Assessment of electrical dyssynchrony in cardiac resynchronization therapy: 12-lead electrocardiogram vs. 96-lead body surface map.

AIMS: The standard deviation of activation time (SDAT) derived from body surface maps (BSMs) has been proposed as an optimal measure of electrical dyssynchrony in patients with cardiac resynchronization therapy (CRT). The goal of this study was two-fold: (i) to compare the values of SDAT in individual CRT patients with reconstructed myocardial metrics of depolarization heterogeneity using an inverse solution algorithm and (ii) to compare SDAT calculated from 96-lead BSM with a clinically easily applicable 12-lead electrocardiogram (ECG). METHODS AND RESULTS: Cardiac resynchronization therapy patients with sinus rhythm and left bundle branch block at baseline (n = 19, 58% males, age 60 ± 11 years, New York Heart Association Classes II and III, QRS 167 ± 16) were studied using a 96-lead BSM. The activation time (AT) was automatically detected for each ECG lead, and SDAT was calculated using either 96 leads or standard 12 leads. Standard deviation of activation time was assessed in sinus rhythm and during six different pacing modes, including atrial pacing, sequential left or right ventricular, and biventricular pacing. Changes in SDAT calculated both from BSM and from 12-lead ECG corresponded to changes in reconstructed myocardial ATs. A high degree of reliability was found between SDAT values obtained from 12-lead ECG and BSM for different pacing modes, and the intraclass correlation coefficient varied between 0.78 and 0.96 (P < 0.001). CONCLUSION: Standard deviation of activation time measurement from BSM correlated with reconstructed myocardial ATs, supporting its utility in the assessment of electrical dyssynchrony in CRT. Importantly, 12-lead ECG provided similar information as BSM. Further prospective studies are necessary to verify the clinical utility of SDAT from 12-lead ECG in larger patient cohorts, including those with ischaemic cardiomyopathy.

The hemodynamic effect of simulated atrial fibrillation on left ventricular function.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained arrhythmia in humans. The onset of the arrhythmia can significantly impair cardiac function. This hemodynamic deterioration has been explained by several mechanisms such as the loss of atrial contraction, shortening of ventricular filling, or heart rhythm irregularity. This study sought to evaluate the relative hemodynamic contribution of each of these components during in vivo simulated human AF. METHODS: Twelve patients undergoing catheter ablation for paroxysmal AF were paced simultaneously from the proximal coronary sinus and the His bundle region according to prescribed sequences of irregular R-R intervals with the average rate of 90 and 130 bpm, which were extracted from the database of digital ECG recordings of AF from other patients. The simulated AF was compared to regular atrial pacing with spontaneous atrioventricular conduction and regular simultaneous atrioventricular pacing at the same heart rate. Beat-by-beat left atrial and left ventricular pressures, including LV dP/dT and Tau index were assessed by direct invasive measurement; beat-by-beat stroke volume and cardiac output (index) were assessed by simultaneous pulse-wave doppler intracardiac echocardiography. RESULTS: Simulated AF led to significant impairment of left ventricular systolic and diastolic function. Both loss of atrial contraction and heart rate irregularity significantly contributed to hemodynamic impairment. This effect was pronounced with increasing heart rate. CONCLUSION: Our findings strengthen the rationale for therapeutic strategies aiming at rhythm control and heart rate regularization in patients with AF.

Impact of access route to the left ventricle on asymptomatic periprocedural brain injury: the results of a randomized trial in patients undergoing catheter ablation of ventricular tachycardia.

AIMS: Catheter ablation of ventricular tachycardia (VT) is an effective treatment in patients with structural heart disease (SHD) and recurrent arrhythmias. However, the procedure is associated with the risk of complications, including both manifest and asymptomatic cerebral thromboembolic events. We hypothesized that periprocedural asymptomatic brain injury (ABI) can be reduced by using transseptal instead of the retrograde access route to the left ventricle (LV). METHODS AND RESULTS: Consecutive patients undergoing VT ablation for SHD were randomized 1:1 to either retrograde or transseptal LV access. All patients underwent radiofrequency ablation in conscious sedation with the use of an irrigated tip catheter. The degree of brain damage was evaluated by serum level of biomarker S100B. Significant ABI was defined as a post-ablation relative increase of S100B level >30%. A total of 144 patients (66 ± 9 years; 14 females; 90% coronary artery disease; LV ejection fraction: 30 ± 8%) were enrolled and 72 were allocated to each study groups. Symptomatic neurological complication of the procedure was not observed in any subject. A significant ABI was detected in 19.4% of patients. It was more commonly observed in subjects randomized to retrograde vs. transseptal LV access (26.4% vs. 12.5%, P = 0.04). In a multivariate analysis, only retrograde LV access and advanced age were independent determinants of significant ABI. CONCLUSION: Significant ABI after ablation of VT in patients with SHD can be detected in one-fifth of subjects. Retrograde access to LV is associated with a two-fold higher probability of significant ABI.

Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

AIMS: To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). METHODS AND RESULTS: Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. CONCLUSION: Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Real-time measurement of ICD lead motion during stereotactic body radiotherapy of ventricular tachycardia.

BACKGROUND: Here we aimed to evaluate the respiratory and cardiac-induced motion of a ICD lead used as surrogate in the heart during stereotactic body radiotherapy (SBRT) of ventricular tachycardia (VT). Data provides insight regarding motion and motion variations during treatment. MATERIALS AND METHODS: We analyzed the log files of surrogate motion during SBRT of ventricular tachycardia performed in 20 patients. Evaluated parameters included the ICD lead motion amplitudes; intrafraction amplitude variability; correlation error between the ICD lead and external markers; and margin expansion in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions to cover 90% or 95% of all amplitudes. RESULTS: In the SI, LL, and AP directions, respectively, the mean motion amplitudes were 5.0 ± 2.6, 3.4. ± 1.9, and 3.1 ± 1.6 mm. The mean intrafraction amplitude variability was 2.6 ± 0.9, 1.9 ± 1.3, and 1.6 ± 0.8 mm in the SI, LL, and AP directions, respectively. The margins required to cover 95% of ICD lead motion amplitudes were 9.5, 6.7, and 5.5 mm in the SI, LL, and AP directions, respectively. The mean correlation error was 2.2 ± 0.9 mm. CONCLUSIONS: Data from online tracking indicated motion irregularities and correlation errors, necessitating an increased CTV-PTV margin of 3 mm. In 35% of cases, the motion variability exceeded 3 mm in one or more directions. We recommend verifying the correlation between CTV and surrogate individually for every patient, especially for targets with posterobasal localization where we observed the highest difference between the lead and CTV motion.

Deep Learning-based Method for Fully Automatic Quantification of Left Ventricle Function from Cine MR Images: A Multivendor, Multicenter Study.

Purpose To develop a deep learning-based method for fully automated quantification of left ventricular (LV) function from short-axis cine MR images and to evaluate its performance in a multivendor and multicenter setting. Materials and Methods This retrospective study included cine MRI data sets obtained from three major MRI vendors in four medical centers from 2008 to 2016. Three convolutional neural networks (CNNs) with the U-NET architecture were trained on data sets of increasing variability: (a) a single-vendor, single-center, homogeneous cohort of 100 patients (CNN1); (b) a single-vendor, multicenter, heterogeneous cohort of 200 patients (CNN2); and (c) a multivendor, multicenter, heterogeneous cohort of 400 patients (CNN3). All CNNs were tested on an independent multivendor, multicenter data set of 196 patients. CNN performance was evaluated with respect to the manual annotations from three experienced observers in terms of (a) LV detection accuracy, (b) LV segmentation accuracy, and (c) LV functional parameter accuracy. Automatic and manual results were compared with the paired Wilcoxon test, Pearson correlation, and Bland-Altman analysis. Results CNN3 achieved the highest performance on the independent testing data set. The average perpendicular distance compared with manual analysis was 1.1 mm ± 0.3 for CNN3, compared with 1.5 mm ± 1.0 for CNN1 (P < .05) and 1.3 mm ± 0.6 for CNN2 (P < .05). The LV function parameters derived from CNN3 showed a high correlation (r2 ≥ 0.98) and agreement with those obtained by experts for data sets from different vendors and centers. Conclusion A deep learning-based method trained on a data set with high variability can achieve fully automated and accurate cine MRI analysis on multivendor, multicenter cine MRI data. © RSNA, 2018 See also the editorial by Colletti in this issue.

Advancement in cardiac imaging for treatment of ventricular arrhythmias in structural heart disease.

Over the last decades, substrate-based approaches to ventricular tachycardia (VT) ablation have evolved into an important therapeutic option for patients with various structural heart diseases (SHD) and unmappable VT. The well-recognized limitations of conventional electroanatomical mapping (EAM) to delineate the complex 3D architecture of scar, and the potential capability of advanced cardiac imaging technologies to provide adjunctive information, have stimulated electrophysiologists to evaluate the role of imaging to improve safety and efficacy of catheter ablation. In this review, we summarize the histological differences between SHD aetiologies related to monomorphic sustained VT and the currently available data on the histological validation of cardiac imaging modalities and EAM to delineate scar and the arrhythmogenic substrate. We review the current evidence of the value provided by cardiac imaging to facilitate VT ablation and to ultimately improve outcome.

Stress-induced phosphorylation of Thr486 in c-Myb by p38 mitogen-activated protein kinases attenuates conjugation of SUMO-2/3.

c-Myb plays an essential role in regulation of properly balanced hematopoiesis through transcriptional regulation of genes directly controlling cellular processes such as proliferation, differentiation, and apoptosis. The transcriptional activity and protein levels of c-Myb are strictly controlled through post-translational modifications such as phosphorylation, acetylation, ubiquitination, and SUMOylation. Conjugation of small ubiquitin-like modifier (SUMO) proteins has been shown to suppress the transcriptional activity of c-Myb. SUMO-1 modifies c-Myb under physiological conditions, whereas SUMO-2/3 conjugation was reported in cells under stress. Because stress also activates several cellular protein kinases, we investigated whether phosphorylation of c-Myb changes in stressed cells and whether a mutual interplay exists between phosphorylation and SUMOylation of c-Myb. Here we show that several types of environmental stress induce a rapid change in c-Myb phosphorylation. Interestingly, the phosphorylation of Thr(486), located in close proximity to SUMOylation site Lys(499) of c-Myb, is detected preferentially in nonSUMOylated protein and has a negative effect on stress-induced SUMOylation of c-Myb. Stress-activated p38 MAPKs phosphorylate Thr(486) in c-Myb, attenuate its SUMOylation, and increase its proteolytic turnover. Stressed cells expressing a phosphorylation-deficient T486A mutant demonstrate decreased expression of c-Myb target genes Bcl-2 and Bcl-xL and accelerated apoptosis because of increased SUMOylation of the mutant protein. These results suggest that phosphorylation-dependent modulation of c-Myb SUMOylation may be important for proper response of cells to stress. In summary, we have identified a novel regulatory interplay between phosphorylation and SUMOylation of c-Myb that regulates its activity in stressed cells.

A novel biomarker-based approach for the detection of asymptomatic brain injury during catheter ablation of atrial fibrillation.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is a widely used method for studying of asymptomatic brain injury during catheter ablation of atrial fibrillation (AF). However, this technique lacks sensitivity for subtle or diffuse brain lesions. We investigated whether detection of the ablation-related brain injury can improve by assessment of a biomarker of brain damage-protein S100B. METHODS AND RESULTS: DW-MRI and assessment of S100B were performed in 58 patients undergoing radiofrequency catheter ablation of paroxysmal or persistent AF 1 day before and after the procedure. We observed no symptomatic neurological complications. S100B levels increased after ablation above the upper reference limit of 105 ng/L in 3 patients. One of them developed a new ischemic lesion on the DW-MRI. No acute lesions emerged on DW-MRI in the patients with normal postablation S100B levels. CONCLUSION: Serial assessment of serum protein S100B may improve detection of asymptomatic acute brain injury in patients undergoing radiofrequency catheter ablation of AF. In our study, the incidence of these events was 1.7% when evaluated only by DW-MRI, but the incidence increased to 5% after employing the more sensitive biomarker-based approach.

Development and validation of a prognostic score integrating remote heart failure symptoms and clinical variables in mortality risk prediction after myocardial infarction. The PragueMi score.

AIMS: While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients' stratification. The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended GRACE score. METHODS: A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. RESULTS: Data from 1,135 patients (aged 64±12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) questionnaire and clinical variables were used as possible predictors. The best model included the following variables - age, heart failure history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months (AUC 90.1, 95% CI 81.8-98.4 vs. 77.4, 95% CI 62.2-92.5, p=0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5-96.0 vs. 76.2, 95% CI 64.7-87.7, p=0.004). CONCLUSION: The PragueMi score combining heart failure symptoms and clinical variables performs better than the currently recommended GRACE score.

The prognosis of patients after myocardial infarction is heterogeneous. Thus, risk stratification is needed to identify and intervene patients at increased risk. While heart failure (HF) symptoms are associated with adverse prognosis, they are not used for patients' stratification. We have developed and internally validated the PragueMi score, which integrates clinical risk factors at the time of hospitalization and HF symptoms determined remotely by a questionnaire 1 month after hospital discharge. PragueMi score was able to better stratify patients' risk as compared to the currently recommended GRACE score.

Remote Heart Failure Symptoms Assessment After Myocardial Infarction Identifies Patients at Risk for Death.

BACKGROUND: Heart failure is a common complication after myocardial infarction (MI) and is associated with increased mortality. Whether remote heart failure symptoms assessment after MI can improve risk stratification is unknown. The authors evaluated the association of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) with all-cause mortality after MI. METHODS AND RESULTS: Prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart center between June 2017 and September 2022 were used. Patients remotely completed the KCCQ 1 month after discharge. A total of 1135 (aged 64±12 years, 26.7% women) of 1721 eligible patients completed the KCCQ. Ranges of KCCQ scores revealed that 30 (2.6%), 114 (10.0%), 274 (24.1%), and 717 (63.2%) had scores <25, 25 to 49, 50 to 74, and ≥75, respectively. During a mean follow-up of 46 months (interquartile range, 29-61), 146 (12.9%) died. In a fully adjusted analysis, KCCQ scores <50 were independently associated with mortality (hazard ratio [HR], 6.05 for KCCQ <25, HR, 2.66 for KCCQ 25-49 versus KCCQ ≥50; both P<0.001). Adding the 30-day KCCQ to clinical risk factors improved risk stratification: change in area under the curve of 2.6 (95% CI, 0.3-5.0), Brier score of -0.6 (95% CI, -1.0 to -0.2), and net reclassification improvement of 0.71 (95% CI, 0.45-1.04). KCCQ items most strongly associated with mortality were walking impairment, leg swelling, and change in symptoms. CONCLUSIONS: Remote evaluation of heart failure symptoms using the KCCQ among patients recently discharged for MI identifies patients at risk for mortality. Whether closer follow-up and targeted therapy can reduce mortality in high-risk patients warrants further study.

Iron deficiency and all-cause mortality after myocardial infarction.

BACKGROUND: Data on the clinical significance of iron deficiency (ID) in patients with myocardial infarction (MI) are conflicting. This may be related to the use of various ID criteria. We aimed to compare the association of different ID criteria with all-cause mortality after MI. METHODS: Consecutive patients hospitalized for their first MI at a large tertiary heart center were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality. RESULTS: From the 1,156 patients included (aged 64±12 years, 25 % women), 194 (16.8 %) patients died during the median follow-up of 3.4 years. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95 % CI 1.19-2.34) and the combination of iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L (HR 2.56, 95 % CI 1.64-3.99) termed as PragueID criteria were associated with increased mortality risk and had additional predictive value to the GRACE score. Compared to the model including iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95 % CI 0.52-0.69) by reclassifying patients into a higher-risk group. No association between ferritin level and mortality was found. 51 % of patients had low iron levels, and 58 % fulfilled the PragueID criteria. CONCLUSION: Iron deficiency is common among patients with the first MI. The PragueID criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality and should be evaluated in future interventional studies for the identification of patients potentially benefiting from intravenous iron therapy.

Efficacy and Safety of Stereotactic Radiotherapy in Patients With Recurrent Ventricular Tachycardias: The Czech Experience.

BACKGROUND: Stereotactic arrhythmia radiotherapy (STAR) has been proposed recently in patients with refractory ventricular tachycardia (VT). OBJECTIVES: The purpose of this study was to describe the efficacy and safety of STAR in the Czech Republic. METHODS: VT patients were recruited in 2 expert centers after at least 1 previously failed catheter ablation (CA). A precise strategy of target volume determination and CA was used in 17 patients treated from December 2018 until June 2022 (EFFICACY cohort). This group, together with an earlier series of 19 patients with less-defined treatment strategies, composed the SAFETY cohort (n = 36). A dose of 25 Gy was delivered. RESULTS: In the EFFICACY cohort, the burden of implantable cardioverter-defibrillator therapies decreased, and this drop reached significance for direct current shocks (1.9 ± 3.2 vs 0.1 ± 0.2 per month; P = 0.03). Eight patients (47%) underwent repeated CA for recurrences of VT during 13.7 ± 11.6 months. In the SAFETY cohort (32 procedures, follow-up >6 months), 8 patients (25%) presented with a progression of mitral valve regurgitation, and 3 (9%) required intervention (median follow-up of 33.5 months). Two cases of esophagitis (6%) were seen with 1 death caused by the esophago-pericardial fistula (3%). A total of 18 patients (50%) died during the median follow-up of 26.9 months. CONCLUSIONS: Although STAR may not be very effective in preventing VT recurrences after failed CA in an expert center, it can still modify the arrhythmogenic substrate, and when used with additional CA, reduce the number of implantable cardioverter-defibrillator shocks. Potentially serious sides effects require close follow-up.

A Multicenter Study of Stellate Ganglion Block as a Temporizing Treatment for Refractory Ventricular Arrhythmias.

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are life-threatening conditions and can be refractory to conventional drug and device interventions. Stellate ganglion blockade (SGB) has been described as an adjunct, temporizing intervention in patients with refractory ventricular arrhythmia. We examined the association of SGB with VT/VF in a multicenter registry. OBJECTIVES: This study examined the efficacy of SGB for treatment/temporization of refractory VT/VF. METHODS: The authors present the first analysis from a multicenter registry of patients treated for refractory ventricular arrhythmia at a clinical site in the Czech Republic and the United States. Data were collected between 2016 and 2022. SGB was performed at the bedside by anesthesiologists and/or cardiologists. Outcomes of interest were VT/VF burden and defibrillations at 24 hours before and after SGB. RESULTS: In total, there were 117 patients with refractory ventricular arrhythmias treated with SGB at Duke (n = 49) and the Institute for Clinical and Experimental Medicine (n = 68). The majority of patients were male (94.0%), were White (87.2%), and had an implantable cardioverter-defibrillator (70.1%). The most common etiology of heart disease was ischemic cardiomyopathy (52.1%), and monomorphic VT was the most common morphology (70.1%). Within 24 hours before SGB (0-24 hours), the median episodes of VT/VF were 7.5 (Q1-Q3: 3.0-27.0), and 24 hours after SGB, the median decreased to 1.0 (Q1-Q3: 0.0-4.5; P < 0.001). At 24 hours before SGB, the median defibrillation events were 2.0 (Q1-Q3: 0.0-8.0), and 24 hours after SGB, the median decreased to 0.0 (Q1-Q3: 0.0-1.0; P < 0.001). CONCLUSIONS: In the largest cohort of patients with treatment-refractory ventricular arrhythmia, we demonstrate that SGB use was associated with a reduction in the ventricular arrhythmia burden and need for defibrillation therapy.

Clinical presentation, shock severity and mortality in patients with de novo versus acute-on-chronic heart failure-related cardiogenic shock.

AIMS: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute-on-chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute-on-chronic HF-CS. METHODS AND RESULTS: In this international observational study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30-day mortality, adjusted logistic/Cox regression models were fitted. Patients (n = 1030) with HF-CS were analysed, of whom 486 (47.2%) presented with de novo HF-CS and 544 (52.8%) with acute-on-chronic HF-CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute-on-chronic HF-CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute-on-chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.72, p = 0.005). CONCLUSION: In this large HF-CS cohort, acute-on-chronic HF-CS was associated with more severe CS and higher mortality risk compared to de novo HF-CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF-CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

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.

Sex-related differences in patients presenting with heart failure-related cardiogenic shock.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS. METHODS: In this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS. RESULTS: N = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75-1.19). CONCLUSIONS: In this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.

GTP-binding protein-like domain of AGAP1 is protein binding site that allosterically regulates ArfGAP protein catalytic activity.

AGAPs are a subtype of Arf GTPase-activating proteins (GAPs) with 11 members in humans. In addition to the Arf GAP domain, the proteins contain a G-protein-like domain (GLD) with homology to Ras superfamily proteins and a PH domain. AGAPs bind to clathrin adaptors, function in post Golgi membrane traffic, and have been implicated in glioblastoma. The regulation of AGAPs is largely unexplored. Other enzymes containing GTP binding domains are regulated by nucleotide binding. However, nucleotide binding to AGAPs has not been detected. Here, we found that neither nucleotides nor deleting the GLD of AGAP1 affected catalysis, which led us to hypothesize that the GLD is a protein binding site that regulates GAP activity. Two-hybrid screens identified RhoA, Rac1, and Cdc42 as potential binding partners. Coimmunoprecipitation confirmed that AGAP1 and AGAP2 can bind to RhoA. Binding was mediated by the C terminus of RhoA and was independent of nucleotide. RhoA and the C-terminal peptide from RhoA increased GAP activity specifically for the substrate Arf1. In contrast, a C-terminal peptide from Cdc42 neither bound nor activated AGAP1. Based on these results, we propose that AGAPs are allosterically regulated through protein binding to the GLD domain.

Acute Effect of Atrial Fibrillation on Circulating Natriuretic Peptides: The Influence of Heart Rate, Rhythm Irregularity, and Left Atrial Pressure Overload.

Plasma natriuretic peptides (NPs) are increased in patients with atrial fibrillation (AF) compared with the patients with sinus rhythm. This study investigated whether this phenomenon is intrinsic to heart rhythm irregularity and independent of the heart rate and left atrial pressure (LAP) overload. We investigated 46 patients (age: 59 ± 10 years, male gender: 77%) with non-valvular paroxysmal AF who were scheduled for catheter ablation and had documented stable sinus rhythm for at least 18 hours before the procedure. All patients underwent direct measurement of right atrial pressure and LAP, simultaneously with assessment of plasma B-type NP, N-terminal pro-brain NP, and mid-regional pro-atrial NP. The baseline measurement was followed by induction of AF by rapid atrial pacing in the first 24 patients and by regular pacing from the coronary sinus at 100/min (corresponding to the mean heart rate during induced AF) in the latter 22 patients. Hemodynamic assessment and blood sampling were repeated after 20 min of the ongoing AF or fast regular paging. The baseline characteristics and hemodynamic measurements were comparable between study groups; however, patients in the regular atrial pacing group had a higher body mass index and a larger left atrial diameter compared with the induced AF group. Plasma levels of all 3 NPs increased significantly during induced AF but not during fast regular pacing, and the increase of NPs was independent of right atrial pressure and LAP. Baseline concentrations of NPs and heart rhythm irregularity were the only independent predictors of increased NPs.

Heart failure-related quality-of-life impairment after myocardial infarction.

AIMS: Recent advances in therapy led to a significant decrease in mortality and morbidity after myocardial infarction (MI). However, little is known about quality of life (QoL) after MI. We examined heart failure (HF)-related quality-of-life (QoL) impairment, its trajectories, and determinants after MI. METHODS: Data from a single-center prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were utilized. At 1 month and 1 year after hospital discharge, patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: In total, 850 patients (aged 65 ± 12 years, 27% female) hospitalized between June 2017 and October 2020 completed KCCQ at 1 month after discharge. Of these, 38.7% showed HF-related QoL impairment (KCCQ ≤ 75). In addition to characteristics of MI (MI size, diuretics need, heart rate), comorbidities as renal dysfunction and anemia were associated with QoL impairment. Of the 673 eligible, 500 patients (74.3%) completed KCCQ at 1 year after MI. On average, QoL improved by 5.9 ± 16.8 points during the first year after MI (p < 0.001); but, in 18% of patients QoL worsened. Diabetes control and hemoglobin level at the time of hospitalization were associated with QoL worsening. CONCLUSION: Two out of 5 patients after MI present with HF-related QoL impairment. In addition to guideline-directed MI management, careful attention to key non-cardiac comorbidities as chronic kidney disease, anemia and diabetes may lead to further augmentation of the benefit of modern therapies in terms of QoL.