External assessment of the EUROMACS right-sided heart failure risk score.

The EUROMACS Right-Sided Heart Failure Risk Score was developed to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. The predictive ability of the EUROMACS score has not been tested in other cohorts. We performed a single center analysis of a continuous-flow (CF) LVAD cohort (n = 254) where we calculated EUROMACS risk scores and assessed for right ventricular heart failure after LVAD implantation. Thirty-nine percent of patients (100/254) had post-operative RVF, of which 9% (23/254) required prolonged inotropic support and 5% (12/254) required RVAD placement. For patients who developed RVF after LVAD implantation, there was a 45% increase in the hazards of death on LVAD support (HR 1.45, 95% CI 0.98-2.2, p = 0.066). Two variables in the EUROMACS score (Hemoglobin and Right Atrial Pressure to Pulmonary Capillary Wedge Pressure ratio) were not predictive of RVF in our cohort. Overall, the EUROMACS score had poor external discrimination in our cohort with area under the curve of 58% (95% CI 52-66%). Further work is necessary to enhance our ability to predict RVF after LVAD implantation.

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy.

AIMS: To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. CONCLUSION: The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP.

Actual state of "triple therapy" for heart failure patients in eight regions of Japan: An analysis of a nationwide medical claims database.

BACKGROUND: This study aimed to collect data on "triple therapy" for heart failure (HF) with angiotensin-converting enzyme inhibitors (or receptor blockers), ß-blockers, and mineralocorticoid receptor antagonists in all eight regions of Japan and clarify the reason for the selection of this therapeutic approach. METHODS AND RESULTS: We used data from April 2017 to March 2018 from the Medical Data Vision database (380 facilities) to analyze factors impacting triple therapy for HF. Among patients who were hospitalized for HF during the study period, 51,933 patients met the inclusion criteria and underwent further analyses. A reference value of 20.45% from Kanto was used to compare the eight Japanese regions. From the patient cohort, 10,006 (19.27%) patients receiving triple therapy were identified. The highest and lowest rates of triple therapy were in Chugoku (21.90%) and Shikoku (14.27%), respectively, suggesting regional differences in the use of triple therapy at discharge for patients with HF (P < 0.001). Regression analysis revealed a decrease in the administration of triple therapy for patients with chronic kidney disease (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.43-0.48]; P < 0.001), those aged 75 years and older (OR, 0.46, 95% CI: 0.44-0.49; P < 0.001), those from Shikoku (OR, 0.69; 95% CI, 0.60-0.80; P < 0.001), those with chronic obstructive pulmonary disease (OR, 0.75; 95% CI, 0.68-0.84; P < 0.001), those with anemia (OR, 0.78; 95% CI, 0.62-0.98; P = 0.034), and those from Tohoku (OR, 0.83; 95% CI, 0.75-0.92; P < 0.001). CONCLUSIONS: Future efforts to rectify the regional variance in drug therapy conforming to the guidelines for the treatment of acute and chronic HF will help to extend the healthy lifespans of patients with HF. Further clarification is required to determine instances where triple therapy should be avoided based on patient factors, and appropriate countermeasures should be identified.

Galectins for Diagnosis and Prognostic Assessment of Human Diseases: An Overview of Meta-Analyses.

An increasing number of studies have explored the activities and functions of galectins. However, translation of these researches into clinical practice seems to be lacking. As compared to scattered individual studies, meta-analyses can provide a more comprehensive review of current evidence and reach a more unbiased and powered conclusion by synthesizing data from diverse studies. In this paper, findings from meta-analyses were reviewed to establish the role of galectins in diagnosis and prognostic assessment of various human diseases. First, in patients with cancer, galectin-1 expression is often associated with poorer survival, but galectin-9 expression is associated with better survival. Galectin-3 is a diagnostic biomarker for thyroid cancer and a predictor of worse survival in patients with colorectal cancer and improved survival in patients with gastric cancer. Second, galectin-3 is useful for diagnosis and prognostic assessment of heart failure and prediction of atrial fibrillation and its recurrence. Third, in chronic kidney disease, galectin-3 is valuable for predicting poor survival. Fourth, during pregnancy, galectin-13 is potentially helpful for identifying patients who do not have preeclampsia.

Cardiac Resynchronization Therapy for Improving Non-Uniform Thickening of Left Ventricular Wall: Assessment by Quantitative Gated Myocardial Perfusion SPECT.

Cardiac resynchronization therapy (CRT) improves cardiac dyssynchrony in heart failure patients with a wide QRS electrocardiogram (ECG). Assessment of left ventricular (LV) dyssynchrony using echocardiography or other imaging modalities is important to predict CRT effectiveness. In this study, we retrospectively evaluated cardiac nuclear imaging of ECG-gated myocardial perfusion single-photon emission computed tomography (SPECT) with 99mTc-sestamibi for CRT candidate (n = 120) with severe heart failure and wide QRS (> 120 msec) in ECG. To analyze LV non-uniformity, we used the quantitative gated SPECT (QGS) software to calculate changes in regional LV wall thickness during a cardiac cycle (i.e., wall thickening scores). Cardiac events (heart failure, ventricular arrhythmias and cardiac death) after CRT during 38 ± 22 (SD) months were also evaluated. In 97 of 120 patients who underwent QGS before and 6 months after CRT, CRT homogenized non-uniform wall thickening between septal and lateral of the LV especially in CRT responders. This observation was indicated as increase in the lateral deflection (XWT) of wall thickening scores before CRT and its decrease after CRT. In 120 patients with QGS before CRT, the larger XWT before CRT (≥ 16.5) predicted better prognoses after CRT. This finding was similarly observed even in patients with narrower baseline QRS (≤ 140 msec; n = 41 of 120), who usually have less benefits from CRT. In conclusion, CRT improved non-uniformity of wall thickening between the LV septal and lateral regions evaluated using QGS, which is predictive of better prognosis in the chronic phase after CRT.

Diffuse idiopathic skeletal hyperostosis in subjects with congestive heart failure undergoing cardiac rehabilitation: A decision tree analysis.

OBJECTIVE: To assess the prevalence of diffuse idiopathic skeletal hyperostosis and its relationship with vascular risk factors among patients with congestive heart failure. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 584 consecutive patients admitted to a Rehabilitative Cardiology Unit. METHODS: Chi-square Automatic Interaction Detector (CHAID) decision tree analysis was used to build a predictive model. RESULTS: The mean age (standard deviation) of the study population was 68.1 years (standard deviation 12.3), and 77.7% of the subjects were men. The overall prevalence of diffuse idiopathic skeletal hyperostosis in the cohort was 49.8%. Logistic regression analysis showed that age was a predictor of diffuse idiopathic skeletal hyperostosis (odds ratio: 1.034; 95% confidence interval 1.021-1.047, p < 0.001), with increasing odds ratios for increasing age tertiles. The CHAID prediction model identified 2 age "buckets": < 69 and ≥ 69 years. Patients ≥ 69 years had a diffuse idiopathic skeletal hyperostosis prevalence of 60.1%, compared with 39.2% among those < 69 years. Notably, body mass index was a predictor of diffuse idiopathic skeletal hyperostosis in this younger subset of patients (p = 0.028), with 2 body mass index "buckets", ≤ 23.3 and > 23.3 kg/m2, the latter showing more than twice the prevalence of diffuse idiopathic skeletal hyperostosis (43.2% vs 20%). CONCLUSION: Diffuse idiopathic skeletal hyperostosis is extremely frequent among patients with congestive heart failure, with age and body mass index being the strongest predictors.

Planejamento e desenvolvimento de ligantes não peptídicos com atividade agonista enviesada no receptor de angiotensina II tipo 1 empregando-se técnicas de modelagem molecular e ensaios in vitro / Drug design of non-peptidic biased agonists for angiotensin II type 1 receptor using molecular modeling techniques and in vitro tests

A insuficiência cardíaca (IC) é uma síndrome de elevada morbimortalidade, correspondendo a um grave problema de saúde pública. Uma das abordagens terapêuticas para IC consiste no uso de antagonistas do receptor de angiotensina II do tipo 1 (AT1R), conhecidos como sartanas. Estudos apontam que uma nova classe de compostos, os agonistas enviesados, é capaz de induzir a sinalização da via da ß-arrestina sem ativação da via da proteína G. Essa seletividade funcional é particularmente interessante, pois a via dependente da proteína G é responsável pelo aumento da pressão arterial, morte celular e fibrose tecidual, levando a hipertrofia cardíaca e progressão da IC. No entanto, a via da ß-arrestina está associada com renovação celular e aumento do inotropismo. Além disso, estudos in vivo sugerem que agonistas enviesados poderiam corresponder a uma terapia superior à dos antagonistas convencionais, que bloqueiam ambas as vias. Apesar do potencial terapêutico, esses compostos possuem estrutura peptídica e, por isso, tem sua administração restrita à via intravenosa. A resolução da estrutura cristalográfica do AT1R permitiu estudos de modelagem molecular mais acurados. Tendo isso em mente, nesse trabalho foram propostos agonistas enviesados de natureza não peptídica para o AT1R por meio de técnicas de modelagem molecular e validação das hipóteses levantadas por ensaios in vitro. Foram realizados estudos de dinâmica molecular com o AT1R (PDB ID: 4YAY) em uma bicamada lipídica e ensaios de ancoramento molecular da angiotensina II (AngII) e do ligante enviesado TRV027. As poses de ancoramento molecular selecionadas foram utilizadas em dinâmicas de complexo, que revelaram diferenças entre os sistemas apo (sem nenhum ligante) e holo (com o ligante no sitio de ligação). Nossos resultados sugerem que o TRV027 induz um padrão exclusivo de ligações de hidrogênio e de estrutura secundária, enquanto que a AngII afeta os resíduos do bolso hidrofóbico do sitio de ligação, principalmente a conformação do Trp2536.48. Com base nas simulações, três farmacóforos foram criados e utilizados de maneira complementar em triagens virtuais na base de dados ZINC15, resultando na seleção de cinco compostos. Um desses compostos apresentou afinidade pelo receptor AT1R e, ainda que estudos complementares de ativação de vias especificas sejam necessários para que o composto possa ser classificado como agonista enviesado, já se constitui em molécula potencialmente promissora. Além disso, esses estudos permitiram a proposição de estruturas inéditas que podem vir a ser hits no processo de desenvolvimento de agonistas enviesados para AT1R. Portanto, como continuidade desse trabalho, essas moléculas serão sintetizadas e investigadas quanto à possível interação com o receptor.

Heart Failure (HF) is a common syndrome with high morbimortality, being considered a serious public health problem. One of the therapeutic approaches for HF consists in the use of the sartan class, which are angiotensin II type 1 receptor (AT1R) antagonists. Recent studies have shown that a new class of compounds, known as biased agonists, is able to induce signaling via ß-arrestin without G-protein activation. This functional selectivity is particularly interesting since G-protein dependent signaling is responsible for cell death and cardiac tissue fibrosis, which leads to cardiac muscle hypertophy and HF progression. On the other hand, ß-arrestin signaling is associated with cellular renewal and increased inotropism. In vivo studies suggests that biased agonists could correspond to a superior therapy over conventional angiotensin II type 1 receptor antagonists, which blocks cell signaling as a whole, however their peptidic structure restricts their use to intravenous administration. Moreover, the AT1R crystal structure determination holds great promise for more accurate molecular modeling studies. With that being said, the aim of this work was to plan and develop new non-peptidic biased agonists for ATR1 employing molecular modeling techniques and in vitro tests for hypothesis validation. Molecular dynamics (MD) simulations of the refined AT1R crystal (PDB ID: 4YAY) embedded in a lipid bilayer and molecular docking studies with angiotensin II (AngII) and TRV027 (biased agonist) were conducted. Selected docking poses from both ligands underwent complex MD simulations revealing differences between apo (ligand free) and holo (ligand in the binding site) systems. Our results suggest that TRV027 induces an exclusive hydrogen bond and secondary structure pattern, while AngII affects the hydrophobic pocket conformation, mainly Trp253. Based on the simulations, three pharmacophore models were created and used in virtual screenings in the ZINC15 database, resulting in the selection of five compounds that were tested in vitro. One of the compounds displayed affinity for AT1R and is a promising molecule. Nonetheless, it needs further pathway activation characterization in order to be a classified as a biased agonist. Furthermore, these results have contributed significantly for the proposition of new structures that could be hits with biased agonist activity for AT1R. Thus, for future works, we point out the necessity for synthesis and characterization of this new compounds

Endomyocardial Fibrosis: an Update After 70 Years.

PURPOSE OF REVIEW: This review aims at highlighting the need to better understand the pathogenesis and natural history of endomyocardial fibrosis when set against its changing endemicity and disease burden, improvements in diagnosis, and new options for clinical management. RECENT FINDINGS: Progress in imaging diagnostic techniques and availability of new targets for drug and surgical treatment of heart failure are contributing to earlier diagnosis and may lead to improvement in patient survival. Endomyocardial fibrosis was first described in Uganda by Davies more than 70 years ago (1948). Despite its poor prognosis, the etiology of this neglected tropical restrictive cardiomyopathy still remains enigmatic nowadays. Our review reflects on the journey of scientific discovery and construction of the current guiding concepts on this mysterious and fascinating condition, bringing to light the contemporary knowledge acquired over these years. Here we describe novel tools for diagnosis, give an overview of the improvement in clinical management, and finally, suggest research themes that can help improve patient outcomes focusing (whenever possible) on novel players coming into action.

In-hospital cardiopulmonary resuscitation of patients with cirrhosis: A population-based analysis.

OBJECTIVE: To examine the epidemiology and outcomes of in-hospital cardiopulmonary resuscitation (CPR) among patients with cirrhosis. METHODS: We used the Texas Inpatient Public Use Data File to identify hospitalizations aged ≥ 18 years with and without cirrhosis during 2009-2014 and those in each group who have undergone in-hospital CPR. Short-term survival (defined as absence of hospital mortality or discharge to hospice) following in-hospital CPR was examined. Multivariate logistic regression modeling was used to assess the prognostic impact of cirrhosis following in-hospital CPR and predictors of short-term survival among cirrhosis hospitalizations. RESULTS: In-hospital CPR was reported in 2,511 and 51,969 hospitalizations with and without cirrhosis, respectively. The rate of in-hospital CPR (per 1,000 hospitalizations) was 7.6 and 4.0 among hospitalizations with and without cirrhosis, respectively. The corresponding rate of in-hospital CPR among decedents was 10.7% and 13.4%, respectively. Short-term survival following in-hospital CPR among hospitalizations with and without cirrhosis was 14.9% and 27.3%, respectively, and remained unchanged over time on adjusted analyses among the former (p = 0.1753), while increasing among the latter (p = 0.0404). Cirrhosis was associated with lower odds of short-term survival following in-hospital CPR (adjusted odds ratio [aOR] 0.55 [95% CI: 0.49-0.62]). Lack of health insurance (vs. Medicare) (aOR] 0.47 [95% CI: 0.34-0.67]) and sepsis ([aOR] 0.67 [95% CI: 0.53-85]) were associated with lower odds of short-term survival following in-hospital CPR among cirrhosis hospitalizations. CONCLUSIONS: The rate of in-hospital CPR was nearly 2-fold higher among hospitalizations with cirrhosis than among those without it, though it was used more selectively among the former. Short-term survival following in-hospital CPR remained markedly lower among cirrhosis hospitalizations, while progressively improving among those without cirrhosis. Strategies to increase access to health insurance and improve early identification and control of infection should be explored in future preventive and interventional efforts.

A comparison of two quasi-static computational models for assessment of intra-myocardial injection as a therapeutic strategy for heart failure.

Myocardial infarction, or heart attack, is the leading cause of mortality globally. Although the treatment of myocardial infarct has improved significantly, scar tissue that persists can often lead to increased stress and adverse remodeling of surrounding tissue and ultimately to heart failure. Intra-myocardial injection of biomaterials represents a potential treatment to attenuate remodeling, mitigate degeneration, and reverse the disease process in the tissue. In vivo experiments on animal models have shown functional benefits of this therapeutic strategy. However, a poor understanding of the optimal injection pattern, volume, and material properties has acted as a barrier to its widespread clinical adoption. In this study, we developed two quasistatic finite element simulations of the left ventricle to investigate the mechanical effect of intra-myocardial injection. The first model employed an idealized left ventricular geometry with rule-based cardiomyocyte orientation. The second model employed a subject-specific left ventricular geometry with cardiomyocyte orientation from diffusion tensor magnetic resonance imaging. Both models predicted cardiac parameters including ejection fraction, systolic wall thickening, and ventricular twist that matched experimentally reported values. All injection simulations showed cardiomyocyte stress attenuation, offering an explanation for the mechanical reinforcement benefit associated with injection. The study also enabled a comparison of injection location and the corresponding effect on cardiac performance at different stages of the cardiac cycle. While the idealized model has lower fidelity, it predicts cardiac function and differentiates the effects of injection location. Both models represent versatile in silico tools to guide optimal strategy in terms of injection number, volume, site, and material properties.

Management of Iron Deficiency in Heart Failure.

Anemia is a common finding in patients with heart failure (HF). The cause for anemia is multifactorial, with iron deficiency being the most common cause. Anemia with HF is an established predictor of morbidity and mortality. Iron deficiency in systolic HF, even without anemia, has been associated with increased mortality, increased hospitalizations, and decreased functional capacity and quality of life measures. Data from several randomized controlled trials and meta-analyses of iron deficiency and systolic HF show a beneficial effect for intravenous (IV) iron in terms of quality of life and functional capacity (improvements in 6-min walk test, and improvements in New York Heart Association functional class), as well as decreased hospitalizations for HF and reduction in cardiovascular mortality rates. Limited evidence exists for a beneficial effect of IV iron in diastolic dysfunction. Patients with symptomatic systolic HF should undergo an anemia diagnostic work-up. When iron deficiency (defined as ferritin <100 ng/mL or serum ferritin 100-299 ng/mL and transferrin saturation <20%) is present, current evidence supports treating HF patients with iron deficiency with IV iron.

Application of Telemedicine for the Control of Patients with Acute and Chronic Heart Diseases.

Introduction: Telemedicine (TM) has transformed the field of emergency cardiology, particularly the treatment of acute myocardial infarction (AMI). The ability to record an electrocardiogram (EKG) in the early prehospital phase, thus avoiding any delay in diagnosing myocardial infarction with direct transfer to the cath-lab for primary angioplasty, has proven to significantly reduce treatment times and mortality. Materials and Methods: We analyzed the available evidence and organizational models based on a support by TM in cardiology, including the applications of TM in cardiovascular disease based on a review of the literature. Results: The most important areas of application of TM in the field of cardiology are as follows: (1) Early prehospital diagnosis of AMI with EKG transmission; (2) Patient Remote control through wearable and devices; (3) Monitoring of patients with chronic heart failure; (4) Monitoring of patient's arrhythmias; and (5) Transmission of echo images to a III level center for a "second opinion". Conclusions: TM services should, therefore, be considered as a true diagnostic/therapeutic aspect of cardiovascular emergencies. It is necessary to educate medical staff and to provide a tempting environment for software engineers. Investing in infrastructure and equipment is imperative, as well as a positive climate for its implementation.

Relationship Between Noninvasive Assessment of Lung Fluid Volume and Invasively Measured Cardiac Hemodynamics.

Background Right heart catheterization is the gold standard in clinical practice for the assessment of cardiovascular hemodynamics, but it is an invasive procedure requiring expertise in both insertion and reading. Remote dielectric sensing (Re DS ) is a noninvasive electromagnetic-based technology intended to quantify lung fluid content. Methods and Results In this prospective single-center study, Re DS readings were obtained in supine position just before right heart catheterization procedure in patients with heart failure. Agreement between Re DS and pulmonary artery wedge pressure ( PAWP ) was analyzed. Of all, 139 patients with heart failure received hemodynamic assessment and Re DS measurement. A good correlation was found between Re DS and PAWP measurement ( r=0.492, P<0.001). Receiver operating characteristic analysis of the ability to identify a PAWP ≥18 mm Hg resulted in a Re DS cutoff value of 34%, with an area under the curve of 0.848, a sensitivity of 90.7%, and a specificity of 77.1%. Overall, Re DS <34% carries a high negative predictive value of 94.9%. Conclusions Lung fluid content, as measured by Re DS , correlates well with PAWP . The high sensitivity and specificity and especially the high negative predictive value make Re DS a reliable noninvasive tool at the point of care, to rule out elevated PAWP in patients with heart failure and to help with medical management of patients with heart failure. Further studies are warranted to compare this tool with existing tests and to relate the findings to the clinical outcomes.

Healthcare Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study.

BACKGROUND: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial's 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. METHODS: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non-device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. RESULTS: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P=0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P=0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P<0.001) and stroke (HM3: 2.8% versus HMII: 11.3%; P=0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P<0.001) and similar in either bridge to transplant or destination therapy intent. CONCLUSIONS: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

Cost-effectiveness of a transitional home-based palliative care program for patients with end-stage heart failure.

BACKGROUND: Studies have shown positive clinical outcomes of specialist palliative care for end-stage heart failure patients, but cost-effectiveness evaluation is lacking. AIM: To examine the cost-effectiveness of a transitional home-based palliative care program for patients with end-stage heart failure patients as compared to the customary palliative care service. DESIGN: A cost-effectiveness analysis was conducted alongside a randomized controlled trial (Trial number: NCT02086305). The costs included pre-program training, intervention, and hospital use. Quality of life was measured using SF-6D. SETTING/PARTICIPANTS: The study took place in three hospitals in Hong Kong. The inclusion criteria were meeting clinical indicators for end-stage heart failure patients including clinician-judged last year of life, discharged to home within the service area, and palliative care referral accepted. A total of 84 subjects (study = 43, control = 41) were recruited. RESULTS: When the study group was compared to the control group, the net incremental quality-adjusted life years gain was 0.0012 (28 days)/0.0077 (84 days) and the net incremental costs per case was -HK$7935 (28 days)/-HK$26,084 (84 days). The probability of being cost-effective was 85% (28 days)/100% (84 days) based on the cost-effectiveness thresholds recommended both by National Institute for Health and Clinical Excellence (£20,000/quality-adjusted life years) and World Health Organization (Hong Kong gross domestic product/capita in 2015, HK$328117). CONCLUSION: Results suggest that a transitional home-based palliative care program is more cost-effective than customary palliative care service. Limitations of the study include small sample size, study confined to one city, clinic consultation costs, and societal costs including patient costs and unpaid care-giving costs were not included.

'The importance of planning for the future': Burden and unmet needs of caregivers' in advanced heart failure: A mixed methods study.

BACKGROUND: While studies have evaluated caregiver outcomes in heart failure, the burden and support needs when caring for someone with advanced heart failure at the end of life have yet to be outlined. AIM: To identify psychosocial factors associated with caregiver burden and evaluate the support needs of caregivers in advanced heart failure. DESIGN: A sequential mixed methods study comprising two phases: (1) postal survey with advanced heart failure patients and their caregivers and (2) interviews with current and bereaved caregivers. Correlation, chi-square, t test, regression and thematic analysis were undertaken on the data. PARTICIPANTS: Advanced heart failure patients ( n = 112) and their caregivers ( n = 84) were recruited from secondary care settings across the United Kingdom and Ireland. For phase 2 interviews, current caregivers ( n = 20) were purposively recruited from phase 1, and bereaved caregivers ( n = 10) were purposively recruited via voluntary organisation, social media and email. RESULTS: More than half the caregivers (53%) had levels of distress associated with depression (Zarit Burden score >24). Caregiver depression score, preparedness for caregiving and patients' depression score predicted caregiver burden. Qualitative analysis identified an overarching theme of lack of future care planning and four subthemes: (1) seeking emotional support from someone who understands, (2) want information on prognostication, (3) lack of knowledge on how to and where to get support and (4) require knowledge on what to expect at the end of life. CONCLUSION: Caregivers have unmet needs and feel unprepared for the future. Implementation of future care planning by clinical teams should address patient and caregiver support needs and in turn alleviate caregiver burden.

Paying for the Tolls: The High Cost of the Innate Immune System for the Cardiac Myocyte.

The cardiac myocyte differs strikingly from the specialized cells of the immune system, which has two different responses to invading organisms and tissue damage. Adaptive or acquired immunity generates highly specific antibodies in response to threats and is an essential component of immunity; however, adaptive immunity can take 4-7 days to mobilize, and a more primitive response, innate immunity, fills the gap. Innate immunity is expressed in complex and in primitive life forms. Specialized receptors, Toll-like receptors (TLRs), which are widely distributed throughout different tissues recognize danger signals and rapidly respond with the release of noxious substances, such as TNFα. The problem is that many endogenous molecules have been found to act as ligands for specific TLRs, and when these molecules are released into the extracellular environment, they can cause problems by activating innate immunity and an inflammatory response. In cardiac myocytes heat shock protein (HSP)60 can activate TLR4, as can HMGB1, and this type of response can amplify the response to ischemia/reperfusion leading to increased cell and tissue injury. Activation of TLRs can potentially amplify chronic, inflammatory diseases, such as ischemic heart failure. Thus, it is important to understand the regulation of the TLRs and their downstream effects. This chapter will focus on the TLRs and cardiac myocytes.

Role of Echocardiography in the Diagnostic Assessment and Etiology of Heart Failure in Older Adults: Opacify, Quantify, and Rectify.

Echocardiography allows the assessment of systolic and diastolic function and identifies many of the common causes of heart failure (HF). Patients with minimally symptomatic or unsuspected left ventricular systolic dysfunction may be identified and receive the benefits of angiotensin-converting enzyme inhibitor therapy. Echocardiography is also for assessing prognosis and can be used serially to evaluate treatment. Ventricular filling pressures, pulmonary artery pressures, and cardiac output can be sequentially determined. The authors believe that all patients with HF should receive careful assessment echocardiography. The authors believe using echocardiography is especially valuable in the elderly.

Functional status and quality of life among breast cancer survivors with heart failure: results of the Medicare Health Outcomes Survey.

PURPOSE: The purpose of this population-based study was to examine health-related quality of life (HRQOL) and functional status among breast cancer survivors with heart failure. METHODS: We examined Medicare Health Outcomes Survey data from women aged 65 and older diagnosed with breast cancer in the past 5 years. Surveys were linked to Surveillance, Epidemiology, and End Results cancer registries. Each woman identified with self-reported heart failure (n = 239) was matched to controls without heart failure (n = 685) using propensity scores. The Short Form-36/Veterans Rand-12 measured eight domains of HRQOL. Functional status impairment was measured by limitations in six activities of daily living (ADLs). Linear models estimated associations between heart failure status and HRQOL. Logistic regression models estimated odds ratios for associations between heart failure and ADL impairment. We examined associations for the total study population and subgroups stratified by cancer stage. RESULTS: Among all study participants, heart failure was associated with significant deficits in every HRQOL domain and impairment in all ADLs (p < 0.01, ORs ranged from 1.74 to 2.47). After stratification by cancer stage, heart failure was associated with physical HRQOL deficits across all cancer stages (physical function, vitality, general health) and mental HRQOL deficits only in women with stage I/II cancer (role-emotional, social function). Women with early stage cancer experienced the greatest HRQOL deficits associated with heart failure. CONCLUSIONS: Heart failure in breast cancer survivors is associated with substantial HRQOL deficits and functional status impairment, particularly in early stage cancer. Tailored interventions are needed to improve physical function and mental wellbeing in this high-risk population.