David Kass (physician)

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David Kass
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Alma mater Harvard College (BA 1975); Yale University (MD 1980); George Washington University
Known forPressure-volume analysis; Cardiac resynchronization therapy (CRT); Heart failure and cGMP/protein kinase G signaling
AwardsOutstanding Investigator Award (National Institutes of Health, 2017 - 2023); Louis Artur Lucien Prize in Cardiovascular Diseases (2020); International Society of Heart Research Innovator Award (2020); Clinical Innovator and Mentor Award (Johns Hopkins University, 2017); Basic Science Research Prize (American Heart Association, 2008)
Scientific career
Institutions Johns Hopkins University
Website www.kasslab.johnshopkins.edu

David Kass, M.D. is the Abraham and Virginia Weiss Professor of Cardiology at Johns Hopkins University. He also serves as a Professor of Medicine, Pharmacology, Molecular Sciences, and Biomedical Engineering. [1] He obtained a Bachelor of Arts degree from Harvard College in 1975, majoring in Applied Physics and Engineering, and a Doctor of Medicine degree from Yale University in 1980. Following his medical studies, he completed an Internal Medicine residency at George Washington University in Washington, DC before joining the Cardiology Division at Johns Hopkins University. [2] Kass' research has ranged from fundamental molecular and cellular studies to human clinical research. His publication record includes over 550 original papers, with more than 55,000 citations. [3]

Contents

Kass is the Director of the Institute of CardioScience and co-directs a post-doctoral NIH-training program in Cardiovascular Disease. He has received honors including awards from the American Heart Association. [4] the Inaugural Janice Pfeffer Award from the International Society for Heart Research, [5] and an Outstanding Investigator Award from the National Institutes of Health. In 2020, he received the Louis and Artur Lucien Prize in Cardiovascular Diseases [6] and the Inaugural NAS-International Society of Heart Research Innovator Award. He received two Outstanding Investigator Awards from the National Heart Lung and Blood Institute in 2017 and 2023. [7]

Kass is a member of professional societies such as the American Society for Clinical Investigation, American Heart Association, and Association of American Physicians. He has served on the editorial board for journals like Circulation Research and as an Associate Editor the American Journal of Physiology. [8]

Early career

Kass' first research work was during undergraduate studies in applied mathematics in the laboratory of Martin Moore-Ede, a circadian rhythm biologist at Harvard's Physiology Department. He merged understanding of bio-oscillatory mathematics with the biology of diurnal biological behavior, focusing on regulation of renal excretion of both sodium and potassium. [5] Kass showed that the volume sensing mechanism, which was coupled to atrial stretch (later shown to relate to natriuretic peptide), was blunted during the nighttime by central circadian regulation. [9] [10]

Kass completed medical residency with the Internal Medicine Department at the George Washington University then a Fellowship in Cardiology at the Johns Hopkins University, working with Kiichi Sagawa in the Bioengineering Department in cardiac systemic engineering and mechanics pressure-volume relationships in the heart. Kass applied pressure-volume analysis to the intact mouse heart in situ [11] and shortly thereafter in human patients, [12] [13] advancing the understanding of cardiac disease pathophysiology. [14] His work established the factors regulating pressure-volume relations in the intact heart and in particular its maximal elastance, an index of contractility, and the role of external constraints on measures of diastolic function. [15] [16]

In the latter 1990’s Kass began research into applying pacing stimuli to both sides of a failing heart. This approach was later called cardiac resynchronization therapy (CRT). His work showed that with CRT net systolic function was enhanced without commensurate increases in oxygen consumption, [17] that is, the heart became more mechanically efficient. [18] He also showed how to predict which patients were most likely to benefit from the treatment. [19]

Kass also explored a canine model of heart failure with dyssynchronous contraction and studied cellular and molecular mechanisms relevant to the improvement from resynchronizing contraction. Among the studies from this work was the discovery of how CRT altered adrenergic signaling to improve contractile reserve, [20] [21] and improved sarcomere force-calcium dependence. [22]

Kass later developed a novel pacing therapy for heart failure where a normally contracting heart (not affected by a conduction delay to induce dyssynchrony) could be treated by temporarily making it contract dyssynchronously by means of right ventricular pacing, but then restored to normal contraction within 6 hours. The approach improved failing canine heart function, adrenergic signaling, and contractile function at the sarcomere level. [23]

Major contributions to cardiology

While the Kass Laboratory was exploring the mechanisms for CRT, he discovered that a relative of nitric oxide (NO), termed nitroxyl (HNO), conferred positive contractile changes differently from NO and could improve the function of the failing heart. [24] [25] [26] This led to founding the pharmaceutical company Cardioxyl Inc., which developed room stable HNO donor molecules that were ultimately advanced to Phase II clinical trials. The company was acquired by Bristol Meyers Squibb in 2015. [27]

In the early 2000s, Kass began to incorporate molecular and cellular biology along with traditional bioengineering to better study heart failure mechanisms and novel therapies. The lab discovered that inhibiting phosphodiesterase type 5A(PDE5A), which degraded cyclic guanosine onophosphate (cGMP) and was inhibited by the drug sildenafil (Viagra®), blunted heart contractility from adrenergic stimuli in animal and human hearts, [28] [29] [30] and when chronically administered to animals, it improved their heart function and heart disease in response to pressure-stress. [31] Subsequent studies identified various mechanisms underlying this benefit. [32] [33] [34] [35]

In 2015, the Kass lab found another phosphodiesterase that controls cGMP – PDE9A, showing that it specifically regulated cardiac signaling linked to natriuretic peptides. [36] PDE9A was later reported by his laboratory to stimulate fatty acid oxidation and lipolysis in fat and cardiac muscle, and improve disease related to diet-induced obesity and cardiometabolic syndrome. [37] Kass's lab linked cGMP regulation to control of the mechanistic target of rapamycin to control abnormal heart growth and protein quality control, and this was later translated to a immune therapy for cancer. [38]

Ongoing work

In the late 2010s and early 2020s, Kass' research has shifted towards investigating heart failure with preserved ejection fraction (HFpEF), with a focus on the role of obesity and metabolic defects in this condition. His laboratory has reported the first human data from heart muscle detailing abnormalities in gene transcription, metabolism, and muscle sarcomere function. [39] [40] [41]

Kass' research team includes clinicians, physician-scientists, graduate and undergraduate students. [42] His research has been supported by the National Institutes of Health, [43] American Heart Association, [4] and Leducq Foundation. [44]

Related Research Articles

<span class="mw-page-title-main">Heart failure</span> Failure of the heart to provide sufficient blood flow

Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms, caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling. The shortness of breath may occur with exertion or while lying down, and may wake people up during the night. Chest pain, including angina, is not usually caused by heart failure, but may occur if the heart failure was caused by a heart attack. The severity of the heart failure is mainly decided based on ejection fraction and also measured by the severity of symptoms. Other conditions that may have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease.

An ejection fraction (EF) is the volumetric fraction of fluid ejected from a chamber with each contraction. It can refer to the cardiac atrium, ventricle, gall bladder, or leg veins, although if unspecified it usually refers to the left ventricle of the heart. EF is widely used as a measure of the pumping efficiency of the heart and is used to classify heart failure types. It is also used as an indicator of the severity of heart failure, although it has recognized limitations.

<span class="mw-page-title-main">Frank–Starling law</span> Relationship between stroke volume and end diastolic volume

The Frank–Starling law of the heart represents the relationship between stroke volume and end diastolic volume. The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction, when all other factors remain constant. As a larger volume of blood flows into the ventricle, the blood stretches cardiac muscle, leading to an increase in the force of contraction. The Frank-Starling mechanism allows the cardiac output to be synchronized with the venous return, arterial blood supply and humoral length, without depending upon external regulation to make alterations. The physiological importance of the mechanism lies mainly in maintaining left and right ventricular output equality.

<span class="mw-page-title-main">Dilated cardiomyopathy</span> Medical condition

Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.

cGMP-specific phosphodiesterase type 5 Mammalian protein found in Homo sapiens

Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.

In cardiology, ventricular remodeling refers to changes in the size, shape, structure, and function of the heart. This can happen as a result of exercise or after injury to the heart muscle. The injury is typically due to acute myocardial infarction, but may be from a number of causes that result in increased pressure or volume, causing pressure overload or volume overload on the heart. Chronic hypertension, congenital heart disease with intracardiac shunting, and valvular heart disease may also lead to remodeling. After the insult occurs, a series of histopathological and structural changes occur in the left ventricular myocardium that lead to progressive decline in left ventricular performance. Ultimately, ventricular remodeling may result in diminished contractile (systolic) function and reduced stroke volume.

<span class="mw-page-title-main">Ventricular hypertrophy</span> Medical condition

Ventricular hypertrophy (VH) is thickening of the walls of a ventricle of the heart. Although left ventricular hypertrophy (LVH) is more common, right ventricular hypertrophy (RVH), as well as concurrent hypertrophy of both ventricles can also occur.

<span class="mw-page-title-main">Milrinone</span> Chemical compound

Milrinone, sold under the brand name Primacor, is a pulmonary vasodilator used in patients who have heart failure. It is a phosphodiesterase 3 inhibitor that works to increase the heart's contractility and decrease pulmonary vascular resistance. Milrinone also works to vasodilate which helps alleviate increased pressures (afterload) on the heart, thus improving its pumping action. While it has been used in people with heart failure for many years, studies suggest that milrinone may exhibit some negative side effects that have caused some debate about its use clinically.

<span class="mw-page-title-main">Amrinone</span> Chemical compound

Amrinone, also known as inamrinone, and sold as Inocor, is a pyridine phosphodiesterase 3 inhibitor. It is a drug that may improve the prognosis in patients with congestive heart failure. Amrinone has been shown to increase the contractions initiated in the heart by high-gain calcium induced calcium release (CICR). The positive inotropic effect of amrinone is mediated by the selective enhancement of high-gain CICR, which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A (PKA) and Ca2+ calmodulin kinase pathways.

<span class="mw-page-title-main">PRKCE</span> Protein-coding gene in the species Homo sapiens

Protein kinase C epsilon type (PKCε) is an enzyme that in humans is encoded by the PRKCE gene. PKCε is an isoform of the large PKC family of protein kinases that play many roles in different tissues. In cardiac muscle cells, PKCε regulates muscle contraction through its actions at sarcomeric proteins, and PKCε modulates cardiac cell metabolism through its actions at mitochondria. PKCε is clinically significant in that it is a central player in cardioprotection against ischemic injury and in the development of cardiac hypertrophy.

<span class="mw-page-title-main">MYH6</span> Protein-coding gene in the species Homo sapiens

Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.

Management of heart failure requires a multimodal approach. It involves a combination of lifestyle modifications, medications, and possibly the use of devices or surgery.

<span class="mw-page-title-main">Coronary perfusion pressure</span>

Coronary perfusion pressure (CPP) refers to the pressure gradient that drives coronary blood pressure. The heart's function is to perfuse blood to the body; however, the heart's own myocardium must, itself, be supplied for its own muscle function. The heart is supplied by coronary vessels, and therefore CPP is the blood pressure within those vessels. If pressures are too low in the coronary vasculature, then the myocardium risks ischemia with subsequent myocardial infarction or cardiogenic shock.

A plot of a system's pressure versus volume has long been used to measure the work done by the system and its efficiency. This analysis can be applied to heat engines and pumps, including the heart. A considerable amount of information on cardiac performance can be determined from the pressure vs. volume plot. A number of methods have been determined for measuring PV-loop values experimentally.

<span class="mw-page-title-main">Omecamtiv mecarbil</span> Chemical compound

Omecamtiv mecarbil (INN), previously referred to as CK-1827452, is a cardiac-specific myosin activator. It is being studied for a potential role in the treatment of left ventricular systolic heart failure.

Cardiac contractility modulation is a therapy which is intended for the treatment of patients with moderate to severe heart failure with symptoms despite optimal medical therapy who can benefit from an improvement in cardiac output. The short- and long-term use of this therapy enhances the strength of ventricular contraction and therefore the heart's pumping capacity by modulating (adjusting) the myocardial contractility. This is provided by a pacemaker-like device that applies non-excitatory electrical signals adjusted to and synchronized with the electrical action in the cardiac cycle.

<span class="mw-page-title-main">Heart failure with preserved ejection fraction</span> Medical condition

Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the ejection fraction – the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled – is normal, defined as greater than 50%; this may be measured by echocardiography or cardiac catheterization. Approximately half of people with heart failure have preserved ejection fraction, while the other half have a reduction in ejection fraction, called heart failure with reduced ejection fraction (HFrEF).

CXL 1020 is an experimental drug that is being investigated as a treatment for acute decompensated heart failure. CXL 1020 functions as a nitroxyl donor; nitroxyl is the reduced, protonated version of nitric oxide. Nitroxyl is capable of enhancing left ventricular contractility without increasing heart rate by modifying normal Ca2+ cycling through the sarcoplasmic reticulum as well as increasing the sensitivity of cardiac myofilaments to Ca2+.

<span class="mw-page-title-main">Istaroxime</span> Chemical compound

Istaroxime is an investigational drug under development for treatment of acute decompensated heart failure

<span class="mw-page-title-main">Pathophysiology of heart failure</span>

The main pathophysiology of heart failure is a reduction in the efficiency of the heart muscle, through damage or overloading. As such, it can be caused by a wide number of conditions, including myocardial infarction, hypertension and cardiac amyloidosis. Over time these increases in workload will produce changes to the heart itself:

References

  1. ↑ "David A. Kass, M.D., Professor of Medicine".
  2. ↑ "2022 Distinguished Scientist David A. Kass, MD, FAHA".
  3. ↑ "David A. Kass".
  4. 1 2 "2022 Distinguished Scientist David A. Kass, MD, FAHA".
  5. 1 2 "ISHR Hall of Fame - International Society for Heart Research".
  6. ↑ "Kass Receives Lucian Award | Medicine Matters". 13 July 2020.
  7. ↑ "Kass' Outstanding Investigator Award Renewed | Medicine Matters". 13 December 2022.
  8. ↑ https://www.ahajournals.org/res/editorial-board
  9. ↑ Kass DA, Sulzman FM, Fuller CA, and Moore-Ede MC. Renal responses to central vascular expansion are suppressed at night in conscious primates. Am J Physiol. 1980;239:F343-f351. doi: 10.1152/ajprenal.1980.239.4.F343
  10. ↑ Kass DA and Moore-Ede MC. Renal responses to prolonged central volume expansion in conscious primates. Am J Physiol. 1982;242:F649-56. doi: 10.1152/ajprenal.1982.242.6.F649
  11. ↑ Kass DA, Maughan WL, Guo ZM, Kono A, Sunagawa K and Sagawa K. Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure-volume relationships. Circulation. 1987;76:1422-36. doi: 10.1161/01.cir.76.6.1422
  12. ↑ Kass DA, Midei M, Brinker J and Maughan WL. Influence of coronary occlusion during PTCA on end-systolic and end-diastolic pressure-volume relations in humans. Circulation. 1990;81:447-460
  13. ↑ Kelly RP, Ting CT, Yang TM, Liu CP, Maughan WL, Chang MS and Kass DA. Effective arterial elastance as index of arterial vascular load in humans. Circulation. 1992;86:513-521
  14. ↑ Dauterman K, Pak PH, Nussbacher A, Arie S, Liu CP and Kass DA. Contribution of external forces to left ventricle diastolic pressure: Implications for the Clinical Use of the Frank-Starling Law. Annals Int Med. 1995;122:737-742.
  15. ↑ Kass DA. Assessment of diastolic dysfunction. Invasive modalities. CardiolClin. 2000;18:571-586
  16. ↑ Kass DA, Bronzwaer JG and Paulus WJ. What mechanisms underlie diastolic dysfunction in heart failure? Circ Res. 2004;94:1533-1542
  17. ↑ Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B and Nevo E. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation. 1999;99:1567-1573
  18. ↑ Nelson GS, Berger RD, Fetics BJ, Talbot M, Hare JM, Spinelli JC and Kass DA. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation. 2000;102:3053-3059
  19. ↑ Nelson GS, Curry CW, Wyman BT, Kramer A, Declerck J, Talbot M, Douglas MR, Berger RD, McVeigh ER and Kass DA. Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation. 2000;101:2703-2709
  20. ↑ . Chakir K, Daya SK, Aiba T, Tunin RS, Dimaano VL, Abraham TP, Jaques-Robinson KM, Lai EW, Pacak K, Zhu WZ, et al. Mechanisms of enhanced beta-adrenergic reserve from cardiac resynchronization therapy. Circulation. 2009;119:1231-40
  21. ↑ Chakir K, Depry C, Dimaano VL, Zhu WZ, Vanderheyden M, Bartunek J, Abraham TP, Tomaselli GF, Liu SB, Xiang YK, et al. Galphas-biased beta2-adrenergic receptor signaling from restoring synchronous contraction in the failing heart. Sci Transl Med. 2011;3:100ra88
  22. ↑ Kirk JA, Holewinski RJ, Kooij V, Agnetti G, Tunin RS, Witayavanitkul N, de Tombe PP, Gao WD, Van Eyk J and Kass DA. Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3beta. J Clin Invest. 2014;124:129-38
  23. ↑ Kirk JA, Chakir K, Lee KH, Karst E, Holewinski RJ, Pironti G, Tunin RS, Pozios I, Abraham TP, de Tombe P, et al. Pacemaker-induced transient asynchrony suppresses heart failure progression. Sci Transl Med. 2015;7:319ra207
  24. ↑ Paolocci N, Saavedra WF, Miranda KM, Martignani C, Isoda T, Hare JM, Espey MG, Fukuto JM, Feelisch M, Wink DA, et al. Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling. ProcNatlAcadSciUSA. 2001
  25. ↑ Paolocci N, Katori T, Champion HC, St John ME, Miranda KM, Fukuto JM, Wink DA and Kass DA. Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: independence from beta-adrenergic signaling. ProcNatlAcadSciUSA. 2003;100:5537-5542
  26. ↑ Tocchetti CG, Wang W, Froehlich JP, Huke S, Aon MA, Wilson GM, Di Benedetto G, O'Rourke B, Gao WD, Wink DA, et al. Nitroxyl improves cellular heart function by directly enhancing cardiac sarcoplasmic reticulum Ca2+ cycling. Circ Res. 2007;100:96-104
  27. ↑ "Bristol-Myers Squibb Buys Cardioxyl Pharmaceuticals". 13 May 2016.
  28. ↑ Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A, Paolocci N, Tomaselli GF, Hare JM and Kass DA. Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J. 2001;15:1718-1726
  29. ↑ Takimoto E, Champion HC, Belardi D, Moslehi J, Mongillo M, Mergia E, Montrose DC, Isoda T, Aufiero K, Zaccolo M, et al. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res. 2005;96:100-109
  30. ↑ Borlaug BA, Melenovsky V, Marhin T, Fitzgerald P and Kass DA. Sildenafil inhibits beta-adrenergic-stimulated cardiac contractility in humans. Circulation. 2005;112:2642-2649
  31. ↑ Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y and Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. NatMed. 2005;11:214-222.
  32. ↑ Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, Bedja D, Gabrielson KL, Blanton R, Siderovski DP, et al. RGS2 mediates cardiac compensation to pressure-overload and anti-hypertrophic effects of PDE5 inhibition. J Clin Invest. 2009;53(2)
  33. ↑ Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF and Kass DA. Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol. 2010;48:713-24.
  34. ↑ counter adverse cardiac stress. Nature. 2019;566:264-269.
  35. ↑ Ranek MJ, Oeing C, Sanchez-Hodge R, Kokkonen-Simon KM, Dillard D, Aslam MI, Rainer PP, Mishra S, Dunkerly-Eyring B, Holewinski RJ, et al. CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury. Nat Commun. 2020;11:5237.
  36. ↑ Lee DI, Zhu G, Sasaki T, Cho GS, Hamdani N, Holewinski R, Jo SH, Danner T, Zhang M, Rainer PP, et al. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015;519:472-6
  37. ↑ Mishra S, Sadagopan N, Dunkerly-Eyring B, Rodriguez S, Sarver DC, Ceddia RP, Murphy SA, Knutsdottir H, Jani VP, Ashok D, et al. Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice. J Clin Invest. 2021;131
  38. ↑ Patel CH, Dong Y, Koleini N, Wang X, Dunkerly-Eyring BL, Wen J, Ranek MJ, Bartle LM, Henderson DB, Sagert JG, et al. TSC2 S1365A mutation potently regulates CD8+T cell function and differentiation improving adoptive cellular cancer therapy. JCI Insight. 2023
  39. ↑ Aslam MI, Hahn VS, Jani V, Hsu S, Sharma K and Kass DA. Reduced Right Ventricular Sarcomere Contractility in Heart Failure With Preserved Ejection Fraction and Severe Obesity. Circulation. 2021;143:965-967
  40. ↑ Hahn VS, Knutsdottir H, Luo X, Bedi K, Margulies KB, Haldar SM, Stolina M, Yin J, Khakoo AY, Vaishnav J, et al. Myocardial Gene Expression Signatures in Human Heart Failure With Preserved Ejection Fraction. Circulation. 2021;143:120-134
  41. ↑ Hahn VS, Petucci C, Kim MS, Bedi KC, Jr., Wang H, Mishra S, Koleini N, Yoo EJ, Margulies KB, Arany Z, et al. Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction. Circulation. 2023;147:1147-1161
  42. ↑ https://www.kasslab.johnshopkins.edu/
  43. ↑ "RePORT ⟩ RePORTER".
  44. ↑ "Funded Networks |".
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