Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data.

BACKGROUND: Absolute treatment benefits-expressed as numbers needed to treat-of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome. METHODS: From Kaplan-Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI). RESULTS: Twelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months. CONCLUSION: The present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.

Accredited cardiac arrest centers facilitate eCPR and improve neurological outcome.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a frequent medical emergency with low survival rates even after a return of spontaneous circulation (ROSC). Growing evidence supports formation of dedicated teams in scenarios like cardiogenic shock to improve prognosis. Thus, the European Resuscitation Council (ERC) recommended introduction of Cardiac Arrest Centers (CAC) in their 2015 guidelines. Here, we aimed to elucidate the effects of newly introduced CACs in Germany regarding survival rate and neurological outcome. METHODS: A multicenter retrospective observational cohort study was performed at three university hospitals and outcomes after OHCA were compared before and after CAC accreditation. Primary outcomes were survival until discharge and favorable neurological status (CPC 1 or 2) at discharge. RESULTS: In total 784 patients (368 before and 416 after CAC accreditation) were analyzed. Rates of immediate percutaneous coronary intervention (40 vs. 52%, p = 0.01) and implementation of extracorporeal CPR (8 vs. 13%, p < 0.05) increased after CAC accreditation. Likelihood of favorable neurological status at discharge was higher after CAC accreditation (71 vs. 87%, p < 0.01), whereas overall survival remained similar (35 vs. 35%, p > 0.99). CONCLUSION: CAC accreditation is linked to higher rates of favorable neurological outcome and unchanged overall survival.

Prevalence, mechanisms, and prognostic impact of dynamic mitral regurgitation assessed by isometric handgrip exercise.

AIMS: The extent of mitral regurgitation (MR) may vary depending on the haemodynamic situation; thus, exercise testing plays an important role in assessing the haemodynamic relevance of MR. We aim to assess prevalence, mechanisms, and prognostic impact of exercise-induced changes in MR in patients with degenerative MR (DegMR) and functional MR (FMR). METHODS AND RESULTS: We enrolled 367 patients with at least mild MR who underwent standardized echocardiography at rest and during handgrip exercise. Handgrip exercise led to an increase in MR by one grade or more in 19% of DegMR and 28% of FMR patients. In FMR, patients with exercise-induced increases in MR, handgrip exercise led to a reduction in left ventricular stroke volume index, being maintained in DegMR patients. Exercise-induced changes in systolic pulmonary artery pressure were linked to changes in effective regurgitant orifice area (DegMR: r = 0.456; P < 0.001; FMR: r = 0.326; P < 0.001). Thus, 26% of patients with DegMR and FMR developed pulmonary hypertension during exercise. In both cohorts, a significant proportion of patients with non-severe MR at rest and exercise-induced severe MR underwent mitral valve surgery/intervention during follow-up. In FMR patients (but not in DegMR patients), early mitral valve surgery/intervention was independently associated with lower event rates during follow-up [0.177 (0.027-0.643); P = 0.025]. CONCLUSIONS: Handgrip exercise echocardiography provides important information regarding the dynamic nature of MR, exercise-induced changes in left ventricular function, and pulmonary circulation with subsequent consequences for further therapeutic decision making. Thus, it should be considered as a diagnostic tool in symptomatic patients with non-severe MR at rest.

Association between left ventricular ejection fraction, mortality and use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

BACKGROUND: Currently, use of mechanical circulatory support (MCS) in non-ischaemic cardiogenic shock (CS) is predominantly guided by shock-specific markers, and not by markers of cardiac function. We hypothesise that left ventricular ejection fraction (LVEF) can identify patients with a higher likelihood to benefit from MCS and thus help to optimise their expected benefit. METHODS: Patients with non-ischaemic CS and available data on LVEF from 16 tertiary-care centres in five countries were analysed. Cox regression models were fitted to evaluate the association between LVEF and mortality, as well as the interaction between LVEF, MCS use and mortality. RESULTS: N = 807 patients were analysed: mean age 63 [interquartile range (IQR) 51.5-72.0] years, 601 (74.5%) male, lactate 4.9 (IQR 2.6-8.5) mmol/l, LVEF 20 (IQR 15-30) %. Lower LVEF was more frequent amongst patients with more severe CS, and MCS was more likely used in patients with lower LVEF. There was no association between LVEF and 30-day mortality risk in the overall study cohort. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with LVEF ≤ 20% (hazard ratio 0.72, 95% confidence interval 0.51-1.02 for LVEF ≤ 20% vs. hazard ratio 1.31, 95% confidence interval 0.85-2.01 for LVEF > 20%, interaction-p = 0.017). CONCLUSION: This retrospective study may indicate a lower mortality risk with MCS use only in patients with severely reduced LVEF. This may propose the inclusion of LVEF as an adjunctive parameter for MCS decision-making in non-ischaemic CS, aiming to optimise the benefit-risk ratio.

Heparin dosing in patients with Impella-supported cardiogenic shock.

BACKGROUND: Impella™ is increasingly used in cardiogenic shock. However, thromboembolic and bleeding events are frequent during percutaneous mechanical circulatory support (pMCS). OBJECTIVE: Therefore, we aimed to explore the optimal anticoagulation regime for pMCS to prevent thromboembolism and bleedings. METHODS: This hypothesis-generating multi-center cohort study investigated 170 patients with left-Impella™ support. We (A) compared bleeding/thrombotic events in two centers with therapeutic range (TR-aPTT) activated partial thromboplastin time (60-80s) and (B) compared events of these centers with one center with intermediate range aPTT (40-60s). RESULTS: After matching, there were no differences in patients' characteristics. In centers aiming at TR-aPTT, major bleeding was numerically lower with aPTT <60s within 48 h of left-Impella™ support, versus patients that achieved the aimed aPTT of ≥60s [aPTT ≥60s: 22 (37.3%) vs. aPTT<60s 14 (23.7%); Hazard ratio [HR], 0.62 (95%) CI, 0.28-1.38; p = 0.234]. Major cardiovascular and cerebrovascular adverse events (MACCE) did not differ between groups. In comparison of centers, TR-aPTT strategy showed higher major bleeding rates [TR: 8 (47.1%) vs. intermediate range: 1 (5.9%); HR, 0.06 (95%) CI, 0.01-0.45; p = 0.006]. MACCE were lower in the intermediate range aPTT group as well [TR 12 (70.6%) vs. intermediate range 5 (29.4%) HR, 0.32 (95%) CI, 0.11-0.92; p = 0.034]. CONCLUSION: This pilot analysis showed that lowering UFH-targets in left-Impella™ supported CS patients seems to be a safe and promising strategy for reducing major bleedings without increasing MACCE. This needs to be validated in larger, randomized clinical trials.

Prevalence and prognostic impact of dynamic atrial functional mitral regurgitation assessed by isometric handgrip exercise.

AIMS: In atrial functional mitral regurgitation (aFMR), a considerable proportion of patients displays a discrepancy between symptoms and echocardiographic findings at rest. Exercise testing plays a substantial role in assessing the haemodynamic relevance of mitral regurgitation (MR) and is recommended by current guidelines. Here, we aimed to assess the prevalence, extent, and prognostic impact of exercise-induced changes in patients with aFMR. METHODS AND RESULTS: Patients with at least mild MR who underwent handgrip exercise echocardiography at the University Hospital Duesseldorf between January 2019 and September 2021 were enrolled. Patients were followed-up for one year to assess clinical outcomes. Eighty patients with aFMR were included (median age: 80 (77-83) years; 53.8% female). The median N-terminal pro brain natriuretic petide level was 1756 (1034-3340) ng/l. At rest, half of the patients (53.8%) had mild MR, 20 patients (25.0%) had moderate MR, and 17 patients (21.2%) had severe MR. In approximately every fifth patient (17.5%) with non-severe MR at rest, the MR became severe during exercise. Handgrip exercise led to a re-classification of MR severity in 28 patients (35.0%). At one-year follow-up, adverse events occurred more often in patients with severe MR at rest (76.5%) and exercise-induced dynamic severe MR (66.7%) than in those with non-severe MR (28.6%) (p < 0.001). CONCLUSIONS: Handgrip exercise during echocardiography revealed exercise-induced changes in aFMR in every third patient. These data may have implications for therapeutic decision-making in symptomatic patients with non-severe aFMR at rest.

Questionable Validity of Creatinine-Based eGFR in Elderly Patients but Cystatin C Is Helpful in First-Line Diagnostics.

BACKGROUND: The recommended chronic kidney disease (CKD) first-line diagnostic test is based on the creatinine-derived (estimated) glomerular filtration rate (eGFR). Cystatin C use may provide a better assessment. METHODS: We compared creatinine- and cystatin C-derived eGFR determination as the first-line diagnostic test for 112 hospital patients aged > 60 years (median = 76 years). The patients were judged to not have CKD (no-CKD group) according to the first-line diagnostic recommendations (n = 61, eGFR (CKD Epidemiology Collaboration (CKD-EPI)) ≥ 60 mL/min/1.73 m2, total urine protein < 150 mg/g creatinine, urinary red/white blood cells not increased) or classified to be at risk for kidney insufficiency due to aortic valve dysfunction (at-risk group; n = 51). The accuracy of the eGFR values was evaluated retrospectively with the final case diagnoses. RESULTS: The eGFR (Caucasian, Asian, pediatric, and adult formula (CAPA)) was found to be linearly correlated to the eGFR (CKD-EPI) (R2 = 0.5, slope = 0.69, p < 0.0001). In 93/112 (>80%) cases, the eGFR (CAPA) yielded lower values (on average ≈-20%). In 55/112 (49%) cases, the cystatin C-derived CKD stage was lower. CKD reclassification from no-CKD to a kidney-insufficient state (i.e., CKD1/2 to CKD3a/b or 4) or reclassification to a more severe kidney insufficiency (i.e., CKD3a → 3b/4 or 3b → 4) was found in 41/112 (37%) cases. A worse CKD classification (no-CKD → kidney-insufficient) based on the eGFR (CAPA) was plausible in 30% of cases in light of the final case diagnoses. CONCLUSION: In elderly patients (>60 years), renal function appears to be systematically overestimated by the creatinine-based eGFR (CKD-EPI), indicating that, for this group, the cystatin C-based eGFR (CAPA) should be used as the first-line diagnostic test.

Supervised exercise training in patients with advanced heart failure and left ventricular assist device: A multicentre randomized controlled trial (Ex-VAD trial).

AIMS: Small studies and observations suggested that exercise training may improve peak oxygen consumption (peakVO2 ) in patients with advanced heart failure and left ventricular assist device (LVAD). We investigated whether in this patient group a supervised exercise training can improve exercise capacity. METHODS AND RESULTS: In this multicentre, prospective, randomized, controlled trial, patients with stable heart failure and LVAD were randomly assigned (2:1) to 12 weeks of supervised exercise training or usual care, with 12 weeks of follow-up. The primary endpoint was the change in peakVO2 after 12 weeks (51 patients provided a power of 90% with an expected group difference in peakVO2 of 3 ml/kg/min). Secondary endpoints included changes in submaximal exercise capacity and quality of life. Among 64 patients enrolled (97% male, mean age 56 years), 54 were included in the analysis. Mean difference in the change of peakVO2 after 12 weeks was 0.826 ml/min/kg (95% confidence interval [CI] -0.37, 2.03; p = 0.183). There was a positive effect of exercise training on 6-min walk distance with a mean increase in the intervention group by 43.4 m (95% CI 16.9, 69.9; p = 0.0024), and on the Kansas City Cardiomyopathy Questionnaire physical domain score (mean 14.3, 95% CI 3.7, 24.9; p = 0.0124), both after 12 weeks. The overall adherence was high (71%), and there were no differences in adverse events between groups. CONCLUSION: In patients with advanced heart failure and LVAD, 12 weeks of exercise training did not improve peakVO2 but demonstrated positive effects on submaximal exercise capacity and physical quality of life.

Clinical outcomes of hundred large Impella implantations in cardiogenic shock patients based on individual clinical scenarios.

BACKGROUND: Large Impella systems (5.0 or 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) help achieve better clinical outcomes through relevant left ventricular unloading in acute cardiogenic shock (CS). Here, we report our experience with Impella 5+, while focusing on the clinical outcomes depending on individual case scenarios in patients with acute CS. METHODS: This single-center retrospective observational study included 100 Impella 5+ implantations conducted on patients with acute CS from November 2018 to October 2021. After excluding 10 reimplantation cases, 90 cases were enrolled for further analysis. RESULTS: In-hospital and 30-day mortality rates were 56.7% (n = 51) and 48.9% (n = 44), respectively. In-hospital mortality was lower in patients with acute myocardial infarction (AMI) than in non-AMI patients (p = 0.07). Young age and low lactate levels were the independent predictors of successful transition and survival after permanent mechanical circulatory support/heart transplantation (pMCS/HTX) (age, p = 0.03; lactate level, p = 0.04; survived after pMCS/HTX, n = 11; died on Impella, n = 41). During simultaneous utilization of venoarterial extracorporeal membrane oxygenation therapy and Impella 5+, termed ECMELLA therapy, high dose of noradrenaline was a predictive factor for in-hospital mortality by multivariate analysis (n = 0.02). CONCLUSIONS: Our results suggest that enhanced Impella support might have better clinical outcomes among acute CS patients supported with large Impella, those with AMI than those with no AMI. Young age and low lactate levels were predictors of successful bridging to pMCS/HTX and favorable clinical outcomes thereafter. The clinical outcomes of ECMELLA therapy might depend on noradrenaline dose at the time of Impella 5+ implantation.

Early Postoperative Neurologic Events Are Associated With Worse Outcome and Fatal Midterm Survival After Adult Heart Transplantation.

Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P=0.009), longer mechanical ventilation (192 versus 48 hours; P<0.001), and higher need for blood transfusion, and need for hemodialysis after HTx was substantially higher (81% versus 55%; P=0.01). Resternotomy (36% versus 26%; P=0.05) and mechanical life support (extracorporeal life support) after HTx (46% versus 24%; P=0.02) were also significantly higher in patients with neurologic events. Covariable-adjusted multivariable Cox regression analysis revealed a significant independent association of neurologic events and increased 30-day (hazard ratio [HR], 2.5 [95% CI, 1.0-6.0]; P=0.049), 1-year (HR, 2.2 [95% CI, 1.1-4.3]; P=0.019), and overall (HR, 2.5 [95% CI, 1.5-4.2]; P<0.001) mortality after HTx and reduced Kaplan-Meier survival up to 5 years after HTx (P<0.001). Conclusions Neurologic events after HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after HTx.

Clinical effects of cognitive behavioral therapy in heart failure patients: a meta-analysis of randomized controlled trials.

BACKGROUND: About 20-40% of people with Heart failure (HF) suffer from some depression, which is 4-5% greater than the overall population. This depression can lead to undesirable outcomes, including elevated mortality rate and frequent hospitalization. PURPOSE: The current study aims to evaluate the impact of cognitive behavioural therapy (CBT) on self-care and the symptoms of depression and anxiety in HF patients. METHODS: We searched PubMed, Web of Science (WOS), Scopus, and Cochrane Library till 15 October 2022. All relevant randomized controlled trials (RCTs) were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). Continuous data were pooled as mean difference and 95% confidence interval (CI). RESULTS: Our search retrieved 1146 records, and 7 studies (611 patients) were finally included. We assessed the Beck Depression Inventory-II (BDI-II) as the primary outcome of the study. Hamilton Rating Scale for Depression (HRSD-17), Change in Beck Anxiety Inventory, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Self-Care of Heart Failure Index (SCHFI) were also assessed as secondary outcomes. With CBT, BDI-II showed a significant reduction after 4 to 6 months follow-up (MD = -4.87, 95% CI: [-8.06; -1.69], P = 0.003) as well as 8 to 9 months follow-up (MD = -5.71, 95% CI: [-8.95; -2.46], P = 0.0006). But no significant difference was shown with 3 months follow-up (M.D=-4.34; 95%CI: [-10.70; 2.03], P = 0.18). CONCLUSIONS: CBT has long-term (4-9 months) significant favorable outcomes decreasing anxiety and depression compared to non-CBT groups. No significant short-term (less than 3 months) impact on HF patients' self-care, depression, or anxiety were shown.

Reply to Thet et al. Comment on "Oehler et al. Outcome and Midterm Survival after Heart Transplantation Is Independent from Donor Length of Stay in the Intensive Care Unit. Life 2022, 12, 1053".

Myat Soe Thet et al. published a letter [...].

Clinical Course of Patients in Cardiogenic Shock Stratified by Phenotype.

BACKGROUND: Cardiogenic shock (CS) patients remain at 30% to 60% in-hospital mortality despite therapeutic innovations. Heterogeneity of CS has complicated clinical trial design. Recently, 3 distinct CS phenotypes were identified in the CSWG (Cardiogenic Shock Working Group) registry version 1 (V1) and external cohorts: I, "noncongested;" II, "cardiorenal;" and III, "cardiometabolic" shock. OBJECTIVES: The aim was to confirm the external reproducibility of machine learning-based CS phenotypes and to define their clinical course. METHODS: The authors included 1,890 all-cause CS patients from the CSWG registry version 2. CS phenotypes were identified using the nearest centroids of the initially reported clusters. RESULTS: Phenotypes were retrospectively identified in 796 patients in version 2. In-hospital mortality rates in phenotypes I, II, III were 23%, 41%, 52%, respectively, comparable to the initially reported 21%, 45%, and 55% in V1. Phenotype-related demographic, hemodynamic, and metabolic features resembled those in V1. In addition, 58.8%, 45.7%, and 51.9% of patients in phenotypes I, II, and III received mechanical circulatory support, respectively (P = 0.013). Receiving mechanical circulatory support was associated with increased mortality in cardiorenal (OR: 1.82 [95% CI: 1.16-2.84]; P = 0.008) but not in noncongested or cardiometabolic CS (OR: 1.26 [95% CI: 0.64-2.47]; P = 0.51 and OR: 1.39 [95% CI: 0.86-2.25]; P = 0.18, respectively). Admission phenotypes II and III and admission Society for Cardiovascular Angiography and Interventions stage E were independently associated with increased mortality in multivariable logistic regression compared to noncongested "stage C" CS (P < 0.001). CONCLUSIONS: The findings support the universal applicability of these phenotypes using supervised machine learning. CS phenotypes may inform the design of future clinical trials and enable management algorithms tailored to a specific CS phenotype.

Lactate versus Phosphate as Biomarkers to Aid Mechanical Circulatory Support Decisions in Patients with Out-of-Hospital Cardiac Arrest and Return of Spontaneous Circulation.

AIMS: Identifying patients who may benefit from mechanical circulatory support (MCS) after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) remains challenging; thus, a search for helpful biomarkers is warranted. We aimed to evaluate phosphate and lactate levels on admission regarding their associations with survival with and without MCS. METHODS: In 224 OHCA patients who achieved ROSC, the initial phosphate and lactate levels were investigated to discriminate in-hospital mortality by receiver operating characteristic (ROC) curves. According to the Youden Index (YI) from the respective ROC, the groups were risk stratified by both biomarkers, and 30-day mortality was analyzed in patients with and without MCS. RESULTS: Within the entire collective, MCS was not associated with a better chance of survival. Both phosphate and lactate level elevations showed good yet comparable discriminations to predict mortality (areas under the curve: 0.80 vs. 0.79, p = 0.74). In patients with initial phosphate values > 2.2 mmol/L (>YI), 30-day mortality within the MCS cohort was lower (HR 2.3, 95% CI: 1.4-3.7; p = 0.0037). In patients with lower phosphate levels and groups stratified by lactate, 30-day mortality was similar in patients with and without MCS. CONCLUSIONS: We found a significant association between survival and MCS therapy in patients with phosphate levels above 2.2 mmol/L (Youden Index), and a similar discrimination of patient overall survival by lactate and phosphate. Prospective studies should assess the possible independent prognostic value of phosphate and its clearance for MCS efficiency.

Simple and safe digitoxin dosing in heart failure based on data from the DIGIT-HF trial.

BACKGROUND: The present study aimed to develop a simple dosing score when starting the cardiac glycoside digitoxin in heart failure with reduced ejection fraction (HFrEF) employing first data from the randomized, double-blinded DIGIT-HF trial. METHODS AND RESULTS: In DIGIT-HF, digitoxin was started with a dose of 0.07 mg once daily (o.d.) in all patients. For score derivation, 317 patients were analyzed who had been randomized to digitoxin. In these patients, after scheduled determination of serum levels at study week 6, the digitoxin dose had remained unchanged or had been reduced to 0.05 mg o.d. (97% of patients) to achieve serum concentrations within a predefined range (10.5-23.6 nmol/l). In logistic regression analyses, sex, age, body mass index (BMI), and estimated glomerular filtration rate (eGFR) were associated with need for dose reduction and, therefore, selected for further developing the dosing score. Optimal cut-points were derived from ROC curve analyses. Finally, female sex, age ≥ 75 years, eGFR < 50 ml/min/1.73 m2, and BMI < 27 kg/m2 each were assigned one point for the digitoxin dosing score. A score of ≥ 1 indicated the need for dose reduction with sensitivity/specificity of 81.6%/49.7%, respectively. Accuracy was confirmed in a validation data set including 64 patients randomized to digitoxin yielding sensitivity/specificity of 87.5%/37.5%, respectively. CONCLUSION: In patients with HFrEF, treatment with digitoxin should be started at 0.05 mg o.d. in subjects with either female sex, eGFR < 50 ml/min/1.73m2, BMI < 27 kg/m2, or age ≥ 75 years. In any other patient, digitoxin may be safely started at 0.07 mg o.d.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

Impact of the route of adrenaline administration in patients suffering from out-of-hospital cardiac arrest on 30-day survival with good neurological outcome (ETIVIO study).

BACKGROUND: Over the past decades, international guidelines for cardiopulmonary resuscitation (CPR) have changed the recommendation for alternative routes for drug administration. Until now, evidence for the substantial superiority of one route with respect to treatment outcome after CPR has been lacking. The present study compares the effects of intravenous (IV), intraosseous (IO) and endotracheal (ET) adrenaline application during CPR in out-of-hospital cardiac arrest (OHCA) on clinical outcomes within the database of the German Resuscitation Registry (GRR). METHODS: This registry analysis was based on the GRR cohort of 212,228 OHCA patients between 1989 and 2020. Inclusion criteria were: OHCA, application of adrenaline, and out-of-hospital CPR. Excluded from the study were patients younger than 18 years, those who had trauma or bleeding as suspected causes of cardiac arrest, and incomplete data sets. The clinical endpoint was hospital discharge with good neurological outcome [cerebral performance category (CPC) 1/2]. Four routes of adrenaline administration were compared: IV, IO, IO + IV, ET + IV. Group comparisons were done using matched-pair analysis and binary logistic regression. RESULTS: In matched-pair group comparisons of the primary clinical outcome hospital discharge with CPC 1/2, the IV group (n = 2416) showed better results compared to IO (n = 1208), [odds ratio (OR): 2.43, 95% confidence interval (CI): 1.54-3.84, p < 0.01] and when comparing IV (n = 8706) to IO + IV (n = 4353), [OR: 1.33, 95% CI: 1.12-1.59, p < 0.01]. In contrast, no significant difference was found between IV (n = 532) and ET + IV (n = 266), [OR: 1.26, 95% CI: 0.55-2.90, p = 0.59]. Concurrently, binary logistic regression yielded a highly significant effect of vascular access type (χ² = 67.744(3), p < 0.001) on hospital discharge with CPC1/2, with negative effects for IO (regression coefficient (r.c.) = - 0.766, p = 0.001) and IO + IV (r.c. = - 0.201, p = 0,028) and no significant effect for ET + IV (r.c. = 0.117, p = 0.770) compared to IV. CONCLUSIONS: The GRR data, collected over a period of 31 years, seem to emphasize the relevance of an IV access during out-of-hospital CPR, in the event that adrenaline had to be administered. IO administration of adrenaline might be less effective. ET application, though removed in 2010 from international guidelines, could gain importance as an alternative route again.