer, BioMarin, Greenstone Bioscience, and Spark Therapeutics. Dr Taylor receives research funding from Bristol Myers Squibb, Tenaya Therapeutics, Rocket Pharmaceuticals, BioMarin, and Spark Therapeutics. Dr Patel receives a research grant from GE Healthcare. Dr Soslow is involved in unrelated consulting for Sarepta, Pfizer, Immunoforge, and WCG Imaging. Dr Claggett is involved in statistical consulting for Alnylam, Cardurion, Corvia, CVRx, Cytokinetics, Intellia, and Rocket. Dr Ho is a consultant for and receives research funding from Bristol Myers Squib, Pfizer, Cytokinetics, Tenaya, BioMarin, viz.AI, and Lexicon (none relevant). The other authors report no conflicts.
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- 2024
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36. Training the Next Generation of Data Monitoring Committee Members: An Initiative of the Heart Failure Collaboratory.
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Fleming TR, Wittes J, Fiuzat M, Bristow MR, Rockhold FW, Connor JT, Saville BR, Claggett B, Cavagna I, Abraham WT, Cook TD, Lindenfeld J, O'Connor C, and DeMets DL
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- Humans, Clinical Trials as Topic, Heart Failure therapy, Clinical Trials Data Monitoring Committees
- Abstract
Clinical trials are vital for assessing therapeutic interventions. The associated data monitoring committees (DMCs) safeguard patient interests and enhance trial integrity, thus promoting timely, reliable evaluations of those interventions. We face an urgent need to recruit and train new DMC members. The HFC (Heart Failure Collaboratory), a multidisciplinary public-private consortium of academics, trialists, patients, industry representatives, and government agencies, is working to improve the clinical trial ecosystem. The HFC aims to improve clinical trial efficiency and quality by standardizing concepts, and to help meet the demand for experienced individuals on DMCs by creating a standardized approach to training new members. This paper discusses the HFC's training workshop, and an apprenticeship model for new DMC members. It describes opportunities and challenges DMCs face, along with common myths and best practices learned through previous experiences, with an emphasis on data confidentiality and need for quality independent statistical reporting groups., Competing Interests: Funding Support and Author Disclosures Dr Fleming has received consulting fees from the National Institutes of Health, the World Health Organization, the Food and Drug Administration, and the pharmaceutical and biotech industry in the design, monitoring, and analysis of clinical trials; and he has received fees for serving on several industry-sponsored Data Monitoring Committees (DMCs). Dr Wittes has received compensation for her membership on several DMCs sponsored by industry, government, and not-for-profit organizations; and has received consulting fees from a variety of pharmaceutical and medical device companies. Dr Bristow is the President/CEO/Director at ARCA biopharma. Dr Rockhold has received consulting fees from Intercept, Clover, and Inventprise; has received compensation for serving on several industry-sponsored DMCs; and holds stock in Clover, GSK, Athira, Spence, Adaptic, and Doctor Evidence. Dr Claggett has received consulting fees from Alnylam, Axon, Cardior, Cardurion, CVRx, Cytokinetics, Intellia, and Rocket. Dr Abraham has received consulting fees from Boehringer Ingelheim, Cardionomic, Zoll Respicardia, scPharmaceuticals, Sensible Medical, and Vectorious; has received salary support from V-Wave Medical; and has served as a speaker for Edwards Lifesciences. Dr Lindenfeld has received consulting fees from Abbott, ADI, Alleviant, Amgen, AstraZeneca, Axon, Boston Scientific, Cordio, CVRx, Cytokinetics, Edwards Lifesciences, Medtronic, Merck, VWave, Vascular Dynamics, Vectorious, and Whiteswell; and has received grants from Analog Devices Inc, AstraZeneca, and Volumetrix. Dr DeMets has received consulting fees from the National Institutes of Health, the U.S. Food and Drug Administration, and the pharmaceutical and medical device industry on the design, monitoring, and analysis of clinical trials; and he has received compensation for serving on several recent industry-sponsored data and safety monitoring committees or steering committees including AstraZeneca, Bristol Meyers Squib, GSK, Merck, Boston Scientific, Medtronic, USONA, LivaNova, AnthosTherapy, ARCA biopharma, Duke Clinical Research Institute, and the Population Health Research Institute of Hamilton Ontario. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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37. Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF.
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Dewan P, Shen L, Pedro Ferreira J, Jhund PS, Anand IS, Chandra A, Chiang LM, Claggett B, Desai AS, Gong J, Lam CSP, Lefkowitz MP, Maggioni AP, Martinez F, Packer M, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Solomon SD, and McMurray JJV
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- Humans, Male, Female, Aged, Middle Aged, Prospective Studies, Neprilysin antagonists & inhibitors, Treatment Outcome, Cognitive Dysfunction drug therapy, Aged, 80 and over, Biphenyl Compounds therapeutic use, Valsartan therapeutic use, Valsartan adverse effects, Aminobutyrates therapeutic use, Aminobutyrates adverse effects, Heart Failure drug therapy, Heart Failure physiopathology, Drug Combinations, Cognition drug effects, Stroke Volume drug effects, Angiotensin Receptor Antagonists therapeutic use, Angiotensin Receptor Antagonists adverse effects, Tetrazoles therapeutic use, Tetrazoles adverse effects
- Abstract
Background: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction)., Methods: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events., Results: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P =0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype., Conclusions: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711., Competing Interests: Dr Jhund reports receiving grant support from Boehringer Ingelheim and fees for serving on an advisory board from Cytokinetics. Dr Anand reports receiving fees for serving on a steering committee from AstraZeneca, ARCA biopharma, Amgen, and LivaNova; fees for serving as chair of a data and safety monitoring board from Boston Scientific; fees for serving on an end-point committee from Boehringer Ingelheim; and fees for serving on an advisory board from Zensun. Dr Claggett received consulting fees from AOBiome, Biogen, Boehringer Ingelheim, Corvia Medical, Gilead Sciences, and MyoKardia. Dr Desai received consulting fees from Abbott, Boehringer Ingelheim, DalCor Pharmaceuticals, and Regeneron; grant support, paid to Brigham and Women’s Hospital, consulting fees, and fees for serving on an advisory board from Alnylam Pharmaceuticals and AstraZeneca; consulting fees and fees for serving on a steering committee from Biofourmis; consulting fees and fees for serving on a data and safety monitoring committee from Boston Scientific; fees for serving on an advisory board from Corvidia; and fees for serving on an advisory board and consulting fees from Relypsa. Drs Chiang, Gong, and Lefkowitz are employed by Novartis Pharmaceuticals. Dr Lam received grant support and fees for serving on an advisory board from Boston Scientific and Roche Diagnostics; grant support, fees for serving on an advisory board, and fees for serving on steering committees from Bayer; grant support from Medtronics; grant support and fees for serving on a steering committee from Vifor Pharma; fees for serving on an advisory board and fees for serving on steering committees from AstraZeneca and Novartis; fees for serving on an advisory board from Amgen, Boehringer Ingelheim, and Abbott Diagnostics; consulting fees from Merck and Stealth BioTherapeutics; fees for serving on a steering committee from Janssen Research and Development; lecture fees and consulting fees from Menarini; and fees for serving on a scientific committee from Corvia Medical and holding a pending patent (PCT/SG2016/050217) on a method regarding diagnosis and prognosis of chronic heart failure. Dr Maggioni received fees for serving on a study committee from Bayer and Fresenius. Dr Packer received consulting fees from AbbVie, Akcea Therapeutics, Actavis, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Daiichi Sankyo, Gilead Sciences, Johnson & Johnson, Novo Nordisk, Pfizer, Relypsa, Sanofi, Synthetic Biologics, and Theravance Biopharma. Dr Rouleau received consulting fees from AstraZeneca. Dr van Veldhuisen received fees for serving on a steering committee and travel support from ARCA Biopharma and Corvia Medical. Dr Zannad received fees for serving on a steering committee from Janssen, Bayer, Boston Scientific, CVRx, and Boehringer Ingelheim; consulting fees from Amgen, Vifor Pharma–Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, and Merck; and consulting fees and fees for serving on a steering committee from AstraZeneca and serving as founder of cardiorenal and CVCT. Dr Zile received fees for serving on a steering committee from Abbott and Ironwood Pharma; consulting fees from Boston Scientific and MyoKardia; grant support and fees for serving on a steering committee from CVRx and Medtronic; fees for serving on an eligibility committee from EBR Systems and V-Wave; fees for serving on a clinical-events committee from Endotronics; and fees for serving on a data and safety monitoring board from Merck. Dr Solomon received grant support, paid to Brigham and Women’s Hospital, and consulting fees from Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, MyoKardia, Novartis, Theracos, Bayer, and Cytokinetics; grant support, paid to Brigham and Women’s Hospital, from Bellerophon Therapeutics, Celladon, Ionis Pharmaceuticals, Lonestar Heart, Mesoblast, Sanofi Pasteur, and Eidos Therapeutics; consulting fees from Akros Pharma, Corvia Medical, Ironwood Pharma, Merck, Roche, Takeda Pharmaceutical, Quantum Genomics, AOBiome, Cardiac Dimensions, Tenaya Therapeutics, and Daiichi Sankyo; and fees for serving on a data and safety monitoring board from Janssen. Dr McMurray reports that his employer, Glasgow University, has been paid by Novartis for serving as an executive committee member and coprincipal investigator of ATMOSPHERE, PARADIGM-HF, and PARAGON-HF trials and executive/steering committee member of the PARADISE-MI and PERSPECTIVE trials (with sacubitril/valsartan) and for meetings/presentations related to these trials, aliskiren, and sacubitril-valsartan. Novartis has also paid for his travel and accommodation for some of these meetings. Glasgow University has also been paid by Novartis for advisory board; by Bayer for serving as a steering committee member of the PANACHE trial using neladenoson bialanate (BAY 1067197); by Cardiorentis for serving as a steering committee member and end-point committee chair for the TRUE-AHF trial and attending meetings related to this trial; by Cardiorentis for travel and accommodation to attend some of these meetings; by Amgen for serving as steering committee member for the ATOMIC-HF and COSMIC-HF trials and attending meetings related to this trial; by Amgen for travel and accommodation for some of these meetings; by Oxford University (which received a grant from Bayer, which manufactures acarbose) for serving as a steering committee member for the ACE trial (using acarbose) and attending meetings related to this trial; by Theracos for serving as principal investigator for the BEST trial and attending meetings related to this trial; by Theracos for travel and accommodation to attend some of these meetings; by Abbvie (which manufactures atrasentan) for serving as steering committee member for the SONAR trial (using atrasentan) and to attend meetings related to this trial; by Abbvie for his travel and accommodation to attend some of these meetings; by DalCor Pharmaceuticals for serving as steering committee member for the Dal-GenE trial and to attend meetings related to this trial; by Pfizer for serving on the data safety monitoring committee for the SPIRE trial and to attend meetings related to this trial; by Merck for serving on the data safety monitoring committee for the MK-3102 program, for the VICTORIA trial, and to attend meetings related to these trials; by AstraZeneca (which markets dapagliflozin) for serving as principal investigator of DAPA-HF and coprincipal investigator of DELIVER (trials using dapagliflozin on heart failure) and to attend meetings related trial; by AstraZeneca for his travel and accommodation to attend meetings; by GSK for serving as coprincipal investigator and steering committee member for the Harmony-Outcomes trial (albiglutide) and the trials ASCEND-D and ASCEND-ND, using daprodustat, respectively, and to attend meetings related to these trials; by GSK for his travel and accommodation to attend some of the meetings; by BMS for serving as a steering committee member for the STAND-UP clinical trial (using an HNO donor) on heart failure and to attend meetings related to this trial; and by Kings College Hospital (which has received a grant from KRUK and Vifor-Fresenius, which manufactures intravenous iron) for serving as steering committee member for the PIVOTAL trial (using intravenous iron) and for running the end-point adjudication committee for this trial, to attend meetings related to PIVOTAL, and for his travel and accommodation for to attend some of the meetings. All payments were made through consultancies with Glasgow University, and Dr McMurray has not received any personal payments in relation to the trials or drugs. The other authors report no conflicts. The study supporters had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
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- 2024
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38. Diagnostic Utility of SGLT2 Inhibitors to Facilitate Myocardial Glucose Suppression During Evaluation of Myocardial Inflammation.
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Selvaraj S, Vidula MK, Claggett B, Rojulpote C, Bhattaru A, Clancy CB, Rossman M, Pryma DA, Goldberg LR, and Bravo PE
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- Aged, Female, Humans, Male, Middle Aged, Biomarkers blood, Blood Glucose metabolism, Blood Glucose drug effects, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diagnosis, Myocarditis diagnostic imaging, Myocarditis drug therapy, Predictive Value of Tests, Treatment Outcome, Myocardium pathology, Myocardium metabolism, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Sodium-Glucose Transporter 2 Inhibitors adverse effects
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- 2024
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39. Safety and Tolerability of Angiotensin Receptor-Neprilysin Inhibitor Initiation in High-Risk Acute Myocardial Infarction Relative to Care Setting: A Subgroup Analysis of the PARADISE-MI Trial.
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De Pasquale CG, Claggett B, Jering K, McMurray JJV, Mann D, Miao ZM, Granger CB, Køber L, Maggioni AP, Rouleau JL, Solomon SD, Steg PG, van der Meer P, Braunwald E, and Pfeffer MA
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- Humans, Male, Biphenyl Compounds, Female, Aged, Treatment Outcome, Tetrazoles therapeutic use, Tetrazoles adverse effects, Middle Aged, Drug Combinations, Risk Factors, Myocardial Infarction drug therapy, Angiotensin Receptor Antagonists adverse effects, Angiotensin Receptor Antagonists therapeutic use, Neprilysin antagonists & inhibitors, Aminobutyrates therapeutic use, Aminobutyrates adverse effects, Valsartan
- Abstract
Competing Interests: Dr De Pasquale reports research funding from AstraZeneca and Novartis; consulting fees or speaker honoraria from AstraZeneca, Novartis, Vifor, Boehringer Ingelheim, Bayer, Eli Lilly, and Roche. Dr Claggett reports statistical consulting at Alnylam, Cardurion, Corvia, CVRx, Cytokinetics, Intellia, and Rocket. Dr McMurray received support from British Heart Foundation Centre of Research Excellence grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund; has received payments through the Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline (GSK), KBP Biosciences, and Novartis; has received personal consulting fees from Alnylam Pharma, Bayer, Bristol Myers Squibb (BMS), George Clinical Pty Ltd, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharma, J.B. Chemicals and Pharma Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy; and is a director of Global Clinical Trial Partners Ltd. Dr Granger reports consulting fees from Abbvie, Abiomed, Alnylam Pharmaceuticals, Anthos, Bayer Corporation, Boehringer Ingelheim, Boston Scientific Corporation, BMS, Cardionomics, CeleCor Therapeutics, Janssen Pharmaceutical, Merck, Novo Nordisk, Novartis Pharmaceutical Company, Pfizer, Philips, Reata, and NephroSynergy; salary funded by Duke; grants sponsored by Alnylam, Boehringer Ingelheim, BMS, Daiichi Sankyo, Food and Drug Administration, Janssen Pharmaceuticals, National Institutes of Health (NIH), Novartis Pharmaceutical Company, Pfizer, and Philips; and equity in Tenac.io. Dr Køber reports speaker honoraria from AstraZeneca, Bayer, Boehringer, Novartis, and Novo Nordisk. Dr Maggioni reports personal fees for participation in studies from AstraZeneca, Bayer, Novartis, and Sanofi, outside the present work. Dr Rouleau reports DMC membership with Novartis, BMS, Bayer, and AstraZeneca. Dr Solomon reports research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, NIH/National Heart, Lung, and Blood Institute (NHLBI), Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Steg reports research grants from Amarin and Sanofi; clinical trials (Steering Committee, CEC, DSMB) at Amarin, Amgen, AstraZeneca, Bayer, BMS, Idorsia, Janssen, Novartis, and Sanofi; consulting or speaking at Amarin, Amgen, BMS, Novartis, and Novo Nordisk; and senior associate editor at Circulation. Dr van der Meer is supported by a grant from the European Research Council (ERC CoG 101045236, DISSECT-HF). The UMCG, which employs Dr van der Meer, received consultancy fees and grants from Novartis, Pharmacosmos, Vifor Pharma, AstraZeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis. Dr Braunwald has received research grants through his institution from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and has consultancies with Amgen, BMS, Boehringer Ingelheim/Lilly, Cardurion, and Verve. Dr Pfeffer reports research grant support (via institution) from Lexicon and Novartis; consultant at Alnylam, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Lexicon, NHLBI CONNECTs (Master Protocol Committee), Novartis, Novo Nordisk, and Sanofi; and has equity in DalCor. The other authors report no conflicts.
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- 2024
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40. The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials.
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Skaarup KG, Lassen MCH, Modin D, Johansen ND, Loiacono MM, Harris RC, Lee JKH, Dufournet M, Vardeny O, Peikert A, Claggett B, Solomon SD, Jensen JUS, and Biering-Sørensen T
- Subjects
- Humans, Aged, Vaccine Efficacy, Pneumonia prevention & control, Pneumonia mortality, Male, Aged, 80 and over, Female, Hospitalization statistics & numerical data, Influenza Vaccines administration & dosage, Influenza Vaccines immunology, Influenza, Human prevention & control, Influenza, Human mortality, Randomized Controlled Trials as Topic
- Abstract
Objectives: To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes., Methods: A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥ 65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method., Results: Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5 %, [95 %CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3 %, [95 %CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6 % ([95 %CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥ 100 events, and random-effects models provided comparable estimates for all outcomes., Conclusions: HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥ 65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial., Competing Interests: Declaration of Competing Interest KGS has served on advisory boards for Sanofi. MML, RH, and MD are full-time employees of Sanofi and may hold stocks and/or shares in the company. SDS has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi, Theracos, US2. AI and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. TBS is chief investigator of the Boston Scientific financed ”DANLOGIC-HF” trial, the Sanofi financed “NUDGE-FLU” trial, the Sanofi financed “DANFLU-1″ trial, the Sanofi financed “DANFLU-2″ trial and steering committee member of the Boston Scientific sponsored “LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific's Investigational ICM System” trial, the Amgen sponsored GALACTIC-HF trial, the Boehringer Ingelheim financed EASi-KIDNEY trial and served on advisory boards for Sanofi, Amgen, CSL Seqirus and GSK and received speaker honorariums from Bayer, Novartis, Sanofi, GE Healthcare and GSK and received research grants from Boston Scientific, GE Healthcare, AstraZeneca, Novo Nordisk, and Sanofi and consulted for Novo Nordisk, IQVIA and Parexel. The remaining authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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41. Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection.
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Magodoro IM, Guerrero-Chalela CE, Claggett B, Jermy S, Samuels P, Myer L, Zar HJ, Jao J, Ntsekhe M, Siedner MJ, and Ntusi NAB
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- Humans, Female, Adolescent, Male, HIV-1 drug effects, Magnetic Resonance Imaging, Child, Anti-HIV Agents therapeutic use, Anti-HIV Agents administration & dosage, Anti-Retroviral Agents administration & dosage, Anti-Retroviral Agents therapeutic use, Infectious Disease Transmission, Vertical prevention & control, Child, Preschool, HIV Infections drug therapy
- Abstract
Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: -0.51 (-0.91, -0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined., (© 2024. The Author(s).)
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- 2024
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42. Cardiovascular Burden of the V142I Transthyretin Variant.
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Selvaraj S, Claggett B, Shah SH, Mentz RJ, Khouri MG, Manichaikul AW, Khan SS, Rich SS, Mosley TH, Levitan EB, Arora P, Goyal P, Haring B, Eaton CB, Cheng RK, Wells GL, Manson JE, Fontana M, and Solomon SD
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Disease Progression, Heterozygote, Hospitalization statistics & numerical data, Prealbumin genetics, Stroke Volume, United States epidemiology, Cost of Illness, Amyloidosis ethnology, Amyloidosis genetics, Black or African American genetics, Cardiomyopathies ethnology, Cardiomyopathies genetics, Heart Failure ethnology, Heart Failure genetics, Heart Failure mortality
- Abstract
Importance: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments., Objectives: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population., Design, Setting, and Participants: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024., Exposure: V142I carrier status (n = 754, 3.2%)., Main Outcomes and Measures: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data., Results: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant., Conclusions and Relevance: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.
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- 2024
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43. Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.
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Solomon SD, Ostrominski JW, Vaduganathan M, Claggett B, Jhund PS, Desai AS, Lam CSP, Pitt B, Senni M, Shah SJ, Voors AA, Zannad F, Abidin IZ, Alcocer-Gamba MA, Atherton JJ, Bauersachs J, Ma CS, Chiang CE, Chioncel O, Chopra V, Comin-Colet J, Filippatos G, Fonseca C, Gajos G, Goland S, Goncalvesová E, Kang SM, Katova T, Kosiborod MN, Latkovskis G, Lee AP, Linssen GCM, Llamas-Esperón G, Mareev V, Martinez FA, Melenovský V, Merkely B, Nodari S, Petrie MC, Saldarriaga CI, Saraiva JFK, Sato N, Schou M, Sharma K, Troughton R, Udell JA, Ukkonen H, Vardeny O, Verma S, von Lewinski D, Voronkov LG, Yilmaz MB, Zieroth S, Lay-Flurrie J, van Gameren I, Amarante F, Viswanathan P, and McMurray JJV
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- Humans, Female, Male, Aged, Double-Blind Method, Ventricular Function, Left physiology, Ventricular Function, Left drug effects, Middle Aged, Treatment Outcome, Glomerular Filtration Rate physiology, Natriuretic Peptide, Brain blood, Heart Failure physiopathology, Heart Failure drug therapy, Stroke Volume physiology, Mineralocorticoid Receptor Antagonists therapeutic use, Naphthyridines therapeutic use
- Abstract
Aims: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF., Methods and Results: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m
2 , elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials., Conclusions: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)- Published
- 2024
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44. Cardiac Troponin and Treatment Effects of Omecamtiv Mecarbil: Results From the GALACTIC-HF Study.
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Felker GM, Solomon SD, Metra M, Mcmurray JJV, Diaz R, Claggett B, Lanfear DE, Vandekerckhove H, Biering-Sørensen T, Lopes RD, Arias-Mendoza A, Momomura SI, Corbalan R, Ramires FJA, Zannad F, Heitner SB, Divanji PH, Kupfer S, Malik FI, and Teerlink JR
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- Humans, Male, Double-Blind Method, Female, Middle Aged, Aged, Treatment Outcome, Urea analogs & derivatives, Urea therapeutic use, Urea pharmacology, Carbamates therapeutic use, Heart Failure drug therapy, Heart Failure blood, Troponin I blood, Stroke Volume drug effects, Biomarkers blood
- Abstract
Background: Omecamtiv mecarbil improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined the relationship between baseline troponin levels, change in troponin levels over time and the treatment effect of omecamtiv mecarbil in patients enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial (NCT02929329)., Methods: GALACTIC-HF was a double-blind, placebo-controlled trial that randomized 8256 patients with symptomatic HFrEF to omecamtiv mecarbil or placebo. High-sensitivity troponin I (cTnI) was measured serially at a core laboratory. We analyzed the relationship between both baseline cTnI and change in cTnI concentrations with clinical outcomes and the treatment effect of omecamtiv mecarbil., Results: Higher baseline cTnI concentrations were associated with a risk of adverse outcomes (hazard ratio for the primary endpoint of time to first HF event or CV death = 1.30; 95% CI 1.28, 1.33; P < 0.001 per doubling of baseline cTnI). Although the incidence of safety outcomes was higher in patients with higher baseline cTnI, there was no difference between treatment groups. Treatment with omecamtiv mecarbil led to a modest increase in cTnI that was related to plasma concentrations of omecamtiv mecarbil, and it peaked at 6 weeks. An increase in troponin from baseline to week 6 was associated with an increased risk of the primary endpoint (P < 0.001), which was similar, regardless of treatment assignment (P value for interaction = 0.2)., Conclusions: In a cohort of patients with HFrEF, baseline cTnI concentrations were strongly associated with adverse clinical outcomes. Although cTnI concentrations were higher in patients treated with omecamtiv mecarbil, we did not find a differential effect of omecamtiv mecarbil on either safety or efficacy based on baseline cTnI status or change in cTnI., Competing Interests: DISCLOSURES GMF has received research grants from NHLBI, American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; he has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Medtronic, Cardionomic, Boehringer-Ingelheim, American Regent, Abbott, Astra-Zeneca, Reprieve, Myovant, Sequana, Windtree Therapuetics, and Whiteswell and has served on clinical endpoint committees/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, LivaNova, Siemens, and Rocket Pharma. SDS reports receiving grants (via Brigham and Women's Hospital) from Amgen and Cytokinetics during the conduct of the study; grants (via Brigham and Women's Hospital) from Actelion, Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bellerophon Therapeutics, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos Therapeutics, Eli Lilly, Gilead Sciences,GlaxoSmithKline, Ionis Pharmaceuticals, Mesoblast,Myocardium, the National Heart, Lung, and Blood Institute, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos; and consulting fees from Abbott Laboratories, Action Pharma, Akros Pharma, Alnylam Pharmaceuticals, American Regent, Amgen, Arena Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimensions, Cardior Pharmaceuticals, Cardurion Pharmaceuticals, CellProthera, Corvia Medical, Cytokinetics, Daiichi Sankyo, Dinaqor, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, Merck & Co, Moderna, Myokardia, Novartis, Quantum Genomics, Roche, Sanofi Pasteur, Sarepta Therapeutics, Tenaya Therapeutics, Theracos, and Tremeau Pharmaceuticals. MM reports receiving personal fees from Amgen and Servier Laboratories during the conduct of the study and personal fees from Abbott Laboratories, Actelion, AstraZeneca, Edwards Lifesciences, LivaNova, Vifor Pharma, and Windtree Therapeutics. JJVM reports receiving travel fees and nonfinancial support (via the University of Glasgow) from Amgen during the conduct of the study; travel fees and nonfinancial support (via the University of Glasgow) from Alnylam Pharmaceuticals, AstraZeneca, Bayer, Bristol Myers Squibb, Cyclerion Therapeutics, Cytokinetics, DalCor Pharmaceuticals, GlaxoSmithKline, Novartis, Pfizer, Servier Laboratories, and Theracos; and personal fees from Abbott Laboratories, Hikma Pharmaceuticals, Servier Laboratories, and Sun Pharmaceutical Industries. RD reports receiving grants from Amgen during the conduct of the study. BC reports receiving grants (via Brigham and Women's Hospital) from Amgen and Cytokinetics during the conduct of the study and consulting fees from Amgen, Boehringer Ingelheim, Corvia Medical, Myokardia, and Novartis. DEL is supported in part by grants from the National Institutes of Health (P50MD017351, R01HL132154), has received research funding or support from Amgen, Astra Zeneca, Janssen, Eli Lilly, and Somalogic, and has acted as consultant to ACI Clinical (Abbott Laboratories), AstraZeneca, Cytokinetics, Duke Clinical Research Institute (CONNECT-HF), Illumina, Janssen, Martin Pharmaceuticals, Ortho Clinical Diagnostics, and Otsuka. HV reports being a national leader of GALACTIC-HF and has received lecture fees and consultation fees from Amgen. RDL reports research grants or contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis and funding for educational activities or lectures from Pfizer and Daiichi Sankyo and funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Novo Nordisk. S-IM reports being a national leader of GALACTIC-HF and has received lecture and consultation fees from Amgen. TB-S reports being a steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur-financed NUDGE-FLU trial; chief investigator and steering committee chair of the Sanofi Pasteur-financed DANFLU-1 trial; steering committee member of LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific's Investigational ICM System trial; is on the advisory boards of Sanofi Pasteur, Amgen and GSK; receives speaker honoraria from Bayer, Novartis, Sanofi Pasteur, and GSK and research grants from GE Healthcare and Sanofi Pasteur. SBH, PHD, SK, and FIM are employees of Cytokinetics. JRT reports receiving grants from Amgen and Cytokinetics, personal fees from Amgen, Cytokinetics and Servier Laboratories, and nonfinancial support from Amgen and Cytokinetics during the conduct of the study; grants from Abbott Laboratories, Bayer, Boerhinger Ingelheim, Bristol Myers Squibb, EBR Systems, LivaNova, Medtronic, Novartis, and Windtree Therapeutics; and personal fees from Amgen, AstraZeneca, Cytokinetics, Merck & Co, and Servier Laboratories. All other authors report no relevant disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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45. Multi-Organ System Metabolic Stress and Sex-Divergent Vascular Associations.
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Kwan AC, Wang M, Ji H, Claggett B, Ouyang D, Trivedi H, Sharma S, Shyy J, Velazquez A, Ebinger JE, and Cheng S
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Introduction: Women experience excess cardiovascular risk compared to men in the setting of similar metabolic disease burden. This consistent finding could be related to sex differences in the vascular response to various forms of metabolic stress. In this study we examine the association of both systemic and organ-specific metabolic stress with vascular health in women and men., Methods: We conducted an observational study of 4,299 adult participants (52% women, aged 59±13 years) of the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cohort and 110,225 adult outpatients (55% women, aged 64±16 years) of the Cedars-Sinai Medical Center (CSMC) 2019 cohort. We used natural splines to examine the association of systemic and organ-specific measures of metabolic stress including body mass index (BMI), hemoglobin A1c (HbA1c), hepatic FIB-4 score, and CKD-EPI estimated glomerular filtration rate (eGFR) on systolic blood pressure (SBP). Piecewise linear models were generated using normal value thresholds (BMI <25 kg/m
2 , HbA1c <5.7%, FIB-4 <1.3, and eGFR ≥90 ml/min), which approximated observed spline breakpoints. The primary outcome was increase in SBP (relative to a sex-specific physiologic baseline SBP) in association with increase in level of each metabolic measure., Results: Women compared to men demonstrated larger magnitudes and an earlier onset of increase in SBP per increment increase across all metabolic stress measures. The slope of SBP increase per increment of each metabolic measure was greater for women than men particularly for metabolic measures within the normal range, with slope differences of 1.71 mmHg per kg/m2 of BMI, 9.61 mmHg per %HbA1c, 6.45 mmHg per FIB-4 unit, and 0.37 mmHg per ml/min decrement of eGFR in the NHANES cohort (P difference <0.05 for all). Overall results were consistent in the CSMC cohort., Conclusions: Women exhibited greater vascular sensitivity in the setting of multiple types of metabolic stress, particularly in periods representing the transition from metabolic health to disease. These findings underscore the importance of involving early metabolic health interventions as part of efforts to mitigate vascular risks in both women and men.- Published
- 2024
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46. Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction.
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McDowell K, Kondo T, Talebi A, Teh K, Bachus E, de Boer RA, Campbell RT, Claggett B, Desai AS, Docherty KF, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Simpson J, Vaduganathan M, Jhund PS, Solomon SD, and McMurray JJV
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- Humans, Male, Proportional Hazards Models, Prognosis, Cause of Death, Heart Failure, Diastolic diagnosis, Heart Failure, Diastolic mortality, Models, Cardiovascular
- Abstract
Importance: Accurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions., Objective: To develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach., Design, Setting, and Participants: Data were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it. The outcomes were the composite of HF hospitalization (HFH) or cardiovascular death, cardiovascular death, and all-cause death. A total of 30 baseline candidate variables were selected in a stepwise fashion using multivariable analyses to create the models. Data were analyzed from January 2023 to June 2023., Exposures: Models to estimate the 1-year and 2-year risk of cardiovascular death or hospitalization for heart failure, cardiovascular death, and all-cause death., Results: Data from 6263 individuals in the DELIVER trial were used to derive the prediction model and data from 4796 individuals in the PARAGON-HF trial and 4128 individuals in the I-PRESERVE trial were used to validate it. The final prediction model for the composite outcome included 11 variables: N-terminal pro-brain natriuretic peptide (NT-proBNP) level, HFH within the past 6 months, creatinine level, diabetes, geographic region, HF duration, treatment with a sodium-glucose cotransporter 2 inhibitor, chronic obstructive pulmonary disease, transient ischemic attack/stroke, any previous HFH, and heart rate. This model showed good discrimination (C statistic at 1 year, 0.73; 95% CI, 0.71-0.75) in both validation cohorts (C statistic at 1 year, 0.71; 95% CI, 0.69-0.74 in PARAGON-HF and 0.75; 95% CI, 0.73-0.78 in I-PRESERVE) and calibration. The model showed similar discrimination to a biomarker-driven model including high-sensitivity cardiac troponin T and significantly better discrimination than the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (C statistic at 1 year, 0.60; 95% CI, 0.58-0.63; delta C statistic, 0.13; 95% CI, 0.10-0.15; P < .001) and NT-proBNP level alone (C statistic at 1 year, 0.66; 95% CI, 0.64-0.68; delta C statistic, 0.07; 95% CI, 0.05-0.08; P < .001). Models derived for the prediction of all-cause and cardiovascular death also performed well. An online calculator was created to allow calculation of an individual's risk., Conclusions and Relevance: In this prognostic study, a robust prediction model for clinical outcomes in HFpEF was developed and validated using routinely collected variables. The model performed better than NT-proBNP level alone. The model may help clinicians to identify high-risk patients and guide treatment decisions in HFpEF.
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- 2024
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47. Clinical implications of subclinical left ventricular dysfunction in heart failure with preserved ejection fraction: The PARAGON-HF study.
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Minamisawa M, Inciardi RM, Claggett B, Cikes M, Liu L, Prasad N, Biering-Sørensen T, Lam CSP, Shah SJ, Zile MR, O'Meara E, Redfield MM, McMurray JJV, Solomon SD, and Shah AM
- Subjects
- Humans, Female, Male, Aged, Aminobutyrates therapeutic use, Biphenyl Compounds, Tetrazoles therapeutic use, Natriuretic Peptide, Brain blood, Peptide Fragments blood, Angiotensin Receptor Antagonists therapeutic use, Prognosis, Heart Ventricles physiopathology, Heart Ventricles diagnostic imaging, Aged, 80 and over, Drug Combinations, Heart Failure physiopathology, Heart Failure complications, Stroke Volume physiology, Ventricular Dysfunction, Left physiopathology, Valsartan therapeutic use, Echocardiography methods, Hospitalization statistics & numerical data
- Abstract
Aims: Left ventricular (LV) subclinical impairment has been described in heart failure with preserved ejection fraction (HFpEF). We assessed the relationship between LV myocardial deformation by strain imaging and recurrent hospitalization for heart failure (HF) or cardiovascular death in a large international HFpEF population., Methods and Results: We assessed two-dimensional speckle-tracking based global longitudinal strain (GLS) in 790 patients (mean age 74 ± 8 years, 54% female) with adequate image quality enrolled in the PARAGON-HF echocardiography study. We examined the relationship of GLS with total HF hospitalizations and cardiovascular death (the primary composite outcome) after accounting for clinical confounders. Approximately 47% of the population had evidence of LV subclinical dysfunction, defined as absolute GLS <16%. Impaired GLS was significantly associated with higher values of circulating baseline N-terminal pro-B-type-natriuretic peptide. After a median follow-up of 3.0 years, there were 407 total HF hospitalizations and cardiovascular deaths. After multivariable adjustment, worse GLS was associated with a greater risk for the primary composite outcome (adjusted hazard ratio per 1% decrease: 1.06; 95% confidence interval 1.02-1.11; p = 0.008). GLS did not modify the treatment effect of sacubitril/valsartan compared with valsartan for the composite outcome (p for interaction >0.1)., Conclusions: In a large HFpEF population, impaired LV function was observed even among patients with preserved ejection fraction, and was associated with an increased risk of total HF hospitalizations or cardiovascular death, accounting for clinical confounders. These findings highlight the key role of subtle LV systolic impairment in the pathophysiology of HFpEF., (© 2024 European Society of Cardiology.)
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- 2024
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48. Individualized Treatment Effect Prediction with Machine Learning - Salient Considerations.
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Desai RJ, Glynn RJ, Solomon SD, Claggett B, Wang SV, and Vaduganathan M
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- Aged, Female, Humans, Male, Middle Aged, Algorithms, Precision Medicine methods, Stroke Volume drug effects, Treatment Outcome, Heart Failure drug therapy, Heart Failure mortality, Heart Failure physiopathology, Machine Learning, Mineralocorticoid Receptor Antagonists therapeutic use, Spironolactone therapeutic use
- Abstract
Background: Machine learning-based approaches that seek to accomplish individualized treatment effect prediction have gained traction; however, some salient challenges lack wider recognition., Methods: We describe key methodologic considerations for individualized treatment effect prediction models using data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial for spironolactone in heart failure with preserved ejection fraction. The causal survival forest algorithm was used for model development. Calibration and discrimination were evaluated using a bootstrapping-based internal validation procedure. Observed benefits were described for predicted benefit quartiles and quartiles of a known effect modifier: ejection fraction. A negative control analysis with noncardiovascular death as the outcome was implemented to detect confounding., Results: Among 3445 participants, 671 events occurred over a median of 3.3 years of follow-up. In internal validation, a higher average observed benefit was noted among patients in the highest quartile of predicted benefit. The median (interquartile range) of the observed restricted mean survival time difference at 3.3 years at the highest quartile of model-predicted benefit was 62 days (32 to 83) and was 47 days (26 to 67) at the lowest quartile of ejection fraction. Body-mass index had higher contribution to prediction of benefit relative to other included measures (33.7% vs. glomerular filtration rate [27.3%], ejection fraction [15.1%], and younger age [12.8%]) No benefit was observed for noncardiovascular death at higher model-predicted benefit quartiles, although benefit for noncardiovascular death was observed at lower quartiles., Conclusions: Carefully applied and validated predictive models hold promise in identifying heterogeneous treatment effects and are useful for hypothesis generation regarding the role of phenotypic characteristics in modifying the benefit of experimental interventions in clinical trials. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00094302.).
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- 2024
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49. Insulin resistance, and not β-cell impairment, mediates association between Mycobacterium tuberculosis sensitization and type II diabetes mellitus among US adults.
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Magodoro IM, Aluoch A, Claggett B, Nyirenda MJ, Siedner MJ, Wilkinson KA, Wilkinson RJ, and Ntusi N
- Abstract
Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (M.tb) by mechanisms that remain to be fully explained. We evaluated association between M.tb sensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or β-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate β-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); while M.tb sensitization status was ascertained by tuberculin skin testing (TST). Exposure to M.tb was associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted., Research in Context: What is already known about this subject?: Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure to Mycobacterium tuberculosis ( M.tb ) via mechanisms that remain to be unraveled What is the key question?: To what extent do insulin resistance and β-cell failure mediate the association between M.tb sensitization with T2DM among US adults? What are the new findings?: M.tb sensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG) Insulin resistance, and not β-cell impairment, likely independently mediate the observed diabetogenic effects of M.tb sensitization How might this impact on clinical and/or public health practice in the foreseeable future?: If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomesThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM.
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- 2024
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50. Cardioprotective effects of antiretroviral treatment in adolescents with perinatal HIV infection are heterogeneous depending on age at treatment initiation.
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Magodoro IM, Guerrero-Chalela CE, Claggett B, Jermy S, Samuels P, Myer L, Zar H, Jao J, Ntsekhe M, Siedner MJ, and Ntusi NA
- Abstract
The cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) may depend on age at ART initiation. We used cardiovascular magnetic resonance (CMR) to characterize and compare residual cardiac changes in apparently healthy APHIV with early and delayed ART initiation compared to sex- and age-similar HIV uninfected peers. We defined early and delayed ART as, respectively, treatment initiated at <5 years and ≥5 years of age. Cardiac function, mechanical deformation, geometry and tissue composition were assessed. APHIV had distinct albeit subclinical cardiac phenotypes depending on timing of ART initiation. For example, changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined.
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- 2024
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