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29 results on '"Lefkowitz, Marty"'

2. Pulmonary Congestion and Left Ventricular Dysfunction After Myocardial Infarction: Insights From the PARADISE-MI Trial

Author

Petrie, Mark C., Rouleau, Jean L., Claggett, Brian, Jering, Karola, van der Meer, Peter, Køber, Lars, Miao, Zi Michael, Lewis, Eldrin, Granger, Christopher, De Pasqulae, Carmine G., Mann, Douglas, Steg, Philippe Gabriel, Maggioni, Aldo, Amir, Offer, Lefkowitz, Marty, Braunwald, Eugene, Solomon, Scott D, McMurray, John J.V., and Pfeffer, Marc A.

Published
2024
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5. Pulmonary Congestion and Left Ventricular Dysfunction after Myocardial Infarction:Insights from the PARADISE-MI Trial

Author

Petrie, Mark C., Rouleau, Jean L., Claggett, Brian, Jering, Karola, Van Der Meer, Peter, Køber, Lars, Miao, Zi Michael, Lewis, Eldrin, Granger, Christopher, De Pasqulae, Carmine G., Mann, Douglas, Steg, Philippe Gabriel, Maggioni, Aldo, Amir, Offer, Lefkowitz, Marty, Braunwald, Eugene, Solomon, Scott D., McMurray, John J.V., Pfeffer, Marc A., Petrie, Mark C., Rouleau, Jean L., Claggett, Brian, Jering, Karola, Van Der Meer, Peter, Køber, Lars, Miao, Zi Michael, Lewis, Eldrin, Granger, Christopher, De Pasqulae, Carmine G., Mann, Douglas, Steg, Philippe Gabriel, Maggioni, Aldo, Amir, Offer, Lefkowitz, Marty, Braunwald, Eugene, Solomon, Scott D., McMurray, John J.V., and Pfeffer, Marc A.

Published
2024

8. Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF

Author

McMurray, John J.V., Jackson, Alice M., Lam, Carolyn S.P., Redfield, Margaret M., Anand, Inder S., Ge, Junbo, Lefkowitz, Marty P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Pfeffer, Marc A., Pieske, Burkert, Rizkala, Adel R., Sabarwal, Shalini V., Shah, Amil M., Shah, Sanjiv J., Shi, Victor C., van Veldhuisen, Dirk J., Zannad, Faiez, Zile, Michael R., Cikes, Maja, Goncalvesova, Eva, Katova, Tzvetana, Kosztin, Anamaria, Lelonek, Malgorzata, Sweitzer, Nancy, Vardeny, Orly, Claggett, Brian, Jhund, Pardeep S., and Solomon, Scott D.

Published
2020
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9. Clinical characteristics of HFrEF patients with rare pathogenic variants in DCM ‐associated genes: a subgroup analysis of the PARADIGM‐HF trial

Author

Barat, Ana, primary, Chen, Chien‐Wei, additional, Patel‐Murray, Natasha, additional, McMurray, John J.V., additional, Packer, Milton, additional, Solomon, Scott D., additional, Desai, Akshay S., additional, Rouleau, Jean L., additional, Zile, Michael R., additional, Attari, Zenab, additional, Zhang, Cong, additional, Xu, Huilei, additional, Hartman, Nicole, additional, Hon, Claudia, additional, Healey, Margaret, additional, Chutkow, William, additional, O'Donnell, Christopher J., additional, Jacob, Jaison, additional, Lefkowitz, Marty, additional, Mendelson, Michael M., additional, Wandel, Simon, additional, Yates, Denise, additional, and Gimpelewicz, Claudio, additional

Published
2023
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10. Clinical characteristics of heart failure with reduced ejection fraction patients with rare pathogenic variants in dilated cardiomyopathy‐associated genes: A subgroup analysis of the PARADIGM‐HF trial.

Author

Barat, Ana, Chen, Chien‐Wei, Patel‐Murray, Natasha, McMurray, John J.V., Packer, Milton, Solomon, Scott D., Desai, Akshay S., Rouleau, Jean L., Zile, Michael R., Attari, Zenab, Zhang, Cong, Xu, Huilei, Hartman, Nicole, Hon, Claudia, Healey, Margaret, Chutkow, William, O'Donnell, Christopher J., Jacob, Jaison, Lefkowitz, Marty, and Mendelson, Michael M.

Subjects
HEART failure, VENTRICULAR ejection fraction, CLINICAL trials, SUBGROUP analysis (Experimental design), GENES, DILATED cardiomyopathy
Abstract

Aims: To evaluate the prevalence of pathogenic variants in genes associated with dilated cardiomyopathy (DCM) in a clinical trial population with heart failure and reduced ejection fraction (HFrEF) and describe the baseline characteristics by variant carrier status. Methods and results: This was a post hoc analysis of the Phase 3 PARADIGM‐HF trial. Forty‐four genes, divided into three tiers, based on definitive, moderate or limited evidence of association with DCM, were assessed for rare predicted loss‐of‐function (pLoF) variants, which were prioritized using ClinVar annotations, measures of gene transcriptional output and evolutionary constraint, and pLoF confidence predictions. Prevalence was reported for pLoF variant carriers based on DCM‐associated gene tiers. Clinical features were compared between carriers and non‐carriers. Of the 1412 HFrEF participants with whole‐exome sequence data, 68 (4.8%) had at least one pLoF variant in the 8 tier‐1 genes (definitive/strong association with DCM), with Titin being most commonly affected. The prevalence increased to 7.5% when considering all 44 genes. Among patients with idiopathic aetiology, 10.0% (23/229) had tier‐1 variants only and 12.6% (29/229) had tier‐1, ‐2 or ‐3 variants. Compared to non‐carriers, tier‐1 carriers were younger (4 years; adjusted p‐value [padj] = 4 × 10−3), leaner (27.8 kg/m2 vs. 29.4 kg/m2; padj = 3.2 × 10−3), had lower ejection fraction (27.3% vs. 29.8%; padj = 5.8 × 10−3), and less likely to have ischaemic aetiology (37.3% vs. 67.4%; padj = 4 × 10−4). Conclusion: Deleterious pLoF variants in genes with definitive/strong association with DCM were identified in ∼5% of HFrEF patients from a PARADIGM‐HF trial subset, who were younger, had lower ejection fraction and were less likely to have had an ischaemic aetiology. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Sacubitril–valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction

Author

Jackson, Alice M, primary, Jhund, Pardeep S, additional, Anand, Inder S, additional, Düngen, Hans-Dirk, additional, Lam, Carolyn S P, additional, Lefkowitz, Marty P, additional, Linssen, Gerard, additional, Lund, Lars H, additional, Maggioni, Aldo P, additional, Pfeffer, Marc A, additional, Rouleau, Jean L, additional, Saraiva, Jose F K, additional, Senni, Michele, additional, Vardeny, Orly, additional, Wijkman, Magnus O, additional, Yilmaz, Mehmet B, additional, Saito, Yoshihiko, additional, Zile, Michael R, additional, Solomon, Scott D, additional, and McMurray, John J V, additional

Published
2021
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13. Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction

Author

Jackson, Alice M., Jhund, Pardeep S., Anand, Inder S., Duengen, Hans-Dirk, Lam, Carolyn S. P., Lefkowitz, Marty P., Linssen, Gerard, Lund, Lars H., Maggioni, Aldo P., Pfeffer, Marc A., Rouleau, Jean L., Saraiva, Jose F. K., Senni, Michele, Vardeny, Orly, Wijkman, Magnus, Yilmaz, Mehmet B., Saito, Yoshihiko, Zile, Michael R., Solomon, Scott D., McMurray, John J. V, Jackson, Alice M., Jhund, Pardeep S., Anand, Inder S., Duengen, Hans-Dirk, Lam, Carolyn S. P., Lefkowitz, Marty P., Linssen, Gerard, Lund, Lars H., Maggioni, Aldo P., Pfeffer, Marc A., Rouleau, Jean L., Saraiva, Jose F. K., Senni, Michele, Vardeny, Orly, Wijkman, Magnus, Yilmaz, Mehmet B., Saito, Yoshihiko, Zile, Michael R., Solomon, Scott D., and McMurray, John J. V

Abstract

Aims: Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on apparent resistant hypertension in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan. Methods and results: In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n=4795). Apparent resistant hypertension was defined as systolic blood pressure >= 14 0mmHg (>= 135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. Apparent mineralocorticoid receptor antagonist (MRA)-resistant hypertension was defined as systolic blood pressure >= 140 mmHg (>= 135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril-valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6-19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7-14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05-1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril-valsartan vs. valsartan in patients with apparent resistant hypertension [-4.8 (-7.0 to -2.5) and 3.9 (-6.6 to -1.3) mmHg] and apparent MRA-resistant hypertension [-8.8 (-14.0 to -3.5) and -6.3 (-12.5 to, Funding Agencies: A.M.J. is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/18/14/33330) and J.J.V.M. is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217).

Published
2021
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15. Relationship between duration of heart failure, patient characteristics, outcomes, and effect of therapy in PARADIGM‐HF

Author

Yeoh, Su E., primary, Dewan, Pooja, additional, Desai, Akshay S., additional, Solomon, Scott D., additional, Rouleau, Jean L., additional, Lefkowitz, Marty, additional, Rizkala, Adel, additional, Swedberg, Karl, additional, Zile, Michael R., additional, Jhund, Pardeep S., additional, Packer, Milton, additional, and McMurray, John J.V., additional

Published
2020
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16. Effects of Sacubitril-Valsartan, versus Valsartan, in Women Compared to Men with Heart Failure and Preserved Ejection Fraction: Insights from PARAGON-HF

Author

McMurray, John J.V., Jackson, Alice M., Lam, Carolyn S.P., Redfield, Margaret M., Anand, Inder S., Ge, Junbo, Lefkowitz, Marty P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Pfeffer, Marc A., Pieske, Burkert, Rizkala, Adel R., Sabarwal, Shalini V., Shah, Amil M., Shah, Sanjiv J., Shi, Victor C., van Veldhuisen, Dirk J., Zannad, Faiez, Zile, Michael R., Cikes, Maja, Goncalvesova, Eva, Katova, Tzvetana, Kosztin, Annamaria, Lelonek, Malgorzata, Sweitzer, Nancy K., Vardeny, Orly, Claggett, Brian, Jhund, Pardeep S., and Solomon, Scott D.

Abstract

Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction (HFpEF), the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women, compared with men. In a pre-specified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial which compared sacubitril-valsartan and valsartan in patients with HFpEF. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older, had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI 0.59-0.90) in women and 1.03 (0.84-1.25) in men; P interaction=0.017. The benefit from sacubitril-valsartan was due to reduction in heart failure hospitalization. The improvement in NYHA class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in KCCQ-CSS was less in women than in men. The difference in adverse events, between sacubitril-valsartan and valsartan, was similar in women and men. As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. While the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. URL: https://clinicaltrials.gov Unique Identifier: NCT01920711.

Published
2020

17. Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction

Author

McMurray, John J.V., Jackson, Alice M., Lam, Carolyn S.P., Redfield, Margaret M., Anand, Inder S., Ge, Junbo, Lefkowitz, Marty P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Pfeffer, Marc A., Pieske, Burkert, Rizkala, Adel R., Sabarwal, Shalini V., Shah, Amil M., Shah, Sanjiv J., Shi, Victor C., van Veldhuisen, Dirk J., Zannad, Faiez, Zile, Michael R., Cikes, Maja, Goncalvesova, Eva, Katova, Tzvetana, Kosztin, Anamaria, Lelonek, Malgorzata, Sweitzer, Nancy, Vardeny, Orly, Claggett, Brian, Jhund, Pardeep S., and Solomon, Scott D.

Subjects
heart failure, hospitalization, neprilysin, women
Abstract

BACKGROUND: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men. METHODS: In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON- HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril- valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. RESULTS: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59-0.90) in women and 1.03 (95% CI, 0.84-1.25) in men (P interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men. CONCLUSIONS: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding.

Published
2020
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18. CARDIOVASCULAR AND RENAL OUTCOMES OF MINERALOCORTICOID RECEPTOR ANTAGONIST USE IN PARAGON-HF

Author

Jering, Karola, primary, Causland, Finnian Mc, additional, Zannad, Faiez, additional, Claggett, Brian, additional, Lefkowitz, Marty, additional, Pieske, Burkert Mathias, additional, Rouleau, Jean L., additional, Shi, Victor, additional, Ben-Gal, Turia, additional, Lam, Carolyn, additional, Shah, Sanjiv, additional, McMurray, John, additional, Solomon, Scott D., additional, and Pfeffer, Marc A., additional

Published
2020
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19. Elevation in High-Sensitivity Troponin T in Heart Failure and Preserved Ejection Fraction and Influence of Treatment With the Angiotensin Receptor Neprilysin Inhibitor LCZ696

Author

Jhund, Pardeep S., primary, Claggett, Brian L., additional, Voors, Adriaan A., additional, Zile, Michael R., additional, Packer, Milton, additional, Pieske, Burkert M., additional, Kraigher-Krainer, Elisabeth, additional, Shah, Amil M., additional, Prescott, Margaret F., additional, Shi, Victor, additional, Lefkowitz, Marty, additional, McMurray, John J.V., additional, and Solomon, Scott D., additional

Published
2014
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20. Reply

Author

Shah, Amil M., primary, Kraigher-Krainer, Elisabeth, additional, Gupta, Deepak K., additional, Santos, Angela, additional, Claggett, Brian, additional, Pieske, Burkert, additional, Zile, Michael R., additional, Voors, Adriaan A., additional, Lefkowitz, Marty P., additional, Packer, Milton, additional, McMurray, John J.V., additional, and Solomon, Scott D., additional

Published
2014
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21. Impaired Systolic Function by Strain Imaging in Heart Failure With Preserved Ejection Fraction

Author

Kraigher-Krainer, Elisabeth, primary, Shah, Amil M., additional, Gupta, Deepak K., additional, Santos, Angela, additional, Claggett, Brian, additional, Pieske, Burkert, additional, Zile, Michael R., additional, Voors, Adriaan A., additional, Lefkowitz, Marty P., additional, Packer, Milton, additional, McMurray, John J.V., additional, and Solomon, Scott D., additional

Published
2014
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22. LEFT VENTRICULAR DYSSYNCHRONY IS ASSOCIATED WITH WORSE DIASTOLIC DYSFUNCTION IN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION

Author

B.S. Santos, Angela, primary, Kraigher-Krainer, Elisabeth, additional, Zile, Michael, additional, Pieske, Burkert, additional, Voors, Adriaan A., additional, McMurray, John J.V., additional, Packer, Milton, additional, Bransford, Toni, additional, Lefkowitz, Marty, additional, Shah, Amil, additional, and Solomon, Scott D., additional

Published
2013
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