Inotropic Therapy Research Articles

Abstract 14366: Young, Healthy Female With Myocarditis and Cardiogenic Shock After Mild COVID-19 Infection

Background: We present a case of a young female with no pre-existent conditions, who presented to the hospital one month after a mild COVID-19 infection with severe myocarditis complicated by cardiogenic shock. Case: A 40-year-old female with no prior medical history and a regular, vigorous exercise program developed a mild COVID-19 infection with symptoms of mild fatigue, myalgias, chills, fever, and loss of taste, which resolved within a week. A month later, she presented to the hospital with exertional dyspnea, weakness, chest pressure, abdominal pain, and fatigue. A transthoracic echocardiogram revealed a left ventricular ejection fraction of 15% with a severely dilated left ventricle, global hypokinesis and severe mitral regurgitation. Right heart catheterization demonstrated cardiogenic shock with a cardiac index of 1.4 liters per minute by Fick equation, and she was admitted to the cardiac intensive care unit. Cardiac magnetic resonance revealed subepicardial delayed enhancement along the lateral and inferolateral walls and elevated T1 mapping consistent with myocarditis. A right ventricle biopsy revealed myocyte hypertrophy and patchy interstitial fibrosis without evidence of inflammatory tissue. She was diuresed, supported with inotropic therapy, and empirically treated with high doses of glucocorticoids. She clinically improved with weaning of inotropes and was discharged in stable condition on goal-directed medical therapy after 2.5 weeks. Conclusion: This patient represents a case of severe cardiogenic shock, after initial infection and in the absence of previously identified risk factors for development of COVID myocarditis. The absence of inflammatory tissue on pathology raises questions regarding the centrality of inflammatory processes in COVID-19-related myocardial injury leading to “long COVID” syndrome. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Abstract 12272: Pericardial Decompression Syndrome Following Low Volume Pericardiocentesis for Malignant Cardiac Tamponade

Introduction: Cardiac tamponade is a life-threatening condition requiring emergent intervention. Pericardial decompression syndrome (PDS) is a rare complication that presents as acute ventricular dysfunction following pericardiocentesis with a mortality rate up to 29%. In this case, we present a patient with PDS who developed cardiogenic shock following pericardiocentesis for cardiac tamponade. Clinical course: A 58-year-old female with no significant cardiac history presented with chest pain and dyspnea. Computed topography revealed a mediastinal mass and large pericardial effusion. Transthoracic echocardiogram (TTE) demonstrated the effusion with tamponade physiology. Left ventricular (LV) systolic function was preserved at this time. A total of 450ml of serosanguinous fluid was removed by pericardiocentesis, with minimal residual volume around the RV and a large effusion remaining around the LV. Repeat TTE 14 hours later revealed severe global hypokinesis and biventricular failure with an LV EF of 15%. The patient was started on inotropic therapy and transferred to our tertiary care center. Continuous diuresis and vasopressor therapy were initiated. Once stable, the patient was taken for pericardial window with further removal of 600ml of fluid. Subsequent TTE demonstrated recovery of LV systolic function to 47%. Discussion: Our patient developed cardiogenic shock secondary to biventricular heart failure following pericardiocentesis. This presentation is concerning for pericardial decompression syndrome. While the exact mechanism of PDS is not known, the current hypothesis postulates that drainage of fluid compressing the RV leads to a sudden increase in venous return. This abrupt change causes septal bowing and decreased LV systolic function. Some sources recommend draining pericardial fluid in smaller quantities; however, PDS may still occur at smaller volumes as was seen in our patient. PDS is a rare but life-threatening complication that requires vigilance post-pericardiocentesis regardless of volume removed.

Clinical presentation and outcomes of acute heart failure in the critically ill patient: A prospective, observational, multicentre study

AimsTo assess the clinical profile and factors associated with 30-day mortality in patients with acute heart failure (AHF) admitted to the intensive care unit (ICU). DesignProspective, multicentre cohort study. ScopeThirty-two Spanish ICUs. PatientsAdult patients admitted to the ICU between April and June 2017. InterventionPatients were classified into three groups according to AHF status: without AHF (no AHF); AHF as the primary reason for ICU admission (primary AHF); and AHF developed during the ICU stay (secondary AHF). Main variables of interestIncidence of AHF and 30-day mortality. ResultsA total of 4330 patients were included. Of these, 627 patients (14.5%) had primary (n=319; 7.4%) or secondary (n=308; 7.1%) AHF. Among the main precipitating factors, fluid overload was more common in the secondary AHF group than in the primary group (12.9% vs 23.4%, p<0.001). Patients with AHF had a higher risk of 30-day mortality than those without AHF (OR 2.45; 95% CI: 1.93–3.11). APACHE II, cardiogenic shock, left ventricular ejection fraction, early inotropic therapy, and diagnostic delay were independently associated with 30-day mortality in AHF patients. Diagnostic delay was associated with a significant increase in 30-day mortality in the secondary group (OR 6.82; 95% CI 3.31–14.04). ConclusionsThe incidence of primary and secondary AHF was similar in this cohort of ICU patients. The risk of developing AHF in ICU patients can be reduced by avoiding modifiable precipitating factors, particularly fluid overload. Diagnostic delay was associated with significantly higher mortality rates in patients with secondary AHF.

Temporal trend mortality and in-hospital mortality predictors in an ischemic cardiogenic shock population: a 10 years single-centre retrospective study

Abstract Background Cardiogenic shock (CS) after acute myocardial infarction (AMI) is a life-threatening condition with an high rate of in-hospital mortality. Purpose This study aims to 1) describe predictors of in-hospital mortality; 2) evaluate ten years mortality temporal trend in our Cardiac Intensive Care Unit (CICU); 3) assess the feasibility of CARDSHOCK risk score in our population; 4) elaborate a simpler version of CARDSHOCK risk score. Methods All consecutive patients with CS after AMI admitted at our CICU from March 2012 to July 2021 were included in this single-centre retrospective study. Results We included 167 patients [males 67%; age 71 (61–80) years] with ischemic CS. Patients had severe LV dysfunction in 66%. Baseline serum lactate was 5.2 (3.1–8.8) mmol/L. All patients required inotropes: 71% required dopamine [mean dose 5.6 (2.4–11,3) mcg/kg/min], 65% required noradrenaline [mean dose 0.10 (0.05–0.18) mcg/kg/min], 32% required dobutamine [mean dose 4.5 (2.2–15.9) mcg/kg/min]; 17.4% received levosimendan alone [mean dose 0.1 mcg/kg/min]. Mechanical cardiac support (MCS) was pursued in 91.1% [65% IABP, 23% Impella CP, 4% VA-ECMO]. From March 2012 to July 2021 we observed a significative temporal trend mortality reduction (OR=0.90, 95% CI: 0.84–0.96, p=0.0015), in particular in-hospital mortality has reduced from 57% of first time-quartile to 29% of the fourth quartile (Figure 1). In addition we also noted a significant increase in Impella catheter use (p=0.0005) with a consequent reduction of IABP (p=0.01), a reduction in dopamine administration (p=0.0007) and a greater use of dobutamine and levosimendan (p=0.015 and p=0.0001). In our population of AMI-CS patients CARDSHOCK risk score was a reliable in-hospital mortality predictor tool (OR 1.11; 95% CI, 1.06–1.17; p=0.00011). After the multivariate analysis only ejection fraction (EF) at baseline (OR=0.99, 95% CI: 0.98–0.99, p=0.009), lactate level at presentation (OR=1.03, 95% CI: 1.01–1.06, p=0.015) and presence of three-vessels coronary artery disease (OR=0.73, 95% CI: 0.59–0.90, p=0.0038) resulted to be in-hospital mortality predictors. For this reason, a prediction model composed by those three variables was created which exhibited better predictive performance for in-hospital mortality than Cardshock risk score (AUC of 0.94 vs AUC of 0.72 respectively, p=0.015) (Figure 2). Conclusions In our retrospective single-centre study a significant reduction of mortality through the years is observed, probably due to more extensive use of micro axial pumps and better manipulation of inotropic drug therapies. The use of Cardshock risk score has been proven to be a feasible tool in prediction on in-hospital mortality also in our sample composed only of AMI-CS patients. In addition, a more simplified risk score made up of only three clinical variables demonstrates at least the same predictive performance. Future validation in a larger population could be advisable to validate the simplified score. Funding Acknowledgement Type of funding sources: None.

Midodrine in treatment of post coronary revascularization vasoplagia; pilot, open label, assessor blinded randomized clinical trial

Abstract Purpose Post cardiac surgery hypotension and inotrope dependence are among major causes of prolonged intensive care unit (ICU) stay. Besides routine managements, catecholamine inotrope-vasopressors are the traditional treatment. However, there is an increasing interest to catecholamine-sparing agents, such as Midodrine, oral alfa1 agonist, in patients with vasoplegia. Up to now there are no randomized study with midodrine on post cardiac surgery patients. Material and method In this pilot, open label, assessor blind, randomized clinical trial from June 2020 to December 2021, 65 patients with refractory (more than 24 hours inotropes) hypotension after coronary revascularization were included. Patients were randomly assigned to receive Midodrine add-on therapy (10 mg stat and 5 mg po every 12 hours) or placebo add-on routine treatment. The primary outcome was liberation time from IV inotrope-support. Secondary outcomes were ICU admission time and total vasopressor dosage after randomization. Results 32 patients enrolled in Midodrine group, with a mean age of 60.72, and 33 patients received placebo with mean age of 63.27. Median liberation time from inotrope was 27 hours in Midodrine group and 49 hours in placebo group (p=0.022). ICU admission time for Midodrine and placebo groups were 115 and 121 hours, respectively (p=0.990). Total vasopressor dosage after randomization were similar in two studied groups, 4352 μg in Midodrine group and 5637 μg in placebo group (p=0.405). No adverse event was observed in Midodrine group. Conclusion Midodrine add-on inotrope therapy was a safe medication with appropriate compliance in ICU admitted patients after cardiac surgery, which seems to decrease the inotrope dependent time. Funding Acknowledgement Type of funding sources: None.

Transcatheter mitral valve repair for inotrope dependent cardiogenic shock – Design and rationale of the CAPITAL MINOS trial

Functional mitral regurgitation (MR) is an important clinical consideration in patients with heart failure. Transcatheter edge-to-edge repair (TEER) has emerged as a useful therapeutic tool for patients with chronic heart failure, however the role of TEER in patients with cardiogenic shock (CS) and MR has not yet been studied in a randomized trial. The Transcatheter Mitral Valve Repair for Inotrope Dependent Cardiogenic Shock (CAPITAL MINOS) trial was therefore designed to determine if TEER improves clinical outcomes in the CS population. The CAPITAL MINOS trial is an open-label, multi-center randomized clinical trial comparing TEER to medical therapy in patients with CS and MR. A total of 144 patients with Society for Cardiovascular Angiography and Interventions (SCAI) class C or D CS and at least 3+ MR will be randomized in a 1:1 ratio to TEER or medical therapy alone. The primary outcome will be a composite of in-hospital all-cause mortality, cardiac transplantation, implantation of durable left ventricular assist device, or discharge on palliative inotropic therapy. Patients will be followed for the duration of their index hospitalization for the primary outcome. Secondary outcomes include 6 month mortality. The CAPITAL MINOS trial will determine whether TEER improves outcomes in patients with CS and MR and will be an important step in optimizing treatment for this high-risk patient population.

Intentional avermectin pesticide ingestion: a retrospective multicenter study

Context Avermectin pesticides are widely used in agriculture, and are thought to have low toxicity in humans. However, information on their toxicity after accidental or deliberate ingestion is limited. Objective The aim of this study was to evaluate the clinical manifestations of avermectin pesticide ingestion and identify factors associated with severe outcomes (death, intubation, or sustained hypotension requiring inotrope therapy). Materials and Methods This multicenter retrospective study included patients who visited the emergency departments of six teaching hospitals due to acute avermectin pesticide ingestion between January 2012 and May 2020. Patients who reported ingestion of any other pesticides, drugs, or substances were excluded. Results In total, 64 patients (median age, 72 years) were included: 60 had ingested emamectin pesticides, and 4 had ingested abamectin. Almost all (98%) were cases of self-harm. The most common presentation was drowsiness (47%), with a median Glasgow Coma Scale (GCS) score of 14, followed by shortness of breath (SOB)/dyspnea (33%) and nausea/vomiting (22%). Concurrent methanol exposure (via the solvent) was confirmed or suspected in five patients. Seventeen patients (27%) were intubated. Three patients who developed respiratory failure were not intubated because of a “do-not-resuscitate” (DNR) order. Four patients developed sustained hypotension requiring inotrope therapy. Fifty patients (78%) were admitted, of whom 27 (42%) required intensive care unit (ICU) admission. Four patients died, three of whom had a DNR order. Based on our definition, 20 patients (31%) had severe outcomes. A multivariate logistic regression model showed that a GCS score < 13 (OR 68.1, 95% CI 3.8–999) and the presence of SOB/dyspnea (OR 50.2, 95% CI 3.0–849.9) were associated with severe outcomes. Conclusions Most patients who intentionally ingested avermectin pesticides required inpatient treatment. Forty-two percent needed ICU care and 31% had severe outcomes. A GCS score < 13 and SOB/dyspnea were independently associated with severe outcomes.

Inotrope and vasopressor use in cardiogenic shock: what, when and why?

Despite increasing interest in the management of cardiogenic shock (CS), mortality rates remain unacceptably high. The mainstay of supportive treatment includes vasopressors and inotropes. These medications are recommended in international guidelines and are widely used despite limited evidence supporting safety and efficacy in CS. The OptimaCC trial further supports that norepinephrine should continue to be the first-line vasopressor of choice in CS. The CAPITAL DOREMI trial found that milrinone is not superior to dobutamine in reducing morbidity and mortality in CS. Two studies currently underway will offer the first evidence of the necessity of inotrope therapy in placebo-controlled trials: CAPITAL DOREMI2 will randomize CS patients to inotrope or placebo in the initial resuscitation of shock to evaluate the efficacy of inotrope therapy and LevoHeartShock will examine the efficacy of levosimendan against placebo in early CS requiring vasopressor therapy. Review of the current literature fails to show significant mortality benefit with any specific vasopressor or inotropic in CS patients. The upcoming DOREMI 2 and levosimendan versus placebo trials will further tackle the question of inotrope necessity in CS. At this time, inotrope selection should be guided by physician experience, availability, cost, and most importantly, individual patients' response to therapy.

Esophageal Atresia and Tracheoesophageal Fistula

A survey of neonates with esophageal atresia and tracheoesophageal fistula (EA ± TEF) to determine additional factors responsible for poor surgical outcomes in our institution where employing an improved standard of care can ameliorate the outcome. We carried out a retrospective review of 54 neonates, who underwent surgical repair of EA± TEF over a 5-year period. We collected data regarding the patients' demographics, perioperative findings, records of neonatal intensive care, and ascertained the effects of gender, gestational age, birth weight, age at operation, type of anomaly, coexisting major anomalies, preoperative inotrope therapy, and duration of postoperative ventilation on the surgical outcome. The mortality rate was 51.9%, out of which, 42.8% of neonates succumbed to ventilator-associated conditions. Age at the time of surgery, gestational age, preoperative inotrope support, presence of coexisting anomalies, and duration of postoperative ventilation were determined as the significant variables predicting mortality(P < 0.05). The area under the Receiver Operating Curve showed the duration of postoperative ventilation as the best indicator of mortality. The Logistic regression model (χ2 = 11.204, P = 0.019) with the above-mentioned variables showed that neonates who were operated before 2.5 days and who required <74.5 hours of postoperative ventilation were 3.91 and 48.30 times more likely to survive respectively, than their counterparts. A delay in surgery due to delayed diagnosis and or delayed transportation to tertiary centres and prolonged ventilatory support have an additional detrimental effect on the surgical outcomes of EA ± TEF.

Guillain — Barré syndrome following asymptomatic COVID-19 in an adolescent: a clinical case

Guillain — Barré syndrome (GBS) is a rare disease that occurs with an approximate incidence of 1.7 cases per 100,000 children in the pediatric population. The gender difference in the prevalence of the disease is characterized by a 20% greater vulnerability of boys than girls. The exact cause of Guillain — Barre syndrome is unknown; however, it can occur after respiratory infection by Haemophilus influenzae, recent or ongoing Campylobacter jejuni infection or poliovirus. Since the beginning of the COVID-19 pandemic, there have been some reported Guillain — Barré diagnoses among adults following SARS-CoV-2 infection. The article describes a clinical case of an adolescent girl who was admitted to the Regional Municipal Non-Profit Facility “Chernivtsi Regional Children’s Clinical Hospital” with signs of flaccid paraplegia of the lower extremities, pelvic dysfunction and paraparesis of the upper extremities after she had suffered a sudden severe pain syndrome. She had previously been diagnosed with asymptomatic SARS-CoV-2. Initial complex investigations were as follows: high white blood cells count, elevated levels of procalcitonin (PCT), C-reactive protein and D-dimer, low SARS-CoV-2 IgM level and positive IgG titer, high levels of protein in spinal fluid. Electroneuromyography findings and nerve conduction test of lower extremities showed decreased M amplitude and H reflex response. The patient received oxygen therapy, hemodynamic support, cardiac support (infusions and inotrope therapy), gradual antibacterial therapy and was administrated with intravenous normal human immunoglobulin. She was also treated with a short course of parenteral glucocorticoids, vasoactive neurometabolites, nootropics, anticholinesterases, non-steroidal anti-inflammatory drugs along with physical therapy and massages. The patient began demonstrating slow but positive improvement in her limb motor functions and sensitivity within one month.

EFFICACY OF SGLT2I IN ACUTE DECOMPENSATED HEART FAILURE WITH TYPE 2 DIABETES MELLITUS

Objective: We hypothesized that Sodium Glucose cotransporter 2 inhibitors (SGLT2i) exerts positive effects in patients admitted with ADHF and type 2 diabetes mellitus (T2DM). Design and method: Prospective case control study with 1-month follow up. All the patients who admitted to Cardiology center, Hue Central Hospital between 01/12/2020 and 01/06/2021. Inclusion criteria: Adults diagnosed with T2DM with hypervolemic ADHF reduce LVEF and planned treatment with IV loop diuretic therapy. Exclusion criterias: fasting blood glucose (FBG) &lt; 4.4 mmol/L, Systolic blood pressure &lt; 90mmHg, requires inotrope therapy, eGFR &lt; 30 ml/min/1.73m2, severe anemia, breastfeeding or pregnant, severe AS or MS without repair, severe hepatic impairment, acute coronary syndrome or history of coronary artery stenting. The study primary end-point: Length of hospitalization, in-hospital death, death within 30 days after discharge and re-hospitalized within 30 days. The study safety end-point: Urinary tract infection, worsening renal function, ketonacidosis or hypovolemic shock. Results: The proportion of in-hospital mortality, 30-days mortality and the length of hospitalization by day tended to be higher in the group of patients not using SGLT2i but not significant. The proportion of re-hospitalized for 30 days was higher in group not using SGLT2i (p = 0.014). The patient group of non-SGLT2i using re-hospitalized sooner than the patient using SGLT2i (p = 0.029). The eGFR of the patient use the SGLT2i show significantly improvement after 30 days (p = 0.024) but in day 4, it’s shown no improvement. In patient who don’t use the agent, the eGFR get worst in day 4 with p = 0.01 then it improve in day 30 but not significant. The group of using SGLT2i seems much more effective in reduce NT-proBNP and FBG (p values: NT-proBNP:0.026 to 0.044; FBG: 0.021 to 0.038, respectively). Complications that should be considered in patients using SGLT2i were UTIs and discontinuation of treatment due to feeling lose weight too fast. Conclusions: The using of SGLT2i reduce the numbers of re-hospitalization in first 30-day after discharged, prolong the duration between re-hospitalization period and only the patient groups using SGLT2i could improve the eGFR after 30-days with no significant adverse effects.

Comparative Effectiveness and Safety of Milrinone and Levosimendan as Initial Inotrope Therapy in Patients With Acute Heart Failure With Renal Dysfunction.

Levosimendan and milrinone are 2 effective inotropic drugs used to maintain cardiac output in acute heart failure (AHF). Using data from patients with AHF with and without abnormal renal function, we performed this single-center, retrospective cohort study to compare the effectiveness and safety of milrinone and levosimendan for the initial management of AHF. Patients admitted for heart failure between December 2016 and September 2019 who received levosimendan or milrinone as initial inotrope therapy in the cardiology department were identified. A total of 436 levosimendan and 417 milrinone patients with creatinine clearance (CrCl) ≥30 mL/min and 50 levosimendan and 71 milrinone patients with CrCl <30 mL/min or on dialysis were included. The primary outcome was a composite of changes in clinical status at 15 and 30 days after initial inotrope therapy discontinuation. Between subgroups of patients with CrCl ≥30 mL/min, there were no significant differences in primary outcomes; milrinone was associated with more frequent hypotension and cardiac arrhythmias during the infusion period (P < 0.01), while levosimendan was associated with more frequent cardiac arrhythmias within 48 hours after discontinuation (P < 0.05). Of the patients with CrCl <30 mL/min or on dialysis, more initial levosimendan than milrinone patients and those who switched to alternative inotropes experienced clinical worsening at 15 days and 30 days (P < 0.05). According to our results, patients with AHF with severe renal dysfunction should avoid initial inotrope therapy with levosimendan.

P38 HEART FAILURE IN TRANSPLANTED HEART DUE TO TOXOCARA CANIS

Abstract Toxocara Canis is a parasitic roundworm which cause zoonotic infections worldwide. It could affect heart causing myocarditis, pericarditis and Loffler’s endocarditis, with a clinical presentation ranged from asymptomatic to life threating conditions with heart failure. After heart transplantation, patients are immunosuppressed, therefore they could experience reactivation of hidden parasitosis like Toxocariasis. To our knowledge, some cases of Toxocara Canis affecting the heart have been described in literature, but there are no described cases of this infection in a transplanted heart. A 65–year–old woman underwent transplant heart surgery due to post–ischaemic dilatative cardiomyopathy. After transplantation she experienced supraventricular tachycardia, reduction of the new heart ejection fraction from 52% to 30% (Figure 1) requiring inotropic drug therapy and mild to severe mitral valve regurgitation due to ventricular dilatation. The unique finding was the presence of antibodies against Toxocara Canis in her blood and high level of immunoglobulin E. In addition, endomyocardial biopsy revealed a cystic intracellular inclusion. Specific therapy with albendazole and corticosteroids was immediately started: heart ejection fraction slowly grew up and mitral regurgitation became milder. Time correlation between Toxocara Canis antibodies positivity and worsening of heart ejection fraction, moreover the recovery with specific antibiotic therapy against this parasite, make us think that it could have been the cause of heart function deterioration in this patient. Often diagnostic findings of Toxocara Canis infection are not specific, heart damage seemed to be driven by direct invasion of the larvae and by immunological reaction. In conclusion, Toxocara Canis could be a cause of heart function deterioration after heart transplant. It should be considered in differential diagnosis of post–transplant heart failure.

Persistent Critical Illness in Newborns

The problem of persistent critical illness (PCI) in newborns is poorly understood. The epidemiology of this pathological condition in newborns has not been precisely established, however, it is known that PCI is considered a predictor of an unfavorable outcome in any pathology and proceeds more severely then in adults and children. Long-term outcomes of PCI in surviving newborns are associated with subsequent asthenia, cognitive impairment, chronic fatigue syndrome, a high incidence of disability, complex physiological abnormalities, and chronic organ dysfunction from which they rarely recover.Nutritional, respiratory and hemodynamic supports are key components of neonatal PCI therapy. The physiology of a newborn is different from that of an adult patient; therefore, inotropic therapy in this category of patients requires special approaches. In the past few years, in addition to dopamine, dobutamine and adrenaline, newborns have been prescribed milrinone, norepinephrine, vasopressin, and levosimendan as hemodynamic support. The clinical potential of these drugs in neonates is still under evaluation but there is some evidence for their benefits for use in PCI.

Use of levosimendan in acute heart failure: readmissions, mortality and impact on NT-proBNP

Abstract Funding Acknowledgements Type of funding sources: None. Background Acute heart failure (AHF) is a complex clinical condition associated with high morbidity and mortality. Treatment of AHF remains a therapeutic challenge, with inotropic agents playing an important role. Levosimendan (LVS) is distinguished from other catecholaminergic inotropic by its three mechanisms of action - inotropic, vasodilator and cardioprotection - and by the presence of a long-acting metabolite. Objective We aimed to characterize the predictors of mortality and readmission rate following AHF hospitalizations treated with LVS. Methods and Results This is a retrospective analysis of all 69 patients treated with LVS in a Cardiology Department at a Tertiary Center (84% male, mean age 65 ± 13 years and mean left ventricular ejection fraction 27 ± 12%). 30-day and 6-month mortality was 23.2% and 36.2%, respectively. Risk factors for 30-day mortality (p &amp;lt;0.05) were: obesity (41% vs 17%), absence of valvular heart disease (48% vs 13%) and plasma creatinine (pCr) variation after LVS infusion (+0.05 mg/dL vs -0.24 mg/dL). Patients with ischemic heart disease have higher mortality at 6 months (68% vs 25%, p=0.001). Risk factors for both 30-day and 6-month mortality (p&amp;lt;0.05) were: chronic kidney disease stage ≥3 (40% vs 10%; 63% vs 15%), pCr before LSV (1.97 vs 1.43mg/dL; 1.83 vs 1.48mg/dL) and pCr after LVS (1.82 vs 1.23mg/dL; 1.71 vs 1.22mg/dL). The readmission rate at 30 days and 6 months was 7.4% and 36.0%, respectively. We did not find any significant predictors for 30-day readmission. Factors associated with higher readmission rate at 6 months (p &amp;lt;0.05) were: pre-infusion NYHA IV class (71% vs 30%), decompensated chronic HF (44% vs 9%) and atrial fibrillation or atrial flutter rhythm (56% vs 26%). In 27 cases, pre and post treatment NT-proBNP values were available. LVS therapy significantly reduced NT-proBNP from 10467 ± 8984 ng/L to 8237 ± 9500 ng/L (p=0.012) and improvement was observed in 93% of patients. Survival at 30 days and 6 months can be predicted by percentage of NT-proBNP improvement (-84.4% vs -28.4%, p=0.047; -92.3% vs -16.3%; p=0.012). Conclusion AHF patients requiring inotropic therapy have high mortality and readmission rates. Several clinical features and analytical responses to LVS perfusion are predictors of these events. LVS significantly reduces NT-proBNP. The magnitude of this reduction is a predictor of short- and long-term mortality.

Ten years of experience in pre-transplant patients from an advanced heart failure center - when is the best time to step in?

Abstract Funding Acknowledgements Type of funding sources: None. Background INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles provide important prognostic information for patients with advanced heart failure (AHF) hospitalized for clinical worsening. Purpose Assess the prognosis and fate of patients with Advanced HF (AHF), in INTERMACS I-IV, admitted to an Advanced Heart Failure Unit during 10-years. Methods Retrospective, single-center study with AHF’ patients admitted for acute HF during January 2010 and December 2020 in an Advanced Heart Failure Care Unit (AHFCU), who required inotropic therapy (INTERMACS I-IV) and were candidates for heart transplant (&amp;lt;65 years). We assessed the baseline characteristics at the time of admission and the long-term outcomes: death, alive with optimized medical therapy (OMT) and device or transplantation, according to INTERMACS profiles. Results For 10 years, 175 patients who met the inclusion criteria were admitted to the AHFC, mostly men (66.2%) and ischemic (30%), with a mean age of 52±10 years. At admission the patients had a mean Left Ventricle Ejection Fraction (LVEF) of 27±10% and a median NT-proBNP of 7230 pg/ml (IQR 3801 to 19882). During the 10-years on focus, 42% patients were transplanted (n=73), 38% (n=66) remained alive with optimized MT and device and 20% (n= 36) died. In-hospital mortality was significant different between profiles (p=0.001), 55% in INTERMACS I patients, 25% in II, and 17% in III-IV. Most transplanted patients (63%) were in INTERMACS IV, 16.4% in III, 12.3% in II and only 11% (n=8) in INTERMACS I (p=0.043). Conclusion Our results reinforce the importance of early action in these patients, using INTERMACS profile to prognostic stratification, who is important to identify the ideal time for referral to an appropriate centre, to properly convey expectations to patients and families, and to plan treatment and follow-up strategies (transplant, circulatory mechanical support, or palliative care).

Acute hemodynamic effect of ketone bodies in patients with decompensated heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Chronically failing heart increases utilization of ketone bodies as an energy substrate. Purpose This study investigated feasibility, safety and acute hemodynamic effect of exogenous ketosis induced by administration of beta-hydroxybutyrate (OHB) in patients with decompensated heart failure and low cardiac output syndrome. Methods Patients with acutely decompensated heart failure with reduced ejection fraction (HFrEF), who were on inotropic support for at least 24 hours (milrinone 0.5±0.1 ug/kg/min), were given oral solution of OHB (25g of OHB monoester in 65 ml of solution; H.V.M.N Ketone Ester, H.V.M.N, USA) in 3-hour intervals up to a total dose of 75g. Serum concentration of OHB and invasive hemodynamics (Swan-Ganz catheter with continuous thermodilution) were measured repeatedly before and during 24 hours after administration of OHB. The primary endpoint was the maximum change in cardiac index (CI). Results The study included 8 patients with decompensated HFrEF (male/female gender: 6/2; age: 58 ± 6 years; left ventricular ejection fraction: 19 ± 5%; non-ischemic/ischemic cardiomyopathy: 7/1). The baseline OHB concentration was 0.4 ± 0.2 mmol/L (normal range: 0 - 0.6 mmol/L). Mild ketosis (1.8 ± 0.6 mmol/L) was induced in all patients within one hour after administration of OHB. The maximum OHB concentration (2.5 ± 0.8 mmol/L) was reached after a median of 5 hours (IQR, 2 to 7 hours). No complications occurred except of temporary dyspepsia in one patient. Within 3 hours after administration of OHB, the CI increased from the baseline by 39 ± 25% (CI 3.4 ± 0.8 vs. 2.5 ± 0.5 L/min/m2; absolute increase of 1.0 ± 0.6 L/min/m2, p = 0.003). The maximum increase of CI reached 52 ± 20% (1.2 ± 0.4 L/min/m2 from the baseline, p &amp;lt;0.001) and it was observed after a median of 5 hours (IQR 3 to 8 hours). After 24 hours, CI returned to the baseline values (p = 0.4). The increase of CI was nor related to changes in the heart rate (at baseline vs. at the maximum CI: 101 ± 5 vs. 103 ± 6 beats/min, p = 0.5). Conclusion Induction of mild ketosis by administration of OHB on top of established inotropic therapy caused a significant temporary increase in myocardial contractility. This novel therapeutic concept might be a promising adjunction to the inotropic support in patients with decompensated HFrEF.

PO-644-02 CARDIAC CONTRACTILITY MODULATION AND AMBULATORY MILRINONE FOR CONGESTIVE HEART FAILURE: WHO GETS OPTIMIZED?

Cardiac Contractility Modulation (CCM) is indicated for patients with Class III systolic congestive heart failure (CHF), ejection fraction (EF) 25-45% and narrow QRS not indicated for biventricular pacing. CCM efficacy in patients also managed with intravenous inotropic therapy is unknown due to exclusion in all trials in CCM.

Beta-blockers and Ambulatory Inotropic Therapy

Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02). In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.

Repurposing Probenecid for the Treatment of Heart Failure (Re-Prosper-HF): a study protocol for a randomized placebo-controlled clinical trial

BackgroundImproving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes—istaroxime and probenecid—improve contractility through an increase in systolic intracellular calcium without activating cAMP production.Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF.MethodsThe Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3).DiscussionFindings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates.Trial tegistrationThe Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020.