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3. Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF

Author

Dewan, Pooja, Shen, Li, Pedro Ferreira, João, Jhund, Pardeep S., Anand, Inder S., Chandra, Alvin, Chiang, Lu-May, Claggett, Brian, Desai, Akshay S., Gong, Jianjian, Lam, Carolyn S.P., Lefkowitz, Martin P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Redfield, Margaret M., Rouleau, Jean L., van Veldhuisen, Dirk J., Zannad, Faiez, Zile, Michael R., Solomon, Scott D., and McMurray, John J.V.

Published
2024
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11. Clinical and non-clinical markers of prognosis in heart failure

Author

Dewan, Pooja

Abstract

Heart failure (HF) is a major cause of morbidity and mortality, and the prevalence of HF is only increasing globally. The rise in prevalence is primarily attributed to a combination of increasing survival especially in patients in industrialized countries and increasing incidence in low- and middle-income countries (mostly in a younger population). The clinical course of HF varies from patient to patient. For some, an initial diagnosis of HF is soon followed by multiple hospitalisations deeply impacting their quality of life, others have a fairly indolent course and some die soon after a diagnosis of HF is made. The treatment for many also depends on various factors including the phenotype of HF, the aetiology of HF and other co-existent chronic conditions to name a few. There are patients with HF who may not be candidates for intensive invasive procedures but would on the other hand benefit from supportive care and palliative care advice with treatment being directed towards preservation of quality of life. Physicians are therefore often faced with the question of the prognosis their patients with HF face. Accurate assessment of prognosis is therefore important in shared decision making for patients with HF. However, assessment of prognosis is not straightforward. Reliance on a clinician's acumen or single prognostic markers such as left ventricular ejection fraction (LVEF) and New York heart association (NYHA) class can be inaccurate and is not advised. Therefore, multivariable models were turned to in order to paint a more accurate picture of a patient's prognosis by incorporating different individual markers known to be associated with clinical outcomes in HF. Multiple prognostic models have consequently been developed for assessment of prognosis in HF. However, uptake of these in clinical practice remain low. Many factors contribute including issues with reproducibility of prognostic ability in different populations, unavailability of variables and complexity of statistical methodologies. The evolving risk of different outcomes due to pharmacological and non-pharmacological advances in HF is another influencing factor. I consequently conducted a systemic analysis of the literature of prognostic models in HF - focusing primarily on a single phenotype of HF - HF with reduced ejection fraction (HFrEF). I identified several variables common to most models, with LVEF, sex, age, NYHA class being some of the most frequently featured. Inclusion of more contemporary prognostic markers such as NT-proBNP and non-clinical markers such as region, race/ethnicity and socioeconomic status was however very less frequent or absent altogether. Given this background, the aim of this thesis was to explore a select set of clinical and non-clinical markers, some of which have featured in previous models to review their prognostic importance along with a few which have not been featured in risk models in the past. The analyses presented were conducted in three contemporary clinical trial datasets in HFrEF - ATMOSPHERE, PARADIGM-HF and DAPA-HF. I used a variety of statistical measures to assess the association between 3 commonly used markers - LVEF, sex & chronic obstructive pulmonary disease (COPD) and 4 uncommonly/previously unused markers - geography & ethnicity, income inequality and frailty - and common clinical outcomes examined in HF. Different outcomes were tested - including cardiovascular, non-cardiovascular & all-cause death and first & recurrent HF, cardiovascular & all-cause hospitalisations. Cox regression was used to study the association between LVEF and COPD with various clinical outcomes. I used competing risk regression to study the other markers of prognosis and their association with clinical outcomes. In the DAPA-HF cohort, each 5% decrease in LVEF was associated with a 20% higher risk of HF hospitalisation (95% CI 1.13 - 1.27) and a 20% higher risk of cardiovascular death (95% CI 1.13 - 1.28). The risks of the same outcomes in those with COPD was 78% (95% CI 1.44 - 2.20) and 28% (95% CI 1.00 - 1.63) respectively. The rest of the analyses were carried out in a pooled cohort of the ATMOSPHERE and PARADIGM-HF trials. Women had a 19% lower risk of HF hospitalisation (95% CI 0.74 - 0.90) and 26% lower risk of cardiovascular death (95% CI 0.67 - 0.81). Among the Asian countries, the highest and lowest risk of hospitalisation for HF was seen in patients belonging to Taiwan (1.88; 95% CI 1.46 - 2.42) and India (0.44; 95% CI 0.36 - 0.54) respectively. In the same patients living in the Philippines had the highest risk of cardiovascular death (sHR 1.87; 95% CI 1.36 - 2.57) and the lowest risk of the same outcome was seen in those living in Japan (subdistribution hazard ratio (sHR) 0.68; 95% CI 0.46 - 0.98). When levels of income inequality were examined, patients lining in countries with the greatest inequality had a 57% higher risk of hospitalisation for HF (95% CI 1.36 - 1.81) and the risk of cardiovascular death was 50% greater (95% CI 1.29 - 1.74) compared to patients living in countries with the lowest income inequality. Using an acceptable method, I found that 69% of the population in ATMOSPHERE and PARADIGM-HF were frail. In the same population, the frailest patients carried a 89% higher risk of HF hospitalisation (95% CI 1.69 - 2.11) and the sHR for cardiovascular death was 2.14 (95% CI 1.92 - 2.38). All the above listed associations were statistically significant. In conclusion, I found that a select set of traditionally featured markers in prognostic models in HF remained strong predictors of hospitalisation and mortality in contemporary set of HF populations. In addition, several non-clinical and clinical markers that have infrequently featured in previous prognostic markers also carry significant value in measuring risk of clinical outcomes in HF. The inclusion of such markers may improve the predictive ability and clinical applicability of prognostic models in HF in the future.

Published
2021
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13. Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics

Author

Chandra, Jagdish, Dewan, Pooja, Kumar, Praveen, Mahajan, Amita, Singh, Preeti, Dhingra, Bhavna, Radhakrishnan, Nita, Sharma, Ratna, Manglani, Mamta, Rawat, Ashok Kumar, Gupta, Piyush, Gomber, Sunil, Bhat, Sunil, Gaikwad, Parag, Elizabeth, K. E., Bansal, Deepak, Dubey, Anand Prakash, Shah, Nitin, Kini, Pranoti, Trehan, Amita, Datta, Kalpana, Basavraja, G. V., Saxena, Vineet, and Kumar, Remesh R.

Published
2022
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18. A Composite Score Summarizing Use and Dosing of Evidence-Based Medical Therapies in Heart Failure: A Nationwide Cohort Study

Author

Johansen, Niklas Dyrby, Vaduganathan, Muthiah, Zahir, Deewa, Fiuzat, Mona, DeFilippis, Ersilia M., Januzzi, James L., Butler, Javed, O’Connor, Christopher M., Abraham, William T., Psotka, Mitchell A., McMurray, John J.V., Dewan, Pooja, Claggett, Brian L., Solomon, Scott D., Modin, Daniel, Butt, Jawad H., Jensen, Jens Ulrik Stæhr, Schou, Morten, Torp-Pedersen, Christian, Køber, Lars, Gislason, Gunnar H., and Biering-Sørensen, Tor

Published
2023
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19. Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction

Author

Butt, Jawad H., Dewan, Pooja, Jhund, Pardeep S., Anand, Inder S., Atar, Dan, Ge, Junbo, Desai, Akshay S., Echeverria, Luis E., Køber, Lars, Lam, Carolyn S.P., Maggioni, Aldo P., Martinez, Felipe, Packer, Milton, Rouleau, Jean L., Sim, David, Van Veldhuisen, Dirk J., Vrtovec, Bojan, Zannad, Faiez, Zile, Michael R., Gong, Jianjian, Lefkowitz, Martin P., Rizkala, Adel R., Solomon, Scott D., and McMurray, John J.V.

Published
2022
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20. Effects of Dapagliflozin According to the Heart Failure Collaboratory Medical Therapy Score: Insights From DAPA-HF

Author

Butt, Jawad H., Dewan, Pooja, DeFilippis, Ersilia M., Biering-Sørensen, Tor, Docherty, Kieran F., Jhund, Pardeep S., Kosiborod, Mikhail N., Martinez, Felipe A., Bengtsson, Olof, Johansen, Niklas Dyrby, Langkilde, Anna Maria, Sjöstrand, Mikaela, Vaduganathan, Muthiah, Solomon, Scott D., Sabatine, Marc S., Køber, Lars, Fiuzat, Mona, and McMurray, John J.V.

Published
2022
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21. Achieved dose and treatment discontinuation of candesartan in men and women with chronic heart failure: data from CHARM.

Author

Qin, Hailun, Dewan, Pooja, Santema, Bernadet T., ter Maaten, Jozine M., Swedberg, Karl, McMurray, John J. V., and Voors, Adriaan A.

Subjects
ANGIOTENSIN-receptor blockers, HEART failure, VENTRICULAR ejection fraction, TERMINATION of treatment, CLINICAL trials
Abstract

Aims: Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. Methods and results: We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF) ≤ 40%] in New York Heart Association class II–IV were randomized to candesartan or placebo. Every 2 weeks, patients were up‐titrated from 4 or 8, to16, to 32 mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64 years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5 ± 12.6 mg in men and 20.7 ± 12.9 mg in women (P = 0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32 mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person‐years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person‐years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P‐value for all > 0.05). There was no significant interaction between sex and treatment‐related discontinuation for hypotension (P = 0.520), an increase in creatinine (P = 0.102), and hyperkalaemia (P = 0.905). Conclusions: In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment‐related discontinuation due to adverse events were also similar between men and women. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Peer Support for Type 2 Diabetes Management in Low- and Middle-Income Countries (LMICs): A Scoping Review

Author

Sherifali, Diana, primary, Da Silva, Lilian Pinto, additional, Dewan, Pooja, additional, Cader, F. Aaysha, additional, Dakhil, Zainab, additional, Gyawali, Bishal, additional, Klassen, Sheila, additional, Yaseen, Israa Fadhil, additional, Jovkovic, Milos, additional, Khalid, Saira, additional, Fitzpatrick-Lewis, Donna, additional, Alliston, Paige, additional, and Racey, Megan, additional

Published
2024
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29. Prognostic significance of morphology markers of chromosomal instability in acute leukaemia and myelodysplastic syndrome.

Author

Khairwa, Anju, Kotru, Mrinalini, Dewan, Pooja, and Narang, Shiva

Subjects
ACUTE leukemia, MYELODYSPLASTIC syndromes, PROGNOSIS, BONE marrow, REGRESSION analysis
Abstract

Objective: This study aimed to assess the prognostic significance of various morphological markers of chromosomal instability (CI). Design: This is a cross-sectional analytical study. Setting: Single centre study from the Department of Pathology of a tertiary care centre in India. Participants: The study included samples of bone marrow aspirates (BMA) and biopsies of patients with acute leukaemia (AL) and myelodysplastic syndrome (MDS) performed between June 2019 and June 2021. Inadequate samples were excluded. We included 178 samples from 80 cases. Interventions: BMA and biopsies slides examined for CI markers like chromatin bridges, multipolar mitosis, nuclear budding, micronuclei, laggards, chromatin string (CS) and nuclear heterogeneity (NH). CI markers were correlated with the type, severity and prognosis of acute leukaemia and MDS. Main outcome measures: Evaluation of CI markers as prognostic markers in AL and MDS. Results: We included B-cell ALL (35), AML (11), MDS (04), relapse of AL (12), and remission of AL (116). All CI markers were significantly increased in AL and MDS compared to the remission group. All CI markers were significantly higher in non-responders to therapy than in responders. In regression analysis, the median (IQR) values of CS and NH were significantly higher among non-survivors than survivors. Conclusion: CI markers of morphology are significantly associated with poor prognosis, including Non-survival of the disease. These markers are easy to identify and cost-effective. We recommend incorporating morphological markers of CI in routine reporting of haematological malignancies to assist in prognostication before reports from sophisticated techniques are available. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

Author

Jackson, Alice M., Dewan, Pooja, Anand, Inder S., Bělohlávek, Jan, Bengtsson, Olof, de Boer, Rudolf A., Böhm, Michael, Boulton, David W., Chopra, Vijay K., DeMets, David L., Docherty, Kieran F., Dukát, Andrej, Greasley, Peter J., Howlett, Jonathan G., Inzucchi, Silvio E., Katova, Tzvetana, Køber, Lars, Kosiborod, Mikhail N., Langkilde, Anna Maria, Lindholm, Daniel, Ljungman, Charlotta E.A., Martinez, Felipe A., O’Meara, Eileen, Sabatine, Marc S., Sjöstrand, Mikaela, Solomon, Scott D., Tereshchenko, Sergey, Verma, Subodh, Jhund, Pardeep S., and McMurray, John J.V.

Published
2020
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43. Sex-Related Differences in Heart Failure With Preserved Ejection Fraction

Author

Dewan, Pooja, Rørth, Rasmus, Raparelli, Valeria, Campbell, Ross T., Shen, Li, Jhund, Pardeep S., Petrie, Mark C., Anand, Inder S., Carson, Peter E., Desai, Akshay S., Granger, Christopher B., Køber, Lars, Komajda, Michel, McKelvie, Robert S., O’Meara, Eileen, Pfeffer, Marc A., Pitt, Bertram, Solomon, Scott D., Swedberg, Karl, Zile, Michael R., and McMurray, John J.V.

Published
2019
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