Joyce Njoroge, MD

All Publications

• High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life. JAMA cardiology Ramonfaur, D., Buckley, L. F., Arthur, V., Yang, Y., Claggett, B. L., Ndumele, C. E., Walker, K. A., Austin, T., Odden, M. C., Floyd, J. S., Sanders-van Wijk, S., Njoroge, J., Kizer, J. R., Kitzman, D., Konety, S. H., Schrack, J., Liu, F., Windham, B. G., Palta, P., Coresh, J., Yu, B., Shah, A. M. 2024

  Abstract

  Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023.Protein aptamers, measured at study V3 and V5.Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty.A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF.In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

  View details for DOI 10.1001/jamacardio.2024.1178

  View details for PubMedID 38809565

• Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF. JACC. Heart failure Lanfear, D. E., Njoroge, J. N., Adams, K. F., Anand, I., Fang, J. C., Ramires, F., Sliwa-Hahnle, K., Badat, A., Burgess, L., Gorodeski, E. Z., Williams, C., Diaz, R., Felker, G. M., McMurray, J. J., Metra, M., Solomon, S., Miao, Z. M., Claggett, B. L., Heitner, S. B., Kupfer, S., Malik, F. I., Teerlink, J. R. 2023; 11 (5): 569-579

  Abstract

  Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic.The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients.In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants.Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro-B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs -0.7 mm Hg, P for interaction = 0.02).GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.

  View details for DOI 10.1016/j.jchf.2022.11.021

  View details for PubMedID 36881396

• Nurturing Diverse Generations of the Medical Workforce for Success With Authenticity: An Association of Black Cardiologists' Roundtable. Circulation. Cardiovascular quality and outcomes Haynes, N. A., Johnson, M., Lewsey, S. C., Alexander, K. M., Anstey, D. E., Dillenburg, T., Njoroge, J. N., Gordon, D., Ofili, E. O., Yancy, C. W., Albert, M. A. 2023: e009032

  Abstract

  The COVID-19 pandemic exposed the consequences of systemic racism in the United States with Black, Hispanic, and other racial and ethnic diverse populations dying at disproportionately higher rates than White Americans. Addressing the social and health disparities amplified by COVID-19 requires in part restructuring of the healthcare system, particularly the diversity of the healthcare workforce to better reflect that of the US population. In January 2021, the Association of Black Cardiologists hosted a virtual roundtable designed to discuss key issues pertaining to medical workforce diversity and to identify strategies aimed at improving racial and ethnic diversity in medical school, graduate medical education, faculty, and leadership positions. The Nurturing Diverse Generations of the Medical Workforce for Success with Authenticity roundtable brought together diverse stakeholders and champions of diversity and inclusion to discuss innovative ideas, solutions, and opportunities to address workforce diversification.

  View details for DOI 10.1161/CIRCOUTCOMES.122.009032

  View details for PubMedID 36603043

• Chapter 33: Cardiovascular Disease in Pregnancy Current Diagnosis and Treatment: Cardiology Tolstrup , K., Njoroge, J. McGraw Hill. 2023; 6th
• Circulating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study JOURNAL OF THE AMERICAN HEART ASSOCIATION Njoroge, J. N., Tressel, W., Biggs, M. L., Matsumoto, A. M., Smith, N. L., Rosenberg, E., Hirsch, C. H., Gottdiener, J. S., Mukamal, K. J., Kizer, J. R. 2022; 11 (21): e026953

  Abstract

  Background Circulating androgen concentrations in men decline with age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship has been reported for low total testosterone and incident heart failure (HF) but remains unstudied for free testosterone or the more potent androgen dihydrotestosterone (DHT). We hypothesized that total/free testosterone are inversely related, sex hormone-binding globulin is positively related, and total/free DHT bear a U-shaped relationship with incident HF. Methods and Results In a sample of men from the CHS (Cardiovascular Health Study) without atherosclerotic cardiovascular disease or HF, serum testosterone and DHT concentrations were measured by liquid chromatography-tandem mass spectrometry, and sex hormone-binding globulin by immunoassay. Free testosterone or DHT was calculated from total testosterone or total DHT, sex hormone-binding globulin, and albumin. We used Cox regression to estimate relative risks of HF after adjustment for potential confounders. In 1061 men (aged 76±5 years) followed for a median of 9.6 years, there were 368 HF events. After adjustment, lower calculated free testosterone was significantly associated with higher risk of HF (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]). Risk estimates for total testosterone (HR, 1.12 [95% CI, 0.99-1.26]), total DHT (HR, 1.10 [95% CI, 0.97-1.24]), calculated free dihydrotestosterone (HR, 1.09 [95% CI, 0.97-1.23]), and sex hormone-binding globulin (HR, 1.07 [95% CI, 0.95-1.21]) were directionally similar but not statistically significant. Conclusions Calculated free testosterone was inversely associated with incident HF, suggesting a contribution of testosterone deficiency to HF incidence among older men. Additional research is necessary to determine whether testosterone replacement therapy might be an effective strategy to lower HF risk in older men.

  View details for DOI 10.1161/JAHA.122.026953

  View details for Web of Science ID 000877032700025

  View details for PubMedID 36285783

  View details for PubMedCentralID PMC9673636

• Hospitalized Patients With COVID-19 Have Higher Plasma Aldosterone-Renin Ratio and Lower ACE Activity Than Controls JOURNAL OF THE ENDOCRINE SOCIETY Parikh, N., Arowolo, F., Durstenfeld, M. S., Nah, G., Njoroge, J., Vittinghoff, E., Long, C. S., Ganz, P., Pearce, D., Hsue, P., Wu, A. S., Hajizadeh, N., Liu, K. D., Lynch, K. L. 2022; 6 (12): bvac144

  Abstract

  SARS-CoV-2 infects cells via the angiotensin converting enzyme 2 (ACE2) receptor, whose downstream effects "counterbalance" the classical renin angiotensin aldosterone system (RAAS).We aimed to determine to what extent circulating RAAS biomarker levels differ in persons with and without COVID-19 throughout the disease course.We measured classical (renin, aldosterone, aldosterone/renin ratio [ARR], Ang2, ACE activity) and nonclassical (ACE2, Ang1,7) RAAS biomarkers in hospitalized COVID-19 patients vs SARS-CoV-2 negative controls. We compared biomarker levels in cases with contemporaneous samples from control patients with upper respiratory symptoms and a negative SARS-CoV-2 PCR test. To assess RAAS biomarker changes during the course of COVID-19 hospitalization, we studied cases at 2 different times points ∼ 12 days apart. We employed age- and sex-adjusted generalized linear models and paired/unpaired t tests.Mean age was 51 years for both cases (31% women) and controls (50% women). ARR was higher in the first sample among hospitalized COVID-19 patients vs controls (P = 0.02). ACE activity was lower among cases at their first sample vs controls (P = <0.001). ACE2 activity, Ang 1,7, and Ang2 did not differ at the 2 COVID-19 case time points and they did not differ in COVID-19 cases vs controls. Additional adjustment for body mass index (BMI) did not change our findings.High ARR, independent of BMI, may be a risk marker for COVID-19 hospitalization. Serum ACE activity was lower in patients with COVID-19 vs controls at the beginning of their hospitalization and then increased to similar levels as controls, possibly due to lung injury, which improved with inpatient disease management.

  View details for DOI 10.1210/jendso/bvac144

  View details for Web of Science ID 000877757100003

  View details for PubMedID 36338506

  View details for PubMedCentralID PMC9619433

• Association of immune cell subsets with incident heart failure in two population-based cohorts ESC HEART FAILURE Sinha, A., Sitlani, C. M., Doyle, M. F., Fohner, A. E., Buzkova, P., Floyd, J. S., Huber, S. A., Olson, N. C., Njoroge, J. N., Kizer, J. R., Delaney, J. A., Shah, S. S., Tracy, R. P., Psaty, B., Feinstein, M. 2022; 9 (6): 4177-4188

  Abstract

  Circulating inflammatory markers are associated with incident heart failure (HF), but prospective data on associations of immune cell subsets with incident HF are lacking. We determined the associations of immune cell subsets with incident HF as well as HF subtypes [with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF)].Peripheral blood immune cell subsets were measured in adults from the Multi-Ethnic Study of Atherosclerosis (MESA) and Cardiovascular Health Study (CHS). Cox proportional hazard models adjusted for demographics, HF risk factors, and cytomegalovirus serostatus were used to evaluate the association of the immune cell subsets with incident HF. The average age of the MESA cohort at the time of immune cell measurements was 63.0 ± 10.4 years with 51% women, and in the CHS cohort, it was 79.6 ± 4.4 years with 62% women. In the meta-analysis of CHS and MESA, a higher proportion of CD4+ T helper (Th) 1 cells (per one standard deviation) was associated with a lower risk of incident HF [hazard ratio (HR) 0.91, (95% CI 0.83-0.99), P = 0.03]. Specifically, higher proportion of CD4+ Th1 cells was significantly associated with a lower risk of HFrEF [HR 0.73, (95% CI 0.62-0.85), <0.001] after correction for multiple testing. No association was observed with HFpEF. No other cell subsets were associated with incident HF.We observed that higher proportions of CD4+ Th1 cells were associated with a lower risk of incident HFrEF in two distinct population-based cohorts, with similar effect sizes in both cohorts demonstrating replicability. Although unexpected, the consistency of this finding across cohorts merits further investigation.

  View details for DOI 10.1002/ehf2.14140

  View details for Web of Science ID 000852970300001

  View details for PubMedID 36097332

  View details for PubMedCentralID PMC9773780

• Emerging Genotype-Phenotype Associations in Dilated Cardiomyopathy. Current cardiology reports Njoroge, J. N., Mangena, J. C., Aribeana, C., Parikh, V. N. 2022

  Abstract

  The disease burden of inherited dilated cardiomyopathy (DCM) is large and likely underestimated. This population stands to benefit immensely from therapeutic approaches tailored to the underlying genetic causes. Here, we review recent advances in understanding novel genotype-phenotype relationships and how these can improve the care of patients with inherited DCM.In the last several years, discovery of novel DCM-associated genes, gene-specific DCM outcomes, and nuanced information about variant-environment interactions have advanced our understanding of inherited DCM. Specifically, novel associations of genes with specific clinical phenotypes can help to assess sudden cardiac death risk and guide counseling around behavioral and environmental exposures that may worsen disease. Important expansions of the current genotype-phenotype profiling include the newly DCM-associated FLNC variant, prognostically significant LMNA, DSP inflammatory cardiomyopathy, and the highly penetrant features of RBM20 variants as well as the role of TTN variants in compounding the effects of environmental factors on toxin-mediated DCM. Future directions to improve diagnostic accuracy and prognostic improvement in DCM will center not just on identification of new genes, but also on understanding the interaction of known and novel variants in known DCM genes with patient genetic background and environment.

  View details for DOI 10.1007/s11886-022-01727-z

  View details for PubMedID 35900642

• The shock team: a multidisciplinary approach to early patient phenotyping and appropriate care escalation in cardiogenic shock CURRENT OPINION IN CARDIOLOGY Brusca, S. B., Caughron, H., Njoroge, J. N., Cheng, R., O'Brien, C. G., Barnett, C. F. 2022; 37 (3): 241-249

  Abstract

  Cardiogenic shock (CS) is a highly morbid condition with mortality remaining greater than 30% despite improved pathophysiologic understanding and access to mechanical circulatory support (MCS). In response, shock teams modeled on successful multidisciplinary care structures for other diseases are being implemented nationwide.Primary data supporting a benefit of shock team implementation on patient outcomes are relatively limited and entirely observational. Four single-center before-and-after studies and one multicenter registry study have demonstrated improved outcomes in patients with CS, potentially driven by increased pulmonary artery catheter (PAC) utilization and earlier (and more appropriate) initiation of MCS. Shock teams are also supported by a growing body of literature recognizing the independent benefit of the interventions they seek to implement, including patient phenotyping with PAC use and an algorithmic approach to CS care. Though debated, MCS is also highly likely to improve CS outcomes when applied appropriately, which further supports a multidisciplinary shock team approach to patient and device selection.Shock teams likely improve patient outcomes by facilitating early patient phenotyping and appropriate intervention. Institutions should strongly consider adopting a multidisciplinary shock team approach to CS care, though additional data supporting these interventions are needed.

  View details for DOI 10.1097/HCO.0000000000000967

  View details for Web of Science ID 000799949500008

  View details for PubMedID 35612936

• We Need a Bigger Tent: Expanding the Reach and Coverage of Training in Advanced Heart Failure American College of Cardiology Expert Analysis Belkin , M., Njoroge, J., Reza, N. 2022
• How Cardiovascular Disease Fellows Can Promote Diversity and Inclusion in Cardiology Doing Our Part JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Njoroge, J. N., Youmans, Q. R., Chuzi, S. 2021; 78 (11): 1188-1191

  View details for DOI 10.1016/j.jacc.2021.07.012

  View details for Web of Science ID 000693560900011

  View details for PubMedID 34503686

• Racial and Ethnic Disparities in Transthyretin Cardiac Amyloidosis. Current cardiovascular risk reports Spencer-Bonilla, G., Njoroge, J. N., Pearson, K., Witteles, R. M., Aras, M. A., Alexander, K. M. 2021; 15 (6)

  Abstract

  Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease that disproportionately affects older adults and people of African descent. This review discusses current knowledge regarding racial and ethnic disparities in the diagnosis and management of ATTR-CM.Historically, ATTR-CM was thought to be a rare cause of heart failure. Recent evidence has shown that ATTR-CM is more common among older adults, men, and people of African descent. In addition, significant geographic variation exists in the identification of amyloid cardiomyopathy. Despite the high burden of ATTR-CM among Black individuals, most clinical data for ATTR-CM are from North America and Europe. Moreover, only a minority of clinical trial participants thus far have been Black patients. In addition to racial differences, socioeconomic disparities may be further compounded by the potentially prohibitive cost and limited accessibility of disease-modifying ATTR therapies.ATTR-CM is an important cause of heart failure that disproportionately affects people of African descent. Efforts to promote earlier identification of ATTR-CM in general practice will likely improve clinical outcomes for all groups. Future trials should strive to enroll a higher proportion of Black patients. Furthermore, enhanced efforts are warranted to improve treatment accessibility among racial and ethnic minority groups that may be more likely to be affected by ATTR-CM.

  View details for DOI 10.1007/s12170-021-00670-y

  View details for PubMedID 35280930

  View details for PubMedCentralID PMC8916707

• Pathophysiology and Therapeutic Approaches to Acute Decompensated Heart Failure CIRCULATION RESEARCH Njoroge, J. N., Teerlink, J. R. 2021; 128 (10): 1468-1486

  Abstract

  Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.

  View details for DOI 10.1161/CIRCRESAHA.121.318186

  View details for Web of Science ID 000650958900005

  View details for PubMedID 33983837

  View details for PubMedCentralID PMC8126502

• Disproportionate left atrial myopathy in heart failure with preserved ejection fraction among participants of the PROMIS-HFpEF study SCIENTIFIC REPORTS Patel, R. B., Lam, C. P., Svedlund, S., Saraste, A., Hage, C., Tan, R., Beussink-Nelson, L., Tromp, J., Sanchez, C., Njoroge, J., Swat, S. A., Faxen, U., Fermer, M., Venkateshvaran, A., Gan, L., Lund, L. H., Shah, S. J. 2021; 11 (1): 4885

  Abstract

  Impaired left atrial (LA) function in heart failure with preserved ejection fraction (HFpEF) is associated with adverse outcomes. A subgroup of HFpEF may have LA myopathy out of proportion to left ventricular (LV) dysfunction; therefore, we sought to characterize HFpEF patients with disproportionate LA myopathy. In the prospective, multicenter, Prevalence of Microvascular Dysfunction in HFpEF study, we defined disproportionate LA myopathy based on degree of LA reservoir strain abnormality in relation to LV myopathy (LV global longitudinal strain [GLS]) by calculating the residuals from a linear regression of LA reservoir strain and LV GLS. We evaluated associations of disproportionate LA myopathy with hemodynamics and performed a plasma proteomic analysis to identify proteins associated with disproportionate LA myopathy; proteins were validated in an independent sample. Disproportionate LA myopathy correlated with better LV diastolic function but was associated with lower stroke volume reserve after passive leg raise independent of atrial fibrillation (AF). Additionally, disproportionate LA myopathy was associated with higher pulmonary artery systolic pressure, higher pulmonary vascular resistance, and lower coronary flow reserve. Of 248 proteins, we identified and validated 5 proteins (involved in cardiomyocyte stretch, extracellular matrix remodeling, and inflammation) that were associated with disproportionate LA myopathy independent of AF. In HFpEF, LA myopathy may exist out of proportion to LV myopathy. Disproportionate LA myopathy is a distinct HFpEF subtype associated with worse hemodynamics and a distinct proteomic signature, independent of AF.

  View details for DOI 10.1038/s41598-021-84133-9

  View details for Web of Science ID 000625352000004

  View details for PubMedID 33649383

  View details for PubMedCentralID PMC7921666

• Working Agenda for Black Mothers A Position Paper From the Association of Black Cardiologists on Solutions to Improving Black Maternal Health CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES Bond, R. M., Gaither, K., Nasser, S. A., Albert, M. A., Ferdinand, K. C., Njoroge, J. N., Parapid, B., Hayes, S. N., Pegus, C., Sogade, B., Grodzinsky, A., Watson, K. E., McCullough, C. A., Ofili, E., Assoc Black Cardiologists 2021; 14 (2): 223-234

  Abstract

  Following decades of decline, maternal mortality began to rise in the United States around 1990-a significant departure from the world's other affluent countries. By 2018, the same could be seen with the maternal mortality rate in the United States at 17.4 maternal deaths per 100 000 live births. When factoring in race/ethnicity, this number was more than double among non-Hispanic Black women who experienced 37.1 maternal deaths per 100 000 live births. More than half of these deaths and near deaths were from preventable causes, with cardiovascular disease being the leading one. In an effort to amplify the magnitude of this epidemic in the United States that disproportionately plagues Black women, on June 13, 2020, the Association of Black Cardiologists hosted the Black Maternal Heart Health Roundtable-a collaborative task force to tackle the maternal health crisis in the Black community. The roundtable brought together diverse stakeholders and champions of maternal health equity to discuss how innovative ideas, solutions and opportunities could be implemented, while exploring additional ways attendees could address maternal health concerns within the health care system. The discussions were intended to lead the charge in reducing maternal morbidity and mortality through advocacy, education, research, and collaborative efforts. The goal of this roundtable was to identify current barriers at the community, patient, and clinician level and expand on the efforts required to coordinate an effective approach to reducing these statistics in the highest risk populations. Collectively, preventable maternal mortality can result from or reflect violations of a variety of human rights-the right to life, the right to freedom from discrimination, and the right to the highest attainable standard of health. This is the first comprehensive statement on this important topic. This position paper will generate further research in disparities of care and promote the interest of others to pursue strategies to mitigate maternal mortality.

  View details for DOI 10.1161/CIRCOUTCOMES.120.007643

  View details for Web of Science ID 000639301400013

  View details for PubMedID 33563007

  View details for PubMedCentralID PMC7887097

• Dismantling Structural Discrimination in Cardiology Fellowship Recruitment. JAMA network open Njoroge, J., Rodriguez, F., Albert, M. A. 2021; 4 (1): e2031473

  View details for DOI 10.1001/jamanetworkopen.2020.31473

  View details for PubMedID 33427879

• Racial and Ethnic Disparities in Transthyretin Cardiac Amyloidosis Curr Cardiovasc Risk Rep Spencer-Bonilla, G., Njoroge, J. N., Pearson, K., Witteles, R. M., Aras, M. A., Alexander, K. M. 2021

  View details for DOI 10.1007/s12170-021-00670-y

• Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction Results From the PROMIS-HFpEF Study CIRCULATION Sanders-van Wijk, S., Tromp, J., Beussink-Nelson, L., Hage, C., Svedlund, S., Saraste, A., Swat, S. A., Sanchez, C., Njoroge, J., Tan, R., Fermer, M., Gan, L., Lund, L. H., Lam, C. P., Shah, S. J. 2020; 142 (21): 2029-2044

  Abstract

  A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm.In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure.Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e' ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%-35%), E/e' ratio (18%-29%), tricuspid regurgitation velocity (27%-41%), and tricuspid annular plane systolic excursion (13%) (P<0.05 for all), but not right ventricular free wall strain. TNFR1 (tumor necrosis factor receptor 1), UPAR (urokinase plasminogen activator receptor), IGFBP7 (insulin-like growth factor binding protein 7), and GDF-15 (growth differentiation factor-15) were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort.Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.

  View details for DOI 10.1161/CIRCULATIONAHA.120.045810

  View details for Web of Science ID 000592103900008

  View details for PubMedID 33034202

  View details for PubMedCentralID PMC7686082

• Cardiovascular Implications and Therapeutic Considerations in COVID-19 Infection CARDIOLOGY AND THERAPY Judson, G. L., Kelemen, B. W., Njoroge, J. N., Mahadevan, V. S. 2020; 9 (2): 293-305

  Abstract

  The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has profoundly impacted all fields of medicine. Infection with SARS-CoV-2 and the resulting coronavirus of 2019 (COVID-19) syndrome has multiorgan effects. The pandemic has united researchers from bench to bedside in attempts to understand the pathophysiology of the disease and define optimal treatment strategies. Cardiovascular disease is highly prevalent and a leading cause of death across gender, race, and ethnic groups. As the pandemic spreads, there is increasing concern about the cardiovascular effects of the viral infection and the interaction of infection with existing cardiovascular disease. Additionally, there are concerns about the cardiac effects of the numerous treatment agents under study. It will be essential for cardiologists to understand the interplay between underlying cardiac comorbidities, acute cardiovascular effects of COVID-19 disease, and adverse effects of new treatments. Here we describe emerging evidence of the epidemiology of SARS-CoV-2 infection and underlying cardiovascular disease, the evidence for direct myocardial injury in SARS-CoV-2 infection, the specific presentations of cardiovascular involvement by SARS-CoV-2, and the cardiac effects of emerging treatments.

  View details for DOI 10.1007/s40119-020-00184-5

  View details for Web of Science ID 000541364300002

  View details for PubMedID 32535752

  View details for PubMedCentralID PMC7292941

• Understanding Health Disparities in Cardiovascular Diseases in Pregnancy Among Black Women: Prevalence, Preventive Care, and Peripartum Support Networks CURRENT CARDIOVASCULAR RISK REPORTS Njoroge, J. N., Parikh, N. 2020; 14 (7)

  View details for DOI 10.1007/s12170-020-00641-9

  View details for Web of Science ID 000535782800001

• Systolic time intervals in patients with heart failure: time to teach new dogs old tricks EUROPEAN JOURNAL OF HEART FAILURE Njoroge, J. N., Teerlink, J. R. 2020; 22 (7): 1183-1185

  View details for DOI 10.1002/ejhf.1725

  View details for Web of Science ID 000513169000001

  View details for PubMedID 32056362

  View details for PubMedCentralID PMC7540403

• Subsequent Pregnancy in Peripartum Cardiomyopathy- Is the Answer Always No? Njoroge, J., Okwuosa, I. S., Mendelson, M. A. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2019: S96

  View details for DOI 10.1016/j.cardfail.2019.07.275

  View details for Web of Science ID 000482698000259

• Expanded algorithm for managing patients with acute decompensated heart failure HEART FAILURE REVIEWS Njoroge, J. N., Cheema, B., Ambrosy, A. P., Greene, S. J., Collins, S. P., Vaduganathan, M., Mebazaa, A., Chioncel, O., Butler, J., Gheorghiade, M. 2018; 23 (4): 597-607

  Abstract

  Heart failure is a complex disease process, the manifestation of various cardiac and noncardiac abnormalities. General treatment approaches for heart failure have remained the same over the past decades despite the advent of novel therapies and monitoring modalities. In the same vein, the readmission rates for heart failure patients remain high and portend a poor prognosis for morbidity and mortality. In this context, development and implementation of improved algorithms for assessing and treating HF patients during hospitalization remains an unmet need. We propose an expanded algorithm for both monitoring and treating patients admitted for acute decompensated heart failure with the goal to improve post-discharge outcomes and decrease rates of rehospitalizations.

  View details for DOI 10.1007/s10741-018-9697-9

  View details for Web of Science ID 000435806900011

  View details for PubMedID 29611010

  View details for PubMedCentralID PMC6551605

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  View details for Web of Science ID 000359392200274

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  View details for Web of Science ID 000340214100019

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  View details for Web of Science ID 000340214100071