State-of-the-art review on management of end-stage heart failure in amyloidosis: transplant and beyond.

Cardiac involvement occurs in light-chain (AL), transthyretin wild-type (wtATTR), and hereditary (hATTR) amyloidosis; other types of amyloidosis account for < 5% of all cardiac amyloidosis (CA). CA can present subclinically on screening, insidiously with symptoms such as exertional dyspnea, or abruptly as cardiogenic shock. Initially, CA patients were thought to be poor candidates for transplant due to short long-term survival; however, there is a marked improvement in heart and multi-organ transplant outcomes over the past 10 years with newer treatments and improvements in support with temporary and durable mechanical circulatory support while awaiting transplant. Patients with AL CA were reported to have worse post-OHT outcomes than patients with ATTR CA, but this gap is quickly closing with improved patient selection, novel chemotherapeutics, and perhaps with selected use of bone marrow transplantation. Waitlist mortality and transplantation rates have markedly improved for CA after the United Network for Organ Sharing (UNOS) policy change in October 2018. In this review, we will evaluate contemporary data from the last 5 years on advances in the field of transplantation and mechanical circulatory support in this patient population.

Degree of change in right ventricular adaptation measures during axillary Impella support informs risk stratification for early, severe right heart failure following durable LVAD implantation.

Risk assessment for early, severe right heart failure (RHF) after LVAD implantation remains imperfect. We sought to define the differences in RV adaptation and load after axillary Impella support between patients who experienced RHF and those who did not. Seventeen of 18 patients included were deemed intermediate or high risk for RHF by EUROMACS-RHF score. Before Impella insertion, RV adaptation parameters (RAP, RAP:PCWP, PAPi) were worse in the non-RHF group compared to the RHF group. In both groups, RV load parameters (effective pulmonary arterial elastance, pulmonary vascular resistance, and pulmonary vascular compliance) improved after Impella insertion. Lesser improvements in RV adaptation were seen in the RHF group. Moreover, load-to-adaptation relationships (EA/RAP and EA/RAP:PCWP) worsened to a greater degree. In patients at intermediate or high risk for RHF after LVAD, assessment of RV adaptation and load during axillary Impella support may improve risk stratification.

QCA to Guide Treatment of Inter-Clip Mitral Regurgitation Between Two Previously Implanted MitraClips.

Treatment of recurrent MR after initially successful MitraClip procedure can pose therapeutic challenges. We report a successful case of redo MitraClip to treat recurrent inter-clip MR due to progression of underlying degenerative valvular pathology with prolapsing posterior mitral leaflet between the two prior clips. In this vignette, we describe the novel use of quantitative coronary arteriography (QCA) to select redo MitraClip as the treatment strategy.

A multi-institutional retrospective analysis on impact of RV acute mechanical support timing after LVAD implantation on 1-year mortality and predictors of RV acute mechanical support weaning.

BACKGROUND: There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning. METHODS: A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors. RESULTS: There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean. CONCLUSIONS: In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion.

Prediction of right heart failure after left ventricular assist implantation: external validation of the EUROMACS right-sided heart failure risk score.

AIMS: Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant remains a challenge. The EUROMACS right-sided heart failure (EUROMACS-RHF) risk score was proposed as a prediction tool for post-LVAD RHF but lacks from large external validation. The aim of our study was to externally validate the score. METHODS AND RESULTS: From January 2007 to December 2017, 878 continuous-flow LVADs were implanted at three tertiary centres. We calculated the EUROMACS-RHF score in 662 patients with complete data. We evaluated its predictive performance for early RHF defined as either (i) need for short- or long-term right-sided circulatory support, (ii) continuous inotropic support for ≥14 days, or (iii) nitric oxide for ≥48 h post-operatively. Right heart failure occurred in 211 patients (32%). When compared with non-RHF patients, pre-operatively they had higher creatinine, bilirubin, right atrial pressure, and lower INTERMACS class (P < 0.05); length of stay and in-hospital mortality were higher. Area under the ROC curve for RHF prediction of the EUROMACS-RHF score was 0.64 [95% confidence interval (CI) 0.60-0.68]. Reclassification of patients with RHF was significantly better when applying the EUROMACS-RHF risk score on top of previous published scores. Patients in the high-risk category had significantly higher in-hospital and 2-year mortality [hazard ratio: 1.64 (95% CI 1.16-2.32) P = 0.005]. CONCLUSION: In an external cohort, the EUROMACS-RHF had limited discrimination predicting RHF. The clinical utility of this score remains to be determined.

Predicting and measuring mortality risk after transcatheter aortic valve replacement.

Introduction: Over the last decade, transcatheter aortic valve replacement (TAVR) has emerged as a treatment option for most patients with severe symptomatic aortic stenosis (AS). With growing indications and exponential increase in the number of TAVR procedures, it is important to be able to accurately predict mortality after TAVR.Areas covered: Herein, we review the surgical and TAVR-specific mortality prediction models (MPMs) and their performance in their original derivation and external validation cohorts. We then discuss the role of other important risk assessment tools such as frailty, echocardiographic parameters, and biomarkers in patients, being considered for TAVR.Expert opinion: Conventional surgical MPMs have suboptimal predictive performance and are mis-calibrated when applied to TAVR populations. Although a number of TAVR-specific MPMs have been developed, their utility is also limited by their modest discriminative ability when applied to populations external to their original derivation cohorts. There is an unmet need for robust TAVR MPMs that accurately predict post TAVR mortality. In the interim, heart teams should utilize the currently available TAVR-specific MPMs in conjunction with other prognostic factors, such as frailty, echocardiographic or computed tomography (CT) imaging parameters, and biomarkers for risk assessment of patients, being considered for TAVR.

Three-Dimensional Control on Lingually Rolled in Molars using a 3D Lingual Arch.

The fixed lingual arches that are used for mandibular molar uprighting works in two dimensions, whereas the 3D lingual arch works in all the three dimensions. The 3D lingual arch was fabricated from a 0.028 "round S.S wire with parts consisting of an adaptor, activator, friction lock and extender. The friction lock was inserted into the vertical stubs welded on the molar bands of the lingually tipped molar. They provided greater stability and anchorage to the molars. Up righting of the lingually tipped mandibular molars was attained within one month after insertion of the Wilson's 3D lingual arch. Correction was attained in all three dimensions with a buccal crown torque and lingual root torque. Levelling and alignment of the anterior segment was also attained by this multipurpose modular appliance. The 3D lingual arch enabled the clinician to set up a more positive anchorage for a greater variety of treatment applications than earlier lingual arches. Quality treatment results were attained with less span of time and were cost effective.

What do the basal ganglia do? A modeling perspective.

Basal ganglia (BG) constitute a network of seven deep brain nuclei involved in a variety of crucial brain functions including: action selection, action gating, reward based learning, motor preparation, timing, etc. In spite of the immense amount of data available today, researchers continue to wonder how a single deep brain circuit performs such a bewildering range of functions. Computational models of BG have focused on individual functions and fail to give an integrative picture of BG function. A major breakthrough in our understanding of BG function is perhaps the insight that activities of mesencephalic dopaminergic cells represent some form of 'reward' to the organism. This insight enabled application of tools from 'reinforcement learning,' a branch of machine learning, in the study of BG function. Nevertheless, in spite of these bright spots, we are far from the goal of arriving at a comprehensive understanding of these 'mysterious nuclei.' A comprehensive knowledge of BG function has the potential to radically alter treatment and management of a variety of BG-related neurological disorders (Parkinson's disease, Huntington's chorea, etc.) and neuropsychiatric disorders (schizophrenia, obsessive compulsive disorder, etc.) also. In this article, we review the existing modeling literature on BG and hypothesize an integrative picture of the function of these nuclei.

Understanding Parkinsonian handwriting through a computational model of basal ganglia.

Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease.