Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association

Abstract

Malnutrition can affect patients with various acute cardiovascular disease conditions, including acute coronary syndromes, arrhythmias, or valvular disease; however, most of the literature has focused on patients with heart failure. Malnutrition prevalence estimates range from 20% to 60% for hospitalized patients. Use of Global Leadership Initiative on Malnutrition criteria for malnutrition diagnosis for patients with cardiovascular disease has confirmed prognostic value, correlating with poorer physical function and higher mortality. Nutritional support plays a key role for inpatients, particularly in the cardiac intensive care unit, and includes initiation of feeding within 48 hours of hospitalization, preferably through enteral nutrition. Enteral nutrition is more cost-effective compared with parenteral nutrition and can decrease mortality and shorten lengths of stay. Parenteral nutrition is reserved for patients with severe gastrointestinal dysfunction or to supplement nutrition when enteral nutrition is contraindicated, for example, during high pressor doses that preclude adequate intestinal perfusion or when achieving <70% of nutritional targets after the first week. The optimal protein intake for patients with cardiogenic shock is an area of ongoing research, with higher protein approaches not appearing beneficial in recent critical care trials.

Malnutrition is a disorder characterized by deficiencies or excesses in nutrient intake, an imbalance of nutrients, or impaired nutrient utilization,¹ resulting in alterations in body composition and impaired physiological function.² Although the broadest definition of malnutrition encompasses both undernutrition and overweight, obesity, and dietary-related noncommunicable diseases, this scientific statement focuses on undernutrition, specifically the consequences of protein-energy and micronutrient insufficiencies in patients with acute cardiac conditions.

Malnutrition can affect patients with various acute cardiovascular conditions, including acute coronary syndromes, arrhythmias, or valvular disease; however, most of the literature has focused on patients with heart failure (HF).^3–5 Some cardiovascular populations are disproportionately affected by nutritional abnormalities such as patients with a Fontan circulation who frequently experience protein-losing enteropathy.⁶ The prevalence of malnutrition in patients with acute cardiovascular disease (CVD) ranges widely between 20% and 60%, depending on diagnostic criteria and the population studied^7,8 (Table 1).

Table 1. Prevalence of Malnutrition (Undernutrition) Across CVD Populations.

Population	Prevalence of malnutrition	Malnutrition criteria or tool	Association of malnutrition with mortality	Association of malnutrition with hospitalizations
HF (any ejection fraction)	16%–90% (75%–90% advanced or acutely decompensated HF)9	PNI, CONUT, SNS, NSI, NRS, MNA-SF, NRI, GNRI	MNA-SF scores were the strongest predictors of mortality in HF (HR, 4.32 [95% CI, 2.30–8.11])9	At least moderate malnutrition per CONUT score associated with twice the readmission risk of nonmalnourished patients10
HFrEF	43%11	GNRI	Mortality rate is 37% among malnourished patients vs 15% in patients with normal nutritional status (HR, 2.46 [95% CI, 1.55–3.89]; P<0.001)12	Malnutrition associated with HF exacerbation (82% vs 30%; P=0.004)12 Malnutrition also associated with longer hospital stays (mean, 15.2 d vs 10.1 d; P<0.001)
HFpEF	40%–63%13,14	CONUT, PNI, GNRI	Moderate–severe malnutrition associated with increased risk of cardiovascular death (HR, 2.06 [95% CI, 1.40–3.03]; P<0.001) and all-cause death (HR, 1.79 [95% CI, 1.33–2.42]; P=0.002)15	Moderate–severe malnutrition is associated with an increased risk of heart failure hospitalization (HR, 1.73 [95% CI, 1.29–2.33]; P<0.001)15 Malnutrition associated with more frequent readmissions within 30 d (OR, 1.85 [95% CI, 1.10–3.13]; P=0.020)
Heart transplantation/LVAD	60%16	NRI	Patients with moderate or severe nutritional risk had an 18% higher likelihood of mortality in the first year after transplantation (HR, 0.82 [95% CI, 0.75–0.89]; P<0.001)16 Patients with LVAD with preimplantation cachexia or malnutrition had a significantly higher mortality risk during LVAD support (HR, 1.23 [95% CI, 1.07–1.42]; P=0.005)17	Malnutrition associated with prolonged hospital stays and increased complications (P<0.05)16
Acute coronary syndrome (ACS)	27%–50%18–21	CONUT, PNI, GNRI	Malnutrition associated with higher mortality (HR, 2.66 [95% CI, 1.78–3.96]; P=0.004)21	Higher incidence of in-hospital composite adverse outcomes (CS, HF, major bleeding, stroke; OR, 1.12 [95% CI, 1.04–1.21]; P=0.003) and in-hospital all-cause mortality (OR, 1.41 [95% CI, 1.26–1.58]; P<0.001)22
Pediatric and congenital conditions	31%–66%23,24	Digital screening tool, WFA, HFA, WFH, MUAC	Underweight associated with increased odds of mortality (OR, 3.54 [95% CI, 1.62–7.74]; P<0.001) Stunted growth associated with increased mortality (OR, 3.31 [95% CI, 1.65–6.64]; P<0.001)25	Higher prevalence of undernutrition in children with recent admissions (OR, 1.46 [95% CI, 0.72–2.94]; P=0.001)23 Malnutrition associated with longer inhospital stay (12.0 d [8.0–17.0 d] vs (8.4 d [5.0–12.0 d]; P<0.01)24
Cardiac arrhythmias	31%–34% in patients with AF 26,27	CONUT	Mild malnutrition associated with increased mortality (HR, 1.48 [95% CI, 1.30–1.69]; P<0.001) Moderate–severe malnutrition associated with further increased mortality (HR, 2.45 [95% CI, 1.97–3.05]; P<0.001)26	Malnutrition associated with higher rates of ischemic stroke/TIA and major bleeding in patients with AF (HR, 2.25 [95% CI, 1.11–4.56]; P=0.02)28
Other cardiac surgeries	18%–20%29–31	MUST, GLIM, PA	Malnutrition found to be an independent risk factor for survival in postoperative patients (HR, 2.34 [95% CI, 1.50–3.64]; P<0.001)31	Malnutrition associated with a tendency toward prolonged hospitalization (>14 d) in 50.8% vs 37.8%; P=0.06331 Increased postoperative infectious complications and longer ICU stays32

ACS indicates acute coronary syndrome; AF, atrial fibrillation; BMI, body mass index; CONUT, Controlling Nutritional Status; CS, cardiogenic shock; CVD, cardiovascular disease; ESPEN, European Society for Clinical Nutrition and Metabolism; GLIM, Global Leadership Initiative on Malnutrition; GNRI, Geriatric Nutritional Risk Index; HF, heart failure; HFA, height for age; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; ICU, intensive care unit; LVAD, left ventricular assist device; MUAC, mid upper arm circumference; MUST, Malnutrition Universal Screening Tool; NRS-2002, Nutritional Risk Screening 2002; NSI, Nutritional Screening Initiative; OR, odds ratio; PA, phase angle; PNI, Prognostic Nutritional Index; SNS, Subjective Nutritional State; TIA, transient ischemic attack; WFA, weight for age; and WFH, weight for height.

Acutely decompensated CVD often exacerbates pre-existing nutritional deficiencies, which in turn may worsen prognosis, making timely identification and intervention critical yet challenging. Malnutrition often remains unrecognized and untreated in clinical practice, particularly among older adults with CVD.³³ Similarly, the implementation of effective nutritional interventions also remains suboptimal, related to gaps in awareness among clinicians and insufficient integration of nutritional care into clinical CVD workflows.³⁴

PREVALENCE AND CONSEQUENCES OF MALNUTRITION IN ACUTE CARDIOVASCULAR CARE

The Agency for Healthcare Research and Quality report on malnutrition in hospitalized adults highlights the critical need for improved identification and management of malnutrition in clinical settings.³⁵ It also underscores the significant impact of malnutrition on patient outcomes, including morbidity, mortality, and length of stay, as well as higher readmission rates and health care costs. The malnutrition prevalence estimates ranging from 20% to 60% for hospitalized patients are probably underestimates resulting from limitations in documentation, coding, and diagnostic criteria.⁸ Current prevalence estimates and associated clinical outcomes across the cardiac populations are given in Table 1.

Use of Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for patients with CVD has confirmed prognostic value, demonstrating associations with poorer physical function and higher mortality.³⁵ Among older adults with HF, GLIM-defined malnutrition was linked to higher mortality independently of other prognostic factors and demonstrated better prognostic ability than the Geriatric Nutritional Risk Index (Table 2).⁷ Similarly, GLIM criteria effectively predicted complications and survival in patients undergoing cardiac surgery.³⁰

Table 2. Screening Tools to Identify Patients With or at Risk for Malnutrition, Cachexia, and Sarcopenia.

Screening tool	Intended use	Scoring	Components						Use in cardiovascular populations		Limitations
			Age	Medical history	Physical examination (anthropometrics, muscle wasting, muscle function, ascites, general assessment)	Laboratories	Other	Acuity/ severity of illness	Cardiovascular populations studied	Clinical outcomes assessed in cardiovascular populations
Nutritional status
CONUT37	Hospitalized patients, often used in oncology population	0–9; 0–1=normal nutritional status, higher scores indicate higher risk for malnutrition				Albumin, lymphocytes, TC			ADHF,38 ACS,21,40 CCD,40 HF,38 PAD,41	Mortality, MACEs, stroke, clinical events, limb events, complications, amputation	Biomarkers used may be abnormal due to concomitant disease or disease-related inflammation.
GNRI42	Older adults, validated for patients with CVD	GNRI=(albumin g/L/5)×100+ (current weight/IBW); higher scores indicate lower malnutrition risk			X	Albumin			ADHF,38 ACS,21,40 PAD,41 CCD,40 HF38	Mortality, ACS, MACEs, stroke, limb events, amputation, complications	Use of body weight or weight loss may be influenced by volume overload; biomarker may be abnormal due to concomitant disease or disease-related inflammation; sensitivity and specificity vary.43
MNA-SF44	Older adults, highly validated particularly in patients >65 y of age and with HF	0–30, higher scores indicate better nutritional status		Dietary intake, weight loss, comorbid conditions, symptoms	X				ACS,21,40 cardiology inpatients,45 HF,38 PAD41	Mortality, ICU stay, LOS, hospital readmission, amputation	Applies only to patients >65 y of age; low specificity;46 use of body weight or weight loss may be influenced by volume overload; generalizability is limited.47
MST48	Adults, hospitalized and outpatient; excludes older adults	0–5; each question is given a weighted score, scores added together; higher scores indicate higher risk		Weight loss, appetite					ACS,21 cardiology inpatients45	Mortality, complications, ICU stay, LOS, hospital readmission	Use of body weight or weight loss may be influenced by volume overload.
mNU-TRIC49	Adults, critically ill hospitalized patients	0–9, points assigned for age, APACHE II, SOFA, number of comorbidities, ICU LOS, and IL-6 level; higher scores indicate higher risk, >4=high nutrition risk	X	Comorbid conditions		IL-6	Pre-ICU LOS	APACHE II, SOFA	Cardiac surgery50	Mortality	Biomarker may be abnormal due to concomitant disease or disease-related inflammation.
MUST51	Adults, hospitalized and outpatient	Combined scores from each category; assigned low, medium, or high risk		Dietary intake, weight loss	X			X	HF,38 cardiology inpatients45	Mortality, ICU stay, LOS, hospital read-mission	Use of body weight or weight loss may be influenced by volume overload.
NRS52	Hospitalized patients, particularly critically ill; preferred by ESPEN	0–3, combined with disease severity and age, higher score indicates higher risk for malnutrition and indication for starting nutrition support	X	Dietary intake, weight loss	X			X (APACHE II for ICU patients)	ACS,21,40 ADHF,38 cardiology inpatients,45 HF38	Mortality, AKI, ICU stay, LOS, hospital readmission	Use of body weight or weight loss may be influenced by volume overload; generalizability is limited.47
PNI53	Mainly in oncology patients	Higher scores indicate better nutrition status and lower systemic inflammation				Albumin, lymphocytes			ADHF,38 ACS,21,40 HF,38 CCD,40 PAD41	Mortality, MACEs, amputation	Biomarkers used may be abnormal due to concomitant disease or disease-related inflammation.
SGA54	Children and adults, hospitalized and outpatient; validated in critically ill	Categorized as A–C: A=mild, B=moderate, C=severe		Dietary intake, weight loss, symptoms	X	Albumin, lymphocytes, transferrin			ADHF,38 cardiology inpatients,45 HF38	Mortality, ICU stay, LOS, hospital readmission	Use of body weight or weight loss may be influenced by volume overload; biomarkers used may be abnormal due to concomitant disease or disease-related inflammation; it is a subjective assessment of nutritional status with high potential for interobserver variation.
SNAQ55	Adults, including older adults, hospitalized, outpatient, and community	0–5, higher scores indicate higher risk for malnutrition; 0–1 no intervention, 2 moderate malnutrition, ≥3 severely malnourished		Dietary intake (supplements, tube feeds), weight loss, appetite					Cardiology inpatients45	Mortality, ICU stay, LOS, hospital readmission	Use of body weight or weight loss may be influenced by volume overload.
TCBI56	Adults with CAD	Serum triglycerides, serum total cholesterol, and body weight are multiplied together to equal score			X	TC, triglycerides	Body weight		ACS,21 CCD56	Mortality, MACEs	Use of body weight may be influenced by volume overload; biomarkers used may be abnormal due to concomitant disease or disease-related inflammation.
Cachexia/sarcopenia
CASCO, mini-CAS-CO57	Adults with cancer	Score 0–100, <25=mild cachexia, 26–50=moderate cachexia, 51–75=severe, 76–100=terminal		Dietary intake, physical activity, immunosuppression	X	Albumin, lymphocytes, CRP, hemoglobin	QOL		HF	LOS, hospitalizations	CASCO: numerous measurements and questionnaires; mini-CASCO not studied in cardiology patients; assessing physical activity challenging in some hospitalized patients
MSRA58	Community-dwelling elderly adults	7 questions with scored answers, higher scores indicate more robust, scores <30=high risk for sarcopenia	X	Dietary intake (protein and dairy consumption, number of meals per day), weight loss, physical activity, hospitalizations					ADHF58		Patients with HF: overlap between chronic sarcopenia and ADHF, symptom assessment should be done in compensated HF; assessing physical activity challenging in some hospitalized patients
SARC-F59	Late middle-aged to older adults	5 questions with scaled answers, score of 0–10: 0=no difficulty to 2=a lot of difficulty, uses aids or unable to perform; ≥4=symptomatic and 0–3=healthy		Strength, walking assistance, rising from chair, climbing stairs, falls					ADHF,59 cardiology inpatients60,61	Mortality, LOS, hospital readmission, QOL	Low sensitivity62; patients with HF: overlap between chronic sarcopenia and ADHF, symptom assessment should be done in compensated HF; assessing physical activity challenging in some hospitalized patients
Sarcopenia index63	Critically ill adults	Calculated as (SCr/cystatin C)×100, or the ratio of Cr and cystatin C–derived eGFR, or the product of Cr multiplied by cystatin C eGFR64; low indicates lower muscle mass				SCr, cystatin C, eGFR			ACS,65 CCD,66 hypertension67	MACEs, stroke, ventricular arrhythmias	Low accuracy in detecting sarcopenia to date68 and pending validation in cardiovascular populations

ACS indicates acute coronary syndrome; ADHF, acute decompensated heart failure; AKI, acute kidney injury; APACHE, Acute Physiology And Chronic Health Evaluation; CASCO, Cachexia Score; CCD, chronic coronary disease; CONUT, Controlling Nutritional Status; Cr, creatine; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; ESPEN, European Society for Clinical Nutrition and Metabolism; GNRI, Geriatric Nutritional Risk Index; HF, heart failure; IBW, ideal body weight; ICU, intensive care unit; IL-6, interleukin 6; LOS, length of stay; mNUTRIC, modified Nutrition Risk in Critically Ill; MACE, major adverse cardiac event; MNA-SF, Mini Nutritional Assessment-Short Form; MSRA, Mini Sarcopenia Risk Assessment; MST, Malnutrition Screening Tool; MUST, Malnutrition Universal Screening Tool; NRS, Nutritional Risk Screening; PCI, percutaneous coronary intervention; PNI, Prognostic Nutritional Index; QOL, quality of life; SARC-F, strength, assistance with walking, rise from a chair, climb stairs, and falls; SCr, serum creatinine; SGA, Subjective Global Assessment; SNAQ, Short Nutritional Assessment Questionnaire; SOFA, Sequential Organ Failure Assessment; TC, total cholesterol; and TCBI, triglycerides, total cholesterol, body weight index.

DIAGNOSIS OF MALNUTRITION IN ACUTE CARDIAC CONDITIONS

An International Consensus Guideline Committee proposal (2010)⁶⁹ and subsequent 2012 consensus statement from the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (ASPEN)¹ outlined characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). These documents endorse a cause-based construct of (1) malnutrition in the context of acute illness of injury, (2) malnutrition in the context of chronic illness, or (3) malnutrition in the context of social or environmental circumstances (starvation), with each category further divided into mild, moderate, or severe with assessment thresholds across energy intake, weight change, and physical examination criteria (Table 3). Within the acute cardiovascular inpatient population, all patients will have an acute illness, whereafter the clinician should determine whether there is also a preceding chronic cardiac or noncardiac condition affecting prehospitalization nutritional reserve and then finally whether a social or environmental circumstance is exacerbating malnutrition. The predictive validity of the Academy of Nutrition and Dietetics/ASPEN indicators for diagnosing malnutrition tool was recently confirmed across 290 adult inpatients in whom both the original tool and a simplified version showed association with emergency department visits and hospital readmissions for patients with severe malnutrition and longer lengths of stay and greater health care use for those with moderate malnutrition.⁷⁰

Table 3. Academy of Nutrition and Dietetics and ASPEN Characteristics Recommended for the Identification and Documentation of Adult Malnutrition.

	Malnutrition in the context of acute illness or injury				Malnutrition in the context of chronic illness				Malnutrition in context of social/environmental circumstances (starvation)
	Moderate: protein-calorie malnutrition (E44.0)		Severe protein-calorie malnutrition (E43)		Moderate protein-calorie malnutrition (E44.0)		Severe protein-calorie malnutrition (E43)		Moderate protein-calorie malnutrition (E44.0)		Severe protein-calorie malnutrition (E43)
Protein-calorie malnutrition can occur at any BMI
Clinical characteristics: include all that apply
Energy intake: The clinician may obtain or review the food and nutrition history, estimate optimum energy needs, compare them with estimates of energy consumed, and report inadequate intake as a percentage of estimated energy requirements over time	<75% of estimated energy requirement for >7 d		≤50% of estimated energy requirement for ≥5 d		<75% of estimated energy requirement for ≥1 mo		≤75% of estimated energy requirement for ≥1 mo		<75% of estimated energy requirement for ≥3 mo		≤50% of estimated energy requirement for ≥1 mo
Weight loss: Evaluate weight loss in light of other clinical findings, including hydration status. Weight change over time is reported as a percentage of weight lost (or weight change) from baseline. Equation: original weight–current weight/original weight×100=% weight change	% 1–2 5 1 7.5	Time 1wk mo 3 mo	% >2 >5 >7.5	Time 1 wk 1 mo 3 mo	% 5 7.5 10 20	Time 1 mo 3 mo 6 mo 1 y	% >5 >7.5 >10 >20	Time 1 mo 3 mo 6 mo 1 y	% 5 7.5 10 20	Time 1 mo 3 mo 6 mo 1 y	% >5 >7.5 >10 >20	Time 1 mo 3 mo 6 mo 1 y
Muscle mass–physical assessment (all noted): Muscle loss (eg, wasting of the temples (temporalis muscle), clavicles (pectoralis and deltoids), shoulders (deltoids), interosseous muscles, scapula (latissimus dorsi, trapezius, deltoids), thigh (quadriceps), and calf (gastrocnemius)	Mild depletion		Moderate depletion		Mild depletion		Severe depletion		Mild depletion		Severe depletion
Body fat–physical assessment (all noted): Loss of subcutaneous fat (eg, orbital, triceps, overlying ribs)	Mild depletion		Moderate depletion		Mild depletion		Severe depletion		Mild depletion		Severe depletion
Fluid accumulation–physical assessment: Generalized or localized fluid accumulation evident on examination (extremities, vulvar/scrotal, or ascites)	Mild		Moderate–severe		Mild		Severe		Mild		Severe
Functional assessment: Handgrip strength: Consult normative standards supplied by the manufacturer of the measurement device	NA		Measurably reduced		NA		Measurably reduced		NA		Measurably reduced

A minimum of 2 of the 6 characteristics above is recommended for diagnosis of either severe or moderate protein-calorie malnutrition. Usual weight should be obtained to determine the percentage and to interpret the significance of weight loss. International Classification of Diseases, 10th Revision code displayed under diagnostic term. The National Center for Health Statistics defines chronic as a disease or condition lasting ≥3 months.

ASPEN indicates American Society for Parenteral and Enteral Nutrition; BMI, body mass index; and NA, not applicable.

Source: Academy of Nutrition and Dietetics and ASPEN consensus characteristics of adult malnutrition.¹

More recently, the GLIM program engaged international clinical nutrition societies to pursue a standardized malnutrition diagnostic approach.⁷¹ GLIM reported a strong consensus favoring a 2-step process of a validated malnutrition risk screening tool to identify at-risk individuals such as the Nutritional Risk Screening 2002, Mini Nutritional Assessment-Short Form, or Malnutrition Universal Screening Tool, followed by a second step of assessment for the diagnosis of malnutrition and severity grading. This document proposes that selected core phenotypic and etiologic criteria be used for grading malnutrition into stage 1 (moderate) and stage 2 (severe; Table 3). Phenotypic grading is based on percent weight loss, body mass index (BMI), and skeletal muscle assessment, with GLIM endorsing dual x-ray absorptiometry (DXA), bioelectrical impedance analysis, ultrasound, computed tomography, or magnetic resonance imaging options, as available, for lean mass evaluation.

Further diagnostic challenges are posed by the International Classification of Disease, 9th Revision and current International Classification of Disease,10th Revision, which do not fully align with the diagnostic recommendations from these clinical practice guidelines. This has led to misalignment between academic constructs and billing codes that hampers educational efforts to raise awareness of inpatient malnutrition recognition, as well as the fidelity of prevalence estimates based on International Classification of Disease coding. For instance, GLIM criteria identified a higher malnutrition prevalence than International Classification of Disease,10th Revision codes in a large cohort of 2 multicenter observational studies with 2794 patients with cancer; malnutrition according to GLIM was nearly twice as prevalent (23% versus 12.6%).⁷² Elsewhere, GLIM criteria identified a higher prevalence of malnutrition compared with definitions outlined by the European Society for Clinical Nutrition and Metabolism and the Malnutrition Screening Tool⁷³ and showed reasonable sensitivity and specificity compared with the Subjective Global Assessment tool.⁷⁴

Although several malnutrition screening tools include albumin, which is a strong prognostic biomarker in many cardiac conditions, albumin is now considered a poor tool for malnutrition detection because it is influenced by factors unrelated to nutritional status such as inflammation, liver function, and hydration levels; in addition, its long half-life (≈3 weeks) makes it poorly responsive to acute changes in dietary intake.⁷⁵ The nutrition-focused physical examination has been advanced by the Academy of Nutrition and Dietetics and ASPEN through clinical practice guidelines and educational initiatives, with growing acceptance within the inpatient malnutrition assessment. It is also increasingly recognized that malnutrition and skeletal muscle wasting commonly coexist in patients with obesity and that basing an assessment of nutritional status on weight or BMI is frequently misleading, especially among patients with CVD, who may experience alterations in extracellular fluid compartment volume. In addition, BMI is now viewed as a flawed metric for representing normative weight ranges because of its insensitivity to differences in body type and lean versus fat mass and inconsistency across race and sex groups.^76–80 Thus, malnutrition screening tools that rely on body weight changes, ideal weight, or BMI may be particularly vulnerable to bias.

DISTINCTIONS BETWEEN MALNUTRITION AND CACHEXIA, SARCOPENIA, AND FRAILTY

Malnutrition, cachexia, sarcopenia, and frailty are phenotypically distinct but interconnected conditions with interrelated pathophysiological processes that lead to different magnitudes of wasting and susceptibility to adverse outcomes.^81–83 Sarcopenia is defined as the age-related loss of muscle mass and function, which can be exacerbated by chronic conditions, including CVD and potentially malnutrition. Frailty is a state of increased vulnerability that further complicates clinical conditions, leading to elevated risk of adverse outcomes. Cachexia defined as a chronic catabolic syndrome characterized by unintentional edema-free weight loss, associated with anorexia, inflammation, and abnormal biochemistry, in the setting of an underlying disease.^84,85 The unintentional weight loss of cachexia is predominantly loss of muscle mass with or without loss of fat; however, not all individuals with sarcopenia are cachectic.⁸⁶ In fact, sarcopenic obesity, when lean mass wasting and fat mass expansion occur concurrently, is increasingly recognized and may incur a distinct phenotype of low physical functioning and higher mortality rates, especially in older adults with HF.^87,88

Criteria for cachexia have variously ranged from unintentional edema-free body weight loss ≥7.5% of previous normal weight over the prior 6 months⁸⁹ to ≥5% body weight loss over ≥12 months or absolute BMI <20 kg/m² accompanied by 3 of 5 criteria: decreased muscle strength, fatigue, anorexia, low fat-free mass index, or abnormal biochemistry.⁸⁴ A practical consensus definition of cardiac cachexia has been proposed as “a catabolic syndrome in patients with symptomatic HF characterized by muscle mass loss (by physical exam or imaging methods) and unintentional edema-free weight loss (≥5% pre-HF body weight), in which dietary macronutrient intake may be sufficient or insufficient.”⁹⁰ Aging and chronic diseases such as CVD are 2 principal risk factors for the wasting continuum, and these conditions adversely influence outcomes for older adults with CVD at greater risk of disability and mortality.^91,92 Recognizing and differentiating between malnutrition, sarcopenia, and cachexia is clinically important because these conditions differ in their scope for reversibility and appropriate interventions. For example, malnutrition, especially when contributed to by inadequate intake due to dietary restrictions, frequent fasting for procedures, or food insecurity, may be addressed by initiatives that focus on food access and education, whereas the current pathophysiological paradigm supports underlying cardiac disease treatment as the only intervention that substantially reverses cardiac cachexia.⁹⁰ If weight loss or muscle wasting persists despite adequate protein calorie provision, cachexia is likely the more appropriate diagnosis. If the weight, fat, or muscle loss can be halted by improving nutrient intake and absorption, malnutrition is likely the dominant diagnosis.

PATHOPHYSIOLOGY OF MALNUTRITION AND CACHEXIA IN INPATIENTS WITH CARDIAC CONDITIONS

Patients with malnutrition typically have inadequate in-take of the macronutrients, including protein, carbohydrates, and fats, needed to support energy requirements, as well as the micronutrients, including vitamins and minerals, that are required for physiological processes, enzymatic functions, and immunity. Nutritional insufficiency refers to nutrient intake below the recommended or beneficial range; deficiency describes a more severe intake decrement that results in a disease state (eg, clinical syndromes from vitamin deficiency). In settings of insufficient protein intake, homeostatic mechanisms in skeletal muscle will diminish amino acid turnover such that the body limits nitrogen excretion in the urine. Thus, the body conserves all available protein substrate for essential functions. Chronic negative nitrogen balance leads to progressive erosion of lean body mass, impaired immune function, delayed wound healing, and overall deterioration in nutritional status.⁹³ Conversely, cardiac cachexia is characterized by a catabolic metabolism and accelerated turnover of protein stores, degrading fat-free mass and leading to elevated urine nitrogen excretion. The pathophysiological basis of this catabolic state is thought to stem from complex interplay between the neurohormonal dysregulation of the advanced HF (particularly HF with reduced ejection fraction) syndrome, chronic inflammation, myocardial substrate demands of the failing heart, abnormalities of mesenteric perfusion, and venous pressures and may be exacerbated by inadequate macronutrient intake in relation to the HF symptoms of anorexia and early satiety.⁹⁰

Risk factors for malnutrition in cardiac inpatients include advanced age, poor appetite, reduced dietary intake, and increased metabolic demands due to heart disease. These factors, along with comorbidities such as dental disease, chronic kidney disease (CKD), and dementia, significantly increase the risk of impaired dietary intake and nutrient absorption. Specifically in HF, a low-flow or congestive state impairs nutrient delivery and absorption, with associated decreased appetite, gastrointestinal dysfunction, and malnutrition.⁹⁴ In addition, cardiac medications such as digoxin, amiodarone, and mexiletine can lead to nausea and taste changes that exacerbate inadequate calorie intake. Furthermore, strict dietary counseling on sodium, saturated fat, and calories, as well as dietary patterns recommended for patients receiving warfarin anticoagulation or being managed for advanced kidney disease or diabetes, can lead to dietary confusion and inadequate protein-calorie intake. Repeated inpatient arrangements for nil per os (NPO) before procedures can further exacerbate poor dietary intake. Last, the limited meal options on hospital food menus are frequently poor in taste and misaligned with cultural expectations of the patient population.

OPPORTUNITIES FOR NUTRITIONAL INTERVENTIONS IN THE INPATIENT AND POSTDISCHARGE SETTINGS

The Dietary Guidelines for Americans and American Heart Association Dietary Guidance provide a foundation for eating to promote cardiovascular health, emphasizing the consumption of nutrient-dense foods.⁹⁵ For patients with established cardiac conditions, the DASH (Dietary Approaches to Stop Hypertension), Mediterranean, and plant-based dietary patterns are broadly thought to be beneficial, although the evidence base in established disease is weaker than for primary CVD prevention. The DASH diet focuses on fruits, vegetables, whole grains, and lean proteins, promoting low sodium intake and rich potassium, magnesium, and calcium sources to manage blood pressure. The Mediterranean diet emphasizes healthy fats from olive oil, nuts, and fish, combined with a high intake of fruits, vegetables, and whole grains. Plant-based diets prioritize minimally processed plant foods, which are naturally low in unhealthy fats and high in fiber, vitamins, and minerals. It is also strongly recommended that patients avoid trans fats, found in partially hydrogenated oils, and processed foods high in sodium, added sugars, and saturated fats, although limits on each of these components vary across conditions and guidelines.^95,96

SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) provided new insights into sodium intake for patients with HF (any ejection fraction). This study demonstrated that a sodium-restricted diet (goal <1500 mg/d) did not significantly reduce the composite end point of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death compared with a usual-sodium diet (average intake, 2073 mg/d at 12 months).⁹⁷ Although HF guidance still favors avoidance of excessive sodium in those with congestive symptoms, the most stringent American Heart Association sodium guidance is for individuals with hypertension.⁹⁵ However, the focus on restrictive dietary counseling across the cardiometabolic conditions, whether for sodium in populations with HF, sugars for those with diabetes, saturated fats for those with coronary artery disease, or caloric restriction for those with obesity, may prompt excessively restrictive eating patterns that risk exacerbating micronutrient deficiencies and inadequacy of protein-calorie intake. To date, improvements in dietary quality rather than restrictive dietary counseling have shown benefits in primary and secondary CVD prevention,^98,99 with restrictive approaches to HF sodium or fluid intake not yielding clear outcome benefits^97,100 and small studies suggesting associations between restrictive diets and undernutrition.^101,102 Thus, there has been a recent trend toward more permissive dietary education for patients with CVD, with the emphasis of pursuing balanced, nutrient-dense food patterns, in the hope of promoting a more sustainable and healthful approach. Dietary counseling should always be personalized to the specific conditions and meet patients’ caloric and micronutrient requirements, and such an ethos may help prevent malnutrition development, although supportive evidence is minimal.¹⁰³

NUTRITIONAL SUPPORT FOR CARDIAC INPATIENTS

The EFFORT study (Effect of Early Nutritional Support on Frailty, Functional Outcomes and Recovery of Malnourished Medical Inpatients) highlighted the potential value of individualized nutritional support provided by registered dietitian nutritionists (RDNs) for hospitalized patients.¹⁰⁴ The EFFORT study was a large, multicenter, randomized controlled trial conducted in 8 Swiss hospitals to evaluate whether individualized nutritional support improves outcomes in hospitalized adults with elevated malnutrition risk, as indicated by a Nutritional Risk Screening 2002 score ≥3 and anticipated length of stay ≥4 days.¹⁰⁴ Participants were randomized to receive either RDN protocol–guided individualized nutritional support (targeting energy, protein, and micronutrient goals) or standard hospital food with no dietary counseling. Individualized nutritional support significantly reduced the risk of adverse clinical outcomes (composite of mortality, intensive care unit [ICU] admission, readmission, major complications, and functional decline) at 30 days (adjusted odds ratio, 0.79 [95% CI, 0.64–0.97]; P=0.023) and reduced 30-day mortality (adjusted odds ratio, 0.65 [95% CI, 0.47–0.91]; P=0.011) compared with standard care. A post hoc analysis of participants with chronic HF demonstrated that the group receiving RDN-led deployment of tailored nutritional interventions experienced lower 30-day mortality (odds ratio, 0.44 [ 95% CI, 0.26–0.75]; P=0.002), with a particularly marked effect among patients with highest risk as per the Nutritional Risk Screening tool.¹⁰⁵ The results underscore the potential benefits of personalized nutritional plans during hospitalizations, although this trial was not designed specifically for patients with CVDs and thus a future clinical trial of a cardiac-specific inpatient nutritional intervention in patients at high malnutrition risk would be important to define the efficacy of this short-term inpatient approach.

Micronutrient insufficiencies, particularly water-soluble vitamin B₁ (thiamine) deficiency in those receiving high-dose loop diuretics, can become prevalent in cardiac inpatients. Inadequate micronutrient intake has been associated with higher mortality and cardiovascular events in patients with HF.^106,107 It remains controversial as to whether thiamine deficiency can exacerbate HF symptoms, and supplementation studies suggesting improvements in cardiac function or symptom status are small and of poor quality.^108–110 Vitamin E, folate, or selenium supplementation has minimal evidence as interventions to improve cardiac stability.¹¹¹ Coenzyme Q10 supplementation has limited clinical trial support in patients with HF but has not been routinely adopted.¹¹² Laboratory assessment and supplementation of magnesium and potassium is commonly performed, especially for inpatients undergoing diuresis, but the value of measuring and repleting other micronutrients does not have evidence as standard of care for hospitalized patients with CVD.

There are several methods for estimating patients’ energy needs during an acute cardiac illness, including indirect calorimetry with a metabolic cart and predictive equations. The Academy of Nutrition and Dietetics recommends indirect calorimetry as the most accurate and ideal way to assess an individual’s resting metabolic rate. Indirect calorimetry is a noninvasive method used to estimate energy expenditure through measurement of oxygen consumption ($\dot{\mathrm{V}}{\mathrm{o}}_2$) and carbon dioxide production ($\dot{\mathrm{V}}{\mathrm{o}}_2$). The ratio of $\dot{\mathrm{V}}{\mathrm{o}}_2$ to $\dot{\mathrm{V}}{\mathrm{o}}_2$ at the cellular level is the respiratory quotient; because measurement of the respiratory quotient is not easily achieved, an indirect measurement is obtained as the respiratory exchange ratio, which reflects the relative utilization of carbohydrates and fats for energy. An respiratory exchange ratio of 0.7 suggests predominant fat oxidation, whereas 1.0 indicates carbohydrate utilization. The metabolic cart performs indirect calorimetry by capturing and analyzing inhaled and exhaled gases through a canopy or ventilator circuit. The resting energy expenditure (kilocalories per day) is derived from $\dot{\mathrm{V}}{\mathrm{o}}_2$ and $\dot{\mathrm{V}}{\mathrm{o}}_2$ with the Weir formula: $\dot{\mathrm{V}}{\mathrm{o}}_2$ This calculation provides a patient-specific estimate of daily caloric requirements, which can guide tailored nutrition support, particularly in critically ill or metabolically complex individuals. However, indirect calorimetry is resource intensive and not easily available in all settings, leading to predictive equations being the most frequently used clinical method (Supplemental Table).

Dietary protein is generally considered a major determinant of muscle mass,¹¹⁸ but it is controversial whether enhanced dietary macronutrient intake can overcome the inflammatory catabolic metabolism of advanced cardiac conditions and achieve net gains in fat-free mass.^119,120 Protein intake goals for patients with CVD have sparse evidence, but the general adult recommendation for 0.8 g·kg⁻¹·d⁻¹ may be insufficient for many inpatients with active cardiac disease. Small protein turnover studies in patients with HF suggest that at least 1.1 g·kg⁻¹·d⁻¹ may be beneficial,¹²¹ which has formed the basis of recommendations for patients with HF who develop muscle wasting or are at risk of wasting.^111,122 There are, however, safety concerns about augmenting dietary protein above the 0.8 g·kg⁻¹·d⁻¹ range, especially from animal sources, because of concerns of accelerating coronary artery disease and HF incidence, as well as the potential for accelerating CKD progression.^123–125 In the MDRD study (Modification of Diet in Renal Disease), a dietary protein target of 0.6 g·kg⁻¹·d⁻¹ appeared to limit progression of CKD, at least during the 6-year follow-up time frame.^125,126 Therefore, current practice favors that adults with mild CKD (stages 1 and 2) should avoid >1.30 g·kg⁻¹·d⁻¹ protein intake and patients with CKD stages 3 to 5 not on dialysis are recommended to limit to 0.60 to 0.80 g·kg⁻¹·d⁻¹.¹²⁷ However, in a more recent observational study, there were neutral or inverse associations between protein intake up to 1.6 g·kg⁻¹·d⁻¹ and mortality among patients with CKD stages 3 to 5 not on dialysis.¹²⁸ The protein requirements of patients with CKD and a concurrent acute cardiovascular condition are not currently defined. In patients receiving maintenance dialysis, protein requirements may be closer to 1.2 to 1.3 g·kg⁻¹·d⁻¹¹²⁹ as a result of dialysis-related protein loss and systemic inflammation.

To enhance micronutrient and macronutrient dietary sufficiency in hospitals, practical measures include offering nutrient-dense, heart-healthy meals that adhere to established dietary patterns such as DASH or Mediterranean diets. Macronutrient supplementation is increasingly commercially available through protein-calorie–dense shakes, puddings, or bars and is appropriate for inpatients screening positive for moderate or severe malnutrition. In addition, integrating nutrition education and counseling into the care plan can empower patients to make informed dietary choices after discharge. Another potential threat to adequate macronutrient intake for patients with cardiac conditions is NPO orders, often used in preparation for procedures or because of concern for aspiration risks. Although not specifically studied in this population, proactive efforts for individual patients and system-wide efforts to minimize the duration of NPO status may help to ensure timely nutritional intake. Clear liquids or enteral nutrition (EN) should be considered when full oral intake is not feasible to prevent nutritional deficits and to support recovery.

Engaging patients and stakeholders in the nutritional care process is crucial for success, and availability of inpatient RDNs is essential. Providing culturally appropriate meal options can enhance patient satisfaction and adherence to dietary recommendations. Hospitals should capitalize on the opportunity to educate patients about heart-healthy choices, tailoring advice to align with their cultural preferences and being mindful of previous dietary habits. Involving patients in meal planning and offering practical guidance can foster a supportive environment, encouraging long-term adherence to heart-healthy diets.

NUTRITIONAL SUPPORT FOR CARDIAC CRITICAL CARE INPATIENTS

Nutritional support plays a key role in the cardiac ICU (CICU), where malnutrition is frequently encountered.¹⁹ Although most of the data come from patients with HF,^90,130,131 the critically ill cardiac patient has several factors to consider, including their limited cardiopulmonary reserve, fluid status, and use of vasopressors, mechanical ventilation (MV), or mechanical circulatory support, as well as frequent exposure to NPO requirements.¹⁹ Moreover, their higher metabolic demand increases cardiac cachexia and sarcopenia risks, often coexisting with malnutrition and frailty, which negatively affects outcomes.^19,90

General Principles

Modifying nutritional support according to patient characteristics is paramount. In a clinical trial of inpatients with HF (12.5% receiving inotropes) and malnutrition,¹³² an individualized nutritional approach improved mortality and readmissions. Nutritional support in the CICU should consider timing, route, and caloric, fluid, electrolyte, and protein targets and monitor closely for intestinal intolerance, hyperglycemia, or refeeding syndrome. Refeeding syndrome can occur after prolonged starvation with aggressive oral feeding, EN, or parenteral nutrition (PN), and patients with mental health and substance use disorders, malabsorptive syndromes, surgeries, or vomiting are particularly at risk.¹³³ A sudden rise in serum glucose levels stimulates insulin release, which drives intracellular phosphorus and potassium levels, resulting in hypophosphatemia and hypokalemia. Refeeding syndrome can be prevented by initiating 40% to 50% of the caloric goal, followed by slow uptitration of caloric delivery over 3 to 4 days, adequate supplementation of thiamine (eg, 100–200 mg IV daily for 5–7 days plus an oral/enteral multivitamin), and frequent monitoring and supplementation of serum electrolytes, including phosphorus.¹³³

Given the limited CICU-specific data, ICU nutritional support principles are generally applied to critically ill cardiac patients.¹³⁴ These include initiation of feeding within 48 hours of hospitalization, preferable through EN (Figure 1).¹³⁵ EN is more cost-effective; has lower rates of infection, overfeeding, and hyperglycemia compared with PN^19,134,135; and can decrease mortality,^134,136,137 enhance immunity,¹³⁸ and decrease duration of MV and ICU stay. PN is reserved for patients with severe gastrointestinal dysfunction¹³⁵ or to supplement nutrition when EN is contraindicated or limited by gastric function, in the setting of high pressor doses that preclude adequate intestinal perfusion, or when EN is insufficient to achieve at least 70% of the nutritional targets after the first week.^134,139 PN is occasionally started earlier than 1 week if the patient is severely malnourished. Even in patients who are unable to start full EN by 48 hours, it is reasonable to initiate trophic (low) doses of tube feedings (10–20 mL/h) with hypocaloric targets (50–70% of daily expenditure) that aim to stimulate the gut. The infectious risks associated with PN are not specifically quantified for the CICU population, but a large meta-analysis recently compared the complication rates between recipients of PN and recipients of other nutritional strategies among hospitalized patients. When 37 randomized controlled trials investigating PN compared with any other comparator were evaluated, there was an increased risk of infection at any site (relative risk, 1.23 [95% CI, 1.12–1.36]), but mortality was equivalent between the 2 groups.¹⁴⁰ Best practices include placing a new central venous catheter for the PN infusion and not accessing it for other infusions or blood draws.

Figure 1. Summary of nutritional strategies for patients with cardiovascular conditions across the domains of care.

CICU indicates cardiac intensive care unit; CONUT, Controlling Nutritional Status; CS, cardiogenic shock; ECPR, extracorporeal cardiopulmonary resuscitation; EN, enteral nutrition; GNRI, Geriatric Nutritional Risk Index; HD, hemodynamic; MNA, Mini Nutritional Assessment; mNUTRIC, modified Nutrition Risk in the Critically Ill; MUST, Malnutrition Universal Screening Tool; NPO, nil per os; NRS, Nutritional Risk Screening; PNI, Prognostic Nutritional Index; RD, registered dietitian; SNAQ, Short Nutritional Assessment Questionnaire; and TPN, total parenteral nutrition.

The European Society for Clinical Nutrition and Metabolism¹³⁵ recommends a more aggressive approach with early initiation of EN based on recent evidence¹³⁹ compared with the more conservative approach of ASPEN.¹³⁴ After EN initiation, clinicians should monitor for abdominal distention or discomfort, nausea, vomiting, or diarrhea as signs of bowel ischemia. If this occurs, EN should be stopped or feeding rate reduced because mesenteric ischemia carries a mortality exceeding 75%.¹⁴¹ Poor tolerance of EN can be due to higher fat and higher fiber formulations, which are often problematic for critically ill patients. In patients with impaired gastric motility, prokinetic agents may be considered, although they are often limited by QT prolongation. Peptide-based enteral formulas contain proteins that have been hydrolyzed to dipeptides and tripeptides, which can be combined with higher medium-chain triglycerides to aid absorption. Alternatively, postpyloric tube feedings may be used,¹³⁴ although this approach has not been specifically evaluated in the CICU. Routine monitoring of gastric residuals is no longer recommended because it does not decrease aspiration risk and can result in underfeeding.^{134,142–144}

Protein intake goals during critical illness remain controversial. Although providing a high-protein supplementation may appear logical to overcome sarcopenia, a large trial recruiting mechanically ventilated patients in general ICUs called EFFORT Protein (Effect of Higher Protein Dosing in Critically Ill Patients With High Nutritional Risk) (9% with CVD) failed to demonstrate bene-fits of a high-protein EN regimen (≥2.2 g·kg⁻¹·d⁻¹ versus ≤1.2 g·kg⁻¹·d⁻¹) in time to discharge alive from hospital up to 60 days but demonstrated higher mortality in patients with renal failure.¹⁴⁵ Similarly, the recent PRECISe trial (Protein Provision in Critical Illness) assessed higher enteral protein intake (2.0 g·kg⁻¹·d⁻¹) compared with standard enteral protein intake (1.3 g·kg⁻¹·d⁻¹) in critically ill patients with MV (one-quarter hospitalized for CVD) and evaluated quality of life at 180 days after randomization. The EQ-5D-5L health utility score was lower in patients in the high-protein group; there was also more gastrointestinal intolerance of the higher protein EN.¹⁴⁶ Another ICU study (40% with HF, 8% with cardiac arrest) compared high-protein nutrition (target energy, 20 kcal·kg⁻¹·d⁻¹; protein, 1.8 g·kg⁻¹·d⁻¹) with medium-protein nutrition (target energy, 20 kcal·kg⁻¹·d⁻¹; protein, 0.9 g·kg⁻¹·d⁻¹) and showed less femoral muscle volume loss by computed tomography in the high-protein group but only during a period of electric muscle stimulation.¹⁴⁷ At the present time, the most appropriate protein intake approaches for the CICU population are likely those in alignment with evidence-based guidance from ASPEN and the Society of Critical Care Medicine, which favor individualized protein intake targets within the 1.2– to 2.0–g·kg⁻¹·d⁻¹ range, with cautious consideration of higher intake in select patients with burns, trauma, or obesity.^148–150

Nutritional Support in HF and Cardiogenic Shock in the CICU

Patients admitted with HF to the CICU often have poor nutrient absorption from mucosal edema, low cardiac output, inflammation, and neurohormonal activation with mesenteric vasoconstriction and microvascular dysfunction.¹⁹ During cardiogenic shock (CS), these effects are further exacerbated by intestinal venous congestion and pressor use, especially vasopressin, which has a particularly unfavorable impact on mesenteric blood flow.¹⁵¹ In these scenarios, the initiation of EN may prompt mesenteric ischemia due to increased metabolic demand of the intestinal mucosa.^152,153 This can occur despite an observed increase in the mesenteric blood because arteriovenous oxygen extraction in the gut is often impaired in shock states. Accordingly, it may be reasonable to delay EN in patients with worsening CS, uncontrolled acidosis or hypoxemia, gastrointestinal bleeding, nausea, or vomiting.

Although there are no studies specific to CS, 2 trials have evaluated nutritional support in shock. The first study compared early normocaloric EN with PN in shock, including 20% with CS,¹⁵⁴ showing no differences in survival. There were more complications associated with EN, including bowel ischemia, nausea, diarrhea, and acute colonic pseudo-obstruction. Another trial compared patients with shock receiving early (<24 hours) low-calorie (6 kcal·kg⁻¹·d⁻¹), low-protein (0.2–0.4 g/kg) EN with those receiving normocaloric (20–25 kcal·kg⁻¹·d⁻¹), normoproteic (1.0–1.3 g/kg) EN, including ≈18% with CS.¹⁵⁵ In this study, calorie and protein restriction did not affect survival but was associated with lower complications, including less bowel ischemia and liver disease, and with shorter ICU stay.¹⁵⁶

EN is not contraindicated during low-dose vasopressor administration, and the benefits of early versus late EN have been seen in patients receiving low to moderate vasopressor dosing.¹⁵⁷ Standard clinical practice in CS is that EN initiation is reasonable once hemodynamic stability is achieved, when vasopressors are no longer being titrated or used in high doses. Although the dose threshold for safe vasopressor use during EN is not definite, the mean and maximal tolerated doses of norepinephrine for safe EN feeding in 1 study were 7 and 12.5 μg/min, respectively.¹⁵⁸ In addition, the risk of intestinal ischemia is higher for lactate >2.0¹⁵⁹ or Sequential Organ Failure Assessment score >11.¹⁵⁴ This more aggressive approach of early EN initiation aligns with recommendations from the European Society for Clinical Nutrition and Metabolism¹³⁵ and differs from ASPEN recommendations, which suggest delaying EN until appropriate resuscitation is achieved.¹³⁴

Early EN has also been shown to be safe in a prospective observational study with >200 patients with mechanical circulatory support,¹⁶⁰ although that study excluded patients with refractory CS. However, advanced mechanical circulatory support such as venoarterial extracorporeal membrane oxygenation carries a significantly higher risk of mesenteric ischemia, as high as 5% to 9%,^19,161 in contrast to 1% to 2% when vasoactive agents alone are used.¹⁵⁸ Risk factors for mesenteric ischemia in venoarterial extracorporeal membrane oxygenation have included renal replacement therapy and higher vasopressor dosing but not timing or route of nutritional support.¹⁶² Although early EN in venoarterial extracorporeal membrane oxygenation is associated with lower mortality,¹⁶³ it may be appropriate to delay EN after venoarterial extracorporeal membrane oxygenation and use hypocaloric targets (<70%–80%) and higher protein administration for the hypercatabolic state to optimize surivial.^164,165 Indirect calorimetry may become inaccurate during ECMO support,^166,167 and entrapment of micronutrients and macronutrients in the ECMO membrane can occur.¹⁶⁸

An additional CICU consideration is use of intravenous lipid emulsions from propofol, clevidipine, or PN.¹⁶⁹ Propofol provides 1.1 kcal/mL and clevidipine provides 2 kcal/mL; at high rates, these infusions can deliver significant calories, and tube feeding should be adjusted accordingly. For patients receiving PN, ≈30% of calories should come from lipids.¹⁴⁸ A small benefit is shown in critical care patients from using alternative intravenous lipid emulsions that contain more omega 3 fatty acids than purely soybean oil lipid emulsion, which is higher in omega 6. Overall, lipid emulsion choice may be dictated by product availability and possible allergies, and lipid emulsion should be stopped if triglycerides are >400 mg/dL.¹⁴⁸

Last, because respiratory failure is the most common critical care indication for CICU admission,¹⁷⁰ with many patients requiring MV,¹⁷¹ it is important to incorporate insensible losses, metabolic demands, and appropriate periextubation management into their nutritional support. Although there is paucity of data in this area, 1 trial including 30% of patients with HF and 2% with CS demonstrated that EN continuation during MV liberation was associated with shorter extubation times, shorter MV duration, better achievement of caloric goals, lower mortality, and less hypoglycemia without differences in aspiration events compared with EN interruption.¹⁵⁵ This strategy, however, has not been evaluated in the CICU population.

Nutritional Support in Cardiac Arrest in the CICU

In contrast to patients with HF, BMI and nutritional risk scores do not predict outcomes after cardiac arrest.^172,173 Prior recommendations suggested delaying EN in patients after cardiac arrest on the presumption of lower metabolic rates and delayed gastric emptying, particularly when targeted temperature management at 32° C to 36° C is used.¹⁹ However, this practice has changed as the use of targeted temperature management has evolved, and newer data demonstrated no difference in complications with early EN (<48 hours) even during targeted temperature management.^19,174–177 Moreover, early EN may be associated with potential benefits in neurological outcomes and infectious complications after cardiac arrest,^176,178 although this association may not apply to patients with refractory cardiac arrest undergoing extracorporeal cardiopulmonary resuscitation. In those cases, delayed EN (>48 hours) may be associated with better neurological outcomes,¹⁶¹ but this may simply reflect an immortal time bias.¹⁷⁹

NUTRITIONAL SUPPORT FOR PATIENTS UNDERGOING CARDIAC PROCEDURES

Cardiac Catheterization and Implantable Electronic Device Procedures

Evidence supporting prolonged preprocedural fasting for cardiac catheterization or implantation of electronic devices is weak, with no difference in gastric pH or volume between fasting 2 to 4 hours versus >4 hours.^180,181 Recently, small randomized studies of patients undergoing routine cardiac procedures requiring conscious sedation have suggested no differences in adverse procedural events for patients who fasted or did not fast before their procedures. In the investigator-initiated SCOFF trial (Safety and Care of No Fasting Prior to Catheterization Laboratory Procedures), patients were randomized 1:1 to preprocedural fasting, meaning no solid food for 6 hours and no clear liquids for 2 hours, or no fasting (patients were encouraged to have regular meals). The primary composite end point of hypotension, aspiration pneumonia, hyperglycemia, and hypoglycemia occurred in 19.1% of the fasting group and 2.0% of the no-fasting group, with the analyses confirming noninferiority of no fasting (based on a noninferiority margin of 3% and a likelihood of 99.1%).¹⁸² Patient satisfaction was significantly greater in the no-fasting group. Together with data from other similar studies,^183,184 there is an increasing movement toward removing NPO requirements for diagnostic cardiac catheterization cases and routine device procedures, which has the potential to decrease in-hospital malnutrition development.

Cardiac Surgery

Patients classified as malnourished by GLIM criteria have poorer surgical outcomes, with a complication rate of 65.9% compared with 49.7% for those not classified as malnourished.¹⁸⁵ According to Enhanced Recovery After Surgery recommendations,¹⁸⁶ perioperative nutritional optimization is key to expediting recovery. This includes preoperative malnutrition assessment with validated tools (Table 3) to predict postoperative complications¹⁸⁷ and clinical, biochemical, and imaging parameters, for example, quadriceps ultrasound or computed tomography, to assess for sarcopenia.¹⁸⁸ Although not good markers of nutritional status, albumin <3.0 g/dL and prealbumin ≤20 mg/dL have been used as acute-phase markers to trigger nutritional supplementation within 1 week of surgery.^{186,189–191}

Minimizing starvation to prevent iatrogenic malnutrition is key preoperatively.¹⁹² European recommendations have adopted evidence for clear liquids up to 2 hours before and a light meal up to 6 hours before surgery.^180,188,193 Although preoperative oral carbohydrate loading has been proposed to benefit cardiac function and may improve length of stay, its evidence before cardiac surgery is weak.^186,194 During the postoperative period, nutritional support with EN is preferable over PN and should be initiated within 48 hours or within 24 hours if malnutrition present.¹⁹⁵ It is recommended to start with hypocaloric EN, with 80% of the target protein and caloric goals, considering supplemental PN if necessary.¹⁸⁸ As with patients with CS, for patients after cardiotomy who remain hemodynamically unstable, requiring vasopressors or mechanical circulatory support, delaying EN may be appropriate given that the risk of intestinal infarction and bacterial translocation with resulting sepsis is elevated.^196,197 In these cases, delaying EN may be appropriate.¹⁹⁸ If EN cannot be started by day 7, PN is indicated.

NUTRITIONAL SUPPORT AFTER DISCHARGE AND READMISSION REDUCTION

Several small but randomized studies highlight the importance of nutritional interventions in reducing cardiac readmissions, specifically in patients with HF. The PICNIC (Programa de IntervenCión Nutricional en pacientes hospitalizados por Insuficiencia Cardiaca desnutridos) study recruited patients in Spain with HF and risk of malnutrition. Individualized RDN-led dietary counseling and support reduced the composite of hospital readmissions and mortality, as well as mortality as a secondary end point, and improved quality of life.¹³² The next steps would ideally include a similar protocol for postdischarge patients with HF in the United States, with expansion to patients with other CVDs if effective in reducing HF readmissions. Definitive data on malnutrition interventions specifically for patients after myocardial infarction or coronary interventions are not currently available.

GOURMET-HF (Geriatric Out-of-Hospital Randomized Meal Trial in Heart Failure) examined the impact of a tailored DASH diet after HF discharge and found a trend toward improved HF readmissions and mortality,¹⁹⁹ although this was predominantly a sodium-restriction intervention and not a malnutrition intervention. Medically tailored meals (MTMs) based on the DASH pattern were prepared, packaged for refrigerator storage, and home delivered once weekly. Potassium content was modified from 4500 to 3000 mg/d in patients with estimated glomerular filtration rate <45 mL·min⁻¹·1.73 m⁻², or 45 to 60 mL·min⁻¹·1.73 m⁻² with serum potassium >4.5 mmol/L, or potassium >4.5 mmol/L with potassium-sparing diuretic use. A follow-up study, GOURMET-VA (Geriatric Out-of-Hospital Randomized Meal Trial in Heart Failure: Veterans Affairs; NCT05996328) will enroll a larger cohort to define the efficacy and safety of nutritional support in the postdischarge HF setting.

The concept of MTMs is gaining traction, particularly within the Food Is Medicine movement. MTMs provide patients with meals designed to meet their specific medical and nutritional needs, particularly for those with chronic conditions such as CVD. Although some general medical programs have reported neutral results for Food Is Medicine interventions,^200,201 the overall evidence base suggests potential benefits for cardiovascular health and readmission reduction. MTMs can help bridge the gap between inpatient dietary recommendations and practical, daily nutrition after discharge, supporting better health outcomes for patients with CVD. Cardiac rehabilitation offers a prime opportunity to integrate high-quality nutritional counseling into cardiovascular outpatient care. This setting allows comprehensive lifestyle interventions, including dietary education, tailored to the needs of patients with CVD. Effective nutritional counseling during cardiac rehabilitation can enhance patients’ dietary habits, support recovery, and prevent future cardiac events. However, achieving these benefits may require additional training for clinicians to ensure that they are equipped to provide evidence-based nutritional advice. Investing in clinician education on nutrition can strengthen the impact of cardiac rehabilitation programs and improve patient outcomes. There are significant potential opportunities to study integrated nutritional support both during hospitalization and early after discharge, leveraging initiatives such as MTMs and comprehensive cardiac rehabilitation to determine the scope to enhance outcomes for patients with CVD.

RDNs AS KEY MEMBERS OF THE CARDIAC CARE TEAM

Every patient admitted to the CICU should undergo comprehensive nutritional assessment, including physical examination and laboratory parameters; evaluation for cardiac cachexia, sarcopenia, and risk of refeeding syndrome; and specific volume and electrolyte goals. Certain nutritional risk scores previously validated in CICU conditions,²⁰² including Controlling Nutritional Status, Prognostic Nutritional Index, Geriatric Nutritional Risk Index, Subjective Global Assessment, and modified Nutrition Risk in the Critically Ill, can provide useful information outlined in Table 2.¹⁹ This comprehensive and tailored evaluation is best performed by RDNs because they play a pivotal role in identifying and classifying malnutrition; optimizing and individualizing nutritional support,^203,204 including determination of appropriate micronutrient and macronutrient supplementation; and assessing and adjusting caloric, protein, and fluid administration. RDNs also provide key roles in nutrition education, counseling discharge planning for patients and families,²⁰⁵ and longitudinal follow-up for dynamic targets. Suggested criteria for identification of inpatients who may benefit from RDN assessment and counseling are provided in Figure 2.

Figure 2. Practical guidance for the screening, evaluation, and treatment of cardiovascular inpatients at risk of malnutrition or cachexia.

ASPEN/AND indicates American Society for Parenteral and Enteral Nutrition/Academy of Nutrition and Dietetics; BMI, body mass index; CICU, cardiovascular intensive care unit; MNA-SF, Mini Nutritional Assessment Short Form; MST, Malnutrition Screening Tool; MUST, Malnutrition Universal Screening Tool; RDN, Registered Dietitian Nutritionist; and SNAQ, Short Nutritional Assessment Questionnaire. Adapted from Vest et al.¹¹¹ Copyright © 2019, with permission from Elsevier Inc.

Unfortunately, despite increasing implementation of interdisciplinary teams in the CICU,^206,207 the RDN role does not always receive prioritization and may remain underused. To date, no studies have evaluated the impact of RDNs on outcomes in the CICU,²⁰² and research in this area should be prioritized. Furthermore, the availability of RDNs with expertise in acute cardiovascular conditions is limited, highlighting the need to promote training and staffing models to enhance the RDN workforce and to support their role educating and working alongside clinical teams managing patients with acute cardiac care needs.

UNANSWERED QUESTIONS IN THE MANAGEMENT OF MALNUTRITION AND CACHEXIA IN PATIENTS WITH CARDIAC CONDITIONS

Multiple knowledge gaps exist and should serve as research priorities for defining best practices for preventing, screening for, and managing malnutrition and unintentional weight loss in hospitalized adults with CVD (Figure 3).^211a First, there is a lack of consensus on which validated malnutrition tool is most appropriate for cardiac inpatients, both for malnutrition detection and for prediction of mortality and readmission, with recognition that performance may differ by disease state and severity of illness (Table 2).

Figure 3. Unanswered questions and evidence gaps for the management of malnutrition and cachexia in patients with cardiovascular disease.

AI indicates artificial intelligence; CV, cardiovascular; HF, heart failure; DASH, Dietary Approaches to Stop Hypertension; and SRD, sodium-restricted diet. Data from Laimer et al,²⁰⁸ Gullett et al,²⁰⁹ Johnson et al,²¹⁰ Vest et al,¹¹¹ Kadakia et al,²¹¹ Ilonze et al,⁹⁰ and Watanabe and Miyagoe-Suzuki.^211a

Once hospitalized patients with or at risk of malnutrition are identified, the optimal strategy for assessing body composition to diagnose cachexia and sarcopenia is unknown. Choice of diagnostic tool is based largely on cost, availability, influence of volume status, ease of use, and overall body habitus.^212,213 Although DXA is a rapid, inexpensive method to evaluate for sarcopenia, it is ionizing and nonportable, limiting accessibility for inpatients.^90,212,214 Similarly, bioelectrical impedance analysis and bioelectrical impedance spectroscopy are low-cost, nonionizing alternatives to DXA. Bioelectrical impedance analysis of fat mass shows variability at body composition extremes for patients with HF compared with DXA,²¹⁵ but skeletal muscle mass correlates with absolute peak $\dot{\mathrm{V}}{\mathrm{o}}_2$ in patients with HF with reduced ejection fraction and obesity.⁸⁸ The use of ultrasound to directly measure skeletal muscle thickness is attractive because it is portable and nonionizing and can be repeated over time. However, ultrasound lacks standardized protocols and thresholds and is operator dependent.²¹⁶ Deuterated creatine dilution is an evolving tool that assesses total body muscle mass by measuring total body creatine pool size, which may be more precise at predicting mortality than DXA.²¹⁷ However, deuterated creatine has not been validated in patients with CVD and is not yet available for routine clinical practice.^217,218

Unanswered mechanistic questions contribute to uncertainties about the optimal assessment strategies and treatment modalities for malnutrition and cachexia in patients with CVD and warrant further investigation.

Can treatment of underlying CVD reverse cachexia? In patients with HF, this may be possible by improving neurohormonal derangements through guideline-directed medical therapy, implantable devices, and heart transplantation.⁹⁰ There may also be an opportunity for emerging cancer cachexia therapies such as growth differentiation factor-15 inhibition in cardiac cachexia.²¹⁹

How do obesity, weight loss, and body composition affect outcomes for patients with HF? Obesity is a known risk factor for incident HF, yet moderately elevated BMIs may be associated with favorable outcomes in patients with HF (the “obesity paradox”) likely as a result of unintentional cachexia-related weight loss in patients with lower BMIs.^19,111 A similar concern arises with the use of antiobesity medications for patients with HF, in whom lean mass loss may exacerbate functional limitations.²²⁰

How do environmental factors and individual differences influence the development of malnutrition and response to dietary interventions in patients with CVD? In lieu of universal dietary interventions, precision nutrition may incorporate environmental, genomic, epigenomic, and microbiome variations to predict response to diets and to customize dietary interventions in malnourished and cachectic patients with CVD.²²¹

High-quality nutritional evidence in acutely and critically ill patients with CVD is currently inadequate and can be challenging to obtain. Because studies of nutritional and activity-based interventions may not attract industry funding, engagement and strategic partnerships from community-based organizations and philanthropic foundations may be more appropriate.^105,222,223 Enhancing research-focused collaborations with RDNs is crucial, as demonstrated by the EFFORT and PICNIC studies.^104,132 Although several US Food and Drug Administration–approved and investigational medications have been studied to prevent and manage malnutrition and cachexia, their use is largely off-label, and little is known about the safety and efficacy in patients with CVD (Table 4).

Table 4. Pharmacological Interventions and Targets to Manage Malnutrition and Cachexia.

FDA-approved medications
Drug class/drug	Mechanism of action	Outcomes	Adverse effects	Comments
Appetite stimulants:
Megestrol	Unknown	Increase weight gain and fat mass, no increase in LBM	Hypertension, thromboembolism at high doses, edema, palpitations	Not studied in patients with CVD; dose-related effects (range 160–800 mg daily)
Mirtazapine	May be related to increased leptin concentrations	Increase weight gain and fat mass	Drowsiness, dry mouth, constipation, dizziness, edema	7.5–30 mg at bedtime; drowsiness and dizziness may limit use in older adults
Cannabinoids	May stimulate orosensory reward pathway	Inconsistent results on appetite, weight gain in cancer-related cachexia	Drowsiness, tachycardia, hypotension, confusion	Dronabinol dose: 2.5–5 mg twice daily; cannabis use may reduce heart transplantation candidacy
Antiinflammatory:
Omega-3 fatty acids	Decrease inflammation, proinflammatory factors, and proteolytic pathways; increase appetite	Inconclusive	Diarrhea, nausea, belching	1–4 g daily; effects likely dependent on dose, timing, duration, and formulation
Anabolic agents:
Growth hormone	Stimulates production of IGF-1, leading to protein synthesis and muscle growth	Consistent anabolic effects in patients with malnutrition and catabolic states	Sodium retention, edema	Inconsistent efficacy in patients with HF
Steroid derivatives: (testosterone) (nandrolone) (oxandrolone)	Bind to cytosolic receptors, increase protein synthesis and muscle mass	Increase weight gain, LBM, and muscle strength; testosterone did not improve exercise capacity or QOL in patients with HF	Fluid retention, increased liver enzymes, decreased HDL-C, drug interaction with warfarin	Testosterone has limited benefit in HF; oxandrolone FDA approval was withdrawn; nandrolone no longer marketed in the United States
Investigational drugs/drug targets
Ghrelin analogs:
Anamorelin Macimorelin	Stimulates appetite, growth hormone release, antiinflammatory activity	Small increase in fat-free mass, minimal improvement in muscle quality, QOL		Anamorelin not approved in the United States, EMA declined approval citing marginal benefit; macimorelin approved to diagnose GHD
Selective androgen receptor modulators:
MK-0773 LGD-4033 Enobosarm	Selective androgen agonism in skeletal muscle and bones to produce anabolic effects	Increased LBM, inconsistent results in muscle function	None known	Studies ongoing for cancer-related cachexia
GDF-15 antibodies:
Ponsegromab NGM120 AV380 CTL002	Stimulates appetite by preventing GDF-15 binding to GFRAL	Unknown	Unknown	Studies ongoing for cancer-related cachexia
Melanocortin type 4 receptor antagonists:
TCMCB07 PF-07258669	Antagonizes α-melanocyte-stimulating hormone, increasing appetite	Unknown	Unknown	Studies ongoing for cancer-related cachexia
ActRIIB blockers:
Bimagrumab	Antagonizes ActRIIB receptors, reducing muscle catabolism	Increased LBM in older adults with sarcopenia	None known	Studies ongoing in adults with sarcopenia

ActRIIB indicates activin receptor IIB; CVD, cardiovascular disease; EMA, European Medicines Agency; FDA, US Food and Drug Administration; GDF, growth differentiation factor; GFRAL, glial cell-derived neurotrophic factor family receptor α-like; GHD, growth hormone deficiency; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; IGF, insulin-like growth factor; LBM, lean body mass; and QOL, quality of life.

CONCLUSIONS

Despite multiple areas of incomplete knowledge in the diagnosis and management of malnutrition and cachexia among inpatients with cardiovascular conditions, several principles are now well established (Table 5). The prevalence of malnutrition lies between 20% and 60% in this population, with risk factors including age, comorbidities, metabolic demands, and inflammation and health care factors such as inpatient food choices and NPO times. The GLIM criteria are the cornerstone of malnutrition diagnosis. For stable inpatients, a personalized nutrition plan for patients at risk of malnutrition may improve survival, and the provision of culturally acceptable, nourishing hospital food should be a patient safety goal. For critically ill patients, the risks of undernutrition are high. EN initiation is recommended by 48 hours of admission, provided that any pressor requirement is trending down and end-organ perfusion is sufficient; for patients who do not meet these goals by day 7, PN should be initiated. Although protein goals of 1 to 1.2 g·kg⁻¹·d⁻¹ may be appropriate for patients with chronic cardiovascular conditions associated with wasting, higher protein intake targets in the region of >2.0 g·kg⁻¹·d⁻¹ have not proved beneficial in patients with MV. Clinical trial data now support the removal of NPO requirements before cardiac catheterization and electronic device implantation procedures under conscious sedation. Increased awareness and education surrounding the risk of malnutrition and practical steps that can be taken to optimize nutritional health will be of benefit to the diverse populations of patients with CVD admitted to hospital for acute decompensations of their cardiac conditions.

Table 5. Top 10 Clinical Practice Takeaways for Nutritional Support in Cardiovascular Care.

1. Routinely assess nutritional risk in all cardiovascular inpatients. Malnutrition is prevalent yet underrecognized in cardiovascular disease, especially in critical care. Use of validated screening tools to detect higher-risk patients should be followed by the use of the Academy of Nutrition and Dietetics and ASPEN diagnostic criteria.

2. Avoid underfeeding in the CICU. Initiate EN within 24 to 48 of CICU admission for most patients. Hypocaloric, high-protein feeds can be started in those on low-dose vasopressors, with close hemodynamic monitoring to avoid gut ischemia.

3. Delay nutrition when hemodynamically unstable. In patients requiring high-dose vasopressors or MCS, delay EN under cardiovascularly stabilizing to reduce the risk of intestinal ischemia. Use PN by day 7 if the enteral route remains contraindicated.

4. Protein intake requirements are nuanced and require ongoing research. Protein intake goals of 1–1.2 g∙kg−1∙d−1 may be appropriate for patients with cardiac cachexia, and current society guidance for critically ill adults favor the 1.2–2.0 g∙kg−1∙d−1 range; studies of higher protein intake >2.0 g∙kg−1∙d−1 have not proved beneficial.

5. Reassess traditional fasting before cardiac procedures. Fasting before elective procedures such as routine cardiac catheterization or device implantation may be unnecessary and could promote malnutrition. It may be appropriate to allow clear liquids up to 2 h and light meals up to 6 h before some surgical procedures.

6. Integrate nutritional strategies in cardiac surgery pathways. Assess and optimize nutrition preoperatively and consider the use of an Enhanced Recovery After Surgery program pathway. Postoperatively, start enteral nutrition early and consider supplemental parenteral nutrition if enteral feeding is not feasible within 7 d.

7. Address malnutrition to reduce readmissions, especially in HF. Nutritional interventions (eg, tailored diets, RDN counseling) can reduce hospital readmissions and mortality in HF. Studies such as PICNIC and GOURMET-HF highlight the potential impact of individualized dietary support after discharge.

8. Consider MTMs at discharge. MTMs, aligned with the Food Is Medicine model, offer a scalable intervention to support dietary adherence and to reduce cardiovascular readmissions after discharge and should focus on accessibility and cultural acceptability of high-quality foods.

9. Provide cardiac rehabilitation with nutrition counselling. Cardiac rehabilitation is an underused platform for delivering high-impact dietary education. Embedding RDNs in rehabilitation programs can improve patient adherence to heart-healthy diets and support long-term secondary prevention.

10. Strengthen the role of RDNs in cardiovascular care. RDNs are essential to providing individualized, evidence-based nutrition therapy across the cardiovascular continuum, from CICU to discharge planning. Their role remains underused, and the workforce remans understaffed. Clinicians and institutions should advocate for greater integration and training of RDNs in cardiovascular-specific care.

ASPEN indicates American Society for Parenteral and Enteral Nutrition; CICU, cardiac intensive care unit; EN, enteral nutrition; GOURMET-HF, Geriatric Out-of-Hospital Randomized Meal Trial in Heart Failure; HF, heart failure; MCS, mechanical circulatory support; MTM, medially tailored meal; PICNIC, Programa de IntervenCión Nutricional en pacientes hospitalizados por Insuficiencia Cardiaca desnutridos; PN, parenteral nutrition; and RDN, registered dietitian nutritionist.

Disclosures

Writing Group Disclosures.

Writing group member	Employment	Research grant	Other research support	Speakers’ bureau/honoraria	Expert witness	Ownership interest	Consultant/advisory board	Other
Amanda R. Vest	Cleveland Clinic	National Heart, Lung, and Blood Institute (grant R01HL167113); National Center for Advancing Translational Sciences (grant RC2TR004377)	None	None	None	None	None	None
Carlos L. Alviar	New York University	Baxter Medical*	None	None	None	None	Zoll†; JNJ Medtech*	None
Erin Bohula	Brigham and Women’s Hospital and Harvard Medical School	None	Novo Nor-disk†	None	None	None	Novo Nor-disk†	None
Abdulla A. Damluji	Johns Hopkins Medicine Inova Center of Outcomes Research	None	None	None	None	None	None	None
Robert J. DiDomenico	University of Illinois at Chicago	Society of Critical Care Medicine Carolinas and Virginias Chapter (coinvestigator on a grant surveying pharmacists regarding the use of digoxin in patients receiving continuous renal replacement therapy)*; Consortium of Academic and Research Libraries in Illinois|Support for Creation of Open Educational Resources (c/o Fund for the Improvement of Postsecondary Education) (coinvestigator on grant to support development of an open educational resource book on fundamental pharmacology for nursing students)*; Institute for Clinical and Economic Review (coinvestigator on a grant to conduct a cost-effectiveness analysis of new therapies to treat amyloid transthyretin cardiomyopathy)*; Cook County Department of Public Health (co-principal investigator on a grant to provide health information and screening services to underrepresented communities in suburban Cook County)†; Agency for Healthcare Research & Quality (unpaid member of the DSMB for grant 1R18HS028787-01A1)*	American College of Clinical Pharmacy (chair, Research Affairs Committee [unpaid])*; American College of Clinical Pharmacy (board of regents member)*	None	None	None	None	None
Eson Ekpo	Scripps Health	None	None	None	None	None	None	None
Lily Lichtenstein	Tufts Medical Center	None	None	None	None	None	None	None
Tammy Slater	Johns Hopkins University School of Nursing	None	None	None	None	None	None	None

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.

^*Modest.

^†Significant.

Reviewer Disclosures.

Reviewer	Employment	Research grant	Other research support	Speakers’ bureau/honoraria	Expert witness	Ownership interest	Consultant/advisory board	Other
Salvatore Carbone	EVMS at Old Dominion University	None	None	None	None	None	None	None
Elissa Driggin	Columbia University Medical Center/New York–Presbyterian Hospital	None	None	None	None	None	None	None
Alejandra Gutierrez	University of Minnesota	None	None	None	None	None	None	None
Onyedika J. Ilonze	Indiana University School of Medicine	None	None	None	None	None	None	None
Melana Yuzefpolskaya	Columbia University Medical Center	Abbott (Enhanced Nutritional Optimization of Patients Prior to Left Ventricular Assist Device Implantation)*	None	Abbott*	None	None	None	None

This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.

^*Modest.