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4. Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure

Author

Amatruda, Jonathan G, Scherzer, Rebecca, Rao, Veena S, Ivey-Miranda, Juan B, Shlipak, Michael G, Estrella, Michelle M, and Testani, Jeffrey M

Subjects
Cardiovascular, Hypertension, Heart Disease, Clinical Research, Cardiorenal syndrome, diuretic resistance, heart failure, loop diuretics, natriuresis, renin-angiotensin-aldosterone system, torsemide
Abstract

Rationale & objectiveHeart failure treatment relies on loop diuretics to induce natriuresis and decongestion, but the therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response.Study designObservational cohort.Setting & populationEuvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment.PredictorsPlasma total renin, active renin, angiotensinogen, and aldosterone levels. Urine total renin and angiotensinogen levels.OutcomesSodium output per doubling of diuretic dose and fractional excretion of sodium per doubling of diuretic dose.Analytical approachRobust linear regression models estimated the associations of each RAAS intermediate with outcomes.ResultsThe analysis included 56 participants, and the median age was 65 years; 50% were women, and 41% were Black. The median home diuretic dose was 80-mg furosemide equivalents. In unadjusted and multivariable-adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency. Higher plasma total renin remained significantly associated with lower sodium output per doubling of diuretic dose (β = -0.41 [-0.76, -0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower fractional excretion of sodium per doubling of diuretic dose (β = -0.48 [-0.83, -0.14] and β = -0.51 [-0.95, -0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations.LimitationsSmall sample size; highly selected participants; associations may not be causal.ConclusionsAmong multiple measures of RAAS activation, higher plasma total and active renin levels were consistently associated with lower diuretic response. These findings highlight the potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.

Published
2022

9. Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects

Author

Rao, Veena S., Ivey-Miranda, Juan B., Cox, Zachary L., Moreno-Villagomez, Julieta, Maulion, Christopher, Bellumkonda, Lavanya, Chang, John, Field, M. Paul, Wiederin, Daniel R., Butler, Javed, Collins, Sean P., Turner, Jeffrey M., Wilson, F. Perry, Inzucchi, Silvio E., Wilcox, Christopher S., Ellison, David H., and Testani, Jeffrey M.

Published
2024
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10. Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design

Author

Cox, Zachary L., Siddiqi, Hasan K., Stevenson, Lynne W., Bales, Brian, Han, Jin H., Hart, Kimberly, Imhoff, Brant, Ivey-Miranda, Juan B., Jenkins, Cathy A., Lindenfeld, JoAnn, Shotwell, Matthew S., Miller, Karen F., Ooi, Henry, Rao, Veena S., Schlendorf, Kelly, Self, Wesley H., Siew, Edward D., Storrow, Alan, Walsh, Ryan, Wrenn, Jesse O., Testani, Jeffrey M., and Collins, Sean P.

Published
2023
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11. Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events: A Post Hoc Analysis of SOLOIST-WHF

Author

Pitt, Bertram, Bhatt, Deepak L., Szarek, Michael, Cannon, Christopher P., Leiter, Lawrence A., McGuire, Darren K., Lewis, Julia B., Riddle, Matthew C., Voors, Adriaan A., Metra, Marco, Lund, Lars H., Komajda, Michel, Testani, Jeffrey M., Wilcox, Christopher S., Ponikowski, Piotr, Lopes, Renato D., Ezekowitz, Justin A., Sun, Franklin, Davies, Michael J., Verma, Subodh, Kosiborod, Mikhail N., and Steg, Ph. Gabriel

Published
2023
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16. Changes in the Inferior Vena Cava Are More Sensitive Than Venous Pressure During Fluid Removal: A Proof-of-Concept Study

Author

Posada-Martinez, EDITH L., COX, ZACHARY L., CANO-NIETO, MARIANA M., IBARRA-MARQUEZ, NIKEIN D., MORENO-VILLAGOMEZ, JULIETA, GUDIÑO-BRAVO, PEDRO, ARIAS-GODINEZ, JOSE A., LOPEZ-GIL, SALVADOR, MADERO, MAGDALENA, RAO, VEENA S., MEBAZAA, ALEXANDRE, BURKHOFF, DANIEL, COWIE, MARTIN R., FUDIM, MARAT, DAMMAN, KEVIN, BORLAUG, BARRY A., TESTANI, JEFFREY M., and IVEY-MIRANDA, JUAN B.

Published
2023
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17. Effect on Survival of Concurrent Hemoconcentration and Increase in Creatinine During Treatment of Acute Decompensated Heart Failure

Author

Griffin, Matthew, Rao, Veena S, Fleming, James, Raghavendra, Parinita, Turner, Jeffrey, Mahoney, Devin, Wettersten, Nicholas, Maisel, Alan, Ivey-Miranda, Juan B, Inker, Lesley, Tang, Wai Hong Wilson, Wilson, Francis Perry, and Testani, Jeffrey M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Clinical Research, Acute Disease, Aged, Biomarkers, Creatinine, Diuretics, Female, Heart Failure, Hospital Mortality, Humans, Male, Prognosis, Retrospective Studies, Survival Rate, United States, Water-Electrolyte Imbalance, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Hemoconcentration during the treatment of acute decompensated heart failure is a surrogate for plasma volume reduction and is associated with improved survival, but most definitions only allow for hemoconcentration to be determined retrospectively. An increase in serum creatinine can also be a marker of aggressive decongestion, but in isolation is not specific. Our objective was to determine if combined hemoconcentration and worsening creatinine could better identify patients that were aggressively treated and, as such, may have improved postdischarge outcomes. A total of 4,181 patients hospitalized with acute decompensated heart failure were evaluated. Those who experienced both hemoconcentration and worsening creatinine at any point had a profile consistent with aggressive in-hospital treatment and longer length of stay (p

Published
2019

21. Sodium zirconium cyclosilicate in patients with HFrEF and hyperkalemia: REALIZE-K rationale, design, and baseline characteristics

Author

Kosiborod, Mikhail N., primary, Cherney, David, additional, Connelly, Kim, additional, Desai, Akshay S., additional, Guimarães, Patrícia O., additional, Kuthi, Luca, additional, Lala-Trindade, Anuradha, additional, Madrini, Vagner, additional, Merkely, Bela, additional, Villota, Julio Nuñez, additional, Squire, Iain, additional, Testani, Jeffrey M., additional, Vaclavik, Jan, additional, Verma, Subodh, additional, Wranicz, Jerzy, additional, Dahl, Magnus, additional, Eudicone, James M., additional, Friberg, Lovisa, additional, and Petrie, Mark C., additional

Published
2024
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22. Serial direct sodium removal in patients with heart failure and diuretic resistance

Author

Rao, Veena S., primary, Ivey‐Miranda, Juan B., additional, Cox, Zachary L., additional, Moreno‐Villagomez, Julieta, additional, Ramos‐Mastache, Daniela, additional, Neville, Daniel, additional, Balkcom, Natasha, additional, Asher, Jennifer L., additional, Bellumkonda, Lavanya, additional, Bigvava, Tamar, additional, Shaburishvili, Tamaz, additional, Bartunek, Jozef, additional, Wilson, F. Perry, additional, Finkelstein, Fredrick, additional, Maulion, Christopher, additional, Turner, Jeffrey M., additional, and Testani, Jeffrey M., additional

Published
2024
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31. Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects

Author

Rao, Veena S., primary, Ivey-Miranda, Juan B., additional, Cox, Zachary L., additional, Moreno-Villagomez, Julieta, additional, Maulion, Christopher, additional, Bellumkonda, Lavanya, additional, Chang, John, additional, Field, M. Paul, additional, Wiederin, Daniel R., additional, Butler, Javed, additional, Collins, Sean P., additional, Turner, Jeffrey M., additional, Wilson, F. Perry, additional, Inzucchi, Silvio E., additional, Wilcox, Christopher S., additional, Ellison, David H., additional, and Testani, Jeffrey M., additional

Published
2023
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33. Pragmatic Design of Randomized Clinical Trials for Heart Failure: Rationale and Design of the TRANSFORM-HF Trial

Author

Adams, Kirkwood, Long, Tammy, Bhatt, Kunal, Walker, Brandon, DeWald, Tracy, Biever, Kim, Axsom, Kelly, Acosta, Ariana, Murthy, Sandhya, Camilo, Angeline, Rich, Jonathan D., Martinez, Leslie, Testani, Jeffrey M., Tainsh, Jennifer, Smith, Bryan, Bennett, Amy, Vader, Justin, Stilinovic, Stephanie, McCulloch, Michael, Musso, Iris, Skopicki, Hal, Caikauskaite, Indre, Psotka, Mitchell A., Freiler, Allen, Heroux, Alain, Kartje, Carol, Lala-Trindade, Anuradha, Julien, Lovelyne, Stevens, Gerin, Leppla, Keriann, Tang, Wilson, Fonk, Teresa, Lev, Yair, Fizgerald, Kathleen, William, Preethi, Stroster, John, Eberly, Arthur, III, Workman, Celeste, Gottlieb, Stephen, Bowers-Lash, Mary, Haught, Walter Herbert, Abath, Cynthia, Grafton, Gillian, Neaton, Kelsey, Larned, Joshua, Ortiz, Mara-Li, Tejwani, Lokesh, Villalta, Tara, Mody, Freny, Strugatsky, Svetlana, Krim, Selim, Washington, Katasha, Robinson, Monique, Norton, Nadine, Smart, Frank, Worsham, Emily, Fang, James, Goldstein, Joe, Dunlap, Stephanie, Starnes, Nancy, Adler, Alexander, Theodorof, Virginia, Bell, Adrian, Kondramashin, Aleksey, Banerjee, Dipanjan, Yee, Michael, Ruiz-Duque, Ernesto, Larew, Cynthia, Mizyed, Ahmad, Sawaya, Kara, Friedman, Dennis, Rele, Shilpa, Rommel, John, Burkhart, Janet, Arhinful, Justice, Atkinson, Sam, Goyal, Parag, Samdani, Nidha, Hall, Michael, Watson, Connie, Hummel, Scott, Wells, Joanna, Shetty, Sanjay, White, Jackie, Haas, Donald, Marchand, Colleen, Vilaro, Juan, Osman, Alfaroug, Alexy, Tamas, Dicken, Julie, Guglin, Maya, Willig, Meghan, Ferguson, Andrew, Peabody, Mark, Herre, John, McMichael, Brittany, Clark, John, Britton, Nancy, Ambrosy, Andrew P., Tan, Thida, Heitner, John, Meykler, Marcella, Meadows, Judith, Halliday, Janet, Greene, Stephen J., Velazquez, Eric J., Anstrom, Kevin J., Eisenstein, Eric L., Sapp, Shelly, Morgan, Shelby, Harding, Tina, Sachdev, Vandana, Ketema, Fassil, Kim, Dong-Yun, Desvigne-Nickens, Patrice, Pitt, Bertram, and Mentz, Robert J.

Published
2021
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34. Natriuretic Equation to Predict Loop Diuretic Response in Patients With Heart Failure

Author

Rao, Veena S., Ivey-Miranda, Juan B., Cox, Zachary L., Riello, Ralph, Griffin, Matthew, Fleming, James, Soucier, Richard, Sangkachand, Prasama, O’Brien, Margaret, LoRusso, Francine, D’Ambrosi, Julie, Churchwell, Keith, Mahoney, Devin, Bellumkonda, Lavanya, Asher, Jennifer L., Maulion, Christopher, Turner, Jeffrey M., Wilson, F. Perry, Collins, Sean P., and Testani, Jeffrey M.

Published
2021
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37. Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure Current Status and Prospects for Further Research

Author

Costanzo, Maria Rosa, Ronco, Claudio, Abraham, William T, Agostoni, Piergiuseppe, Barasch, Jonathan, Fonarow, Gregg C, Gottlieb, Stephen S, Jaski, Brian E, Kazory, Amir, Levin, Allison P, Levin, Howard R, Marenzi, Giancarlo, Mullens, Wilfried, Negoianu, Dan, Redfield, Margaret M, Tang, WH Wilson, Testani, Jeffrey M, and Voors, Adriaan A

Subjects
Kidney Disease, Heart Disease, Cardiovascular, Renal and urogenital, Blood Volume, Diuretics, Heart Failure, Hemofiltration, Humans, Pilot Projects, Randomized Controlled Trials as Topic, biomarkers, creatinine, diuretics, glomerular filtration rate, venous congestion, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients' vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration.

Published
2017

41. Kidney and heart failure events are bidirectionally associated in patients with type 2 diabetes and cardiovascular disease.

Author

Sharma, Abhinav, Inzucchi, Silvio E., Testani, Jeffrey M., Ofstad, Anne Pernille, Fitchett, David, Mattheus, Michaela, Verma, Subodh, Zannad, Faiez, Wanner, Christoph, and Kraus, Bettina J.

Subjects
TYPE 2 diabetes, KIDNEY failure, CARDIOVASCULAR diseases, HEART failure, LDL cholesterol
Abstract

Aims: This study aimed to evaluate the bidirectional relationship between kidney and cardiovascular (CV) events in trial participants with type 2 diabetes and CV disease. Methods and results: Post hoc analyses of EMPA‐REG OUTCOME using Cox regression models were performed to assess the association of baseline factors with risk of a kidney event and bidirectional associations of incident kidney events and CV events. Among placebo‐treated participants, baseline factors significantly associated with greater kidney event risk included lower baseline estimated glomerular filtration rate, albuminuria, higher uric acid, low‐density lipoprotein cholesterol levels, and prior heart failure (HF). Coronary artery disease was not associated with increased risk. In placebo‐treated participants, occurrence of an incident non‐fatal kidney event increased the subsequent risk of hospitalization for HF (HHF) but not 3‐point major adverse CV events (non‐fatal stroke, non‐fatal myocardial infarction, and CV death). Vice versa, HHF (but not myocardial infarction/stroke) increased the risk of subsequent kidney events. These associations were generally also seen in empagliflozin‐treated participants and in the overall population. Interestingly, the risk of kidney events following HHF was not significantly increased in the relatively small number of placebo‐treated participants already diagnosed with HF at baseline. Conclusions: These findings demonstrate a bidirectional inter‐relationship between HHF and kidney events. Further exploration of this relationship and strategies to optimize the use of therapies to reduce both kidney and HF outcomes is warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Author

Mullens, Wilfried, Dauw, Jeroen, Gustafsson, Finn, Mebazaa, Alexandre, Steffel, Jan, Witte, Klaus K., Delgado, Victoria, Linde, Cecilia, Vernooy, Kevin, Anker, Stefan D., Chioncel, Ovidiu, Milicic, Davor, Hasenfuß, Gerd, Ponikowski, Piotr, von Bardeleben, Ralph Stephan, Koehler, Friedrich, Ruschitzka, Frank, Damman, Kevin, Schwammenthal, Ehud, and Testani, Jeffrey M.

Subjects
ARTIFICIAL implants, IMPLANTABLE cardioverter-defibrillators, HEART failure patients, HEART failure, CARDIAC pacing, CARDIOLOGY, RHYTHM
Abstract

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter‐defibrillators and long‐term mechanical support. For others, more evidence is still needed before large‐scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device‐provided therapy and also device‐guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care. [ABSTRACT FROM AUTHOR]

Published
2024
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