Concomitant Lung and Kidney Disorders in Critically Ill Patients: Core Curriculum 2022.

The lungs and kidneys are cooperative and interdependent organs that secure the homeostasis of the body. Volume and acid-base disorders sit at the nexus between these two systems. However, lung-kidney interactions affect the management of many other conditions, especially among critically ill patients. Therefore, management of one system cannot proceed without a thorough understanding of the physiology of the other. This installment of AJKD's Core Curriculum in Nephrology discusses the complex decision-making required in treating concomitant respiratory and kidney disorders. We cover systemic diseases of the pulmonary and glomerular capillaries, acute decompensated heart failure, management of acid-base disorders in acute respiratory distress syndrome and chronic obstructive pulmonary disease, and venous thromboembolism. Through a case-based approach, we weigh the factors affecting the risks and benefits of therapies to enable the reader to individualize treatment decisions in these challenging scenarios.

AKI-A Relevant Safety End Point?

Acute kidney injury (AKI) is a common outcome evaluated in clinical studies, often as a safety end point in a variety of cardiovascular, kidney disease, and other clinical trials. AKI end points that include modest increases in serum creatinine levels from baseline may not associate with patient-centered outcomes such as initiation of dialysis, sustained decline in kidney function, or death. Surprisingly, data from several randomized controlled trials have suggested that in certain settings, the development of AKI may be associated with favorable outcomes. AKI safety end points that are nonspecific and may not associate with patient-centered outcomes could result in beneficial therapies being inappropriately withheld or never developed for commercial use. We review several issues related to commonly used AKI definitions and suggest that future work in AKI use more patient-centered AKI end points such as major adverse kidney events at 30 days or other later time points.

Implication of Acute Kidney Injury in Heart Failure.

Patients with acute or chronic decompensated heart failure (ADHF) present with various degrees of heart and kidney dysfunction characterizing cardiorenal syndrome (CRS). CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. ADHF is a challenge in the management of heart failure. This review provides an overview the pathophysiology of type 1 CRS together with new approaches to treatment in patients with heart failure with worsening renal function or acute kidney disease.

Oral Metolazone Versus Intravenous Chlorothiazide as an Adjunct to Loop Diuretics for Diuresis in Acute Decompensated Heart Failure With Reduced Ejection Fraction.

Background: Thiazide diuretics are often utilized to overcome loop diuretic resistance when treating acute decompensated heart failure (ADHF). In addition to a large cost advantage, several pharmacokinetic advantages exist when administering oral metolazone (MTZ) compared with intravenous (IV) chlorothiazide (CTZ), yet many providers are reluctant to utilize an oral formulation to treat ADHF. The purpose of this study was to compare the increase in 24-hour total urine output (UOP) after adding MTZ or CTZ to IV loop diuretics (LD) in patients with heart failure with reduced ejection fraction (HFrEF). Methods and Results: From September 2013 to August 2016, 1002 patients admitted for ADHF received either MTZ or CTZ in addition to LD. Patients were excluded for heart failure with preserved ejection fraction (HFpEF) (n = 469), <24-hour LD or UOP data prior to drug initiation (n = 129), or low dose MTZ/CTZ (n = 91). A total of 168 patients were included with 64% receiving CTZ. No significant difference was observed between the increase in 24-hour total UOP after MTZ or CTZ initiation (1458 [514, 2401] mL vs 1820 [890, 2750] mL, P = .251). Conclusions: Both MTZ and CTZ similarly increased UOP when utilized as an adjunct to IV LD. These results suggest that while thiazide agents can substantially increase UOP in ADHF patients with HFrEF, MTZ and CTZ have comparable effects.

The Clinical Profile of Patients With Acute Decompensated Heart Failure Presenting to the Emergency Department at a Tertiary Care Hospital in India.

Background Acute decompensated heart failure (ADHF) poses a significant burden on healthcare systems globally, including in India, due to its high morbidity and mortality rates. This study aimed to evaluate the clinical characteristics of patients presenting with ADHF to the emergency department (ED) of a tertiary care hospital in India. Methodology This observational study was conducted at Dr. D. Y. Patil Medical College, Hospital, and Research Centre in Pune, India. Ninety patients aged 12 years and older who presented with signs and symptoms of heart failure (HF) to the ED between January 2023 and March 2024 were enrolled as participants. Ethical approval was obtained. Written consent was obtained from all participants. Clinical diagnoses were based on patient history, physical examination, chest radiograph, point-of-care ultrasound (POCUS), electrocardiography (ECG), echocardiography, and radiological and laboratory findings. Data were analyzed using IBM SPSS Statistics version 29.0.2.0 (Armonk, NY: IBM Corp.) and represented as mean±SD, frequency (n), and percentage. Results The study involved 90 participants with a mean age of 61.1±16.3 years. The cohort comprised 51 males (56.7%) and females 39 (43.3%). Dyspnea was the most common clinical presentation in all participants, followed by swelling of feet in 58 (64.4%) cases. The mean systolic blood pressure noted was 142.1±42.8 mmHg. Hypertension was the most frequently identified risk factor, present in 52 (57.8%) cases. The most common precipitating factor identified was anemia in 39 (43.3%) cases. Point-of-care ultrasonography (pulmonary) revealed significant B-lines (≥2 of the eight thoracic zones with ≥3 B-lines or B-line count in all eight zones ≥10) in 85 (94.4%) cases. B-type natriuretic peptide (BNP) was elevated in all participants. The mean hemoglobin levels in males and females were 13.2±2.6 g/dL and 10.6±2.8 g/dL, respectively. The mean serum sodium level was 132.4±6.2 mEq/dL. Serum sodium level below 135.0 mEq/L (hyponatremia) was found in 53 (58.9%) cases. The mean serum creatinine level was 1.7±1.4 mg/dL. Diuretics were the most common treatment modality used in the ED. More than half of the patients (72.2%) were transferred to the intensive care unit; the mortality rate in the ED was 2.2%. Conclusion This study provides comprehensive insights into the characteristics, management, and outcomes of ADHF patients presenting to the ED of a tertiary care hospital in India. The findings highlight the challenges and complexities in managing ADHF in this population and underscore the need for tailored therapeutic approaches to improve patient outcomes and reduce healthcare utilization.

Shifting the Paradigm: How Stress Hyperglycemia Alters the Landscape of Heart Failure Management.

Background Acute decompensated heart failure (ADHF) significantly contributes to global morbidity. Stress hyperglycemia (SHGL), although commonly observed in non-diabetic ADHF patients, remains underexplored. This study investigates the predictive value of SHGL for major adverse cardiac events (MACEs) and its impact on coronary intervention outcomes. Methods In this prospective observational study at a tertiary care center, 650 non-diabetic ADHF patients admitted for coronary intervention between April 2021 and April 2022 were assessed. SHGL was defined by random blood sugar levels >140 mg/dl. We monitored the incidence of MACEs, including cardiac death, non-fatal myocardial infarction, and heart failure rehospitalization, alongside the success rates of coronary revascularizations over 12 months. Results SHGL was present in 54% of patients (n=352) and was significantly associated with increased MACEs (p<0.001), higher rehospitalization rates (p<0.01), and lower success in revascularization (p<0.05). Using logistic regression, SHGL, age >65, and prior heart failure hospitalization were identified as independent predictors of MACEs. Statistical analyses were performed using two-tailed Mann-Whitney U tests, with significance levels set at p<0.05 for noteworthy findings and p<0.01 or p<0.001 for highly significant findings. Conclusions SHGL significantly impacts coronary intervention outcomes and the future prognosis of heart failure in non-diabetic ADHF patients, identifying it as a critical, modifiable risk factor. These findings advocate integrating SHGL management into ADHF care, emphasizing the need for further research to develop standardized treatment protocols. Proper management of SHGL could potentially improve patient outcomes, highlighting the importance of metabolic control in heart failure management.

Efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure: a meta-analysis.

Objective: The objective of this study is to investigate the efficacy and safety of early ultrafiltration in patients with acute decompensated heart failure. Methods: A systematic search was conducted on PubMed, Cochrane Library, and EMbase databases from inception to April 2023 to identify randomized controlled trials that compared the efficacy and safety of early ultrafiltration and conventional diuretics in patients with acute decompensated heart failure. Two investigators independently screened all eligible studies and extracted relevant data. The primary outcomes of interest were changes in body weight and creatinine levels, as well as the rate of readmission and mortality within 30 days. Meta-analysis was conducted using RevMan 5.4 software. Results: This meta-analysis included eight studies and found that early ultrafiltration was effective in reducing body weight in patients with acute decompensated heart failure (RR = 1.45, 95% CI: 0.54-2.35, P = 0.002), but it also increased serum creatinine (RR = 0.1, 95% CI: 0.03-0.17, P = 0.003). However, it did not reduce the 30-day rehospitalization rate or mortality rate (30-day rehospitalization rate: RR = 0.84, 95% CI: 0.62-1.14, P = 0.28; Mortality: RR = 0.90, 95% CI: 0.57-1.44, P = 0.67). Conclusion: Although early ultrafiltration is more effective in reducing body weight in patients with acute decompensated heart failure, it is associated with an increase in serum creatinine levels and does not reduce the rate of readmission or mortality within 30 days. Systematic Review Registration: identifier: CRD42023416152.

Effectiveness of pulmonary artery catheter monitoring for patients with cardiogenic shock of various causes: a systematic review and meta-analysis.

Background: Cardiogenic shock is associated with significant morbidity and mortality. Invasive hemodynamic monitoring with pulmonary artery catheterization (PAC) can be useful in the assessment of changes in cardiac function and hemodynamic status; however, the benefits of PAC in the management of cardiogenic shock are not known well. Methods: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials, comparing in-hospital mortality between PAC and non-PAC groups of cardiogenic shock patients with various underlying causes. Articles were obtained from MEDLINE, Embase, and Cochrane CENTRAL. We reviewed titles, abstracts, and full articles and evaluated the quality of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. We used a random-effects model to compare studies in terms of in-hospital mortality findings. Results: We included twelve articles in our meta-analysis. Mortality among patients with cardiogenic shock was not significantly different between the PAC and the non-PAC groups [risk ratio (RR) 0.86, 95% confidence interval (CI): 0.73-1.02, I2=100%, P<0.01]. Two studies investigating cardiogenic shock caused by acute decompensated heart failure determined lower in-hospital mortality in the PAC group than in the non-PAC group (RR 0.49, 95% CI: 0.28-0.87, I2=45%, P=0.18). Six studies investigating cardiogenic shock of any cause determined lower in-hospital mortality in the PAC group than in the non-PAC group (RR 0.84, 95% CI: 0.72-0.97, I2=99%, P<0.01). There was no significant difference in in-hospital mortality between the PAC and non-PAC groups of patients with cardiogenic shock secondary to acute coronary syndrome (RR 1.01, 95% CI: 0.81-1.25, I2=99%, P<0.01). Conclusions: Overall, our meta-analysis demonstrated no significant association between PAC monitoring and in-hospital mortality among patients managed for cardiogenic shock. The use of PAC in the management of cardiogenic shock caused by acute decompensated heart failure was associated with lower in-hospital mortality, but there was no association between PAC monitoring and in-hospital mortality among patients with cardiogenic shock caused by acute coronary syndrome.

Remote Speech Analysis in the Evaluation of Hospitalized Patients With Acute Decompensated Heart Failure.

OBJECTIVES: This study assessed the performance of an automated speech analysis technology in detecting pulmonary fluid overload in patients with acute decompensated heart failure (ADHF). BACKGROUND: Pulmonary edema is the main cause of heart failure (HF)-related hospitalizations and a key predictor of poor postdischarge prognosis. Frequent monitoring is often recommended, but signs of decompensation are often missed. Voice and sound analysis technologies have been shown to successfully identify clinical conditions that affect vocal cord vibration mechanics. METHODS: Adult patients with ADHF (n = 40) recorded 5 sentences, in 1 of 3 languages, using HearO, a proprietary speech processing and analysis application, upon admission (wet) to and discharge (dry) from the hospital. Recordings were analyzed for 5 distinct speech measures (SMs), each a distinct time, frequency resolution, and linear versus perceptual (ear) model; mean change from baseline SMs was calculated. RESULTS: In total, 1,484 recordings were analyzed. Discharge recordings were successfully tagged as distinctly different from baseline (wet) in 94% of cases, with distinct differences shown for all 5 SMs in 87.5% of cases. The largest change from baseline was documented for SM2 (218%). Unsupervised, blinded clustering of untagged admission and discharge recordings of 9 patients was further demonstrated for all 5 SMs. CONCLUSIONS: Automated speech analysis technology can identify voice alterations reflective of HF status. This platform is expected to provide a valuable contribution to in-person and remote follow-up of patients with HF, by alerting to imminent deterioration, thereby reducing hospitalization rates. (Clinical Evaluation of Cordio App in Adult Patients With CHF; NCT03266029).

Early Levosimendan Administration Improved Weaning Success Rate in Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used in patients with refractory cardiogenic shock (CS) or out-of-hospital cardiac arrest. It is difficult to perform VA-ECMO weaning, which may cause circulatory failure and death. Levosimendan is an effective inotropic agent used to maintain cardiac output, has a long-lasting effect, and may have the potential benefit for VA-ECMO weaning. The study aimed to explore the relationship between the early use of levosimendan and the rate of VA-ECMO weaning failure in patients on VA-ECMO support for circulatory failure. Methods: All patients who underwent VA-ECMO in our hospital for CS between January 2017 and December 2020 were recruited in this cohort study and divided into two groups: without and with levosimendan use. Levosimendan was used as an add-on to other inotropic agents as early as possible after VA-ECMO setting. The primary endpoint was VA-ECMO weaning success, which was defined as survival without events for 24 h after VA-ECMO withdrawl. The secondary outcomes were cardiovascular and all-cause mortality at the 30-day and 180-day follow-up periods post-VA-ECMO initialization. Results: A total of 159 patients were recruited for our study; 113 patients were enrolled in the without levosimendan-use group and 46 patients were enrolled in the levosimendan-use group. In levosimendan-use group, the patients received levosimendan infusion within 24 h after VA-ECMO initialization. Similar hemodynamic parameters were noted between the two groups. Poorer left ventricular ejection fraction and a higher prevalence of intra-aortic balloon pumping were observed in the levosimendan group. An improved weaning rate (without vs. with: 48.7 vs. 82.6%; p < 0.001), lower in-hospital mortality rate (without vs. with: 68.1 vs. 43.5%; p = 0.007), and 180-day cardiovascular mortality (without vs. with: 75.3 vs. 43.2%; p < 0.001) were also noted. Patients administered with levosimendan also presented a lower rate of 30-day (without vs. with: 75.3 vs. 41.3%; p = 0.034) and 180-day (without vs. with: 77.0 vs. 43.2%; p < 0.001) all-cause mortality. Conclusion: Early levosimendan administration may contribute to increasing the success rate of VA-ECMO weaning and may help to decrease CV and all-cause mortality.

Acute Kidney Injury, Heart Failure, and Health Outcomes.

Acute kidney injury in acute decompensated heart failure leads to increased readmissions regardless of being transient or sustained at the time of discharge. Timely identification of acute kidney injury and worsening heart failure in patients with acute decompensated heart failure is of utmost importance to optimize different components of heart failure treatment. Acute kidney injury is a strong predictor of poor outcomes and early death in patients with pulmonary artery hypertension and acute right-sided heart failure. Extracorporeal ultrafiltration should not be used as an initial or alternative to diuretic therapy. It should be reserved for diuretic-resistant individuals.

Low Docosahexaenoic Acid, Dihomo-Gamma-Linolenic Acid, and Arachidonic Acid Levels Associated with Long-Term Mortality in Patients with Acute Decompensated Heart Failure in Different Nutritional Statuses.

The clinical significance of polyunsaturated fatty acids (PUFAs) in acute decompensated heart failure (ADHF) in various nutritional statuses remains unclear. For this study, we enrolled 267 patients with ADHF admitted to the cardiac intensive care unit at Juntendo University hospital between April 2012 and March 2014. The association between long-term mortality, the geriatric nutritional risk index (GNRI), and levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) was investigated. The median age was 73 (64-82) years, and mortality was 29% (62 patients). The event-free survival rates for all-cause death were higher in patients with high PUFA levels or GNRI than in those with low PUFA levels or GNRI (p < 0.05 for all). In particular, high DGLA in the low-GNRI group and high DHA or AA in the high-GNRI group were associated with high event-free survival (p < 0.05 for all). After accounting for confounding variables, DHA, DGLA, and AA, but not EPA, were associated with long-term mortality (p < 0.01 for all). This study concludes that in patients with ADHF, decreased levels of DHA, DGLA, and AA are independently associated with long-term mortality in the various nutritional statuses.

Acute decompensated heart failure (ADHF): A comprehensive contemporary review on preventing early readmissions and postdischarge death.

Heart failure (HF) is an increasingly prevalent syndrome and a leading cause of both first hospitalization and readmissions. Strikingly, up to 25% of the patients are readmitted within 30 to 60-days, accounting for HF as the primary cause for readmission in the adult population. Given its poor prognosis, one could describe it as a "malignant condition". Acute decompensation is intrinsically related to increased right heart tele-diastolic pressures and often related to congestive symptoms. In-hospital strategies to adequately compensate and timely discharge patients are limited. Conversely, the fragile early postdischarge phase is a vulnerable period when one could potentially intervene cost-effectively to improve survival and to reduce morbidity. Promising transitional hospital-to-home programs may have a broader role in the near future, namely for selected higher risk patients. However, identifying patients at risk for hospital readmission has been challenging. Novel approaches, such as ferric carboxymaltose and valsartan/sacubitril, and reemerging drugs, particularly digoxin, may reduce hospitalizations. Despite this, optimizing the use of "older" therapies is still warranted. Right heart pressures monitoring may provide novel insights into promptly outpatient management. Unfortunately, randomized trials in the specific ADHF population are scarce. A novel paradigmatic approach is needed in order to suitably improve the currently poor prognosis of ADHF. Both improving survival and reducing hospitalizations are, therefore, primordial therapy goals. Lastly, no single drug has consistently proved to improve survival in HF with preserved ejection fraction (HFpEF); yet, some approaches may efficiently reduce hospitalizations. Awareness on HFpEF management beyond the failing heart is imperative.