High-dose Diuretics Research Articles

Efficacy of tolvaptan on the short and mid-term prognosis in elderly patients with acute heart failure coexisting with oliguria: A retrospective cohort study.

In patients with acute heart failure (AHF) coexisting with oliguria, high doses of loop diuretics are often ineffective in increasing urine output and may adversely affect the patient's prognosis, especially in elderly patients. We investigated the efficacy of adding tolvaptan (TLV) on improving the prognosis in elderly patients with AHF coexisting with oliguria. All data for this retrospective cohort study were extracted from the electronic medical record system of the Second Medical Center of Chinese PLA General Hospital from January 2018 to December 2020. Patients diagnosed with AHF coexisting with oliguria were enrolled in this study and were divided into TLV and non-TLV groups based on the use of TLV. The primary outcome was all-cause mortality at 7 and 90-day. The secondary outcomes were the remission of AHF within 7 and 30 days or continued progression of AHF, and new-onset chronic kidney disease (CKD) after 90 days. Cox proportional hazards regression was used to assess the relationships between all-cause mortality and diuretic regimens, demographics, laboratory parameters, comorbidities, and medications. A total of 308 patients met the study criteria for the final statistical analysis, and they had a median age of 91 years (88, 95). The results showed that the addition of TLV was associated with a decreased risk of the 7 and 90-day all-cause mortality in patients with AHF with oliguria [adjusted HR, 95% CI: 0.60 (0.37, 0.98), p = 0.042; 0.56 (0.41, 0.75), p < 0.001, respectively]. Adding TLV significantly increased urine output and decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in 7 days, and alleviated the progression of AHF within 30 days. There were no statistically significant differences between the patients with or without TLV in terms of the occurrence of hypernatremia, the development of hepatic impairment within 30 days, and new-onset CKD after 90 days. This study demonstrated that the addition of TLV was clinically effective in increasing urine output, and had favorable effects on alleviating AHF progression and may reduce the risk of all-cause mortality at 7 and 90-day in elderly patients with AHF with oliguria, and TLV had a good safety profile. http://www.chictr.org.cn/showprojen.aspx?proj=148046, identifier: ChiCTR2200055518.

A Clinical Audit of Diuretic Use in a Cohort of Patients with Decompensated Chronic Liver Disease in South India

Background and Aim: Diuretic doses for the optimal management of ascites may be influenced by the patient profile and conditions. We undertook this study to map the usage of common diuretics, alone or in combination, for the management of patients with decompensated cirrhosis and to determine the prevalence of adverse effects with the administered regimens and factors that predict the need for paracentesis while on diuretics. Methods: This prospective study was done in an outpatient clinic among patients with known liver cirrhosis, irrespective of etiology, belonging to Child-Pugh Class B or C, with mild to moderate ascites and no dyselectrolemia on diuretics. The primary outcome of the study was the need for paracentesis. The type and dose of diuretic at this instance were noted. Results: A total of 200 patients (168 male), predominantly from southern Indian states, formed the study group. The median model for endstage liver disease score was 18 and 70% of cases required paracentesis within 3 months. The single diuretic agent was used in 18% of cases while combination of two diuretics was used in 82%. Spironolactone was the most common single agent used (26, 72.2%). The combination of furosemide and spironolactone was the most common diuretic combination used (89.6%, 147 cases). One hundred and thirty patients (65%) reported the adverse effects to diuretics. Renal dysfunction and electrolyte disturbances were the most common adverse effects. Adverse effects to diuretic use and frequency of large volume paracentesis were significantly more common in patients taking furosemide 40 mg and spironolactone 100 mg per day. Conclusions: Indian patients with decompensated chronic liver disease do not appear to tolerate the high doses of diuretics and 65% of them develop diuretic-related adverse effects. There is a need to formulate the guidelines for the optimal management of ascites in decompensated chronic liver disease in the Indian setting.

The Science of Extracorporeal Ultrafiltration: Introducing a Novel Miniaturized Device

Introduction: Fluid overload has been associated with untoward outcomes in a variety of clinical settings. Isolated extracorporeal ultrafiltration (UF) allows for mechanical extraction of excess fluid and optimization of volume status without the established risks associated with use of high-dose diuretics. Conventional machines for renal replacement therapy can be used to perform isolated UF. However, they typically need high blood flow rates with high circuit volumes and the therapy has to be performed by trained nurses. Herein, we describe a novel device, the Artificial Diuresis-1, or AD 1 (Medica S.p.A., Medolla, Italy), which is a portable technology designed to perform extracorporeal UF at bedside. Materials and Methods: The AD 1 uses a polysulfone mini-filter to generate ultrafiltrate with the help of two forces: blood flow (Qb) and gravity (based on the height at which the ultrafiltrate collection bag is placed). In vitro experiments were performed using human blood to evaluate vascular access pressures and ultrafiltrate volumes using various central venous catheters (CVCs; 12 Fr bilume, 10 Fr with 2 separate lumens, pediatric catheter 7 Fr). A variety of combinations were tested with Qb of 20, 35, 50 mL/min and collection bag height at 20, 40, 60 cm, measuring the UF rate per minute while monitoring the pressures in the venous and arterial lines and filtration fraction. Results: The device’s performance was as expected. Regarding the pediatric CVC, it was possible to perform measurements only with a Qb of 20 mL/min due to increased venous pressure. UF rates when lines were directly connected to the blood container as well as for CVC Tesio ranged from 3.7 to 11 mL/min, for the CVC Niagara™ from 4.5 to 12.5 mL/min, and for the CVC 7 Fr from 8.5 to 10 mL/min. The pressures of the vascular accesses were kept within a range of −5/-40 mm Hg for the artery and +10/+70 mm Hg for the vein. The highest venous pressure values were found with the CVC 7 Fr (+80/+100 mm Hg). Conclusions: This novel device allows to treat patients with fluid overload in a variety of settings, from low-intensity department such as long-term care facilities to the intensive care unit. The device is small and portable, has a simple design, and is user friendly. Future studies will be needed to evaluate whether gentle UF and treatment of volume overload will translate into improvement in clinical outcomes such as a reduction in congestion-related hospital admissions.

Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study.

Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co-morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re-hospitalizations. We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow-up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non-bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71-82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow-up of 651 (IQR 357-1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n=21, 65.6%), and the other events were cerebral bleeding (n=4, 12.5%), intraarticular bleeding (n=2, 6.3%), urogenital bleeding (n=2, 6.3%), haemorrhagic pericardial effusions (n=1, 3.1%), subcutaneous hematomas (n=1, 3.1%), and haemothorax (n=1, 3.1%). There was a significantly lower haemoglobin level (P<0.01), higher proportion of inferior vena cava (IVC) diameter ≥21mm (P<0.01), and higher furosemide equivalent doses per kilogram (P<0.01) in the bleeding group than non-bleeding group. A multivariate analysis revealed an equivalent dose of furosemide per kilogram ≥0.66mg/kg (hazard ratios (HR) of 2.64, 95% confidence interval (CI) 1.26-5.68, P=0.01), haemoglobin ≤10.3g/dL (HR of 2.43, 95% CI 1.14-5.03, P=0.02), and IVC diameter ≥21mm (HR of 2.79, 95% CI 1.16-6.29, P=0.02) were independently associated with bleeding events. The Kaplan-Meier analysis showed that HF re-hospitalization rates were higher in the bleeding group than non-bleeding group (P=0.04). High doses of oral loop diuretics, IVC dilatation, and anaemia were predictors of bleeding events in patients hospitalized with ADHF patients. In addition, bleeding events were associated with HF re-hospitalizations.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Abstract 13593: Rates of Acute Kidney Injury or Discontinuation After SGLT2 Inhibitor Initiation in a Real-World Cohort of Patients With Heart Failure With Reduced Ejection Fraction

Background: SGLT2 inhibitors (SGLT2i) decrease mortality and risk of hospitalizations in patients with HFrEF. SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate real-world rates of acute kidney injury (AKI) in our clinical setting that includes patients concurrently receiving high doses of loop diuretics. Methods: We abstracted patient level data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting in the University of Michigan (1/7/2016 - 2/7/2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. Secondary end points consisted of diuretic dose reduction, change in potassium, change in serum creatinine (SCr), and other side effects not requiring discontinuation. Results: The majority of patients were male (64%) with a mean LVEF of 27%. A total of 104 (52%) patients had diabetes mellitus. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. Twenty-two (11%) patients had AKI and 18 patients (9%) discontinued their SGLT2i. Yeast infection (3%), hypotension (2.5%), and AKI (2%) were the most common reasons for discontinuation. Using ROC curve analysis, the strongest predictors for AKI were A1C (AUC = 75.8, empirical confidence interval [ECI] 66.5-83.5); baseline SCr (AUC = 72.0 ECI 65.7-78.7); LVEF (AUC = 67.6 ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0 ECI 57.5-74.6). Similarly, the strongest positive predictors for SGLT2i discontinuation were A1C (AUC = 81.1 ECI 74.8-87.2); baseline Scr (AUC = 67.4 ECI 58.7-75.5); LVEF (AUC = 68.7 ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2 ECI 58.2-76.0). Conclusions: A1C was the strongest predictor of AKI and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. SCr, LVEF, and furosemide equivalents also predicted these outcomes.

Abstract 10869: Late Pericardial Effusion After Resolution of Takotsubo Cardiomyopathy in Covid-19 Infection. A Rare but Life-threatening Complication

Background: Various cardiac complications such as cardiomyopathy and sudden cardiac death have been associated with Coronavirus disease 2019 (COVID-19) pandemic. We present a case of late pericardial effusion after resolution of takotsubo cardiomyopathy in COVID-19. Case Report: A 46-year-old male presented with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. His left ventricular ejection fraction (LVEF) was 55% at admission. Over the next two days, his condition worsened requiring mechanical ventilation and inotropic support. A repeat echocardiogram revealed severe biventricular systolic dysfunction with basal hypercontractility and a drop in LVEF to 25%. Cardiac catheterization showed clean coronaries, elevated filling pressures, and reduced cardiac index (CI:1.44L/min/m 2 ); hence cardiogenic shock secondary to viral myocarditis/takotsubo cardiomyopathy was suspected and an impella was placed. His condition improved with high-dose steroids, diuretics, and heart failure medication. He was subsequently weaned off circulatory and inotropic support and LVEF improved to 60% in four days, hence a provisional diagnosis of takotsubo cardiomyopathy was made. However, three days post-Impella removal he became tachycardic and hypotensive and a repeat echocardiogram showed moderate pericardial effusion with purulent material and Right Ventricle (RV) free wall diastolic collapse(image). He underwent emergent pericardiocentesis draining 800 ml of purulent fluid with pericardial drain placement. Pericardial fluid cultures returned negative. Thereafter, his condition significantly improved and he was discharged on hospital day 15. Conclusion: Symptomatic pericardial effusion can occur late in the clinical course even after other cardio-pulmonary symptoms have improved. This case highlights the importance of clinician awareness of the various cardiac complications in COVID-19 and their timely diagnosis and management.

Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1–39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40–79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80–119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

Effects of empagliflozin in patients with heart failure and preserved ejection fraction according to baseline diuretic use: results from the EMPEROR-Preserved trial

Abstract Background In the EMPEROR-Preserved trial, empagliflozin reduced the risk of hospitalizations for heart failure (HHF) or cardiovascular (CV) death in patients with heart failure and preserved ejection fraction (HFpEF). Almost one in five patients in the trial were not on baseline diuretic therapy. Purpose To evaluate the efficacy and safety of empagliflozin according to baseline diuretic treatment, as well as change in diuretic therapy after initiation of empagliflozin. Methods Patients were categorized into subgroups as no diuretic and furosemide-equivalent diuretic dose of &amp;lt;40, 40 and &amp;gt;40mg and were compared for first HHF or CV death, HHF, CV death, total HHF, change in eGFR slope, and change in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Scores (KCCQ-CSS) between patients on empagliflozin vs. placebo. Changes in diuretic therapy in the two treatment groups were also compared. Results Amongst 5815 patients with data on diuretic dose, 1179 (20%) were on no diuretic, 2039 (35%) were on &amp;lt;40mg, 1700 (29%) were on 40mg, and 897 (15%) were on &amp;gt;40mg at baseline. Patients on higher diuretic doses at baseline were more likely to be diabetic, had a higher body weight and NT-proBNP, and lower estimated glomerular filtration rate (eGFR) on average. Patients on higher diuretic doses also had worse health status based on NYHA class and KCCQ-CSS estimates. The reduction of the risk of CVD or HHF, total HHF, preservation of eGFR, and KCCQ-CSS improvement with empagliflozin were consistent across all doses of diuretics (Table 1). The findings for all outcomes were consistent in patients on diuretics (any dose) vs. not on diuretics. Treatment with empagliflozin was associated with decreased rates of initiation (HR: 0.73 [0.59,0.90; p=0.004) or intensification (HR: 0.74; [0.65, 0.84]; p&amp;lt;0.001) of diuretics, while there were increased rates in permanent discontinuation of diuretics (HR: 1.46 [1.17, 1.82]; p&amp;lt;0.001) or diuretic dose reduction (HR: 1.22 [1.06, 1.42]; p=0.007). The incidence of adverse events were similar between treatment arms, irrespective of baseline use of diuretics. Volume depletion events were more common with empagliflozin amongst patients treated with diuretics (7.4 vs 5.7 events per 100 patient-years for empagliflozin vs placebo). Conclusion Empagliflozin improved clinical outcomes and health status in patients with HFpEF irrespective of baseline use of diuretics. Additionally, empagliflozin was associated with increased de-escalation or discontinuation of diuretics and decreased chances of initiation or intensification. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim &amp; Eli Lilly and Company Diabetes Alliance

Diuretic use before and after transcatheter aortic valve implantation: a nationwide study

Abstract Background Transcatheter aortic valve implantation (TAVI) is the new standard of care in patients of older age with symptomatic severe aortic stenosis, and these patients often depend upon diuretics for symptom relief. Randomized clinical trials suggest that approximately one third of patients undergoing TAVI do not achieve symptom relief. Furthermore, some patients have more symptoms after intervention, but “real-life” data are lacking. Purpose We examined use of diuretic therapy before and one year after TAVI in order to identify the proportion of patients who had intensification of diuretic treatment after intervention as a proxy for more symptoms. We also examined baseline factors associated with an intensification event. Methods Using Danish nationwide registries, we identified all Danish citizens who underwent TAVI from January 1, 2008 to December 31, 2019 and were alive one year after the intervention. Diuretic use pre-TAVI and 1-year post-TAVI (based on prescription fillings) was divided into the following groups: 1) no use; 2) low diuretic use: 1–40 mg of furosemide (or equivalent bumetanide); 3) intermediate diuretic use: 41–120 mg of furosemide; and 4) high diuretic use: &amp;gt;120 mg furosemide. Diuretic intensification was defined as a change from one pre-TAVI diuretic group to a higher post-TAVI diuretic group. Factors associated with intensified diuretic treatment was examined with logistic regression. In this analysis of intensification, only patients who could potentially have an intensification event were included (i.e., no diuretic use, low diuretic use, or intermediate diuretic use groups). Results A total of 3,978 patients (median age 81 [interquartile range 77–85]; 54% men) undergoing TAVI were identified. Pre-TAVI, 1,279 (32%) had no diuretic use, 1,818 (46%) had low diuretic use and 881 (22%) had intermediate diuretic use. Overall, patients with pre-TAVI intermediate diuretic use had a greater burden of cardiovascular and non-cardiovascular comorbidities (higher prevalence of heart failure, atrial fibrillation, chronic kidney disease and diabetes) compared with those with no or low diuretic use. The distribution of age and sex was similar between diuretic groups. One year post-TAVI, 1,406 (35.3%) had no diuretic use, 1,635 (41.1%) had low diuretic use, 654 (16.4%) had intermediate diuretic use and 283 (7.1%) had high diuretic use (Figure 1). Overall, 1,077 (27%) patients had intensification of diuretic treatment one year after undergoing TAVI. Ischemic heart disease and chronic renal failure were associated with an intensification event (odds ratio 1.23 [95% CI 1.05–1.23] and 1.46 [95% CI 1.10–1.94], respectively). Conclusion Among patients undergoing TAVI not treated with high-dose diuretics at time of intervention, approximately 1 out of 4 patients had intensification of diuretic treatment one year after intervention. Ischemic heart disease and chronic renal failure were associated with intensification. Funding Acknowledgement Type of funding sources: None.

Comprehensive and Safe Decongestion in Acutely Decompensated Heart Failure.

Progressive intravascular, interstitial, and alveolar fluid overload underlies the transition from compensated to acutely decompensated heart failure and loop diuretics are the mainstay of treatment. Adverse effects and resistance to loop diuretics received much attention while the contribution of a depressed cardiac output to diuretic resistance was downplayed. Analysis of experience with positive inotropic agents, especially dobutamine, indicates that enhancement of cardiac output is not consistently associated with increased renal blood flow. However, urinary output and renal sodium excretion increase likely due to dobutamine-mediated decrease in renal and systemic reduced activation of sympathetic nervous- and renin-angiotensin-aldosterone system. Mechanical circulatory support with left ventricular assist devices ascertained the contribution of low cardiac output to diuretic resistance and the pathogenesis and progression of kidney disease in acutely decompensated heart failure. Diuretic resistance commonly occurs in acutely decompensated heart failure. However, failure to resolve fluid overload despite high doses of loop diuretics should alert to the presence of a low cardiac output state.

Гепаторенальний синдром у дитини з муковісцидозом: аналіз клінічного випадку

Hepato-renal syndrome (HRS) is a rare complication that may accompany end-stage cystic fibrosis-associated cirrhosis in patients with cystic fibrosis. There is currently no unified protocol for the diagnosis and treatment of HRS in cystic fibrosis, particularly in pediatric patients. The main approaches to diagnosing the condition are to detect signs of acute renal failure in a patient with severe liver damage in the absence of shock and in the absence of signs of organic kidney damage or the use of nephrotoxic drugs. Treatment is based on the appointment of vasoconstrictors in combination with albumin infusion and the exclusion of factors that promote the development of HRS, but the method of final therapy remains liver transplantation. The article presents an analysis of the clinical case of HRS and its treatment in a child with cystic fibrosis. Immediate detection of liver cirrhosis in patients with cystic fibrosis, exclusion of the risk factors (massive and protracted surgical interventions, significant volume of extracted ascitic rudin, limiting the use of nephrotoxic drugs and high-dose loop diuretics) is a way to prevent the development of severe liver cirrhosis complications. Immediate recognition and proper management of HRS is a way to protect life before liver transplantation, as well as to preserve the quality of life of patients with cystic fibrosis. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: cystic fibrosis, hepatorenal syndrome, liver cirrhosis, ascites, terlipressin.

Remotely-driven management of diuretic therapy in heart failure patients with a multiparametric ICD algorithm

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific Background HeartLogic algorithm combines data from multiple sensors to predict future heart failure (HF) decompensation in patients with an implantable defibrillator (ICD) . An optimal strategy to manage algorithm alerts is not yet known, although decongestive treatment with diuretics is the most frequent alert-triggered action reported so far. Purpose We describe the implementation of HeartLogic for remote monitoring of HF patients, and we evaluate the approach to diuretic dosing and timing of the intervention in patients with device alerts. Methods The study was conducted in eight Italian high-volume arrhythmia centers. The algorithm was activated in 229 ICD patients during a median follow-up was 17 months [25th–75th percentile: 11-24] between December 2017 and July 2020. Remote data reviews and patient phone contacts were undertaken at the time of HeartLogic alerts, to assess the patient’s status and to prevent HF worsening. The study protocol did not mandate any specific intervention algorithm, and physicians were free to remotely implement clinical actions, to schedule extra in-office visits when deemed necessary for additional investigations or for interventions, or to adopt an active monitoring approach. We analyzed alert-triggered augmented HF treatments, consisting of isolated increases in diuretics dosage. Results We reported 242 alerts (0.8 alerts/patient-year) in 123 patients, 137 (56%) alerts triggered clinical actions to treat HF. Overall, timely diuretic changes were associated with a shorter "in-alert" state duration in comparison with late changes, i.e. 28 days [25th-75th percentile: 20-43] versus 62 days [25th-75th percentile: 44-118], p&amp;lt;0.001. By contrast, major and minor diuretic augmentations resulted in comparable durations, i.e. 47 days [25th-75th percentile: 30-58] versus 38 days [25th-75th percentile: 23-79], p=0.954. Of the 56 decongestive treatment adjustments, 47 resolved the alert condition, while in the remaining 9 cases, further treatments were required (augmented HF therapy during hospitalization or unscheduled intravenous decongestive therapy in outpatients). The need of hospitalization for further treatments to resolve the alert condition was associated with higher HeartLogic index values on the day of the diuretics increase (odds ratio: 1.11, 95%CI: 1.02-1.20, p=0.013) and with late interventions (odds ratio: 5.11, 95%CI: 1.09-24.48, p=0.041). No complications were reported after drug adjustments. Conclusions Decongestive treatment adjustments triggered by HeartLogic alerts, even when such adjustments were completely dependent on the physicians’ clinical expertise and were not standardized. The early use of decongestive treatment and the use of high doses of diuretics seem to be associated with more favorable outcomes.

P230 CARDIOGENIC SHOCK NETWORK: FROM PRIMARY PERCUTANEOUS CORONARY INTERVENTION TO VENTRICULAR ASSIST DEVICE IMPLANTATION

Abstract We report the clinical case of a 75 year–old man, previous smoker with mild lower extremity arterial disease, that presented a sudden and intensive chest pain. The emergency medical system documented an anterior STEMI quickly complicated by out–of–hospital cardiac arrest from a shockable rhythm, treated with DC–shock with rapid ROSC and recovery of consciousness. The patient was transported to the local hospital where coronary angiography showed extensive intraluminal thrombosis of ostial Cx and ostial LAD treated with thrombus aspiration and balloon angioplasty. During the procedure the patient was supported with inotropic agents, mechanical ventilation and IABP for a cardiogenic shock. After few hours he was transferred to level II hospital, equipped with all mechanical circulatory supports (MCS) and on–site cardiac surgery, where he was assisted with vaso–inotropic drugs, Impella CP and continuous renal replacement (CRRT). After 3 days for a refractory cardiogenic shock (stage D) the patient was referred and then transferred to our hospital, a level III hospital with cardiac transplantation program, for hemodynamic stabilization and eventual long term ventricular assist device (VAD). After 5 days the patient was weaned by Impella support, then weaned by mechanical ventilation, renal replacement therapy, without any neurological damage. The echocardiography showed a severe left ventricular dysfunction (EF 20%) with severe mitral regurgitation with good right ventricle function, confirmed also by strain assessment. In the following weeks were reported repeated episodes of pulmonary congestion treated with high doses of diuretics, NIV and nitroprusside infusion and episodes of low cardiac output treated with inotropes for prolonged periods. Mitraclip implantation was technically feasible but Heart Team decided to implantation an LVAD due to numerous episodes of low cardiac output and reduced cardiac index values. Screening for VAD showed no contraindications, therefore after 72 days from acute event LVAD was implanted with positive outcome. Conclusion the presence of a local network for cardiogenic shock allowed to optimize the clinical pathway of this patient and to manage in an integrated way the complex treatment of cardiogenic shock.

P59 A COMPLEX PCI IN A CARDIOGENIC SHOCK NSTEMI PATIENT NEEDING PTA AND LEFT VENTRICLE ASSISTANCE

Abstract A 72–years–old man, smoker, type 2 DM and hypertension in history, was admitted for NSTEMI complicated by cardiogenic shock; Echocardiogram revealed LV dilatation with severe disfunction (EF 20%), moderate mitral regurgitation; he started inotropic support and high dose diuretics, then he needed dialysis and positioning of a temporary PM. Coronary angiography revealed chronic total occlusion (CTO) of the left anterior descending artery (LADA) and CTO of the right coronary artery (RCA). A first CTO PCI procedure was attempted for the LADA occlusion, with the support of IABP, using an antegrade approach, polimeric wire (ASAHI Fielder) and more penetrating ones (ASAHI Gaia I and II), unable to gain the true lumen beyond the occlusion. A second attempt was planned, with the support of Impella CP device for left ventricle assistance; due to critical stenosis in the right common iliac artery, a PTA with stenting (8/38 mm) was preparatory for that. For the second attempt a dual coronary approach was prepared (6 F Amplatz left 1,0 for RCA and 7 F XB 3,5 for left coronary artery); at first a novel antegrade attempt was pursued with a step–up technique (ASAHI wires: Gladius, Gaia I, II and III, Conquest pro), ineffective to reach the true lumen distally the occlusion. The retrograde approach was then pursued, through a collateral originating from the acute marginal branch of the RCA to the distal segment of LADA, using the Caravel microcatheter with ASAHI wires Sion blue, Sion black, Suoh 03, effective to reach the distal cap of the occlusion, this one passed by the Gladius wire. The ASAHI RG3 externalization wire (330 mm) was then used, entering from the radial access and the amplatz catheter for the RCA, reaching the XB catheter in the left coronary artery through a Guideliner extension catheter, and externalized in the femoral access. IVUS analysis was then used to confirm good wire position and the vessel calibers, so pre–dilatation was done and 3 drug–eluting stents were implanted (2,25/23 + 3,25/38 + 3,5/18 mm) distal–to–proximal overlap, with final post–dilatation, obtaining a good final result on angiography and IVUS. During the 4–hours procedure clinical condition was stable and Impella was removed with a rapid weaning; the double pre–mounted Proglide device was used for femoral hemostasis. 5 days after the patient was discharged, II–III NYHA class, 25% EF. At the 3 months f–up he was asymptomatic in good clinical condition, 30% EF, he refused ICD implant.

P301 FULMINANT COVID–19 RELATED MYOCARDITIS: A CASE REPORT

The caseA 58–year–old man presented to ED because of fever, non–productive cough and worsening dyspnea. The patient’s medical history was unremarkable. On examination there was a hypoxic respiratory failure and the clinical picture rapidly evolved towards a cardiogenic shock characterized by altered mental status and cool extremities. Vital parameters: peripheral blood pressure was of 60/30 mmHg, pulse rate of 126 bpm, respiratory rate of 30 breaths/min, temperature of 38 °C. Two episodes of ventricular fibrillation were resolved by electrical shocks. The nasopharyngeal swab tested positive for COVID–19 on real–time reverse transcriptase–polymerase chain reaction assay. Arterial blood gas analysis showed a severe metabolic acidosis with hyperlactacidaemia (pH 7.26, excess basis–22 mEq/L, lactates 10 mmol/dL) and hypoxaemia. Situation evolved towards an end–organ hypoperfusion associated with multisystem organ failure (MOF). High resolution chest CT demonstrated bilateral ground glass opacities consisting of COVID–19 related interstitial pneumonia. 12–leads ECG demonstrated sinus rhythm with diffuse concave ST–segment elevation. T–T echocardiogram showed: 1) severely thickened LV walls; 2) decreased LV systolic function; 3) segmental wall motion abnormalities consisting of akinesis of the LV distal segments with relatively preserved function at the base; 4) LVEF) of 25%; 5) pericardial effusion. Thickened LV walls meant myocardial inflammatory infiltration/edema and the final diagnosis was FULMINANT COVID–19 related MYOCARDITIS. Patient underwent oro–tracheal intubation+invasive ventilation. An intra–aortic balloon pump (IABP) was placed on top of adrenaline (0.07μg/kg/min), and noradrenaline (0.1μg/kg/min) was added for worsening hypotension (systolic blood pressure: 80/67/60 mmHg). Additional therapy consisted of intravenous high dose diuretics, methyprednisolone, tucilizumab, immunoglobulin, ceftriaxone, remdesivir. After 3 weeks, patient recovered a good respiratory and haemodinamic status, LV wall thicknesses decreased and EF increased to normal values. The final outcome was favorable. DiscussionThe prevalence of fulminant myocarditis among COVID–19 patients is unclear. This simultaneous presentation of fulminant myocarditis and COVID–19 pneumonia favors an alternative pathogenetic pathway with possible acute replication and direct dissemination of the virus through the blood or the lymphatic system from the respiratory tract to the myocardium.

MO116: Vitamin C Nephrotoxicity in a COVID-19 Patient: A Case Report

BACKGROUND AND AIMSDuring the time of the COVID-19 pandemic, multiple treatment options have been investigated, even though their efficacy and secondary effects remain insufficiently known.We report the case of a vitamin C induced oxalate nephropathy in a COVID-19 patient with preexisting chronic kidney disease (CKD) resulting in irreversible acute renal failure.Vitamin C, also known as ascorbic acid, has been used as an anti-inflammatory therapy for COVID-19, but review of the literature shows similar cases of acute kidney injury (AKI), raising concern.METHODWe report the case of a 73-year-old Caucasian woman admitted for hyperthermia and digestive disorders. She had recently started a first-line chemotherapy for multiple myeloma with partial response. She also displayed preexisting stage 4 CKD (eGFR 18.50 mL/min/1.73 m² using CKD-EPI) of unknown aetiology.She was tested positive for SARS-CoV2 by nasopharyngeal swab and soon transferred to the intensive care unit. She received intravenous corticosteroids using dexamethasone 6 g/24 h for 10 days and a piperacillin + tazobactam probabilistic antibiotherapy. She also received high doses (15 g/24 h) of vitamin C for three consecutive days. No monoclonal antibodies were prescribed due to a previous vaccination with a positive serology upon admission.Although the patient recovered from respiratory tract infection, her kidney function progressively deteriorated with serum creatinine levels rising up to 8.06 g/dL, leading to her admission in our nephrology department. The patient was initially treated with high doses of diuretics for anasarca and an abdominal CT excluded urinary tract obstruction with normal kidney size and aspect. Urinary analysis showed protein to creatinine (p/c) ratio of 1348 g/g, and presence of urinary light chains. Her monoclonal spike was measured at 2.3 g/L and her kappa/lambda fraction was 1.74.Intermittent haemodialysis was initiated, and a kidney biopsy was performed.RESULTSHistology revealed hundreds of intratubular calcium oxalate crystals, with severe and diffuse acute tubular necrosis and interstitial edema. There was no amyloidosis, no sign of active glomerular disease and no interstitial fibrosis. Immunofluorescence (IgA, IgG, IgM, C1Q, C3, kappa and lambda) was negative. We concluded to oxalate nephropathy.After a 2-month follow-up, the patient remains dialysis dependent.Vitamin C is a precursor of oxalate and has been shown to cause secondary oxaluria, particularly with high-dose regimens in patients with altered renal function. Given the histological findings evocative of acute oxalate nephropathy, the accountability of high doses of vitamin C should be considered.No other cause of hyperoxaluria was identified in our patient beside broad spectrum antibiotic use, which could decrease intestinal bacterial oxalate degradation. In particular, there was no malabsorptionThe limitation of our report is the unknown cause of preexisting CKD; therefore, we cannot rule out preexisting hyperoxaluria. Also, no dosage of serum vitamin C and oxalate levels were performed during follow-up. Finally, our patient had other possible causes AKI, such as recent SARS-CoV2 infection, or linked to multiple myeloma, but these were considered unlikely given the proper haematological response to treatment and non-evocative biopsy.The rationale for vitamin C use in COVID-19 is based on in vitro studies showing its antioxidant, anti-inflammatory, anticoagulant and immune modulatory properties. There lack large clinical studies, and the literature shows conflicting results. Multiple cases of acute oxalate nephropathy were described.CONCLUSIONVitamin C is an anti-inflammatory treatment used in COVID-19 that can lead to secondary hyperoxaluria with significant and irreversible AKI. Due to the severity of AKI in patients with preexisting CKD, we believe renal function should be considered before using high doses of vitamin C.Larger controlled trials are needed both to establish the clinical benefit of vitamin C and further describe its potential nephrotoxicity.

Decongestive treatment adjustments in heart failure patients remotely monitored with a multiparametric implantable defibrillators algorithm.

AimsHeartLogic algorithm combines data from multiple implantable defibrillators (ICD)‐based sensors to predict impending heart failure (HF) decompensation. A treatment protocol to manage algorithm alerts is not yet known, although decongestive treatment adjustments are the most frequent alert‐triggered actions reported in clinical practice. We describe the implementation of HeartLogic for remote monitoring of HF patients, and we evaluate the approach to diuretic dosing and timing of the intervention in patients with device alerts.MethodsThe algorithm was activated in 229 ICD patients at eight centers. The median follow‐up was 17 months (25th–75th percentile: 11–24). Remote data reviews and patient phone contacts were undertaken at the time of HeartLogic alerts, to assess the patient's status and to prevent HF worsening. We analyzed alert‐triggered augmented HF treatments, consisting of isolated increases in diuretics dosage.ResultsWe reported 242 alerts (0.8 alerts/patient‐year) in 123 patients, 137 (56%) alerts triggered clinical actions to treat HF. The HeartLogic index decreased after the 56 actions consisting of diuretics increase. Specifically, alerts resolved more quickly when the increases in dosing of diuretics were early rather than late: 28 days versus 62 days, p < .001. The need of hospitalization for further treatments to resolve the alert condition was associated with higher HeartLogic index values on the day of the diuretics increase (odds ratio: 1.11, 95% CI: 1.02–1.20, p = .013) and with late interventions (odds ratio: 5.11, 95% CI: 1.09–24.48, p = .041). No complications were reported after drug adjustments.ConclusionsDecongestive treatment adjustments triggered by alerts seem safe and effective. The early use of decongestive treatment and the use of high doses of diuretics seem to be associated with more favorable outcomes.

Light Chain Cast Nephropathy in Multiple Myeloma: Prevalence, Impact and Management Challenges.

“Cast nephropathy” (CN) is a pathological feature of myeloma kidney, also seen to a lesser extent in the context of severe nephrotic syndrome from non-haematological diseases. The name relates to obstruction of distal tubules by “casts” of luminal proteins concentrated by intensive water reabsorption resulting from dehydration or high-dose diuretics. Filtered proteins form complexes with endogenous tubular Tamm-Horsfall glycoprotein. The resulting gel further slows or stops luminal flow upon complete obstruction of distal convoluted tubules and collecting ducts. Thus, a tubular obstructive form of acute kidney injury (AKI) is a common consequence of CN. The pathogenesis of CN will be reviewed in light of recent advances in the understanding of monoclonal disorders of B lymphocytes, leading to the release of immunoglobulin components (free light chains, FLC) into the bloodstream and their filtration across the glomerular basement membrane. Treatment aiming at reduction of the circulating burden of FLC may help recovery of renal function in a fraction of these patients, besides filling the void between the onset of AKI, histopathological diagnosis, and full response to pharmacologic treatment.

Abstract 51: Too Little, Too Late: Diuresing Inefficiencies At A Veterans Affairs Hospital

Background: Between 2016 and 2021, the average length of stay for congestive heart failure (CHF) patients at our Veterans Affairs (VA) Hospital has ranged from 0.8 to 1.9 days longer than comparable VA hospitals. This extended length of stay (LOS) results in increased healthcare costs and is an institutional focus to increase quality of care. Current cardiology guidelines for patients admitted with an acute CHF exacerbation recommend aggressive diuresis, defined as high-dose loop diuretics at least twice a day. We sought to analyze our institution’s compliance with this guideline-directed care. Methods: We performed a retrospective chart review of Veterans admitted between July and September 2021 with a primary diagnosis of CHF exacerbation. We tabulated the average LOS, days IV diuretics were administered, time(s) of administration, and the number of IV diuretic doses per day. Results: 44 patients were identified. The average LOS and number of days of IV diuretics a Veteran received was 7.5 (SD 3.5) and 4.5 (SD 1.4) days, respectively. The average number of IV diuretics given during days of IV diuresis was 1.4 (SD 0.5). We noted that 11.5% of IV diuretic doses were given before 8AM. Conclusions: Our results demonstrate that the diuresing patterns at our VA hospital fall short of the recommended guidelines. Receiving an average of 1.4 doses of IV diuretic, rather than at least 2, likely contributes to extended length of stay and cost. Additionally, we note that very few doses of diuretics are administered prior to 8AM, which may delay or prevent subsequent dosing. This project identifies clear targets for future quality improvement projects at our institution aimed at improving length of stay and Veteran care by increasing the number of IV diuretic doses per day.