The study, led by Gil Marcus and Avishay Grupper of the Shamir Medical Center in Israel, together with colleagues, analyzed 8,332 hospital admissions for acute decompensated heart failure occurring between December 2006 and 2017. Of these, 6,792 admissions, or 81.5 percent, had sufficient laboratory data to be classified into one of four cardiohepatic injury phenotypes. The classification rested on peak in-hospital values of four routine liver tests: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Rather than treating each enzyme as a separate signal, the investigators combined them into clinically meaningful syndromes that hepatologists have long used to characterize liver disease, applying that framework to the failing heart’s impact on the liver.

The four phenotypes capture fundamentally different mechanisms of hepatic injury. Patients with no hepatic injury had normal values across the panel. Hepatocellular injury, dominated by elevations of the transaminases AST and ALT, reflects damage to the liver cells themselves, a pattern classically associated with hypoxic hepatitis, in which reduced oxygen delivery to the liver causes hepatocyte death. Cholestatic injury, marked by elevations of alkaline phosphatase and bilirubin, points to impaired bile flow, a phenomenon often linked in heart failure to congestion, the backward accumulation of pressure and fluid when the failing heart cannot adequately empty the venous system. Combined injury, in which both patterns coexist, suggests simultaneous cellular damage and biliary stasis, and it turned out to be the most ominous category of all.

The distribution of these phenotypes across the cohort was itself revealing. A majority of patients, 58.1 percent, showed no hepatic injury, but the remaining four in ten carried some form of liver abnormality. Hepatocellular injury was the most common pattern at 22.1 percent, followed by cholestatic injury at 13.1 percent, while combined injury affected 6.7 percent of admissions. This means that in more than four out of ten hospitalizations for acute decompensated heart failure, the liver was sending a measurable distress signal, one that the researchers argue deserves systematic interpretation rather than the per-marker glance it typically receives.

The mortality figures associated with each phenotype were dramatic. In-hospital death occurred in just 3.5 percent of patients with no hepatic injury, but rose to 16.3 percent in those with hepatocellular injury, 9.0 percent in those with cholestatic injury, and 24.3 percent in those with combined injury, a difference that was highly statistically significant. In other words, a patient whose routine liver panel showed the combined pattern faced roughly a one-in-four chance of dying during the same hospitalization, nearly seven times the risk of a patient with a clean panel. After adjustment for other clinical variables using multivariable logistic regression, all three injury phenotypes independently predicted in-hospital death compared with no injury, confirming that the association was not simply explained by patients being sicker in more obvious ways.

The post-discharge story proved more nuanced and, in some respects, more surprising. Among 6,128 patients included in adjusted analyses of outcomes after leaving the hospital, the researchers examined 30-day mortality, 30-day readmission, and a composite of the two, using Cox proportional hazards models and Fine–Gray models to account for competing risks. Here a clear divide emerged: hepatocellular injury and combined injury were independently associated with higher 30-day mortality and with the composite outcome, whereas isolated cholestatic injury was not. Both hepatocellular and combined injury also independently predicted 30-day readmission. The implication is that the specific mechanism of liver injury, not merely its presence, determines which patients remain at risk after they walk out of the hospital door.

Why should hepatocellular involvement carry this extended shadow of risk while cholestasis does not? The authors’ framework suggests a plausible physiological explanation. Hepatocellular enzyme elevations in acute heart failure are thought to reflect forward failure, a drop in cardiac output that deprives the liver of oxygen, essentially a shock-like state affecting the hepatic parenchyma. That kind of circulatory compromise signals profound hemodynamic instability, which plausibly persists beyond discharge and drives both early death and early readmission. Cholestatic patterns, by contrast, may track congestion that responds to decongestive therapy during the index admission; once the patient is euvolemic, the cholestatic signal may lose its independent prognostic weight. The study did not directly test these mechanisms, but the differential outcomes are consistent with this hemodynamic interpretation of the two injury types.

The practical implications are considerable. The four liver tests used in the study are cheap, universally available, and already drawn in virtually every patient admitted with acute heart failure, meaning that pattern-based interpretation requires no new testing, no new equipment, and no additional cost. A clinician reviewing an admission panel could, in principle, immediately place the patient into one of the four phenotypes and adjust the intensity of monitoring, counseling about prognosis, and post-discharge follow-up accordingly. Patients flagged with hepatocellular or combined injury might merit closer early follow-up, tighter diuretic titration schedules, or enrollment in post-discharge transition-of-care programs, while the phenotype could also serve as a stratification variable in future clinical trials of acute heart failure therapies.

The findings also fit into a growing body of literature on cardiohepatic interactions. Previous studies, including analyses from the PROTECT, ASCEND-HF, EVEREST, CHARM, and TOPCAT programs, have documented that abnormal liver function tests are common in heart failure and correlate with worse outcomes, and recent work from the STRONG-HF trial has linked changes in liver tests after discharge to prognosis. What distinguishes the new study is its explicit phenotypic framing: instead of asking whether any individual enzyme is abnormal, it asks what constellation of abnormalities is present, borrowing the hepatological taxonomy of hepatocellular, cholestatic, and mixed injury. This approach mirrors a broader movement in cardiology toward phenotype-driven medicine, in which heterogeneous syndromes like acute heart failure are decomposed into mechanistically coherent subgroups with distinct prognoses and, potentially, distinct treatment responses.

As with any retrospective single-cohort analysis, certain caveats apply. The study relied on peak in-hospital laboratory values, and the cohort spans admissions from 2006 to 2017, an era that predates the widespread adoption of sodium-glucose cotransporter 2 inhibitors, which have since transformed heart failure therapy and may themselves interact with liver outcomes. Residual confounding cannot be excluded, and the classification thresholds and their generalizability to other health systems will require validation in independent cohorts. Nevertheless, the central message stands on solid ground: the pattern of routine liver test abnormalities in acute decompensated heart failure is not noise but signal, and phenotypes with hepatocellular involvement identify patients at elevated risk both during hospitalization and in the vulnerable first month afterward. For a condition that sends millions of patients to hospitals worldwide each year and carries substantial early mortality, a free risk-stratification tool hiding in plain sight on the standard chemistry panel is a finding worth taking seriously.

Subject of Research: Cardiohepatic injury phenotypes and short-term outcomes in acute decompensated heart failure

Article Title: Cardio-hepatic injury phenotypes and short-term outcomes in acute decompensated heart failure

Article References: Marcus, G., Maymon, S. L., Minha, I., Kalmanovich, E., Moravsky, G., Fuchs, S., Minha, S., & Grupper, A. (2026). Cardio-hepatic injury phenotypes and short-term outcomes in acute decompensated heart failure. Clinical Research in Cardiology. https://doi.org/10.1007/s00392-026-03043-w

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03043-w

Keywords: acute decompensated heart failure, cardiohepatic syndrome, hepatocellular injury, cholestatic injury, liver function tests, in-hospital mortality, 30-day readmission, risk stratification, prognosis, retrospective cohort study, hypoxic hepatitis, congestive hepatopathy

The research team, led by investigators at Ruhr University Bochum’s Knappschaft Kliniken University Hospital, analyzed records from 2,002 adults treated for acute decompensated heart failure, a condition in which the heart suddenly cannot pump enough blood to meet the body’s demands, causing fluid buildup in the lungs and tissues. Among these patients, 246 individuals, or 12.3 percent, had laboratory-confirmed SARS-CoV-2 infection detected by reverse transcription quantitative polymerase chain reaction during their hospital stay. This molecular diagnostic technique amplifies and detects viral RNA, providing both a yes-or-no answer about infection and, through the cycle threshold value, an indirect gauge of how much virus a patient is carrying.

The raw numbers were stark. Patients with confirmed SARS-CoV-2 infection died in the hospital at a rate of 32.5 percent, compared with 20.6 percent among those without the infection. Intensive care unit admission was also more frequent in the infected group, at 61.4 percent versus 50.7 percent, and the need for invasive mechanical ventilation, in which a breathing tube and ventilator take over the work of the lungs, was nearly three times as common, affecting 6.5 percent of infected patients against 2.4 percent of uninfected ones. All of these differences reached statistical significance, with p values at or below 0.002.

Because raw comparisons between groups can be distorted by differences in age, comorbidities, and disease severity, the researchers applied multivariable regression models that adjusted for clinically relevant covariates. Even after this statistical correction, SARS-CoV-2 infection remained independently associated with in-hospital mortality, with an adjusted odds ratio of 2.63 and a p value of 0.0002. An adjusted odds ratio above 2 means that, holding other factors constant, infected patients had more than two and a half times the odds of dying during their hospitalization. The infection also remained independently linked to ICU admission, with an adjusted odds ratio of 1.79, and to invasive mechanical ventilation, with an adjusted odds ratio of 2.84.

The burden of infection extended beyond survival and organ support. Hospitalized heart failure patients who also carried SARS-CoV-2 spent significantly longer in the hospital and in the intensive care unit. After adjustment, infection was associated with an additional 9.23 days of hospital stay and an additional 7.85 days of ICU stay, both statistically robust findings. In a condition where timely decongestion and bed capacity are critical, such prolonged stays represent not only worse outcomes for individual patients but also meaningful strain on healthcare resources, particularly during periods when respiratory viruses circulate widely in the community.

One of the more technically interesting aspects of the study involved the use of cycle threshold values as surrogate markers of viral burden. In RT-qPCR testing, the cycle threshold, or Ct value, refers to the number of amplification cycles needed before viral RNA becomes detectable. Lower Ct values indicate that less amplification was required, which in turn suggests a higher concentration of virus in the sampled material. The researchers therefore reasoned that Ct values could serve as a rough proxy for how heavily infected each patient was at the time of testing.

Among the 246 infected patients, the analysis revealed that lower median Ct values were associated with higher in-hospital mortality, with an adjusted odds ratio of 0.89 per Ct unit and a p value of 0.0338. Because the odds ratio is below 1, each unit decrease in Ct value, corresponding to an increase in viral burden, was linked to greater odds of death. Lower minimum Ct values were also associated with longer hospital stays, with an adjusted beta of minus 0.44 days per Ct unit and a p value of 0.0359. Taken together, these findings suggest that patients with higher viral loads fared worse, raising the possibility that viral burden could help stratify mortality risk within this already vulnerable population.

The authors themselves urge caution in interpreting these viral load findings. Cycle threshold values are imperfect surrogate markers of viral burden because they depend on sampling technique, specimen type, timing of testing relative to infection onset, and the specific PCR assay used. A nasal swab taken poorly or late in the course of infection can yield a high Ct value even in a heavily infected patient. The researchers explicitly describe the Ct-based associations as hypothesis-generating and call for prospective validation in future studies before any clinical decision-making relies on viral load measurements in this setting.

Interestingly, the study found that the heart failure phenotype itself, meaning whether patients had reduced, mildly reduced, or preserved ejection fraction, and whether they were receiving guideline-directed medical therapy before admission, showed no consistent associations with major in-hospital outcomes. This suggests that the viral infection, rather than the specific characteristics of the underlying cardiac disease or its chronic treatment, was the dominant modifiable factor driving worse outcomes during hospitalization. In other words, the acute viral insult appeared to overwhelm the prognostic influence of chronic heart failure characteristics.

The clinical implications of this work are considerable. Acute decompensated heart failure patients represent a clinically vulnerable population in whom respiratory infections have long been recognized as dangerous triggers of decompensation. This study quantifies that danger in the specific context of SARS-CoV-2, showing that concomitant infection roughly doubles the adjusted odds of in-hospital death and dramatically extends length of stay. For clinicians, the findings argue for vigilant screening for SARS-CoV-2 in heart failure admissions during periods of viral circulation, for aggressive monitoring of infected patients, and for continued efforts at vaccination and infection prevention in this high-risk group. For researchers, the viral burden signal points toward a future where quantitative PCR results might do more than confirm infection, potentially helping to identify which heart failure patients need the most intensive care.

Subject of Research: Virology

Article Title: Impact of SARS-CoV-2 infection and viral burden on outcomes in acute decompensated heart failure

Article References: Nashtar, M. A., Sehovic, H., Salemdawod, M., Garipoglu, G., Ödemis, B., Tzalavras, A., Steinmetz, M., Canbay, A., Özçürümez, M., Varnavas, V., Patsalis, P. C., & Katsounas, A. (2026). Impact of SARS-CoV-2 infection and viral burden on outcomes in acute decompensated heart failure. BMC Infectious Diseases, 26(1), Article 1694. https://doi.org/10.1186/s12879-026-14407-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14407-y

Keywords: SARS-CoV-2, heart failure, COVID-19, viral load, in-hospital mortality, ICU admission, cycle threshold, acute decompensated heart failure, Impact, infection, viral, burden

The central finding across all three investigations is that well-constructed clinical decision support tools can nudge clinicians toward evidence-based decisions without slowing them down. In the emergency department study, the research team evaluated a tool designed to help clinicians select an appropriate dose of an intravenous loop diuretic for patients arriving with acute decompensated heart failure. This class of medication removes excess fluid that accumulates when the failing heart cannot maintain adequate circulation, allowing the heart to pump more effectively and relieving the profound shortness of breath that drives these patients to seek emergency care in the first place. Clinical guidelines recommend that patients with acute decompensated heart failure receive at least twice the dose of diuretics they take at home when they arrive in the emergency department, a bolus strategy intended to achieve rapid decongestion. In practice, however, the relentless demands of a busy emergency department make it difficult for clinicians to quickly review home medication lists and adjust diuretic therapy accordingly, and recommended dosing is frequently missed.

To address this gap, the University of Michigan team implemented an interruptive alert within the electronic health record that fired when a patient showed signs of fluid overload or kidney dysfunction, prompting the treating clinician to consider guideline-recommended diuretic dosing. The alert was triggered in 223 patient encounters at the U-M Health Emergency Department. In nearly three-quarters of those cases, clinicians followed the recommended diuretic dosing after the alert appeared. Critically, the tool accomplished this without creating the kind of delay that often undermines the adoption of decision support systems: the median time from arrival at the emergency department to diuretic administration was roughly two hours in both groups, meaning the alert influenced the content of the treatment decision rather than its timing.

The researchers were careful to note the limits of what the study demonstrated. The investigation did not assess whether following the digital alerts improved downstream patient outcomes such as the amount of fluid removed or the length of hospital stay. Even so, the results establish something foundational for the field: the tools are easily used in a real clinical setting and measurably affect treatment decisions. As Sarah Adie, Pharm.D., a clinical cardiology pharmacy specialist at U-M Health and an author on all three studies, explained, this is a critical first step toward broad clinical adoption in settings that treat critically ill cardiac patients. Demonstrating feasibility and behavioral impact in a live emergency department environment is a prerequisite for the larger outcome trials that would justify deployment across many institutions.

The second study shifted the setting to the intensive care unit and examined sedation practices in more than 1,600 patients receiving mechanical ventilation in the cardiac and medical intensive care units. Deep sedation is common in intensive care, but leading cardiac and critical care society guidelines favor limiting its use, because prolonged heavy sedation may contribute to worse outcomes, including prolonged ventilator dependence and longer recovery. Changing sedation practice, however, is notoriously difficult, since it requires coordinated action from both physicians and nurses at the bedside, often under time pressure. The research team introduced an electronic health record-based intervention that encouraged the care team to use lighter sedation, surfacing the recommendation at the moment sedative decisions were being made.

The results were striking. After implementation, the average amount of time patients spent deeply sedated during the first 48 hours after intubation dropped in the cardiac intensive care unit from 16.8 hours to 12.4 hours, a reduction of more than four hours per patient. Nurses also reduced the continuous dose of commonly used sedatives, including fentanyl, propofol, midazolam and dexmedetomidine, in 23 percent of cases when the electronic health record generated an alert. These figures suggest that a well-timed digital prompt can shift entrenched practice patterns in an environment where clinicians are managing multiple simultaneous demands. As Anna Barker, M.D., Ph.D., a pulmonologist at University of Michigan Health and senior author of the light sedation paper, emphasized, the alerts are not designed to replace clinical judgment; rather, they are a tool delivered at high-pressure moments to assist clinicians with evidence-based guidance.

The third study tackled one of the most treacherous diagnostic challenges in cardiology: normotensive cardiogenic shock. This condition occurs when the heart cannot pump enough blood to the organs even though the patient’s blood pressure remains normal. Because cardiogenic shock is classically associated with low blood pressure, clinicians may fail to recognize that a normotensive patient is already in shock, and delays in diagnosis can be life threatening. The researchers implemented an electronic health record alert that identified patients displaying additional physiological signs of normotensive cardiogenic shock, such as subtle markers of hypoperfusion that might otherwise be overlooked, and facilitated direct communication with the shock team in the cardiac intensive care unit.

Clinicians engaged with the alert in 14 percent of cases, and those engagements were linked with higher rates of cardiac intensive care unit consultation within 12 hours. While the engagement rate may appear modest, the study illustrates a different design philosophy from the diuretic and sedation alerts: rather than prompting a medication decision, this alert functioned as a recognition and escalation tool, bridging the gap between a bedside clinician who may not suspect shock and a specialized team equipped to deploy advanced therapies. In conditions where early specialist involvement changes the trajectory of illness, even a low-frequency, high-value alert can be clinically meaningful.

Taken together, the three studies map how targeted electronic health record alerts can assist clinicians across the continuum of critical cardiac care, from the first hours in the emergency department through intensive care management. The design of each intervention differed according to the clinical problem. In the emergency department, the tool offered patient-specific recommendations at the moment the diuretic order was placed, embedding the guideline directly into the ordering workflow. In the two intensive care unit studies, alerts prompted clinicians to limit deep sedation or to escalate suspected shock cases to specialized critical care teams. In each case, the intervention respected the existing workflow rather than adding parallel tasks, which the researchers identify as a key principle: these clinical decision support tools are most useful when they help clinicians make the right decision in the moment, rather than adding more noise to already busy workflows, as Scott Ketcham, M.D., a cardiologist at the University of Michigan Health Frankel Cardiovascular Center and an author on all three studies, observed.

The researchers describe the work as proof of concept, and they are explicit that more must be done to ensure electronic alerts are beneficial without disrupting clinical workflow. Alert fatigue remains one of the most persistent problems in health information technology, as clinicians bombarded with low-value notifications learn to dismiss them reflexively, undermining even genuinely useful tools. The Michigan studies suggest a path forward: alerts that are triggered by specific clinical signals, deliver a single actionable recommendation, and arrive at the exact moment a decision is being made. The next step, according to Ketcham, is to evaluate these interventions across multiple health systems to better understand their impact on patient outcomes and determine how they can help improve the care of critically ill cardiac patients nationwide. If those multi-center evaluations confirm what these early studies hint at, the electronic health record, long criticized as a source of friction, may earn a new role as an active partner in the care of the sickest patients with heart disease.

Subject of Research: Electronic health record clinical decision support alerts for critically ill cardiac patients

Article Title: Digital alerts support timely treatment decisions of critically ill cardiac patients

Article References: Digital alerts support timely treatment decisions of critically ill cardiac patients. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: electronic health records, clinical decision support, acute decompensated heart failure, diuretics, cardiac intensive care, sedation, cardiogenic shock, emergency department, ventilators, alert fatigue, Michigan Medicine, patient outcomes