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Introduction Landiolol is a recently innovated ultra-short-acting beta-blocker. Landiolol is the only beta-blocker with a specific dose recommendation for patients with cardiac dysfunction and acute atrial fibrillation (Class I recommendation according to the ESC guidelines). Landiolol has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias. The short duration of action and titratability of landiolol makes it ideal for use in critically ill patients. Purpose of the Study Review the case reports in the literature on the administration of landiolol in critically ill patients with acute decompensated heart failure (ADHF) secondary to tachyarrhythmias. Methods 11 case reports of ADHF secondary to tachyarrhythmias were identified. Personal, clinical and humoral data were collected. The heart rate and systolic pressure values in the time before and after the administration of Landiolol were plotted in a summary graph. Results The mean age of the 11 patients was 55 years old with high proBNP values at admission. The etiological diagnosis of heart failure was heterogeneous but tachyarrhythmia was the trigger event in all patients. Patients were critically ill with a mean EF of 26 ± 16% and an initial shock index of 1.4 ±0.5. Landiolol administered together with other antiarrhythmic drugs (amiodarone in 4/11 patients), epinephrine/norepinephrine (9/11) and levosimendan (4/11) favoured heart rate lowering and an increase in systolic blood pressure.At discharge, 4/11 had improved EF, in 10/11 sinus rhythm was restored, and all patients recovered hemodynamic stability without adverse events related to Landiolol (Figure 1). Conclusion In this case series review, Landiolol was a useful strategy in patients with ADHF refractory to conventional therapy by facilitating rate/rhythm control, limiting the toxicity of inotropic drugs and improving the hemodynamic profile. Figure 1

This clinical case shows the diagnostic challenge and the management of a 79 y-o male with arterial hypertension, tabagism, obesity and a recent hospitalization for infero-lateral STEMI undergoing primary PCI of Right Coronary Artery with 2 DES and following DDDR MRI PM (pacemaker) implantation (through left cephalic vein) due to the development of persistent 2:1 AV block (atrio-ventricular block). One month later, admission at Emergency Department for syncope. The admission therapy included Aspirin plus Clopidogrel, Ramipril, Atorvastatin. Normal parameters were found at laboratory analyses. The electro-stimulator activity evaluation showed a PM malfunction with ventricular capture failure. Thus, the increase of PM output up to electric ventricular capture (8 Volt/120 msec) was performed, but the following Electrocardiogram (ECG) showed a PM-induced rhythm with RBBB-morphology. Then, the bedside Echocardiogram showed an apparent presence of a linear hyper-echogenic image (lead?) into left ventricle with no inter-ventricular septal defect neither inter-ventricular shunt, inter-atrial septal hypermobility with no evident inter-atrial shunt at rest; while a chest Radiography identified the atrial and ventricular leads with no accurate individuation of their position. The patient was admitted in Intensive Cardiac Care Unit with confirmation of intermittent failure to ventricular capture and RBBB-morphology during PM-induced rhythm at telemetry monitoring. Due to Electrocardiographic and (above all) Echocardiographic findings, a strong suspect of abnormal position of the ventricular lead into left ventricle through a possible PFO has been raised. A chest Computed Tomography was performed confirming the anomalous position of the ventricular lead: the atrial lead was in the right atrium whereas the ventricular lead reached the left atrium through an inter-atrial defect/patent foramen ovale (PFO), then crossing the mitral valve up to left ventricle. The PM-lead repositioning was scheduled two days after. With intra-operative fluoroscopy, a further verify of leads position was observed (the ventricular one into left ventricle through PFO and mitral valve, the atrial one mildly displaced upwards) and the leads repositioning was performed. After positioning of temporary stimulator lead in right ventricle, the ventricular lead has been withdrawn from left-side chambers and positioned into septal-apical right ventricle; furthermore, the position of right atrial lead has been optimized (because of frequent spontaneous passage to the left atrium through the PFO, during manual maneuvers). Finally, the optimal stability of the device was obtained, as well as the optimal atrial and ventricular capture during stimulation test. During the observation in Cardiology Unit in following days, the telemetry monitoring and ECG showed a PM-induced rhythm, without capture nor sensing failure. The chest Radiography confirmed the correct position of atrial and ventricular leads. Finally, the pre-discharge transthoracic Echocardiography showed a LVEF 57% with no valvular pathology nor pericardial effusion, and with atrial and ventricular leads into right-side chambers.

Background Patients in heart transplantation (HTx) waiting list for advanced heart failure (HF) are susceptible to acute deterioration refractory to standard HF medical therapies. Limited data are available on long‐term in‐hospital continuous intravenous (IV) inotropic therapy as bridge to definite therapies. Methods and results We reviewed medical records of all heart transplant recipients treated in the pre‐HTx phase with in‐hospital continuous IV inotropes at our institution between 2012 and 2018. We analysed data before the beginning of continuous IV therapy and at the moment of HTx. We report data of 24 patients (mean age of 43.5 ± 15.7 years) treated with IV inotropes as bridge to HTx (median follow‐up of 28 months after HTx). The main length of IV inotropic therapy was 84 ± 66 days (min 22; max 264 days). At the beginning, the most frequently used inotrope was dopamine (median dosage of 3 mcg/kg/min, interquartile range 2.5–3.75), alone (n = 11, 46%) or in combination with other inotropes (n = 13, 54%). In 18 patients, the class of inotropes was changed during the hospitalization. We registered a progressive improvement of perfusion markers and neuro‐hormonal activation. Conclusion In‐hospital continuous parenteral inotropic therapy may serve as a temporary pharmacological bridge to HTx in patients with advanced HF that are actively listed to HTx with good reply in terms of prognosis and perfusion markers.

Background Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap. Methods and design The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients’ survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients. Implications The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.

Objectives: The aim of this study was to evaluate the outcome of transcatheter mitral valve repair (TMVr) in patients with cardiogenic shock and significant mitral regurgitation (MR). Background: Patients in cardiogenic shock with severe MR have a poor prognosis in the setting of conventional medical therapy. Because of its favorable safety profile, TMVr is being increasingly used as an acute therapy in this population, though its efficacy remains unknown. Methods: A multicenter, collaborative, patient-level analysis was conducted. Patients with cardiogenic shock and moderate to severe (3+) or severe (4+) MR who were not surgical candidates were treated with TMVr. The primary outcome was in-hospital mortality. Secondary outcomes included 90-day mortality, heart failure (HF) hospitalization, and the combined event rate of 90-day mortality and HF hospitalization following dichotomization by TMVr device success. Results: Between January 2011 and February 2019, 141 patients across 14 institutions met the inclusion criteria. In-hospital mortality occurred in 22 patients (15.6%), at 90 days in 38 patients (29.5%), and at one year in 55 patients (42.6%). Median length of hospital stay following TMVr was 10 days (interquartile range: 6 to 20 days). HF hospitalization occurred in 26 patients (18.4%) at a median of 73 days (interquartile range: 26 to 546 days). When stratified by TMVr procedural results, successful TMVr reduced rates of in-hospital mortality (hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.13 to 0.98; p = 0.04), 90-day mortality (HR: 0.36; 95% CI: 0.16 to 0.78; p = 0.01), and the composite of 90-day mortality and HF hospitalization (HR: 0.41; 95% CI: 0.19 to 0.90; p = 0.03). Conclusions: TMVr may improve short- and intermediate-term mortality in high-risk patients with cardiogenic shock and moderate to severe MR. Randomized studies are needed to definitively establish MR as a therapeutic target in patients with cardiogenic shock.

The durability of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is uncertain. We aimed to compare the long-term outcomes of CTO PCI with those of complex non-CTO PCI. We built a single-center registry including all patients who underwent CTO and complex non-CTO PCI between 2012 and 2017. Complex non-CTO PCI was defined as: 3 vessels treated, ≥3 stents implanted, total stent length60 mm, saphenous vein graft intervention, 2-stent bifurcation intervention, left main PCI, protected PCI, or rotational/laser atherectomy. The primary endpoint was target-lesion failure, a composite of cardiac death, myocardial infarction, and target-lesion revascularization. A total of 2,396 patients were included (n=609 CTO PCI, n=1,787 complex non-CTO PCI). Patients who underwent CTO PCI were younger and had higher prevalence of cardiovascular comorbidities. CTO PCI patients exhibited worse procedural metrics and success rate (74% vs 98%, p0.001). They also suffered a higher incidence of coronary perforation (3.5% vs 2.0%, p = 0.04) and cardiac tamponade (0.8% vs 0.1%, p = 0.001). However, there was no difference in the overall incidence of in-hospital major adverse cardiac and cerebrovascular events (4.1% vs 5.0%, p = 0.40). At 36 months, there were no differences in the incidence of target-lesion failure (10.1% vs 9.9%, p = 0.91) or its individual components, between the CTO and complex non-CTO group. This finding was confirmed on multivariable analysis. In conclusion, CTO PCI is associated with lower success rates and higher risk for coronary perforation and tamponade compared with complex non-CTO PCI. The incidence of other in-hospital and long-term adverse events is similar and reasonably low.

Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a hypercompliant cortex and secondary ventricular enlargement without primary defects in CSF circulation. These data highlight the importance of precisely regulated neuroepithelial cell fate for normal brain-CSF biomechanics and support a clinically relevant neuroprogenitor-based paradigm of CH.

Aim: The impact on safety and efficacy outcomes of Impella 5.0 in cardiogenic shock (CS) has not been systematically assessed. Materials & methods: We conducted a systematic review of the literature (PROSPERO protocol: CRD42020164680) to critically appraise available evidence on Impella 5.0 comparative safety, efficacy and effectiveness. Results: Of 244 retrieved citations, 17 original articles met the a priori defined inclusion criteria. All included studies had a retrospective study design and, overall, reported on, respectively, 52 and 67 different safety and efficacy/effectiveness outcomes. Thirty-day survival rates ranged from 40 to 94%, myocardial recovery from 18 to 93%. Conclusion: Impella 5.0 provides a full cardiac support, it is associated with a lower rate of vascular complications, it represents a valuable bridge-to-decision and allows for resolution of intercurrent clinical conditions. As available data suggest Impella 5.0 good performance in CS of various etiologies, more solid evidence will come from much-needed large-scale all-comer registries and prospective multicenter randomized trials.

The intra-aortic balloon pump (IABP) is widely implanted as temporary mechanical circulatory support for cardiogenic shock (CS). However, its use is declining following the results of the IABP-SHOCK II trial, which failed to show a clinical benefit of the IABP in acute coronary syndrome (ACS)-related CS. Acute-on-chronic heart failure has become an increasingly recognized, distinct cause of CS (HF-CS). The pathophysiology of HF-CS differs from that of ACS-CS because it typically represents the progression from a state of congestion (with relatively preserved cardiac output) to a low-output state with hypoperfusion. The IABP is a volume-displacement pump that promotes forward flow from a high-capacitance reservoir to low-capacitance vessels, improving peripheral perfusion and decreasing left ventricular afterload in the setting of high filling pressures. The IABP can improve ventricular-vascular coupling and, therefore, myocardial energetics. Additionally, many patients with HF-CS are candidates for cardiac replacement therapies (left ventricular assist device or heart transplantation) and, therefore, may benefit from a bridge strategy that stabilizes the hemodynamics and end-organ function in preparation for more durable therapies. Notably, the new United Network for Organ Sharing donor heart allocation system has recently prioritized patients on IABP support. This review describes the role of IABP in the treatment of HF-CS. It also briefly discusses new strategies for vascular access as well as fully implantable versions for longer duration of support.

The aim of this study was to evaluate the outcome of transcatheter mitral valve repair (TMVr) in patients with cardiogenic shock and significant mitral regurgitation (MR).Patients in cardiogenic shock with severe MR have a poor prognosis in the setting of conventional medical therapy. Because of its favorable safety profile, TMVr is being increasingly used as an acute therapy in this population, though its efficacy remains unknown.A multicenter, collaborative, patient-level analysis was conducted. Patients with cardiogenic shock and moderate to severe (3+) or severe (4+) MR who were not surgical candidates were treated with TMVr. The primary outcome was in-hospital mortality. Secondary outcomes included 90-day mortality, heart failure (HF) hospitalization, and the combined event rate of 90-day mortality and HF hospitalization following dichotomization by TMVr device success.Between January 2011 and February 2019, 141 patients across 14 institutions met the inclusion criteria. In-hospital mortality occurred in 22 patients (15.6%), at 90 days in 38 patients (29.5%), and at one year in 55 patients (42.6%). Median length of hospital stay following TMVr was 10 days (interquartile range: 6 to 20 days). HF hospitalization occurred in 26 patients (18.4%) at a median of 73 days (interquartile range: 26 to 546 days). When stratified by TMVr procedural results, successful TMVr reduced rates of in-hospital mortality (hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.13 to 0.98; p = 0.04), 90-day mortality (HR: 0.36; 95% CI: 0.16 to 0.78; p = 0.01), and the composite of 90-day mortality and HF hospitalization (HR: 0.41; 95% CI: 0.19 to 0.90; p = 0.03).TMVr may improve short- and intermediate-term mortality in high-risk patients with cardiogenic shock and moderate to severe MR. Randomized studies are needed to definitively establish MR as a therapeutic target in patients with cardiogenic shock.

Aims The recent coronavirus disease 19 (COVID‐19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID‐19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year. Methods and results We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter‐year period (21 February to 31 March 2019) and an intra‐year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra‐year period, and 192 during inter‐year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra‐year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56–0.89; P = 0.0037), or with inter‐year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45–0.72; P

Background: Myocardial T1-mapping is increasingly used in multicentre studies and trials. Inconsistent image analysis introduces variability, hinders differentiation of diseases, and results in larger sample sizes. We present a systematic approach to standardize T1-map analysis by human operators to improve accuracy and consistency. Methods: We developed a multi-step training program for T1-map post-processing. The training dataset contained 42 left ventricular (LV) short-axis T1-maps (normal and diseases; 1.5 and 3 Tesla). Contours drawn by two experienced human operators served as reference for myocardial T1 and wall thickness (WT). Trainees (n = 26) underwent training and were evaluated by: (a) qualitative review of contours; (b) quantitative comparison with reference T1 and WT. Results: The mean absolute difference between reference operators was 8.4 ± 6.3 ms (T1) and 1.2 ± 0.7 pixels (WT). Trainees' mean discrepancy from reference in T1 improved significantly post-training (from 8.1 ± 2.4 to 6.7 ± 1.4 ms; p b 0.001), with a 43% reduction in standard deviation (SD) (p = 0.035). WT also improved significantly post-training (from 0.9 ± 0.4 to 0.7 ± 0.2 pixels, p = 0.036), with 47% reduction in SD (p = 0.04). These experimentally-derived thresholds served to guide the training process: T1 (±8 ms) and WT (±1 pixel) from reference. Conclusion: A standardized approach to CMR T1-map image post-processing leads to significant improvements in the accuracy and consistency of LV myocardial T1 values and wall thickness. Improving consistency between operators can translate into 33–72% reduction in clinical trial sample-sizes. This work may: (a) serve as a basis for re-certification for core-lab operators; (b) translate to sample-size reductions for clinical studies; (c) produce better-quality training datasets for machine learning.

ObjectivePulmonary congestion is the main cause of hospital admission in patients with heart failure (HF). Lung ultrasound (LUS) is a useful tool to identify subclinical pulmonary congestion. We evaluated the usefulness of LUS in addition to physical examination (PE) in the management of outpatients with HF.MethodsIn this randomised multicentre unblinded study, patients with chronic HF and optimised medical therapy were randomised in two groups: ‘PE+LUS’ group undergoing PE and LUS and ‘PE only’ group. Diuretic therapy was modified according to LUS findings and PE, respectively. The primary endpoint was the reduction in hospitalisation rate for acute decompensated heart failure (ADHF) at 90-day follow-up. Secondary endpoints were reduction in NT-proBNP, quality-of-life test (QLT) and cardiac mortality at 90-day follow-up.ResultsA total of 244 patients with chronic HF and optimised medical therapy were enrolled and randomised in ‘PE+LUS’ group undergoing PE and LUS, and in ‘PE only’ group. Thirty-seven primary outcome events occurred. The hospitalisation for ADHF at 90 day was significantly reduced in ‘PE+LUS’ group (9.4% vs 21.4% in ‘PE only’ group; relative risk=0.44; 95% CI 0.23 to 0.84; p=0.01), with a reduction of risk for hospitalisation for ADHF by 56% (p=0.01) and a number needed to treat of 8.4 patients (95% CI 4.8 to 34.3). At day 90, NT-proBNP and QLT score were significantly reduced in ‘PE+LUS’ group, whereas in ‘PE only’ group both were increased. There were no differences in mortality between the two groups.ConclusionsLUS-guided management reduces hospitalisation for ADHF at mid-term follow-up in outpatients with chronic HF.

A 3D transoesophageal echocardiography (3D-TOE) reconstruction tool has recently been introduced. The system automatically configures a geometric model of the aortic root and performs quantitative analysis of these structures. We compared the measurements of the aortic annulus (AA) obtained by semi-automated 3D-TOE quantitative software and manual analysis vs. multislice computed tomography (MSCT) ones.One hundred and seventy-five patients (mean age 81.3 ± 6.3 years, 77 men) who underwent both MSCT and 3D-TOE for annulus assessment before transcatheter aortic valve implantation were analysed. Hypothetical prosthetic valve sizing was evaluated using the 3D manual, semi-automated measurements using manufacturer-recommended CT-based sizing algorithm as gold standard. Good correlation between 3D-TOE methods vs. MSCT measurements was found, but the semi-automated analysis demonstrated slightly better correlations for AA major diameter (r = 0.89), perimeter (r = 0.89), and area (r = 0.85) (all P 0.0001) than manual one. Both 3D methods underestimated the MSCT measurements, but semi-automated measurements showed narrower limits of agreement and lesser bias than manual measurements for most of AA parameters. On average, 3D-TOE semi-automated major diameter, area, and perimeter underestimated the respective MSCT measurements by 7.4%, 3.5%, and 4.4%, respectively, whereas minor diameter was overestimated by 0.3%. Moderate agreement for valve sizing for both 3D-TOE techniques was found: Kappa agreement 0.5 for both semi-automated and manual analysis. Interobserver and intraobserver agreements for the AA measurements were excellent for both techniques (intraclass correlation coefficients for all parameters0.80).The 3D-TOE semi-automated analysis of AA is feasible and reliable and can be used in clinical practice as an alternative to MSCT for AA assessment.

BACKGROUND Transcatheter heart valve thrombosis (THV-t) and endocarditis (THV-e) are relevant complications after transcatheter aortic valve implantation (TAVI). Transcatheter heart valve (THV) dysfunction definition is mostly based on Doppler (stenosis/regurgitation) without considering leaflets characteristics. PURPOSE To evaluate the additional diagnostic value of leaflets echocardiographic features over Doppler when prosthetic valve complication is suspected. METHODS Among 621 post-TAVI patients, 128 cases with probable valve complication were identified. THV-t was finally diagnosed in 13 patients (10%) and THV-e in 8 (6%), while the remaining 107 (84%) had no definitive diagnosis of thrombosis/endocarditis (THV-no). We analyzed at 2 time points (baseline and follow-up) both traditional Doppler parameters and leaflets morpho-functional features. RESULTS Both Doppler and leaflets parameters showed high sensitivity (sensitivity 92%) and low specificity (ranging from specificity 32% to 74%) in detecting THV-t. Interestingly, the combination of mean aortic pressure gradient ≥20 mm Hg and leaflet thickening significantly improved the specificity of echocardiography for diagnosis of THV thrombosis (specificity 94%). On the other hand, echocardiographic diagnosis of THV endocarditis remained limited by very low sensitivity despite showing high specificity. CONCLUSIONS The combination of Doppler and leaflets parameters can improve the echocardiographic diagnosis of THV thrombosis in post-TAVI patients with suspicious symptoms, via a significant increase in the overall test specificity. This would potentially allow more rational gatekeeping to more expensive/invasive diagnostic examinations (eg, CT scan) or therapeutic trials (eg, unnecessary anticoagulation).

Aims Renal dysfunction is common in heart failure. Recent evidence suggests a pivotal role for systemic venous congestion and functional tricuspid regurgitation (FTR) in the pathophysiology of renal dysfunction. We investigated the role of FTR as a determinant of renal dysfunction and a predictor of long-term prognosis in chronic systolic heart failure patients. Methods and results Four hundred and thirteen consecutive patients (mean age 74.2 ± 11 years) with chronic heart failure and left ventricular ejection fraction below 50% were enrolled. The FTR severity was quantified by transthoracic echocardiography. Renal function was evaluated with the estimated glomerular filtration rate measured by the simplified Modification of Diet in Renal Disease formula. The association between moderate/ severe FTR and renal dysfunction, and its impact on heart failure episodes and overall mortality were also assessed. The medianfollow-upwas36months(range1-144months). Through multivariate analysis, the interaction between moderate/severe FTR with tricuspid annular plane systolic excursion less than 16mm was found to be an independent determinant of renal dysfunction [odds ratio 1.2, 95% confidence interval (CI) 1.1-1.5, P U0.04]. Moderate/severe FTR (hazard ratio 1.3, 95% CI 1.2-2.7, P U0.02) and tricuspid annular plane systolic excursion below 16mm (hazard ratio 1.2, 95% CI 1.0-3.7, P U0.01) were significantly related to the heart failure episodes. Moreover, the Kaplan-Meier analysis showed a worse outcome in patients with moderate/severe FTR (log-rank test 8.6, P U0.003). Conclusions The combination of significant FTR and right ventricular dysfunction, but not FTR and right ventricular dysfunction alone, is independently associated with renal dysfunction. The presence of significant FTR is related to an excess event rate of heart failure and has significant impact on outcome. J Cardiovasc Med 2017, 18:60-68.

Impella RP has been used to treat right ventricular failure (RVF) developing in various clinical settings that underlay different pathological mechanisms and lead to distinct prognostic implications.This is a single-centre retrospective study including all consecutive patients, from January 2015 to December 2018, with inferior STEMI due to acute thrombotic occlusion of right coronary artery (RCA) and unsuccessful primary percutaneous coronary intervention (PCI) complicated by refractory RVF managed with an Impella RP device.A total of 5 patients have been treated. The mean age was 73 ± 9 years, 80% were males. All patients, except one, were hemodynamically stable at hospital admission. In all patients, PCI resulted unsuccessful (final TIMI flow 3), with subsequent development of refractory RVF and cardiogenic shock in the catheterization laboratory, despite the use of inotropes and intra-aortic balloon pump (IABP). In 80% of the cases, Impella RP was placed immediately after PCI. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in systolic blood pressure from 91 ± 17 to 136 ± 13 mmHg, a decrease in central venous pressure from 16 ± 2.5 to 12 ± 4 mmHg and a resolution in lactates from 4.5 ± 2.5 to 1.6 ± 0.7 mg/dL. Mean duration of IABP and Impella RP support were 4 and 7 days, respectively. RV recovery occurred in 80% of the cases. All patients survived at 30-day.In patients with AMI complicated by unsuccessful revascularization of RCA and refractory RVF, the use of Impella RP device resulted in immediate hemodynamic benefit with reversal of shock and favourable survival at 30-day.

Background The Impella (Abiomed, Danvers, MA) mechanical circulatory support is a catheter-based axial-flow pump. It reduces left ventricular (LV) stroke work and myocardial oxygen demand while increasing systemic and coronary perfusion in the setting of cardiogenic shock (CS), and it provides hemodynamic support during high-risk percutaneous coronary intervention (PCI). Purpose To evaluate the outcomes of Impella-supported patients in the context of CS and protected-PCI. Methods This single-center registry includes all patients implanted with Impella device at our institution between February 2013 and June 2018. Indications for Impella support were CS (hypotension despite adequate filling status with signs of hypoperfusion) and protected-PCI (prophylactic hemodynamic support during non-emergent high-risk PCI). Results A total of 145 patients were implanted with Impella: 130 (89.7%) for CS and 15 (10.3%) for protected-PCI. Among CS patients, mean age was 61.6±12.9, 79.2% males. The prevalence of chronic heart failure (HF) was 26.1%, prior myocardial infarction (MI) 29% and myocardial revascularization 36.6%, chronic kidney disease (CKD) 18.3%. Among protected PCI patients, mean age was 73.4±8.7 years, 86.7% males. The prevalence of HF was 85.7%, prior MI 42.9%, myocardial revascularization 35.7%, CKD 57.1%. In CS group, the indications for Impella implantation were myocarditis in 8 (6.2%) patients, acute coronary syndromes in 77 (59.2%), periprocedural ventricular tachycardia ablation CS in 10 (7.7%), decompensated heart failure in 26.9%. Out of hospital cardiac arrest occurred in 35 (30.4%) patients, INTERMACS I class in 70 (59.3%), mean arterial pressure was 65.4±18.4 mmHg, serum lactate 6.7±5.5 mmol/l, at least 1 inotropic agent use in 73 (66.4%), mean LV EF 21.4±11,7%, right ventricular dysfunction in 53 (48.6%). The rate of device-related complications was not negligible in CS group: 18 (14.5%) patients had limb ischemia and vascular surgery was required in 14, 17 (14.3%) had access-site bleeding. A total of 42 (33.3%) had haemolysis, and 67 (56.8%) acute kidney injury (AKI), half of whom requiring renal replacement therapy. Escalation to other therapies was necessary in 43 cases. Conversely, in the protected-PCI group a low rate of AKI (n=4, 28.6%) and acute limb ischemia (n=1, 7.1%) was observed, whereas no cases of haemolysis nor need of escalation therapy were recorded. Mean Impella support was 135.5±167.21 days for CS group, 60.6±80 for protected-PCI group. Survival at 30 days was 60.33% for CS group and 92.9% for protected-PCI group. One-year all-cause death was 50% for CS group and 13.3% for protected-PCI group. Conclusion Mechanical circulatory support with Impella is associated with good outcomes and reasonable rates of complications in the protected-PCI group, whereas less favorable results were observed in CS population probably due to the greater severity of clinical presentation.

In the setting of HeartWare left ventricular assist device (HVAD, Medtronic) implantation, pre-pump blood flow obstruction has been described due to intraventricular thrombus formation occluding the inflow cannula. This phenomenon often evolves in suboptimal pump performance, and requires prompt management to prevent its progression. However, to date, effective strategies and tools for the diagnosis and management of this complication are poorly described. We report a case of HVAD inflow cannula obstruction that drove later in-pump thrombosis and, eventually, complete cannula occlusion, and discuss gap of knowledge and limitations of currently available diagnostic and therapeutic tools in this scenario. Furthermore, we reinforce the value of time-frequency analysis of the HVAD log files to early identify abnormal pump operation associated with inflow cannula obstruction despite unremarkable trends of pump parameters.

The right ventricle and tricuspid valve (TV) have long been neglected by cardiologists. Functional tricuspid regurgitation (TR) is nowadays the most common cause of severe TR and is emerging as a prognostic factor in many heart diseases. A multimodality imaging approach is fundamental for defining the pathophysiology of TR, using both two-dimensional and three-dimensional echocardiography, as well as CT scan. In particular, 3D echocardiography can characterize TV apparatus and tricuspid annulus; CT offers complementary information about annular structure, and its relationship with the right coronary artery. The following review will describe TV anatomy, define transthoracic and transesophageal echocardiographic views for evaluating TV morphology, function and TR grading with some clues on interventional perspectives.

Persistent experience-driven adaptation of brain function is associated with alterations in gene expression patterns, resulting in structural and functional neuronal remodeling. How synaptic activity—in particular presynaptic performance—is coupled to gene expression in nucleus remains incompletely understood. Here, we report on a role of CtBP1, a transcriptional co-repressor enriched in presynapses and nuclei, in the activity-driven reconfiguration of gene expression in neurons. We demonstrate that presynaptic and nuclear pools of CtBP1 are interconnected and that both synaptic retention and shuttling of CtBP1 between cytoplasm and nucleus are co-regulated by neuronal activity. Finally, we show that CtBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins Bassoon and Piccolo. This association is regulated by neuronal activity via modulation of cellular NAD/NADH levels and restrains the size of the CtBP1 pool available for nuclear import, thus contributing to the control of activity-dependent gene expression. Our combined results reveal a mechanism for coupling activity-induced molecular rearrangements in the presynapse with reconfiguration of neuronal gene expression.

[This corrects the article DOI: 10.1371/journal.pgen.1006684.].

Percutaneous tricuspid valve (TV) repair procedures are emerging therapies for patients with symptomatic severe tricuspid regurgitation (TR) who are deemed inoperable. Some of these procedures target the tricuspid annulus (TA), mimicking the Kay procedure, or the leaflets, mimicking Alfieri stitch

Nowadays some percutaneous options for tricuspid valve (TV) repair are available: Tricinch (4Tech Cardio, Galway, Ireland) mimicking the Kay procedure, Trialign (Mitralign, Boston, MA, USA) aiming to bicuspidise TV, MitraClip (Abbott Vascular, Abbott Park, Illinois, USA) mimicking Alfieri's stitch, direct transcatheter annuloplasty with Cardioband (Valtech Cardio, Or Yehuda, Israel) and transcatheter Forma Repair (Edwards Lifesciences, Irvine, California, USA) providing a surface for leaflet coaptation. A multimodality imaging approach is fundamental for defining the pathophysiology of tricuspid regurgitation (TR), preprocedural planning and intraprocedural monitoring. Both 2-dimensional and 3-dimensional (3D) transthoracic echocardiography and transoesophageal echocardiography (TOE) are essential for grading and anatomical characterisation of TR, and evaluation of dimensions and function of right ventricle (RV) and estimation of pulmonary pressure. In particular, 3D echocardiography provides a better anatomical definition of TV apparatus and tricuspid annulus (TA) and additional information about the anatomical relationships of TV and surrounding structures. CT offers complementary information during the preprocedural planning especially for procedures targeting TA such as annular structure and dimensions, quality and amount of annular tissue and its relationship with the right coronary artery, and the sizing of the inferior vena cava. Moreover, appropriate patient selection is crucial. The best candidate seems to be a patient with functional TR due to predominant annular dilatation with modest apical tethering, at least partial preservation of leaflets coaptation, not severe pulmonary hypertension and not advanced RV dilation and dysfunction. An example of intraprocedural multimodality imaging approach with TOE, fluoroscopy, angiography and intracardiac echocardiography is also reported.

Voltage-dependent Ca(2+) channels (CaVs) represent the principal source of Ca(2+) ions that trigger evoked neurotransmitter release from presynaptic boutons. Ca(2+) influx is mediated mainly via CaV2.1 (P/Q-type) and CaV2.2 (N-type) channels, which differ in their properties. Their relative contribution to synaptic transmission changes during development and tunes neurotransmission during synaptic plasticity. The mechanism of differential recruitment of CaV2.1 and CaV2.2 to release sites is largely unknown. Here, we show that the presynaptic scaffolding protein Bassoon localizes specifically CaV2.1 to active zones via molecular interaction with the RIM-binding proteins (RBPs). A genetic deletion of Bassoon or an acute interference with Bassoon-RBP interaction reduces synaptic abundance of CaV2.1, weakens P/Q-type Ca(2+) current-driven synaptic transmission, and results in higher relative contribution of neurotransmission dependent on CaV2.2. These data establish Bassoon as a major regulator of the molecular composition of the presynaptic neurotransmitter release sites.

A 52-year-old man underwent surgical mitral repair for P2 flail. A conventional Carpentier technique was used (quadrangular resection+sliding plasty and annuloplasty with a 35-mm flexible band). Predischarge echocardiography showed no residual MR and no systolic anterior motion (SAM). One year after surgery, the patient came to our attention complaining dyspnoea on effort (New York Heart Association III). Rest echocardiography showed absence of recurrent MR, but evidence of SAM with mild left ventricular outflow tract (LVOT) obstruction. Exercise echocardiography revealed a significant SAM with severe LVOT obstruction (Figure 1; Movies I–III in the Data Supplement). An induced pressure gradient of 144 mm Hg and a dynamic flow acceleration with late systolic peak velocity were observed across the LVOT with concomitant moderate MR and mild pulmonary hypertension (systolic pulmonary pressure, 40 mm Hg; Figure 1). A pharmacological approach was attempted first (atenolol, 100 mg QID; diltiazem 180 mg QID) without clinical improvements and changes in SAM and LVOT obstruction. Therefore, an interventional strategy was considered. A MitraClip procedure was planned to correct the SAM. Adrenaline infusion was used to induce SAM. After ineffective attempts to place the clip in the central …

INTRODUCTION: Sudden and/or chronic exposure to catecholamines may predispose patients with phaeochromocytoma to cardiac pathology, including left ventricular (LV) hypertrophy, myocardial infarction, stress-induced cardiomyopathy and heart failure. This is a prospective, multicentre study using cardiovascular magnetic resonance (CMR) imaging to describe the variety and incidence of cardiac abnormalities in patients diagnosed with phaeochromocytoma. METHODS: Patients diagnosed with phaeochromocytoma (n = 50) were included. We prospectively recruited patients newly-diagnosed with confirmed phaeochromocytoma (n = 20, age 51 ± 14 yrs) who underwent CMR before and after curative surgical resection of the phaeochromocytoma (median follow-up 1 year). Previously-diagnosed patients who had curative surgery (n = 30, age 52 ± 14 yrs) were also recruited. Patients with known cardiac conditions were excluded. CMR included cine imaging for LV function, T2-weighted imaging for oedema and late gadolinium enhancement imaging to detect scarring. RESULTS: In newly-diagnosed patients, the mean LV ejection fraction was 67 ± 10% (range 47-88%; normal range 57-81%); Of these patients, 20% (n = 4/20) had mild global LV dysfunction (EF 47-56%). A significant proportion (65%, n = 13/20) demonstrated scarring, all with a non-ischaemic pattern (midwall/subepicardial/patchy), but the areas were small (

Chronic functional mitral regurgitation (FMR) is a frequent finding of ischemic heart disease and dilated cardiomyopathy (DCM), associated with unfavourable prognosis. Several pathophysiologic mechanisms are involved in FMR, such as annular dilatation and dysfunction, left ventricle (LV) remodeling, dysfunction and dyssynchrony, papillary muscles displacement and dyssynchrony. The best therapeutic choice for FMR is still debated. When optimal medical treatment has already been set, a further option for cardiac resynchronization therapy (CRT) and/or surgical correction should be considered. CRT is able to contrast most of the pathophysiologic determinants of FMR by minimizing LV dyssynchrony through different mechanisms: Increasing closing forces, reducing tethering forces, reshaping annular geometry and function, correcting diastolic MR. Deformation imaging in terms of two-dimensional speckle tracking has been validated for LV dyssynchrony assessment. Radial speckle tracking and three-dimensional strain analysis appear to be the best methods to quantify intraventricular delay and to predict CRT-responders. Speckle-tracking echocardiography in patients with mitral valve regurgitation has been usually proposed for the assessment of LV and left atrial function. However it has also revealed a fundamental role of intraventricular dyssynchrony in determining FMR especially in DCM, rather than in ischemic cardiomyopathy in which MR severity seems to be more related to mitral valve deformation indexes. Furthermore speckle tracking allows the assessment of papillary muscle dyssynchrony. Therefore this technique can help to identify optimal candidates to CRT that will probably demonstrate a reduction in FMR degree and thus will experience a better outcome.

We address an optimization problem in which two agents, each with a set of weighted items, compete in order to minimize the total weight of their solution sets. The latter are built according to a sequential procedure consisting in a fixed number of rounds. In every round each agent submits one item that may be included in its solution set. We study two natural rules to decide which item between the two will be included. We address the problem from a strategic point of view, that is finding the best moves for one agent against the opponent, in two distinct scenarios. We consider preventive or minimax strategies, optimizing the objective of the agent in the worst case, and best-response strategies, where the items submitted by the opponent are known in advance in each round.

Zn²+ is co-released at glutamatergic synapses throughout the central nervous system and acts as a neuromodulator for glutamatergic neurotransmission, as a key modulator of NMDA receptor functioning. Zn²+ is also implicated in the neurotoxicity associated with several models of acute brain injury and neurodegeneration. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons in the spinal cord and cortex. In this study, we have investigated the modulatory role exerted by Zn²+ in NMDA-mediated neurotoxicity in either near-pure or mixed cortical cultured neurons obtained from either mice over-expressing the G93A mutant form of Cu/Zn superoxide dismutase (SOD1) human gene, a gene linked to familial ALS, or wild type (WT) mice. To that aim, SOD1(G93A) or WT cultures were exposed to either NMDA by itself or to Zn²+ prior to a toxic challenge with NMDA, and neuronal loss evaluated 24 h later. While we failed to observe any significant difference between NMDA and Zn²+/NMDA-mediated toxicity in mixed SOD1(G93A) or WT cortical cultures, different vulnerability to these toxic paradigms was found in near-pure neuronal cultures. In the WT near-pure neuronal cultures, a brief exposure to sublethal concentrations of Zn²+-enhanced NMDA receptor-mediated cell death, an effect that was far more pronounced in the SOD1(G93A) cultures. This increased excitotoxicity in SOD1(G93A) near-pure neuronal cultures appears to be mediated by a significant increase in NMDA-dependent rises of intraneuronal Ca²+ levels as well as enhanced production of cytosolic reactive oxygen species, while the injurious process seems to be unrelated to activation of nNOS or ERK1/2 pathways. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

Amyotrophic lateral sclerosis (ALS) is an adult-onset disease characterized by the progressive degeneration of motoneurons (MNs). Altered electrical properties have been described in familial and sporadic ALS patients. Cortical and spinal neurons cultured from the mutant Cu,Zn superoxide dismutase 1 (SOD1G93A) mouse, a murine model of ALS, exhibit a marked increase in the persistent Na+ currents. Here, we investigated the effects of the SOD1G93A mutation on the expression of the voltage-gated Na+ channel alpha subunit SCN8A (Nav1.6) and the beta subunits SCN1B (beta1), SCN2B (beta2), and SCN3B (beta3) in MNs of the spinal cord in presymptomatic (P75) and symptomatic (P120) mice. We observed a significant increase, within lamina IX, of the beta3 transcript and protein expression. On the other hand, the beta1 transcript was significantly decreased, in the same area, at the symptomatic stage, while the beta2 transcript levels were unaltered. The SCN8A transcript was significantly decreased at P120 in the whole spinal cord. These data suggest that the SOD1G93A mutation alters voltage-gated Na+ channel subunit expression. Moreover, the increased expression of the beta3 subunit support the hypothesis that altered persistent Na+ currents contribute to the hyperexcitability observed in the ALS-affected MNs.

Although variations in the rate of reconciliation have been the subject of extensive studies, variations in conciliatory patterns and their differential use have barely been investigated. In this study, we analysed the postconflict behaviour of a captive group of mandrills, Mandrillus sphinx, and observed a differential use of contact and noncontact postconflict affiliation between former opponents. Mandrills used contact affiliation to reconcile with related opponents and when the original aggressor was lower ranking than the victim, and used noncontact affiliation to reconcile with opponents that had a high probability of renewing aggression. Both contact and noncontact affiliation reduced the probability of renewed aggression. These results suggest accessibility and danger modulated the use of conciliatory patterns and call for further studies of flexible conciliatory strategies.

Thoracic endovascular aortic repair (tevar) is commonly performed in selected patients to treat thoracic aortic pathologies. Transesophageal echocardiography (TEE) is often used as adjunct to fluoroscopy and angiography (ANGIO) during TEVAR, mainly reducing radiation exposure and contrast load.