Search

New Findings: What is the topic of this review? Right heart dysfunction remains a major adverse event in patients with end stage heart failure undergoing left ventricular assist device placement. This article reviews the pathophysiology and clinical considerations of right heart failure in this patient population. What advances does it highlight? This review highlights the anatomic and physiological peculiarities of the interplay between left and right heart function in patients undergoing LVAD therapy. These would allow us to further advance our understanding of right ventricular function., Abstract: The adaptation of the right ventricular (RV) output to a left ventricular assist device (LVAD) often determines the fate of patients with pulmonary hypertension secondary to left heart failure. Pre-existing right heart dysfunction in patients with advanced left heart failure is the consequence of increased (arterial) afterload and not simply the consequence of myocardial disease. If unaccounted for, it has the potential of accelerating into clinical right heart failure after LVAD, leading to significant morbidity and mortality. After LVAD implantation, the RV has to face increased flow generated by the LVAD, cardiac arrhythmias and exaggerated functional interactions between both ventricles. Understanding the key physiological mechanisms of RV dysfunction in patients with end-stage heart failure will allow us to predict and therefore prevent RV failure after LVAD implantation., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the topic of this review? This review discusses how implantation of continuous flow left ventricular assist devices impact arterial stiffness and outcome. What advances does it highlight? Not all patients implanted with continuous flow left ventricular assist devices show an increase in arterial stiffness. However, in those patients where arterial stiffness increases, levels of composite outcome (stroke, gastrointestinal bleeding, pump thrombosis and death) is significantly higher than those who's arterial stiffness does not increase., Abstract: In parallel with the major advances in clinical care, technological advancements and implantation of mechanical circulatory support in patients with severe heart failure have resulted in these patients living longer. However, these patients are still at increased risk of stroke and gastrointestinal bleeding. The unique continuous flow produced by various left ventricular assist devices (LVADs) has been suggested as one potential reason for this increased risk of stroke and gastrointestinal bleeding. Furthermore, these continuous-flow (CF) devices challenge our understanding of circulatory blood pressure and flow regulation in relationship to organ health. In healthy pulsatile and dynamic systems, arterial stiffness is a major independent risk factor for stroke. However, to date, there are limited data regarding the impact of CF-LVAD therapy on arterial stiffness. The purpose of this report is to discuss the variable impact of CF-LVAD therapy on arterial stiffness and attempt to highlight some potential mechanisms linking these associations in this unique population., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? Patients with advanced heart failure who are implanted with left ventricular assist devices (LVADs) present an opportunity to understand the human circulation under extreme conditions. What advances does it highlight? LVAD patients have a unique circulation that is characterized by a reduced or even absent arterial pulse. The remarkable survival of these patients is accompanied by circulatory complications, including stroke, gastrointestinal bleeding and right-heart failure. Understanding the mechanisms related to the complications in LVAD patients will help the patients and also advance our fundamental understanding of the human circulation in general., Abstract: Some humans with chronic, advanced heart failure are surgically implanted with a left ventricular assist device (LVAD). Because the LVAD produces a continuous flow, a palpable pulse is often absent in these patients. This allows for a unique investigation of the human circulation and has created a controversy around the 'need' for a pulse. The medical debate has also generated a more generic, fundamental discussion into what is 'normal' arterial physiology and health. The comprehensive study and understanding of the arterial responses to drastically altered haemodynamics due to continuous-flow LVADs, at rest and during activity, presents an opportunity to significantly increase our current understanding of the fundamental components of arterial regulation (flow, blood pressure, sympathetic activity, endothelial function, pulsatility) in a way that could never have been studied previously. In a series of four articles, we summarize the talks presented at the symposium entitled 'Bionic women and men - Physiology lessons from implantable cardiac devices' presented at the 2019 Annual Meeting of The Physiological Society in Aberdeen, UK. The articles highlight the novel questions generated by physiological phenomena observed in LVAD patients and propose future areas of interest within the field of cardiovascular physiology., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Pulmonary arterial hypertension (PAH) is a chronic disease that ultimately progresses to right-sided heart failure (HF) and death. Close monitoring of pulmonary artery pressure (PAP) and right ventricular (RV) function allows clinicians to appropriately guide therapy. However, the burden of commonly used methods to assess RV hemodynamics, such as right heart catheterization, precludes frequent monitoring. The CardioMEMS HF System (Abbott) is an ambulatory implantable hemodynamic monitor, previously only used in patients with New York Heart Association (NYHA) class III HF. In this study, we evaluate the feasibility and early safety of monitoring patients with PAH and right-sided HF using the CardioMEMS HF System., Methods: The CardioMEMS HF sensors were implanted in 26 patients with PAH with NYHA class III or IV right-sided HF (51.3 ± 18.3 years of age, 92% women, 81% NYHA class III). PAH therapy was tracked using a minimum of weekly reviews of CardioMEMS HF daily hemodynamic measurements. Safety, functional response, and hemodynamic response were tracked up to 4 years with in-clinic follow-ups., Results: The CardioMEMS HF System was safely used to monitor PAH therapy, with no device-related serious adverse events observed and a single preimplant serious adverse event. Significant PAP reduction and cardiac output elevation were observed as early as 1 month postimplant using trends of CardioMEMS HF data, coupled with significant NYHA class and quality of life improvements within 1 year., Conclusions: The CardioMEMS HF System provided useful information to monitor PAH therapy, and demonstrated short- and long-term safety. Larger clinical trials are needed before its widespread use to guide therapy in patients with severe PAH with right-sided HF., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR). Plasma dd-cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd-cfDNA levels were correlated to paired events of biopsy-based diagnosis of rejection. The median dd-cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd-cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd-cfDNA levels were elevated 3-fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd-cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd-cfDNA assay., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex., Methods and Results: Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients-25.8% in 2004 to 21.9% in 2016 ( P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P <0.0001) but not in the continuous-flow era (13.3% versus 12.1%, P =0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45-3.10; P <0.0001) but not during the continuous-flow era (1.18; 0.93-1.48; P =0.16)., Conclusions: Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.

Background. The decision to receive a permanent left ventricular assist device (LVAD) to treat end-stage heart failure (HF) involves understanding and weighing the risks and benefits of a highly invasive treatment. The goal of this study was to characterize end-stage HF patients across parameters that may affect their decision making and to inform the development of an LVAD decision support tool. Methods. A survey of 35 end-stage HF patients at an LVAD implant hospital was performed to characterize their information-seeking habits, interaction with physicians, technology use, numeracy, and concerns about their health. Survey responses were analyzed using descriptive statistics, grounded theory method, and Bayesian network learning. Results. Most patients indicated an interest in using some type of decision support tool (roadmap of health progression: 46%, n = 16; personal prognosis: 51%, n = 18; short videos of patients telling stories of their experiences with an LVAD: 57%, n = 20). Information patients desired in a hypothetical decision support tool fell into the following topics: prognoses for health outcomes, technical information seeking, expressing emotions, and treatment decisions. Desire for understanding their condition was closely related to whether they had difficult interpreting their electronic medical record in the past. Conclusions. Most patients reported interest in engaging in their health care decision making and seeing their prognosis and electronic health record information. Patients who were less interested in their own treatment decisions were characterized by having less success understanding their health information. Design of a decision support tool for potential LVAD patients should consider a spectrum of health literacy and include information beyond the technical specifications of LVAD support., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.

Purpose of Review: Pulmonary arterial hypertension (PAH) is a chronic, progressive, and incurable disease with significant morbidity and mortality. Despite increasingly available treatment options, PAH patients continue to experience disease progression and increased rates of hospitalizations due to right heart failure. Physician's ability to comprehensively assess PAH patients, determine prognosis, and monitor disease progression and response to treatment remains critical in optimizing outcomes., Recent Findings: Risk assessment in PAH should include a range of clinical, hemodynamic, and exercise parameters, performed in a serial fashion over the course of treatment. Approaches to risk assessment in PAH patients include the use of risk variables, scores, and equations that stratify the impact of both modifiable (e.g., 6-min walk distance, functional class, brain natriuretic peptide), and non-modifiable (e.g., age, gender, PAH etiology) risk factors. Such tools allow physicians to better determine prognosis, allocate treatment resources, and enhance the consistency of treatment approaches across providers. Comprehensive and accurate risk prediction is essential to make individualized treatment decisions and optimizing outcomes in PAH.

Use of a left ventricular assist device (LVAD) can benefit patients with end stage heart failure, but only with careful patient selection. In this study, previously derived Bayesian network models for predicting LVAD patient mortality at 1, 3, and 12 months post-implant were evaluated on retrospective data from a single implant center. The models performed well at all three time points, with a receiver operating characteristic area under the curve (ROC AUC) of 78, 76, and 75%, respectively. This evaluation of model performance verifies the utility of these models in "real life" scenarios at an individual institution.

Objectives: This study investigates the use of a Bayesian statistical models to predict survival at various time points in patients undergoing left ventricular assist device (LVAD) implantation., Background: LVADs are being increasingly used in patients with end-stage heart failure. Appropriate patient selection continues to be key in optimizing post-LVAD outcomes., Methods: Data used for this study were derived from 10,277 adult patients from the INTERMACS (Inter-Agency Registry for Mechanically Assisted Circulatory Support) who had a primary LVAD implanted between January 2012 and December 2015. Risk for mortality was calculated retrospectively for various time points (1, 3, and 12 months) after LVAD implantation, using multiple pre-implantation variables. For each of these endpoints, a separate tree-augmented naïve Bayes model was constructed using the most predictive variables., Results: A set of 29, 26, and 31 pre-LVAD variables were found to be predictive at 1, 3, and 12 months, respectively. Predictors of 1-month mortality included low Inter-Agency Registry for Mechanically Assisted Circulatory Support profile, number of acute events in the 48 h before surgery, temporary mechanical circulatory support, and renal and hepatic dysfunction. Variables predicting 12-month mortality included advanced age, frailty, device strategy, and chronic renal disease. The accuracy of all Bayesian models was between 76% and 87%, with an area under the receiver operative characteristics curve of between 0.70 and 0.71., Conclusions: A Bayesian prognostic model for predicting survival based on the comprehensive INTERMACS registry provided highly accurate predictions of mortality based on pre-operative variables. These models may facilitate clinical decision-making while screening candidates for LVAD therapy., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The clinical use of left ventricular assist devices (LVADs) in the growing epidemic of heart failure has improved quality of life and long-term survival for this otherwise devastating disease. The current generation of commercially available devices offers a smaller profile that simplifies surgical implantation, a design that optimizes blood flow characteristics, with less adverse events and improved durability than their predecessors. Despite this, the risk for adverse events remains significant, as do burdens for patients and their caregivers. Appropriate patient selection remains key to optimal LVAD outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Gastrointestinal (GI) bleeding is one of the most common complications after continuous-flow left ventricular assist device implantation. More than one third of patients with incident bleed go on to develop recurrent GI bleeding. Octreotide, a somatostatin analog, is proposed to reduce the risk of recurrent GI bleeding in this population., Methods and Results: This multicenter, retrospective analysis evaluated 51 continuous-flow left ventricular assist device patients who received secondary prophylaxis with octreotide after their index GI bleed from 2009 to 2015. All patients had a hospitalization for GI bleed and received octreotide after discharge. Patient demographics, medical and medication history, and clinical characteristics of patients who rebled after receiving octreotide were compared with non-rebleeders. These data were also compared with matched historical control patients previously enrolled in the HMII (HeartMate II) clinical trials, none of whom received octreotide, to provide a context for the bleeding rates. Twelve patients (24%) who received secondary octreotide prophylaxis developed another GI bleed, whereas 39 (76%) did not. There were similar intergroup demographics; however, significantly more bleeders had a previous GI bleeding history before left ventricular assist device placement (33% versus 5%; P =0.02) and greater frequency of angiodysplasia confirmed during endoscopy (58% versus 23%; P =0.03). Fewer patients in this study experienced a recurrent GI bleed compared with a matched historical control group that did not receive octreotide (24% versus 43%; P =0.04)., Conclusions: Patients with continuous-flow left ventricular assist device receiving secondary prophylaxis with octreotide had a significantly lower GI bleed recurrence compared with historical controls not treated with octreotide. Additional prospective studies are needed to confirm these data., (© 2017 American Heart Association, Inc.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Selection is a key determinant of clinical outcomes after left ventricular assist device (LVAD) placement in patients with end-stage heart failure. The HeartMate II risk score (HMRS) has been proposed to facilitate risk stratification and patient selection for continuous flow pumps. This study retrospectively assessed the performance of HMRS in predicting 90 day and 1 year mortality in patients within the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). A total of 11,523 INTERMACS patients who received a continuous flow LVAD between 2010 and 2015 were retrospectively categorized per their calculated HMRS to predict their 90 day and 1 year risk of mortality. The performance of the score was evaluated by the area under curve (AUC) of the receiver operator characteristic. We also performed multiple regression analysis using variables from the HMRS calculation on the INTERMACS data. The HMRS model showed moderate discrimination for both 90 day and 1 year mortality prediction with AUCs of 61% and 59%, respectively. The predictions had similar accuracy irrespective of whether the pump was axial or centrifugal flow. Multivariable analysis using independent variables used in the original HMRS analysis revealed different set of variables to be predictive of 90 day mortality than those used to calculate HMRS. HMRS predicts both 90 day and 1 year mortality with poor discrimination when applied to a large cohort of LVAD patients. Newer risk prediction models are therefore needed to optimize the therapeutic application of LVAD therapy. Patient selection for appropriate use of LVADs is critical. Currently available risk stratification tools (HMRS) continue to be limited in their ability to accurately predict mortality after LVAD. This study highlights these limitations when applied to a large, comprehensive, multicenter database. HMRS predicts mortality with only modest discrimination when applied to a large cohort of LVAD patients. Better risk stratification tools are needed to optimize outcomes.

Background: Cardiac allograft vasculopathy (CAV) remains an important cause of graft failure after heart transplantation (HT). Although many risk factors for CAV have been identified, there are no clinical prediction models that enable clinicians to determine each recipient's risk of CAV., Methods: We studied a cohort of 14 328 heart transplant recipients whose data were reported to the International Society for Heart and Lung Transplantation Registry between 2000 and 2010. The cohort was divided into training (75%) and test (25%) sets. Multivariable modeling was performed in the test set using variables available at the time of heart transplant using three methods: (i) stepwise Cox proportional hazard, (ii) regularized Cox proportional hazard, and (iii) Bayesian network., Results: Cardiac allograft vasculopathy developed in 4259 recipients (29.7%) at a median time of 3.0 years after HT. The regularized Cox proportional hazard model yielded the optimal performance and was also the most parsimonious. We deployed this model as an Internet-based risk calculator application., Conclusions: We have developed a clinical prediction model for assessing a recipient's risk of CAV using variables available at the time of HT. Application of this model may allow clinicians to determine which recipients will benefit from interventions to reduce the risk of development and progression of CAV., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study hypothesized that the presence of residual mitral regurgitation (MR) post-continuous flow (CF) left ventricular assist device (LVAD) implantation based on quantitative assessment would be negatively associated with right ventricular (RV) size and function and clinical outcomes., Background: MR is associated with elevated left atrial pressure, secondary pulmonary hypertension and RV dysfunction. Implantation of a LVAD leads to mechanical unloading of the left ventricle and generally improves MR. The clinical significance of residual MR in patients supported with CF LVADs is uncertain. Most studies evaluating the presence of MR in LVAD patients have utilized predominantly qualitative assessments of MR., Methods: We retrospectively identified patients implanted with CF LVADs at our institution from 2007 to 2013 who had a pre-operative transthoracic echocardiogram (TTE) within 3 months of LVAD implant and who had a post-operative TTE at least 1 month post-LVAD. MR was assessed quantitatively using the ratio of MR color jet area (CJA)/left atrial area (LAA) in apical views. We also compared quantitative RV metrics, hospitalizations, and mortality in patients with and without significant residual MR (defined as MR CJA/LAA >0.2) on post-implantation TTE., Results: Sixty-nine patients were included in this study. Post-LVAD implantation, 55 patients (80%) had mild or less MR (mean MR CJA/LAA 0.08) but 14 (20%) had significant residual MR (mean MR CJA/LAA 0.34). Patients with residual MR had significantly larger RV size (right ventricular end diastolic dimension 49 mm vs. 45 mm; p = 0.04) and worse RV function (tricuspid annular plane systolic excursion 10 mm vs. 12 mm; p = 0.02; and right ventricular fractional area change 29% vs. 34%; p = 0.02). Post-implantation pulmonary artery pressures were higher in patients with residual MR (pulmonary artery systolic 43 mm Hg vs. 35 mm Hg; p = 0.05). In patients with residual MR there was slightly greater posterior displacement of the mitral coaptation point on pre-operative TTE (28 mm vs. 26 mm; p = 0.16) but this difference was not significant. Time from LVAD implantation to first hospitalization was shorter in patients with residual MR (62 days vs. 103 days; p = 0.05) as was time from LVAD implantation to death (80 days vs. 421 days; p = 0.03)., Conclusions: Significant residual MR post-LVAD implantation assessed by a quantitative measure is associated with persistent pulmonary hypertension, worse RV function, and significantly shorter time to hospitalization and death. MR post-LVAD implantation may serve as a surrogate for adverse outcomes post-LVAD implantation., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigates the use of a Bayesian statistical model to address the limited predictive capacity of existing risk scores derived from multivariate analyses. This is based on the hypothesis that it is necessary to consider the interrelationships and conditional probabilities among independent variables to achieve sufficient statistical accuracy., Background: Right ventricular failure (RVF) continues to be a major adverse event following left ventricular assist device (LVAD) implantation., Methods: Data used for this study were derived from 10,909 adult patients from the Inter-Agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who had a primary LVAD implanted between December 2006 and March 2014. An initial set of 176 pre-implantation variables were considered. RVF post-implant was categorized as acute (<48 h), early (48 h to 14 daysays), and late (>14 days) in onset. For each of these endpoints, a separate tree-augmented naïve Bayes model was constructed using the most predictive variables employing an open source Bayesian inference engine., Results: The acute RVF model consisted of 33 variables including systolic pulmonary artery pressure (PAP), white blood cell count, left ventricular ejection fraction, cardiac index, sodium levels, and lymphocyte percentage. The early RVF model consisted of 34 variables, including systolic PAP, pre-albumin, lactate dehydrogenase level, INTERMACS profile, right ventricular ejection fraction, pro-B-type natriuretic peptide, age, heart rate, tricuspid regurgitation, and body mass index. The late RVF model included 33 variables and was predicted mostly by peripheral vascular resistance, model for end-stage liver disease score, albumin level, lymphocyte percentage, and mean and diastolic PAP. The accuracy of all Bayesian models was between 91% and 97%, with an area under the receiver operator characteristics curve between 0.83 and 0.90, sensitivity of 90%, and specificity between 98% and 99%, significantly outperforming previously published risk scores., Conclusions: A Bayesian prognostic model of RVF based on the large, multicenter INTERMACS registry provided highly accurate predictions of acute, early, and late RVF on the basis of pre-operative variables. These models may facilitate clinical decision making while screening candidates for LVAD therapy., Competing Interests: None of the authors have any financial relationship with any commercial entities that have an interest in the subject of the presented manuscript or other conflicts of interest to disclose., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Significant developments have occurred in the field of pulmonary hypertension (PH) in the past 2 years, especially in terms of treatment options available. These include: approval of new drugs; evidence for use of initial combination therapies in pulmonary arterial hypertension; approved drugs for use in chronic thromboembolic disease not amenable to, or persistent after surgical thromboendarterectomy; and ongoing clinical trials in PH related to left heart disease and hypoxia. The field continues to evolve and address the challenges in treatment of this multifaceted disease with the aim to provide novel solutions and meet the needs of a growing population with PH. This has led to an extensive body of literature, ranging from case series to prospective, multicenter clinical trials, which will enhance the future of patient outcomes in PH. This contemporary review highlights the key articles in treatment updates for PH for the years 2013 to 2015., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) portrays a significant burden in terms of prevalence, morbidity, mortality, and health care costs. There is a lack of consensus on the basic pathophysiology, definition, and therapeutic targets for therapy for this syndrome. To date, there are no approved therapies available for reducing mortality or hospitalization for these patients. Several clinical trials have recently started to try and bridge this major gap. There is an urgent need to focus on drug and device development for HFpEF as well as to understand HFpEF pathophysiology.

Purpose of Review: Pulmonary hypertension associated with left heart disease is the most commonly encountered form of pulmonary hypertension and is associated with a poor prognosis. As the global burden of heart failure grows, this associated disease can be a major impediment to those patients undergoing cardiac transplantation, given its association with post-transplant right ventricular failure. Unfortunately, the pathophysiology of pulmonary hypertension secondary to left heart failure remains poorly understood, thereby rendering targeted treatment strategies largely undefined. In this review, we provide a review of the currently available literature in this unique patient population., Recent Findings: The current focus on better defining the underlying pathophysiology and standardizing diagnostic and therapeutic approaches to pulmonary hypertension associated with left heart disease need to be interpreted and made applicable in the context of clinical practice. Given the relative paucity of successful, targeted pharmacological options, there is an increasing evidence that device-based therapies, used in conjuncture with medical therapy, may help in lowering the pulmonary pressures by causing sustained left ventricular unloading., Summary: Pulmonary hypertension in the context of left heart disease is the most common form of pulmonary hypertension encountered in clinical practice and is associated with worse prognosis in patients being considered for cardiac transplantation. Therapies targeting left ventricular unloading, as well as pulmonary vascular remodeling, are being increasingly studied and used in daily practice.

Existing risk assessment tools for patient selection for left ventricular assist devices (LVADs) such as the Destination Therapy Risk Score and HeartMate II Risk Score (HMRS) have limited predictive ability. This study aims to overcome the limitations of traditional statistical methods by performing the first application of Bayesian analysis to the comprehensive Interagency Registry for Mechanically Assisted Circulatory Support dataset and comparing it to HMRS. We retrospectively analyzed 8,050 continuous flow LVAD patients and 226 preimplant variables. We then derived Bayesian models for mortality at each of five time end-points postimplant (30 days, 90 days, 6 month, 1 year, and 2 years), achieving accuracies of 95%, 90%, 90%, 83%, and 78%, Kappa values of 0.43, 0.37, 0.37, 0.45, and 0.43, and area under the receiver operator characteristic (ROC) of 91%, 82%, 82%, 80%, and 81%, respectively. This was in comparison to the HMRS with an ROC of 57% and 60% at 90 days and 1 year, respectively. Preimplant interventions, such as dialysis, ECMO, and ventilators were major contributing risk markers. Bayesian models have the ability to reliably represent the complex causal relations of multiple variables on clinical outcomes. Their potential to develop a reliable risk stratification tool for use in clinical decision making on LVAD patients encourages further investigation.

Management for continuous flow left ventricular assist device (LVAD) thrombosis often relies on speculation of individual clinical risk factors and integration of indirect evidence for device dysfunction. There are no comprehensive guidelines for treatment of this serious complication, and most of our current knowledge comes from anecdotal experience or observational study. More data on effective treatment, both with aggressive pharmacologic and device-based interventions, are needed for improving our understanding of mechanisms driving device thrombosis and for preventing future events. We present a case of LVAD thrombosis with emphasis on recognition and treatment of acute pump thrombosis, and discuss a potentially novel strategy using percutaneous mechanical circulatory support for pump salvage.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of HF-related morbidity and mortality, with no medical therapy proven to modify the underlying disease process and result in improvements in survival. With long-standing pulmonary venous congestion, a majority of HFpEF patients develop pulmonary hypertension (PH). Elevated pulmonary pressures have been shown to be a major determinant of mortality in this population. Given the paucity of available disease-modifying therapies for HFpEF, there has been a considerable interest in evaluating new therapeutic options specifically targeting PH in this patient population.

Heart failure (HF) is a growing problem in the USA and other industrialized nations. HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) each make up approximately half of the overall HF burden. Although a variety of medical and surgical therapies exist for the treatment of patients with HFrEF, morbidity and mortality remain high, and cardiac transplantation, considered the current gold standard for patients with HFrEF and severe symptoms, is reserved for relatively few eligible patients. Patients with HFpEF have more limited therapeutic options, because no medical therapy to date has been shown to improve survival in these patients. With the rising prevalence of HF and its increasing role in health care expenditure, there is a substantial need for new drug and device therapies for HFrEF and, in particular, HFpEF. This forms the topic of the current review.

The endothelin pathway is a key pathway for the pathogenesis of pulmonary arterial hypertension (PAH). Antagonism of this pathway is recommended as initial therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and inflammation caused by endothelin. Prior to October 2013, ambrisentan, a selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were the only currently available agents for PAH targeting the endothelin pathway. Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit®), a new ETA/ETB antagonist, has been US FDA approved to delay disease progression and reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event-driven strategy with a composite primary end point of morbidity or mortality. Previous trials have focused on short-term outcomes, such as improved 6-min walk distance and WHO functional class.

Novel treatment of congestive heart failure (HF) involves utilizing unique pathways to improve upon contemporary therapies. Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Preclinical studies suggest a favorable myocardial effect of PDE5 inhibitors by blocking adrenergic, hypertrophic and pro-apoptotic signaling, thereby supporting their use in HF. The clinical benefits of acute and chronic PDE5 inhibition on lung diffusion capacity, exercise performance and ejection fraction in humans are emerging and appear promising. Larger, controlled trials are now on-going to assess the safety, efficacy and tolerability of PDE5 inhibitors on morbidity and mortality in patients with both systolic and diastolic heart failure. If the results of these trials are positive, a new avenue for the treatment of HF will open, which will help curtail the societal effects of this costly and morbid disease.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially life-threatening condition characterized by obstruction of pulmonary arterial vasculature by acute or recurrent thromboemboli with subsequent organization, leading to progressive pulmonary hypertension and right heart failure. Until relatively recently, CTEPH was a diagnosis made primarily at autopsy, but advances made in diagnostic modalities and surgical pulmonary endarterectomy techniques have made this disease treatable and even potentially curable. Although published guidelines are available, in the absence of randomized controlled trials regarding CTEPH there is a lack of standardization, and treatment options have to be individualized., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Ovarian vein thrombosis (OVT) is a relatively uncommon but serious postpartum complication. Although infrequent, OVT may progress to involve the inferior vena cava, the renal vein or may cause sepsis and septic pulmonary embolism, all of which are potentially life-threatening. Clinical misdiagnosis is common, and, unfortunately, most affected women undergo laparotomy for possible appendicitis. We present an interesting case of OVT presenting as ureteral obstruction in a postpartum woman who was in her early 20s. Knowledge of this entity and clinical suspicion for its occurrence, in a puerperal patient with fever and abdominal pain not responding to antibiotics, should guide clinicians to appropriate diagnosis and treatment, avoiding misdiagnosis, unnecessary laparotomy and potential complications.

Incidence of sudden cardiac death (SCD) in end-stage renal disease (ESRD) remains high. Limited data is available about whether implantable cardioverter-defibrillators (ICDs) can prevent arrhythmic death in patients with chronic kidney disease (CKD). The purpose of this retrospective study was to determine the impact of CKD on all-cause and sudden cardiac death in ICD recipients. We evaluated 441 consecutive patients who underwent ICD implantation at our center between 1994 and 2002. We found that mortality rate was higher in patients with eGFR <60 mL/min and those with ESRD on hemodialysis (43%, n = 69/162 and 54%, n = 12/22, resp.) than in patients with eGFR >/=60 mL/min (23%, n = 58/257; P < .0005). The SCD rate was also higher in the patients with ESRD (50%) than in CKD patients not on dialysis (10.2%; P < .0005). Mortality rate for single-chamber ICDs was 56.8% in comparison with dual-chamber ICDs (38.1%) and for biventricular ICDs (5.0%) (P < .0005).

Epinephrine is indicated for various medical emergencies, including cardiac arrest and anaphylaxis, but the dose and route of administration are different for each indication. For anaphylaxis, it is given intramuscularly at a low dose, whereas for cardiac arrest a higher dose is required intravenously. We encountered a patient with suspected anaphylaxis who developed transient severe systolic dysfunction because of inappropriately received cardiac arrest dose, ie, larger dose given as an intravenous push. Three additional patients who experienced potentially lethal cardiac complications after receiving inappropriately higher doses intravenously were also identified. These iatrogenic errors resulted from underlying confusion by physicians about proper dosing of epinephrine for anaphylaxis. The risk of error was amplified by the need for rapid decision making in critically ill anaphylactic patients. An e-mail survey of local hospitals in southeast Michigan revealed that 6 of 7 hospitals did not stock prefilled intramuscular dose syringes for emergency use in anaphylaxis. At our institution, we have introduced prefilled and appropriately labeled intramuscularly dosed epinephrine syringes in crash carts, which are easily distinguished from intravenously dosed epinephrine syringes. In this Concepts article, we describe the clinical problem of inadvertent epinephrine overdose and propose a potential solution. Epinephrine must be clearly packaged and labeled to avoid inappropriate usage and unnecessary, potentially lethal complications in patients with anaphylaxis., (Copyright (c) 2009 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

As opposed to iatrogenic coronary dissection, spontaneous dissection is an extremely rare clinical condition. Typically seen in a single coronary vessel of peripartum women presenting with acute coronary syndrome, there are isolated case reports of men presenting multivessel involvement for this life-threatening condition. We describe a 54-year-old male with a history of diabetes, hypertension and methamphetamine abuse who presented to the emergency after a brief, witnessed cardiac arrest. Admission ECG revealed sinus tachycardia with inferior Q waves. He was found to have frequent runs of non-sustained ventricular tachycardia and minimal troponin-T elevation. His 2-D echocardiogram showed apical akinesis with an ejection fraction of 50%. Cardiac catheterization revealed a patent left main artery with a spontaneous dissection involving the mid to distal LAD artery, as well as large first diagonal branch with proximal dissection. His dominant RCA also showed long spontaneous dissection extending from proximal to distal vessel, along with distal focal 90% atherosclerotic lesion. Ramus intermedius and left circumflex vessels were free of disease. The patient underwent a 2-vessel coronary artery bypass grafting (CABG) with excellent outcome. Although cocaine abuse has been known to be associated with spontaneous dissection, this is the first reported case of a methamphetamine user presenting with multivessel coronary dissection.

We present a 17-y-old male who presented to the emergency room with left arm weakness along with slurred speech. On physical examination, he had stable vital signs with left facial weakness suggestive of lower motor neuron seventh nerve palsy. He was also noted to have a small pulsatile mass in the right infraclavicular region. Further questioning revealed that 3 mo earlier he had suffered blunt chest wall trauma during a football game with fracture-dislocation of the right clavicular head, which was managed conservatively. MRI of the brain showed right frontal cortical changes suggestive of infarct versus vasculitis or edema. Chest CT revealed a 2.5- to 3-cm pseudoaneurysm arising from the brachiocephalic artery, with thrombus formation, along with a surrounding 3 x 4.5 cm hematoma. The patient underwent a successful repair of the pseudoaneurysm with no further neurological sequelae. Traumatic pseudoaneurysm with thrombus formation is an extremely rare cause of stroke. It has been reported in association with the carotid artery, but to our knowledge, this is the first reported case with isolated innominate artery pseudoaneurysm. This case highlights the need for a broad differential when evaluating young patients with neurological deficits.

Primary tumors of the heart are rare, with an incidence between 0.0017 and 0.19 percent in unselected patients at autopsy. About three-quarters of these tumors are benign, and nearly half of these benign tumors are myxomas. First described in 1845, myxomas were diagnosed posthumously until the 1950s. The clinical features are determined by their size, locations and mobility. Embolism occurs in one-third of patients, but it is rare for patients to initially present with multiple, simultaneous widespread emboli.

Background: The 2003 Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) recommend the initiation of antibiotic therapy within 4 h of hospitalization. This quality indicator has been linked to the incentive compensation of third-party payers to hospitals. We evaluated the impact of this recommendation on the diagnosis of CAP and the utilization of antibiotics., Methods: All patients with a hospital admission diagnosis of CAP before publication of the guidelines (January to June 2003) and after publication of the guidelines (January-June 2005) were included. We collected data on clinical signs and symptoms on presentation, chest radiograph findings, blood cultures prior to therapy with antibiotics, time to antibiotic administration, pneumonia severity index (PSI) score, confusion, urea, respiratory rate, BP, and age >or= 65 years (CURB-65), and mortality., Results: A total of 518 patients were included in the study. More patients in 2005 had a hospital admission diagnosis of CAP without radiographic abnormalities compared to 2003 (2005, 91 patients [28.5%]; 2003, 41 patients [20.6%]; p = 0.04), and more patients received antibiotics within 4 h of triage (2005, 210 patients [65.8%]; 2003, 107 patients [53.8%]; p = 0.007). Blood cultures prior to antibiotic administration increased (2005, 220 patients [69.6%]; 2003, 93 patients [46.7%]; p < 0.001). However, the final diagnosis of CAP dropped to 58.9% in 2005 from 75.9% in 2003 (p < 0.001). The mean (+/- SD) antibiotic utilization per patient increased to 1.66 +/- 0.54 in 2005 compared to 1.39 +/- 0.58 in 2003 (p < 0.001). There were no significant differences in PSI or CURB-65 scores, or mortality., Conclusions: Linking antibiotic administration within 4 h of hospital admission (as a quality indicator) to financial compensation may result in an inaccurate diagnosis of CAP, inappropriate utilization of antibiotics, and thus less than optimal care.