Current Treatment and Immunomodulation Strategies in Acute Myocarditis.

ABSTRACT: Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.

The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices.

BACKGROUND: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2-I) in patients with left ventricular assist devices (LVAD) are unknown. METHODS: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2-I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2-I. RESULTS: SGLT2-I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2-I initiation was 108 days, IQR (26-477). Following SGLT2-I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2-38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7-4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23-11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2-I initiation (p > 0.2 for all). No adverse events were recorded during median follow-up of 354 days, IQR (206-786). CONCLUSION: SGLT2-I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.

High Attendance Rate of Family Members During Physician Rounds Is Predictive of Worse Clinical Outcomes: A Historic Cohort Study.

BACKGROUND: The prognosis of long-term clinical outcomes for each patient is of utmost importance. OBJECTIVES: To evaluate the association between rates of family attendance during rounds and long-term outcomes. METHODS: We conducted a historic cohort study. RESULTS: We followed 200 consecutive patients for a median of 19 months. Within the group of patients that had family members present in > 75% of rounds, the 30-day re-hospitalization rate was tenfold higher (P = 0.017). The overall prognosis (including median survival length) of patients who had the highest rates of family attendance (> 75%) was significantly worse compared to patients who had lower rates (P = 0.028). High rates of family attendance were found to correlate with other established risk factors for long-term mortality, including advanced age (r = 0.231, P = 0.001) and in-hospital delirium. CONCLUSIONS: High family attendance during physician rounds in an internal medicine department is associated with worse patient prognosis.

Beneficial effect of awake prone position in hypoxaemic patients with COVID-19: case reports and literature review.

We hereby present two case reports of moderate coronavirus disease patients, suffering from profound hypoxaemia, further deteriorating later on. A schedule pre-planned awake prone position manoeuvres were executed during their hospital stay. Following this, the patients' saturation improved, later to be weaned from oxygen support. Paucity of evidence and data regarding this topic led us to review the concept of awake prone position.

Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center.

BACKGROUND: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020. OBJECTIVES: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel. METHODS: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented. RESULTS: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1. CONCLUSIONS: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.

Pericarditis recurrence is associated with milder electrocardiographic, echocardiographic, and laboratory findings.

Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.

Admission Serum Magnesium Levels Is Associated with Short and Long-Term Clinical Outcomes in COVID-19 Patients.

BACKGROUND: In the face of the global pandemic that the coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. OBJECTIVE: To evaluate the association between serum magnesium (sMg) levels on admission and clinical outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively analyzed all patients admitted to a single tertiary center with a primary de novo diagnosis of COVID-19. Patients were followed for a mean of 10 ± 7 months. Demographic, clinical and laboratory data were collected and compared between five groups of patients according to sMg quintiles on hospital admission. RESULTS: The cohort included 1522 patients (58% male, 69 ± 17 years old). A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, renal dysfunction, higher levels of inflammatory markers and stay in the intensive care unit. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4th quintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p < 0.001 for all). After adjusting for significant clinical parameters indicating severe disease and renal dysfunction, only low sMg state was independently associated with increased mortality (HR = 1.57, p < 0.001). CONCLUSIONS: Both low and high sMg levels were associated with increased mortality in a large cohort of hospitalized COVID-19 patients. However, after correction for renal dysfunction and disease severity, only low sMg maintained its prognostic ability.

The burden of heart failure in cardiac intensive care unit: a prospective 7 years analysis.

AIMS: The profiles of patients at cardiac intensive care units (CICU) have evolved towards a patient population with an increasing number of co-morbid medical conditions and acute heart failure (HF). The current study was designed to illustrate the burden of HF patients admitted to CICU, and evaluate patient characteristics, in-hospital course and outcomes of CICU patients with HF compared with patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A prospective study including all consecutive patients admitted to the CICU at a tertiary medical centre between 2014 and 2020. The main outcome was a direct comparison between HF and ACS patients in processes of care, resource use, and outcomes during CICU hospitalization. A secondary analysis compared ischaemic versus non-ischaemic HF aetiology. Adjusted analysis evaluated parameters associated with prolonged hospitalization. The cohort included 7674 patients with a total annual CICU admissions of 1028-1145 patients. HF diagnosis patients represented 13-18% of the annual CICU admissions and were significantly older with higher incidence of multiple co-morbidities compared with patients with ACS. HF patients also required more intensive therapies and demonstrated higher incidence of acute complications as compared with ACS patients. Length of stay at the CICU was significantly longer among HF patients compared with patients with ACS (either STEMI or NSTEMI) (6.2 ± 4.3 vs. 4.1 ± 2.5 vs. 3.5 ± 2.1, respectively, P < 0.001). HF patients represented a disproportionately higher amount of total CICU patient days during the study period, as the total length of hospitalization of HF patients was 44-56% out of the total cumulative days in CICU of patients with ACS every year. In hospital mortality rates were also significantly higher among patients with HF compared with STEMI or NSTEMI (4.2% vs. 3.1% vs. 0.7%, respectively, P < 0.001). Despite several differences in baseline characteristics between patients with ischaemic versus non-ischaemic HF, which can be attributed mainly to disease aetiology, hospitalization length and outcomes were similar among the groups regardless of HF aetiology. In multivariable analysis for the risk of prolonged hospitalization in the CICU adjusted to potential significant co-morbidities associated with poor outcomes, HF was found to be an independent and significant parameter associated with the risk of prolonged hospitalization with an OR of 3.5 (95% CI 2.9-4.1, P < 0.001). CONCLUSIONS: Patients with HF in CICU have higher severity of illness with a prolonged and complicated hospital course, all of which can substantially increase the burden on clinical resources.

Levetiracetam Interaction with Direct Oral Anticoagulants: A Pharmacovigilance Study.

BACKGROUND: Levetiracetam is widely used in post-stroke epilepsy. However, it is suspected to possess P-glycoprotein (P-gp) induction properties, and therefore, a potentially significant interaction with direct oral anticoagulants (DOACs). We aimed to search for ischemic stroke signals with levetiracetam and the DOACs. METHODS: In this retrospective pharmacovigilance study, we used the FAERS database to identify ischemic stroke events associated with DOACs and concomitant use of levetiracetam. We evaluated disproportionate reporting by the adjusted reporting odds ratio (adjROR) and the lower bound of the shrinkage 95% confidence interval. When shrinkage is positive, an increased risk of a specific adverse event occurrence is emphasized over the sum of the individual risks when these same drugs are used separately. RESULTS: We identified 1841 (1.5%), 3731 (5.3%), 338 (4.9%), and 1723 (1.3%) ischemic stroke reports with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The adjROR of the interaction effect was 3.57 (95% CI 2.81-4.58) between DOACs and levetiracetam. The shrinkage analysis detected an interaction between each of the DOACs and levetiracetam. The logistic model and shrinkage analysis failed to detect an interaction when queried for hemorrhagic stroke. A significant signal in the classical enzyme inducer, carbamazepine, strengthened our results (adjROR; 8.47, 95% CI 5.37-13.36). CONCLUSIONS: Our study shows a strong signal for the levetiracetam interaction with the DOACs. Our findings suggest implementation of a drug monitoring strategy.

Ventricular arrhythmias in patients with hypertrophic cardiomyopathy: Prevalence, distribution, predictors, and outcome.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden cardiac death. Ventricular fibrillation (VF) is thought to be the common culprit arrhythmia. OBJECTIVE: The purpose of this study was to describe the incidence and predictors of sustained ventricular arrhythmias (VTAs) in HCM patients. METHODS: We retrospectively analyzed all patients with HCM and an implantable cardioverter-defibrillator (ICD) from a prospectively derived registry in 2 tertiary medical centers. Clinical, electrocardiographic, echocardiographic, ICD interrogation, and genetic data were collected and compared, first between patients with and without VTAs and then between patients with only VF and those with ventricular tachycardia (VT) with or without VF. RESULTS: Of the 1328 HCM patients, 207 (145 [70%] male; mean age 33 ± 16 years) were implanted with ICDs. Over a mean follow-up of 10 ± 6 years, 37 patients with ICDs (18%) developed sustained VTAs. These were associated with a family history of sudden cardiac death and a personal history of VTAs (P = .036 and P = .001, respectively). Sustained monomorphic VT was the most common arrhythmia (n = 26, 70%) and was linked to decreased left ventricular (LV) ejection fraction and increased LV end-systolic and end-diastolic diameters. Antitachycardia pacing (ATP) successfully terminated 258 (79%) of the 326 VT events. Mortality rates were comparable between patients with and without VTAs (4 [11%] vs 29 [17%]; P = .42) and between those with and without ICDs (24 [16%] vs 85 [20%]; P = .367). CONCLUSION: VT rather than VF is the most common arrhythmia in patients with HCM; it is amenable to ATP and is associated with lower LV ejection fraction and higher LV diameters. Therefore, ATP-capable devices may be considered in HCM patients with these LV features.

Atrial fibrillation in young hospitalized patients: Clinical characteristics, predictors of new onset, and outcomes.

BACKGROUND: Atrial fibrillation (AF) in young adults is an uncommon and not well studied entity. METHODS: Consecutive patients aged 18-45 years admitted to internal or cardiology services in a large tertiary medical center (January 1, 2009 through December 31, 2019) were included. Clinical, electrocardiographic, and echocardiographic data were compared between patients with and without AF at baseline. Predictors of new-onset AF in the young were identified using multivariate Cox regression model among patients free of baseline AF. RESULTS: Final cohort included 16,432 patients with median age of 34 (IQR 26-41) years of whom 8914 (56 %) were men. Patients with AF at baseline (N = 366; 2 %) were older, more likely to be men, and had higher proportion of comorbidities and electrocardiographic conduction disorders. Male sex, increased age, obesity, heart failure, congenital heart disease (CHD) and the presence of left or right bundle branch block were all independently associated with baseline AF in a multivariate model (p < 0.001 for all). Sub-analysis of 10,691 (98 %) patients free of baseline AF identified 85 cases of new-onset AF during a median follow up of 3.5 (IQR 1.5-6.5) years. Multivariate model identified increased age, heart failure, and CHD as independent predictors of new-onset AF. Finally, the CHARGE-AF risk score outperformed the CHA2DS2-VASc score in AF prediction [AUC of ROC 0.75 (0.7-0.8) vs. 0.56 (0.48-0.65)]. CONCLUSIONS: AF among hospitalized young adults is not rare. Screening for new-onset AF in young post hospitalization patients may be guided by specific clinical predictors and the CHARGE-AF risk score.

Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients.

BACKGROUND: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. OBJECTIVE: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. METHODS: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2-Q4; sMg ≥ 1.9 mg/dL). RESULTS: The study cohort included 4552 patients (70% male, median age 69 [IQR 59-79]) who were followed for a median of 4.4 (IQR 2.4-6.6) years. The median sMg level in the low sMg group was 1.7 (1.6-1.8) and 2.0 (2.0-2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan-Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11-1.39; p < 0.001). CONCLUSIONS: Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event.

Significance of Anteroseptal Late Gadolinium Enhancement Among Patients With Acute Myocarditis.

Anteroseptal location of late gadolinium enhancement (LGE) in patients with acute myocarditis (AM) detected by cardiovascular magnetic resonance may indicate an independent marker of unfavorable outcomes according to recent data. We aimed to evaluate the clinical characteristics, management, and inhospital outcomes in patients with AM with positive LGE based on its presence in the anteroseptal location. We analyzed data from 262 consecutive patients hospitalized with a diagnosis of AM with positive LGE within 5 days of hospitalization (n = 425). Patients were divided into 2 groups: those with anteroseptal LGE (n = 25, 9.5%) and those with non-anteroseptal LGE (n = 237, 90.5%). Except for age that was higher in patients with anteroseptal LGE, the demographic and clinical characteristics did not differ significantly between both groups including past medical history, clinical presentation, electrocardiogram parameters, and lab values. Moreover, patients with anteroseptal LGE were more likely to present with reduced left ventricular ejection fraction and to receive congestive heart failure treatments. Although univariate analysis showed that patients with anteroseptal LGE were more likely to have inhospital major adverse cardiac events (28% vs 9%, p = 0.003), there was no difference inhospital outcomes on multivariable analysis between both groups (hazard ratio, 1.17 [95% confidence interval, 0.32 to 4.22], p = 0.81). A higher left ventricular ejection fraction in either echocardiography or cardiovascular magnetic resonance corresponded to better inhospital outcomes regardless of the presence or absence of anteroseptal LGE. In conclusion, the presence of anteroseptal LGE did not confer additional prognostic value for inhospital outcomes.

Data processing pipeline for cardiogenic shock prediction using machine learning.

Introduction: Recent advances in machine learning provide new possibilities to process and analyse observational patient data to predict patient outcomes. In this paper, we introduce a data processing pipeline for cardiogenic shock (CS) prediction from the MIMIC III database of intensive cardiac care unit patients with acute coronary syndrome. The ability to identify high-risk patients could possibly allow taking pre-emptive measures and thus prevent the development of CS. Methods: We mainly focus on techniques for the imputation of missing data by generating a pipeline for imputation and comparing the performance of various multivariate imputation algorithms, including k-nearest neighbours, two singular value decomposition (SVD)-based methods, and Multiple Imputation by Chained Equations. After imputation, we select the final subjects and variables from the imputed dataset and showcase the performance of the gradient-boosted framework that uses a tree-based classifier for cardiogenic shock prediction. Results: We achieved good classification performance thanks to data cleaning and imputation (cross-validated mean area under the curve 0.805) without hyperparameter optimization. Conclusion: We believe our pre-processing pipeline would prove helpful also for other classification and regression experiments.

The clinical course of patients with previous acute and recurrent pericarditis receiving the BNT162b2 vaccine.

Background: Vaccines against SARS-COV2 have been crucial in efforts against COVID19, yet there have been reports of pericarditis following vaccination with mRNA-based vaccines. Methods: We questioned consecutive patients with a history of acute pericarditis (AP) evaluated in the pericardial disease clinic during 3-11/2020 in a single tertiary center. Patients with significant myocardial involvement or pericarditis secondary to another systemic disease were excluded. Results: We included 64 patients in the final analysis. Mean age was 53.1 (±18), and 26 (41%) were female. At least 1 recurrence of AP was documented in 47 (73%) cases, 32 (50%) had ≥ 3 recurrences prior to vaccination. AP was considered to be idiopathic\viral in 45 (70%) cases, 20 (31%) cases were post-injury. All patients received at least 2 doses of the vaccine, and 48 patients (75%) received a 3rd dose. Two cases of breakthrough COVID19 infections were documented. Overall, 12 patients (19%) reported any adverse events. Of which, 2 had recurrent pericarditis. There was a trend for a younger age in those patients who had adverse events (median age 45 [IQR 36-61] vs. 60 [38-71], p = 0.08). no other significant difference was seen. Conclusion: In patients with a history of acute\recurrent pericarditis, the use of BNT162b2 was mostly uneventful, but some mild disease recurrences did occur.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients in the intensive cardiac care unit.

BACKGROUND: Frailty is an underrecognized and important entity that bears worse prognosis. Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. METHODS: A retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU)between 1/5/2011 and 1/12/2020 at a single tertiary medical center. RESULTS: The study included 3956 patients after excluding patients with ALT >40 IU/L, cirrhosis, and missing data, followed for a medianduration of 47 months (IQR 20-77).Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT >10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 years vs. 65 years, p<0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, p< 0.001), had higher rates of comorbiditiesat baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (p< 0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, p = 0.99), long-termmortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, p< 0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46-3). CONCLUSIONS: Lower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU.

Effect of levosimendan infusion prior to left ventricular assist device implantation on right ventricular failure.

OBJECTIVE: Investigate the safety and efficacy of preoperative levosimendan in patients undergoing left ventricular assist device (LVAD) implantation. METHODS: Consecutive patients who received LVADs (HeartMate-2, 3, HVAD) in a single tertiary medical center (2012-2018). INTERMACS profile 1 patients were excluded. The primary outcome was post-LVAD right ventricular failure (RVF) and inhospital mortality rates. The secondary outcomes included other clinical, echocardiographic and hemodynamic parameters at follow-up. RESULTS: Final cohort consisted of 62 patients (40[65%] in the levosimendan group and 22[35%] in the no-levosimendan group). Post-operative RVF rate and inotrope or ventilation support time were similar in the levosimendan and no-levosimendan groups (7.5% vs. 13.6%; P = 0.43, median of 51 vs. 72 h; P = 0.41 and 24 vs. 27 h; P = 0.19, respectively). Length of hospitalization, both total and in the intensive care unit, was not statistically significant (median days of 13 vs. 16; P = 0.34, and 3 vs. 4; P = 0.44, respectively). Post-operative laboratory and echocardiographic parameters and in-hospital complication rate did not differ between the groups, despite worse baseline clinical parameters in the Levosimendan group. There was no significant difference in the in-hospital and long term mortality rate (2.5% vs. 4.5%; P > 0.999 and 10% vs. 27.3% respectively; P = 0.64). CONCLUSIONS: Levosimendan infusion prior to LVAD implantation was safe and associated with comparable results without significant improved post-operative outcomes, including RVF.

Characterization of heart failure patients with reverse left ventricular remodelling post-angiotensin receptor blockers/neprilysin inhibitors therapy.

AIMS: To assess the effect of angiotensin receptor blockers/neprilysin inhibitors (ARNI) on left ventricular (LV) ejection fraction (LVEF) and LV dimensions in a real-life cohort of heart failure and reduced ejection fraction (HFrEF) patients, while analysing patient characteristics that may predict reverse LV remodelling. METHODS AND RESULTS: The ARNI-treated HFrEF patients followed at a single tertiary medical centre HF-outpatient clinic were included in the study. Clinical and echocardiographic parameters were evaluated prior to ARNI initiation, and while on ARNI therapy, assessing patient characteristics associated with reverse LV remodelling. The cohort included 91 patients (mean age 60.5 years, 90% male) and 47 (52%) patients exhibited ARNI responsiveness, defined as an increase in LVEF during therapy. Overall, LVEF increased by 19% post-ARNI (23.8 to 28.4%, P < 0.001). Subgroup analysis revealed several parameters associated with significant LVEF improvement, including baseline LVEF <30%, non-ischaemic HF aetiology, lack of cardiac resynchronization therapy (CRT), better initial functional class and ARNI initiation within 3 years from HF diagnosis (P ≤ 0.001 for all). Significant reduction in LV dimensions was noted in patients with lower initial LVEF, non-ischaemic HF and no CRT. Further combined subgrouping of the study population demonstrated that patients with both LVEF <30% and a non-ischaemic HF gained most benefit from ARNI with an average of 51% improvement in LVEF (19.9 to 30%, P < 0.001). CONCLUSIONS: The ARNI treatment response is not uniform among HFrEF patient subgroups. More pronounce reverse LV remodelling is associated with early ARNI treatment initiation in the course of HFrEF, and in those with LVEF <30%, non-ischaemic HF and no CRT.

Low ALT Levels Associated with Poor Outcomes in 8700 Hospitalized Heart Failure Patients.

Sarcopenia and frailty are causes for morbidity and mortality amongst heart failure (HF) patients. Low alanine transaminase (ALT) is a marker for these syndromes and, therefore, could serve as a biomarker for the prognostication of HF patients. We performed a retrospective analysis of all consecutive hospitalized HF patients in our institute in order to find out whether low ALT values would be a biomarker for poor outcomes. Our cohort included 11,102 patients, 35.6% categorized as heart failure with reduced ejection fraction. We excluded patients with ALT > 40 IU/L and cirrhosis. 8700 patients were followed for a median duration of 22 months and included in a univariate analysis. Patients with ALT < 10 IU/L were older (mean age 78.6 vs. 81.8, p < 0.001), had past stroke (24.6% vs. 19.6%, p < 0.001), dementia (7.7% vs. 4.6%, p < 0.001), and malignancy (13.4% vs. 10.2%, p = 0.003). Hospitalization length was longer in the low-ALT group (4 vs. 3 days, p < 0.001), and the rate of acute kidney injury during hospitalization was higher (19.1% vs. 15.6%; p = 0.006). The in-hospital mortality rate was higher in the low-ALT group (6.5% vs. 3.9%; p < 0.001). Long-term mortality was also higher (73.3% vs. 61.5%; p < 0.001). In a multivariate regression analysis, ALT < 10 IU/L had a 1.22 hazard ratio for mortality throughout the follow-up period (CI = 1.09-1.36; p < 0.001). Low ALT plasma level, a biomarker for sarcopenia and frailty, can assist clinicians in prognostic stratification of heart failure patients.