Noncardiac Organ Dysfunction Research Articles

Integrating risks and benefits: pretransplant assessment and patient selection for heart transplantation in adult congenital heart disease.

The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population. There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk. Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.

Syndecan-1: From a Promising Novel Cardiac Biomarker to a Surrogate Early Predictor of Kidney and Liver Injury in Patients with Acute Heart Failure.

(1) Background: Acute heart failure (HF) represents a complex clinical syndrome burdened by increased mortality and a high rate of systemic complications. Although natriuretic peptides (e.g., NT-proBNP) currently represent the diagnostic and prognostic gold standard in acute HF, those molecules do not accurately reflect all the pathophysiological mechanisms involved in the progression of this pathology when determined independently. Therefore, the current paradigm tends to focus on a multi-marker approach for the risk stratification of patients with acute HF. Syndecan-1 is a less studied biomarker in cardiovascular diseases; its assessment in patients with acute HF being potentially able to reflect the myocardial pathological changes, such as fibrosis, inflammation, endothelial dysfunction or global wall stress. (2) Methods: We conducted a single center prospective study that enrolled 173 patients (120 patients admitted for acute HF, compared to 53 controls with stable chronic HF). A complete standardized clinical, echocardiography and laboratory evaluation was performed at admission, including serum samples for the determination of syndecan-1 by the enzyme-linked immunosorbent assay (ELISA) method. (3) Results: The serum concentration of syndecan-1 was significantly higher in patients with acute HF, compared to controls [121.4 (69.3-257.9) vs. 72.1 (41.4-135.8) ng/mL, p = 0.015]. Syndecan-1 was a significant predictor for the diagnosis of acute HF, expressed by an area under the curve (AUC) of 0.898, similar to NT-proBNP (AUC: 0.976) or cardiac troponin (AUC: 0.839). Moreover, syndecan-1 was independently associated with impaired kidney and liver function at admission, being also a predictor for early, subclinical organ dysfunction in patients with normal biological parameters at admission. When included in the multi-marker model, syndecan-1 levels influenced mortality more significantly than NT-proBNP or troponin. A multivariable regression including syndecan-1, NT-proBNP and troponin provided additional prognostic value compared to each independent biomarker. (4) Conclusions: Syndecan-1 can be considered a promising novel biomarker in acute HF, exhibiting adequate diagnostic and prognostic value. Additionally, syndecan-1 can be used as a surrogate biomarker for non-cardiac organ dysfunction, as its highs levels can accurately reflect early acute kidney and liver injury.

Abstract 11098: End-Organ Dysfunction Differs in Patients With Heart Failure-Related vs. Acute Myocardial Infarction-Related Cardiogenic Shock

Introduction: Severity of end-organ dysfunction correlates with outcomes in acute myocardial infarction-related cardiogenic shock (AMI-CS). The epidemiology of end-organ dysfunction in heart failure-related cardiogenic shock (HF-CS) has not been well described. Methods: Cardiac intensive care unit (CICU) admissions with CS in the Critical Care Cardiology Trials Network Registry (2017-2021) were identified and categorized as AMI-CS and HF-CS ( de novo or acute-on-chronic HF). Admissions for each CS sub-type were characterized as having respiratory, kidney, liver, and/or neurologic dysfunction using definitions adapted from the Sequential Organ Failure Assessment score ( Fig A ). Outcomes were assessed by burden of non-cardiac organ dysfunction: no end-organ dysfunction (NEOD), single system end-organ dysfunction (SEOD), or multi-system end-organ dysfunction (MEOD). Results: A total of 2,911 CS admissions from 35 CICUs were identified, most of which were for HF-CS (71%, N = 2,068). The proportions of patients with NEOD, SEOD, and MEOD were 25%, 36%, 39% for HF-CS vs. 16%, 35%, 49% for AMI-CS (p<0.01). NEOD, SEOD, and MEOD rates were 19%, 31%, and 49% for de novo HF-CS vs. 27%, 37%, and 36% for acute-on-chronic HF-CS (p<0.01). Predominant type of organ dysfunction differed among CS sub-types, with higher rates of respiratory dysfunction in AMI-CS and de novo HF-CS (p<0.01) and higher rates of hepatic dysfunction in both de novo and acute-on-chronic HF-CS (p<0.01; Fig A ). In-hospital mortality was lower in acute-on-chronic HF-CS compared with de novo HF-CS or AMI-CS (25% vs. 32% vs. 38%; p<0.01), with a similar gradient of risk according to burden of non-cardiac organ dysfunction (p int = 0.64; Fig B ). Conclusions: End-organ dysfunction pattern and burden differ among de novo HF-CS, acute-on-chronic HF-CS, and AMI-CS. Overall mortality is lowest in acute-on-chronic HF-CS, but mortality is similarly associated with burden of end-organ dysfunction among CS types.

The NHLBI Study on Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC): Design and Objectives

The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. This multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies. The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

Racial Disparities in Hospital Mortality Among Pediatric Cardiomyopathy and Myocarditis Patients.

Racially disparate health outcomes exist for a multitude of populations and illnesses. It is unknown how race and ethnicity impact mortality for children with cardiomyopathy or myocarditis. This retrospective cross-sectional study employed the Kids' Inpatient Database to analyze 34,617 hospital admissions for patients ≤ 18years old with cardiomyopathy, myocarditis, or both, without concomitant congenital heart disease. Multivariate logistic regression models investigated the impact of race/ethnicity on in-hospital mortality adjusting for age, calendar year, sex, insurance type, diagnostic category, treatment at a pediatric hospital, and non-cardiac organ dysfunction. African American race and Hispanic ethnicity were independent risk factors for mortality (African American: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.01-1.53 and Hispanic: OR 1.29, 95% CI 1.03-1.60). African American race was also found to be significantly associated with the use of extracorporeal membrane oxygenation (ECMO), mortality while on ECMO, and cardiac arrest. Adjusting the regression model for ECMO and arrest attenuated the impact of African American race on mortality, suggesting that these variables may indeed play a role in explaining the impact of race on mortality for African American patients with myocardial disease. Hispanic ethnicity remained associated with higher risk of mortality despite controlling for all mechanical circulatory support and transplant (OR 1.30, 95% CI 1.04-1.63). Children of racial and ethnic minorities hospitalized with cardiomyopathy or myocarditis are more likely to die than their white counterparts, a trend that may be due at least in part to in-hospital differences in care or response to therapy.

Non-cardiac Cause of Death And Organ Dysfunction Common Among Patients Admitted To The Cardiac Intensive Care Unit

Introduction Over the past decade, there has been an increase in the proportion of patients admitted to the cardiac intensive care unit (CICU) with non-cardiac comorbidities and admission diagnoses. However, organ system dysfunction and causes of death in CICU patients remains poorly characterized. Given the increasing proportion of admissions to the CICU for non-cardiac diagnoses, we hypothesized that there would be a substantial proportion of non-cardiac organ dysfunction and death due to non-cardiac causes. Methods We identified adult patients admitted to a CICU at a large tertiary care center (2015-2019) who died during the hospitalization. Principal hospitalization diagnosis, demographics, organ system dysfunctions, cause of death, and withdrawal of life support were abstracted via a standardized tool used in prior studies. The primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. Results We identified 258 decedents admitted to the CICU. Most patients (76%) had cardiac dysfunction, defined as cardiogenic shock or sustained ventricular arrhythmia. However, only 11% of patients had cardiac dysfunction alone, 89% experienced non-cardiac organ dysfunction, and 24% died without cardiac dysfunction. Multi-organ failure and sepsis were present in 70% and 54% of patients, respectively. The most common primary causes of death were cardiac (58%), pulmonary (15%), and neurologic dysfunction (11%). The majority of patients (76%) died after withdrawal of life-sustaining interventions. Conclusions In this contemporary cohort of CICU decedents, 3 of 4 patients had cardiogenic shock or sustained ventricular arrhythmias. However, non-cardiac organ dysfunction occurred in the vast majority, and nearly half had a non-cardiac primary cause of death. The high frequency of multi-organ failure and non-cardiac causes of death underscores the importance of broad cardiac and non-cardiac critical care training among physicians practicing in the CICU.

Characterization of the Progression From Ambulatory to Hospitalized Heart Failure With Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Some patients develop elevated filling pressures exclusively during exercise and never require hospitalization, whereas others periodically develop congestion that requires inpatient treatment. The features differentiating these cohorts are unclear. We performed a secondary analysis of 7 National Institutes of Health-sponsored multicenter trials of HFpEF (EF ≥ 50%, N = 727). Patients were stratified by history of hospitalization because of HF, comparing patients never hospitalized (HFpEFNH) to those with a prior hospitalization (HFpEFPH). Currently hospitalized (HFpEFCH) patients were included to fill the spectrum. Clinical characteristics, cardiac structure, biomarkers, quality of life, functional capacity, activity levels, and outcomes were compared. As expected, HFpEFCH (n = 338) displayed the greatest severity of congestion, as assessed by N-terminal pro B-type natriuretic peptide levels, edema and orthopnea. As compared to HFpEFNH (n = 109), HFpEFPH (n = 280) displayed greater comorbidity burden, with more lung disease, renal dysfunction and anemia, along with lower activity levels (accelerometry), poorer exercise capacity (6-minute walk distance and peak exercise capacity), and more orthopnea. Patients with current or prior hospitalization displayed higher rates of future HF hospitalization, but quality of life was similarly impaired in all patients with HFpEF, regardless of hospitalization history. A greater burden of noncardiac organ dysfunction, sedentariness, functional impairment, and higher event rates distinguish patients with HFpEF and prior HF hospitalization from those never hospitalized. Despite lower event rates, quality of life is severely and similarly limited in patients with no history of hospitalization. These data suggest that the 2 clinical profiles of HFpEF may require different treatment strategies.

Early elevation in plasma high-sensitivity troponin T and morbidity after elective noncardiac surgery: prospective multicentre observational cohort study

BackgroundElevated high-sensitivity troponin (hsTnT) after noncardiac surgery is associated with higher mortality, but the temporal relationship between early elevated troponin and the later development of noncardiac morbidity remains unclear. MethodsProspective observational study of patients aged ≥45 yr undergoing major noncardiac surgery at four UK hospitals (two masked to hsTnT). The exposure of interest was early elevated troponin, as defined by hsTnT >99th centile (≥15 ng L−1) within 24 h after surgery. The primary outcome was morbidity 72 h after surgery, defined by the Postoperative Morbidity Survey (POMS). Secondary outcomes were time to become morbidity-free and Clavien–Dindo ≥grade 3 complications. ResultsEarly elevated troponin (median 21 ng L−1 [16–32]) occurred in 992 of 4335 (22.9%) patients undergoing elective noncardiac surgery (mean [standard deviation, sd] age, 65 [11] yr; 2385 [54.9%] male). Noncardiac morbidity was more frequent in 494/992 (49.8%) patients with early elevated troponin compared with 1127/3343 (33.7%) patients with hsTnT <99th centile (odds ratio [OR]=1.95; 95% confidence interval [CI], 1.69–2.25). Patients with early elevated troponin had a higher risk of proven/suspected infectious morbidity (OR=1.54; 95% CI, 1.24–1.91) and critical care utilisation (OR=2.05; 95% CI, 1.73–2.43). Clavien–Dindo ≥grade 3 complications occurred in 167/992 (16.8%) patients with early elevated troponin, compared with 319/3343 (9.5%) patients with hsTnT <99th centile (OR=1.78; 95% CI, 1.48–2.14). Absence of early elevated troponin was associated with morbidity-free recovery (OR=0.44; 95% CI, 0.39–0.51). ConclusionsEarly elevated troponin within 24 h of elective noncardiac surgery precedes the subsequent development of noncardiac organ dysfunction and may help stratify levels of postoperative care in real time.

Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.

Outcomes After In-Hospital Cardiac Arrest in Children With Cardiac Disease

Background— Small studies suggest that children experiencing a cardiac arrest after undergoing cardiac surgery have better outcomes than other groups of patients, but the survival outcomes and periarrest variables of cardiac and noncardiac pediatric patients have not been compared. Methods and Results— All cardiac arrests in patients &lt;18 years of age were identified from Get With the Guidelines–Resuscitation from 2000 to 2008. Cardiac arrests occurring in the neonatal intensive care unit were excluded. Of 3323 index cardiac arrests, 19% occurred in surgical-cardiac, 17% in medical-cardiac, and 64% in noncardiac (trauma, surgical-noncardiac, and medical-noncardiac) patients. Survival to hospital discharge was significantly higher in the surgical-cardiac group (37%) compared with the medical-cardiac group (28%; adjusted odds ratio, 1.8; 95% confidence interval, 1.3–2.5) and the noncardiac group (23%; adjusted odds ratio, 1.8; 95% confidence interval, 1.4–2.4). Those in the cardiac groups were younger and less likely to have preexisting noncardiac organ dysfunction, but were more likely to have ventricular arrhythmias as their first pulseless rhythm, to be monitored and hospitalized in the intensive care unit at the time of cardiac arrest, and to have extracorporeal cardiopulmonary resuscitation compared with those in the noncardiac group. There was no survival advantage for patients in the medical-cardiac group compared with those in the noncardiac group when adjusted for periarrest variables. Conclusion— Children with surgical-cardiac disease have significantly better survival to hospital discharge after an in-hospital cardiac arrest compared with children with medical-cardiac disease and noncardiac disease.

Omnes Viae Romam Ducunt

Despite significant progress in the treatment of heart failure, its incidence and prevalence are rising in the United States. In order to further heart failure prevention efforts, the American Heart Association and the American College of Cardiology proposed a classification scheme for heart failure to include stage A patients (those who do not have structural heart disease but are at risk for heart failure) and stage B patients (those with asymptomatic cardiac structural or functional abnormalities).1 Measures implemented to prevent progression of patients at risk for heart failure rely on our ability to predict accurately who will most likely benefit from early interventions. Because heart failure eventually leads to multiorgan involvement, even mild dysfunction of a noncardiac organ may trigger clinical manifestations of heart failure. In addition, preexisting asymptomatic ventricular dysfunction may interact with a dysfunctional noncardiac organ and accelerate the progression to overt heart failure. To date, there is little information available to describe the contribution of asymptomatic systolic and diastolic dysfunction or that of noncardiac organ dysfunction to the occurrence of heart failure, and the article by Lam et al2 in the present issue of Circulation is bringing forth important data in that regard. Article see p 24 One thousand thirty eight participants from the Framingham Heart Study who were free of heart failure or overt renal failure at enrollment (1987–1990) were followed up for an average of 11 years. Detailed echocardiographic assessment was performed at baseline, and participants with an ejection fraction ≤45% were considered to have asymptomatic systolic dysfunction, whereas those with an ejection fraction >45% and with abnormal relaxation or pseudonormal or restrictive filling were considered to have asymptomatic diastolic dysfunction. In line with their hypothesis that major noncardiac organ dysfunction may accelerate the progression to heart …

Cardiac Dysfunction and Noncardiac Dysfunction as Precursors of Heart Failure With Reduced and Preserved Ejection Fraction in the Community

Heart failure (HF) is a clinical syndrome characterized by signs and symptoms involving multiple organ systems. Longitudinal data demonstrating that asymptomatic cardiac dysfunction precedes overt HF are scarce, and the contribution of noncardiac dysfunction to HF progression is unclear. We hypothesized that subclinical cardiac and noncardiac organ dysfunction would accelerate the manifestation of HF. We studied 1038 participants of the Framingham Heart Study original cohort (mean age, 76±5 years; 39% men) with routine assessment of left ventricular systolic and diastolic function. Major noncardiac organ systems were assessed with the use of serum creatinine (renal), serum albumin (hepatic), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV(1):FVC ratio; pulmonary), hemoglobin concentration (hematologic/oxygen-carrying capacity), and white blood cell count (systemic inflammation). On follow-up (mean, 11 years), there were 248 incident HF events (146 in women). After adjustment for established HF risk factors, antecedent left ventricular systolic dysfunction (hazard ratio, 2.33; 95% confidence interval, 1.43 to 3.78) and diastolic dysfunction (hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.71) were associated with increased HF risk. After adjustment for cardiac dysfunction, higher serum creatinine, lower FEV1:FVC ratios, and lower hemoglobin concentrations were associated with increased HF risk (all P<0.05); serum albumin and white blood cell count were not. Subclinical dysfunction in each noncardiac organ system was associated with a 30% increased risk of HF (P=0.013). Antecedent cardiac dysfunction and noncardiac organ dysfunction are associated with increased incidence of HF, supporting the notion that HF is a progressive syndrome and underscoring the importance of noncardiac factors in its occurrence.

Cardiac surgery in low birth weight infants: current outcomes☆

Low birth weight (LBW) is a risk factor for mortality in neonatal and infant heart surgery. The purpose of this study was to determine the contemporary outcomes and risk factors of cardiac surgery in low weight babies. The records of 75 consecutive infants weighing <2.5 kg having heart surgery were reviewed. The median weight was 2100 g (range 800-2500 g) and median age was 11 days (range 2-86 days). Half (n=38) of the infants were premature. Diagnoses included: arch obstruction (n=14), hypoplastic left heart syndrome (HLHS) (n=12), tetralogy of Fallot (ToF) or pulmonary atresia (PA)/ventricular septal defect (VSD) (n=11), transposition of the great arteries (TGA) (n=7), total anomalous pulmonary venous return (TAPVR) (n=5), and other (n=20). There were two early deaths. Follow-up was available on all infants with a median duration of 1320 days (range 6-3055 days). Cumulative Kaplan-Meier survival at one year was 90% [95% confidence interval (CI), 80-95%] and at five years was 88% (95% CI, 77-94%). Overall mortality amongst patients with genetic/chromosomal abnormalities was higher, 28% vs. 5.4% amongst patients without such abnormalities (P=0.008). Age, prematurity, preoperative mechanical ventilation, prostaglandins, non-cardiac organ dysfunction, extra-cardiac malformations, perioperative extracorporeal membrane oxygenation (ECMO), and type of procedure were not associated with significant differences in mortality. Cardiac surgery in LBW infants can be performed with low early and mid-term mortality. LBW infants with chromosomal/genetic anomalies have a higher risk.

Effect of Prenatal Diagnosis on Outcome in Patients With Congenital Heart Disease

After completing this article, readers should be able to: 1. List the most frequent prenatally diagnosed forms of congenital heart disease. 2. List the fetal indications for echocardiography. 3. List the maternal indications for echocardiography. 4. Review the findings of studies comparing the outcome of prenatally versus postnatally diagnosed newborns who have congenital heart disease. 5. List the advantages of prenatal diagnosis of congenital heart disease. Congenital heart disease (CHD) continues to be a major source of neonatal mortality. Since the development of echocardiographic screening for fetal cardiac anatomy in the 1980s, an increasing number of affected newborns are identified prior to delivery. (1) A recent study in a population that had risk factors for CHD found that the sensitivity of fetal echocardiography was 38%, with a false-positive rate of only 0.05%. (2) However, when performed by skilled operators viewing outflow tracts in addition to the four-chamber view, an accuracy as high as 96% has been reported. (3) These prenatal diagnoses are heavily skewed toward more severe CHD, with disorders of the atrioventricular junction (endocardial cushion defects), univentricular hearts, and hypoplastic left heart syndrome (HLHS) being the most common (Table 1). | Diagnosis | Proportion of All Fetal Diagnoses | Proportion of CHD in Newborns in Study | |:-------------------------------------------:| --------------------------------- | -------------------------------------- | | Hypoplastic left heart syndrome | 31% | 15% | | Atrioventricular septal defect | 30% | 25% | | Univentricular heart | 20% | 9% | | Pulmonary atresia intact ventricular septum | 8% | 5% | | Total anomalous pulmonary venous return | 0.3% | 1% | | Tetralogy of Fallot | 9% | 28% | | Transposition of the great arteries | 1.7% | 17% | Table 1. Relative Frequencies of Congenital Heart Defects (CHD) at Fetal Diagnosis and Seen At Birth* The ability to identify the most severe forms of CHD prior to delivery has changed the population of liveborn infants who have CHD. Prenatal diagnosis allows for extensive parental counseling and coordination of care. The fetal diagnosis of CHD prompts genetic testing to identify chromosomal abnormalities, which are found in 10% of cases, and a detailed anatomic evaluation to assess associated extracardiac anomalies, which coincide in 15% of cases. (1) In cases of poor prognosis, early prenatal diagnosis gives the parents the option of terminating …