Risk Marker Fatigue—Is There an Actionable Outcome?
Risk Marker Fatigue—Is There an Actionable Outcome?
Shah, Sanjiv J.
2021-01-18 00:00:00
During the past several decades, a large and growing number of studies have examined the association between potential risk markers and adverse outcomes in patients with cardiovascular diseases, including heart failure with preserved ejection fraction (HFpEF). Identification of novel risk markers in clinical syndromes such as HFpEF is important because it may (1) elucidate novel biological mechanisms, (2) inform pathophysiology of disease progression, (3) identify potential therapeutic targets, and/or (4) assist with risk prediction. In this issue of JAMA Cardiology, Segar and colleagues1 report that in patients with HFpEF who were enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial, visit-to-visit variability in kidney function and electrolytes was associated with adverse outcomes. However, as noted by the authors (and examined in their sensitivity analyses), there are several potential limitations to their study, the most important of which is reverse causation. In clinical practice, sicker patients with HFpEF are more likely to undergo medication changes and adjustments and therefore could have greater variability of kidney function and electrolytes for this reason alone. The authors adjusted for interim medication changes and found that doing so did not eliminate the observed associations. Nevertheless, questions persist about the potential for reverse causation and the true role of visit-to-visit variability in kidney function and electrolytes in leading to adverse outcomes. Given the findings of the analysis by Segar et al,1 it is tempting to consider the application of variability measures in clinical practice via the electronic health record (eg, automated alerts for increased variability in basic metabolic panel laboratory measures) or via at-home fingerstick electrolyte and kidney function measures (currently under development).2 Such technology could be coupled with wearable sensors (eg, heart rate, blood pressure, pulse oximetry, body position, accelerometry, heart sounds, and electrocardiography) to provide novel multidimensional risk assessment in the future. However, although the secondary analysis of the TOPCAT trial by Segar et al1 is timely, interesting, and novel, and the potential for novel remote monitoring compelling, it is yet another in the long list of risk marker studies for HFpEF. For the practitioner, risk marker fatigue sets in, prompting the question, “Is there an actionable outcome?” With numerous available ways to risk stratify patients with HFpEF, it will be increasingly important to conduct follow-up studies to confirm the findings of risk marker association studies and explore potential mechanisms underlying associations and possible therapeutic options. It may be that patients with increased visit-to-visit variability in kidney function and electrolytes have the cardiorenal syndrome even when the estimated glomerular filtration rate is normal and could benefit from implantable hemodynamic monitoring to guide therapy.3 The steady stream of risk marker studies will no doubt continue to populate the medical literature, but we should challenge ourselves to take these studies forward to investigate fundamental mechanisms underlying the observed associations and develop novel therapeutics to address the findings; otherwise, studies such as that of Segar et al1 are bound to be an exercise in futility. Back to top Article Information Published Online: November 18, 2020. doi:10.1001/jamacardio.2020.5616 Corresponding Author: Sanjiv J. Shah, MD, Bluhm Cardiovascular Institute and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Ste 730, Chicago, IL 60611 (sanjiv.shah@northwestern.edu). Conflict of Interest Disclosures: Dr Shah reported receiving grants from Corvia; grants and personal fees from AstraZeneca, Actelion, Novartis, and Pfizer; and personal fees from Abbott, Axon Therapies, Bayer, Boehringer-Ingelhheim, Bristol Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, GSK, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novo Nordisk, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics during the conduct of the study. References 1. Segar MW, Patel RB, Patel KV, et al. Association of visit-to-visit variability in kidney function and serum electrolyte indexes with risk of adverse clinical outcomes among patients with heart failure with preserved ejection fraction. JAMA Cardiol. Published online November 18, 2020. doi:10.1001/jamacardio.2020.5592Google Scholar 2. Rossignol P, Coats AJ, Chioncel O, Spoletini I, Rosano G. Renal function, electrolytes, and congestion monitoring in heart failure. Eur Heart J Suppl. 2019;21(suppl M):M25-M31. doi:10.1093/eurheartj/suz220 PubMedGoogle ScholarCrossref 3. Adamson PB, Abraham WT, Bourge RC, et al. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail. 2014;7(6):935-944. doi:10.1161/CIRCHEARTFAILURE.113.001229 PubMedGoogle ScholarCrossref
http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.pngJAMA CardiologyAmerican Medical Associationhttp://www.deepdyve.com/lp/american-medical-association/risk-marker-fatigue-is-there-an-actionable-outcome-g910isx0PV
Risk Marker Fatigue—Is There an Actionable Outcome?
Risk Marker Fatigue—Is There an Actionable Outcome?
Abstract
During the past several decades, a large and growing number of studies have examined the association between potential risk markers and adverse outcomes in patients with cardiovascular diseases, including heart failure with preserved ejection fraction (HFpEF). Identification of novel risk markers in clinical syndromes such as HFpEF is important because it may (1) elucidate novel biological mechanisms, (2) inform pathophysiology of disease progression, (3) identify potential therapeutic...
During the past several decades, a large and growing number of studies have examined the association between potential risk markers and adverse outcomes in patients with cardiovascular diseases, including heart failure with preserved ejection fraction (HFpEF). Identification of novel risk markers in clinical syndromes such as HFpEF is important because it may (1) elucidate novel biological mechanisms, (2) inform pathophysiology of disease progression, (3) identify potential therapeutic targets, and/or (4) assist with risk prediction. In this issue of JAMA Cardiology, Segar and colleagues1 report that in patients with HFpEF who were enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial, visit-to-visit variability in kidney function and electrolytes was associated with adverse outcomes. However, as noted by the authors (and examined in their sensitivity analyses), there are several potential limitations to their study, the most important of which is reverse causation. In clinical practice, sicker patients with HFpEF are more likely to undergo medication changes and adjustments and therefore could have greater variability of kidney function and electrolytes for this reason alone. The authors adjusted for interim medication changes and found that doing so did not eliminate the observed associations. Nevertheless, questions persist about the potential for reverse causation and the true role of visit-to-visit variability in kidney function and electrolytes in leading to adverse outcomes. Given the findings of the analysis by Segar et al,1 it is tempting to consider the application of variability measures in clinical practice via the electronic health record (eg, automated alerts for increased variability in basic metabolic panel laboratory measures) or via at-home fingerstick electrolyte and kidney function measures (currently under development).2 Such technology could be coupled with wearable sensors (eg, heart rate, blood pressure, pulse oximetry, body position, accelerometry, heart sounds, and electrocardiography) to provide novel multidimensional risk assessment in the future. However, although the secondary analysis of the TOPCAT trial by Segar et al1 is timely, interesting, and novel, and the potential for novel remote monitoring compelling, it is yet another in the long list of risk marker studies for HFpEF. For the practitioner, risk marker fatigue sets in, prompting the question, “Is there an actionable outcome?” With numerous available ways to risk stratify patients with HFpEF, it will be increasingly important to conduct follow-up studies to confirm the findings of risk marker association studies and explore potential mechanisms underlying associations and possible therapeutic options. It may be that patients with increased visit-to-visit variability in kidney function and electrolytes have the cardiorenal syndrome even when the estimated glomerular filtration rate is normal and could benefit from implantable hemodynamic monitoring to guide therapy.3 The steady stream of risk marker studies will no doubt continue to populate the medical literature, but we should challenge ourselves to take these studies forward to investigate fundamental mechanisms underlying the observed associations and develop novel therapeutics to address the findings; otherwise, studies such as that of Segar et al1 are bound to be an exercise in futility. Back to top Article Information Published Online: November 18, 2020. doi:10.1001/jamacardio.2020.5616 Corresponding Author: Sanjiv J. Shah, MD, Bluhm Cardiovascular Institute and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Ste 730, Chicago, IL 60611 (sanjiv.shah@northwestern.edu). Conflict of Interest Disclosures: Dr Shah reported receiving grants from Corvia; grants and personal fees from AstraZeneca, Actelion, Novartis, and Pfizer; and personal fees from Abbott, Axon Therapies, Bayer, Boehringer-Ingelhheim, Bristol Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, GSK, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novo Nordisk, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics during the conduct of the study. References 1. Segar MW, Patel RB, Patel KV, et al. Association of visit-to-visit variability in kidney function and serum electrolyte indexes with risk of adverse clinical outcomes among patients with heart failure with preserved ejection fraction. JAMA Cardiol. Published online November 18, 2020. doi:10.1001/jamacardio.2020.5592Google Scholar 2. Rossignol P, Coats AJ, Chioncel O, Spoletini I, Rosano G. Renal function, electrolytes, and congestion monitoring in heart failure. Eur Heart J Suppl. 2019;21(suppl M):M25-M31. doi:10.1093/eurheartj/suz220 PubMedGoogle ScholarCrossref 3. Adamson PB, Abraham WT, Bourge RC, et al. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail. 2014;7(6):935-944. doi:10.1161/CIRCHEARTFAILURE.113.001229 PubMedGoogle ScholarCrossref
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