Letter to the Editor: Liver, heart, and kidney crosstalk in cirrhosis: POCUS is the focus

To the editor, We read with interest a study by Premkumar et al1 identifying the predictors of terlipressin-nonresponse and mortality in 140 patients with cirrhosis with hepatorenal syndrome-acute kidney injury (HRS-AKI) using serial point-of-care echocardiography and lung ultrasound. The point-of-care ultrasound data and images were recorded by 2 liver intensivists and corroborated by 2 cardiologists and radiologists. The authors have proven the prognostic significance of identifying cirrhotic-cardiomyopathy(CCM) in predicting HRS-AKI recovery, response to Terlipressin, and mortality. We have a few essential points to note: In this study, 24.3% had Grade 2 and 3 left ventricular diastolic dysfunction and met the CCM criteria. None had systolic dysfunction. This means that detecting subclinical LV dysfunction or "the absence of contractile reserve" requires myocardial stress testing. Additionally, global longitudinal strain<−16% and speckle-tracking-echocardiography can indicate subclinical LV-systolic dysfunction in patients with preserved left ventricular ejection fraction. The authors suggest that an increase in mean arterial pressure across groups over time was similar, while the cardiac index was preserved at presentation but declined in terlipressin nonresponders. In other words, impaired cardiac index with Terlipressin indicates blunted pharmacologic stress responsiveness and latent systolic dysfunction. The unchanged systemic vascular resistance but disturbed cardiac output points to the heart as the main driving factor for tissue perfusion. Existing therapeutic strategies target mean arterial pressure, while there is no strategy to increase cardiac index, as β-adrenergic receptors are typically downregulated in cirrhosis. The use of point-of-care ultrasound in assessing a patient's intravascular volume status and classifying the AKI in cirrhosis is an important evolving domain. In the present study, all patients received 27.9 ± 12.5 g/day of 20% albumin for 48 hours, although the lung ultrasound was abnormal in 34% at presentation. It will be interesting to know how many patients were fluid-depleted versus fluid-expanded or had "intraabdominal-hypertension" at baseline. Of 23.6% of patients with adverse events, 12.8% had ≥ grade 2 adverse events requiring drug cessation/intervention, while 39.4% died. Nonsurvivors had a higher lung ultrasound score(18.4 vs. 12.3, p < 0.05). Although pulmonary edema with respiratory failure developed more in CCM patients (26.4%) and Terlipressin nonresponders (10.5%), we believe that treatment with "albumin and Terlipressin" might have pushed fluid-overloaded patients with subclinical CCM to develop overt cardio-pulmonary adverse events. Of 140, 72.9% of patients responded to Terlipressin, and patients with CCM had more nonresponse (47% vs. 21%, p < 0.001). This finding indicates, plausibly, there are 2 distinct profiles of renal dysfunction in Cirrhosis: (1) HRS-AKI, which responds to Terlipressin, and (2) Hepato-cardio-renal-syndrome, which responds poorly to Terlipressin. Traditional teaching views HRS and CCM as 2 pathophysiologically distinct complications of liver cirrhosis. However, this study highlights a multifactorial and complex crosstalk between the liver, heart, and kidney mediated through hemodynamic and neuro-hormonal activation. In our opinion, CCM is just not a consequence of cirrhosis but precedes and contributes to the subsequent development of HRS. This new prognostically different subset of "hepato-cardio-renal syndrome" needs a more innovative treatment approach. To summarize, this study puts forward the evidence of hepato-cardio-renal crosstalk in cirrhosis and upticks the motivation among hepatologists to simultaneously evaluate the heart(pump), abdominal veins (pipes), and lungs(leaks) with point-of-care ultrasound for adequate hemodynamic assessment of patients who are critically ill with cirrhosis and AKI-HRS.