Heart Transplant: Current Indications and Patient Selection

Heart transplant remains the gold standard treatment for end-stage heart failure, in spite of the recent advances in pharmacological treatment and device therapy. As expected, since the first heart transplant was performed 50 years ago, outcomes in heart transplant have continued to improve over the last decades focusing on perioperative management, the availability of newer and better mechanical circulatory support before and after heart transplant and immunosuppressive drug development. Nonetheless, in the last years we have witnessed a significant drop in the heart donor’s pool as the greatest limiting factor, coupled with a rising number of advanced heart failure patients. Moreover, the difficulty in handling these patients, with multiple and more complex comorbidities, is continuously increasing. More importantly and despite these difficulties, conditional half-life in transplanted patients has nowadays reached 12 years of life expectancy. Thus, besides trying to increase donor numbers, candidate selection emerges as one of the most challenging issues for heart transplant programs. In this chapter we review the latest knowledge on indications for heart transplant, as well as the available screening and optimization tools in candidate selection in order to continue improving outcomes

Adaptation and Evaluation of the Nutrition Environment Measures Survey in Stores to Assess Mediterranean Food Environments (NEMS-S-MED)

The Nutrition Environment Measures Surveys are valid and reliable measures of community and consumer food environments. This article describes the adaptation and evaluation of the Nutrition Environment Measures Survey in Stores (NEMS-S) for Mediterranean urban contexts (NEMS-S-MED). Trained raters used the adapted NEMS-S-MED tool to observe and rate food outlets in 21 census tracts and 43 food stores across the city of Madrid, Spain. We evaluated inter-rater and intra-rater reliabilities, construct validity, and the tool’s ability to discriminate between store types and between stores by area-level Socio-Economic Status (SES). Overall, the mean NEMS-S-MED score was 20.7 (SD = 9.8), which ranged from 7 to 43. Most food items displayed substantial or almost perfect inter-rater and intra-rater agreements; the percentage agreement across availability items was almost perfect and kappa statistics were also very high (median κ = 1.00 for inter-rater; κ = 0.92 for intra-rater). Furthermore, the NEMS-S-MED tool was able to discriminate between store types and census tracts of different SES. The adapted NEMS-S-MED instrument is a reliable and valid audit tool to assess the consumer food environment in Mediterranean urban contexts. Well-constructed measurement tools, such as the NEMS-S-MED, may facilitate the development of effective policy interventions to increase healthy food access and affordability.A.M.-G. was funded by a predoctoral fellowship offered to trainee researchers from the University of Alicante (UAFPU2017-047). J.D. was supported by the Alicia Llácer grant for Young Epidemiologists (14th edition) awarded by the Spanish Society of Epidemiology. U.B. was supported by a grant from the Office of the Director of the National Institutes of Health under award number DP5OD26429. This study was funded by the European Research Council under the European Union’s Seventh Framework Program (FP7/2007–2013/ERC Starting Grant Heart Healthy Hoods Agreement no. 623 336893)

Adaptation and evaluation of the nutrition environment measures survey in stores to assess mediterranean food environments (Nems-s-med)

The Nutrition Environment Measures Surveys are valid and reliable measures of community and consumer food environments. This article describes the adaptation and evaluation of the Nutrition Environment Measures Survey in Stores (NEMS-S) for Mediterranean urban contexts (NEMS-S-MED). Trained raters used the adapted NEMS-S-MED tool to observe and rate food outlets in 21 census tracts and 43 food stores across the city of Madrid, Spain. We evaluated inter-rater and intra-rater reliabilities, construct validity, and the tool's ability to discriminate between store types and between stores by area-level Socio-Economic Status (SES). Overall, the mean NEMS-S-MED score was 20.7 (SD = 9.8), which ranged from 7 to 43. Most food items displayed substantial or almost perfect inter-rater and intra-rater agreements; the percentage agreement across availability items was almost perfect and kappa statistics were also very high (median κ = 1.00 for inter-rater; κ = 0.92 for intra-rater). Furthermore, the NEMS-S-MED tool was able to discriminate between store types and census tracts of different SES. The adapted NEMS-S-MED instrument is a reliable and valid audit tool to assess the consumer food environment in Mediterranean urban contexts. Well-constructed measurement tools, such as the NEMS-S-MED, may facilitate the development of effective policy interventions to increase healthy food access and affordability

Iron deficiency: impact on functional capacity and quality of life in heart failure with preserved ejection fraction

The effects of iron deficiency (ID) have been widely studied in heart failure (HF) with reduced ejection fraction. On the other hand, studies in HF with preserved ejection fraction (HFpEF) are few and have included small numbers of participants. The aim of this study was to assess the role that ID plays in functional capacity and quality of life (QoL) in HFpEF while comparing several iron-related biomarkers to be used as potential predictors. ID was defined as ferritin <100 ng/mL or transferrin saturation <20%. Submaximal exercise capacity, measured by the 6-min walking test (6MWT), and QoL, assessed by the Minnesotta Living with Heart Failure Questionnaire (MLHFQ), were compared between iron deficient patients and patients with normal iron status. A total of 447 HFpEF patients were included in the present cross-sectional study, and ID prevalence was 73%. Patients with ID performed worse in the 6MWT compared to patients with normal iron status (ID 271 ± 94 m vs. non-ID 310 ± 108 m, p < 0.01). They also scored higher in the MLHFQ, denoting worse QoL (ID 49 ± 22 vs. non-ID 43 ± 23, p = 0.01). Regarding iron metabolism biomarkers, serum soluble transferrin receptor (sTfR) was the strongest independent predictor of functional capacity (β = −63, p < 0.0001, R2 0.39) and QoL (β = 7.95, p < 0.0001, R2 0.14) in multivariate models. This study postulates that ID is associated with worse functional capacity and QoL in HFpEF as well, and that sTfR is the best iron-related biomarker to predict both. Our study also suggests that the effects of ID could differ among HFpEF patients by left ventricular ejection fractio

Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells

Background: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. Methods: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. Results: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. Conclusions: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF

Clinical Determinants and Prognosis of Left Ventricular Reverse Remodelling in Non-Ischemic Dilated Cardiomyopathy

Aims: Non-ischaemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of coronary artery disease. Left ventricular reverse remodelling (LVRR) is the ability of a dilated ventricle to restore its normal size, shape and function. We sought to determine the frequency, clinical predictors and prognostic implications of LVRR, in a cohort of heart failure (HF) patients with NIDCM. Methods: We conducted a multicentre observational, retrospective cohort study of patients with NIDCM, with prospective serial echocardiography evaluations. LVRR was defined as an increase of >= 15% in left ventricular ejection fraction (LVEF) or as a LVEF increase >= 10% plus reduction of LV end-systolic diameter index >= 20%. We used multivariable logistic regression analyses to identify the baseline clinical predictors of LVRR and evaluate the prognostic impact of LVRR. Results: LVRR was achieved in 42.5% of 527 patients with NIDCM during the first year of follow-up (median LVEF 49%, median change +22%), Alcoholic aetiology, HF duration, baseline LVEF and the absence of LBBB (plus NT-proBNP levels when in the model), were the strongest predictors of LVRR. During a median follow-up of 47 months, 134 patients died (25.4%) and 7 patients (1.3%) received a heart transplant. Patients with LVRR presented better outcomes, regardless of other clinical conditions. Conclusions: In patients with NIDCM, LVRR was frequent and was associated with improved prognosis. Major clinical predictors of LVRR were alcoholic cardiomyopathy, absence of LBBB, shorter HF duration, and lower baseline LVEF and NT-proBNP levels. Our study advocates for clinical phenotyping of non-ischaemic dilated cardiomyopathy and intense gold-standard treatment optimization of patients according to current guidelines and recommendations in specialized HF units

Therapeutic Management and Long-Term Outcome of Hy-Perthyroidism in Patients with Antithyroid-Induced Agranu-Locytosis: A Retrospective, Multicenter Study

Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/mu L) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously

Weight loss in obese patients with heart failure

BACKGROUND: In heart failure (HF), weight loss (WL) has been associated with an adverse prognosis whereas obesity has been linked to lower mortality (the obesity paradox). The impact of WL in obese patients with HF is incompletely understood. Our objective was to explore the prevalence of WL and its impact on long-term mortality, with an emphasis on obese patients, in a cohort of patients with chronic HF. METHODS AND RESULTS: Weight at first visit and the 1-year follow-up and vital status after 3 years were assessed in 1000 consecutive ambulatory, chronic HF patients (72.7% men; mean age 65.8±12.1 years). Significant WL was defined as a loss of ≥5% weight between baseline and 1 year. Obesity was defined as body mass index ≥30 kg/m(2) (N=272). Of the 1000 patients included, 170 experienced significant WL during the first year of follow-up. Mortality was significantly higher in patients with significant WL (27.6% versus 15.3%, P 0.001). In univariable Cox regression analysis, patients with significant WL had 2-fold higher mortality (hazard ratio 1.95 [95% CI 1.39-2.72], P 0.001). In multivariable analysis, adjusting for age, sex, body mass index, New York Heart Association functional class, left ventricular ejection fraction, HF duration, ischemic etiology, diabetes, and treatment, significant WL remained independently associated with higher mortality (hazard ratio 1.89 [95% CI 1.32-2.68], P 0.001). Among obese patients with HF, significant WL was associated with an even more ominous prognosis (adjusted hazard ratio for death of 2.38 [95% CI 1.31-4.32], P=0.004) than that observed in nonobese patients (adjusted hazard ratio 1.83 [95% CI 1.16-2.89], P=0.01). CONCLUSIONS: Weight loss ≥5% in patients with chronic HF was associated with high long-term mortality, particularly among obese patients with HF

Pulmonary vascular remodeling and prognosis in patients evaluated for heart transplantation: insights from the OCTOPUS-CHF study

[Abstract] Objective: In patients with advanced heart failure, the intravascular optical coherence tomography (OCT) of subsegmental pulmonary artery measurements is correlated with right heart catheterization parameters. Our aim was to study the prognostic value of pulmonary OCT, right heart catheterization data, and the echocardiographic estimation of pulmonary pressure in patients studied for elective heart transplants. Methods: This research is an observational, prospective, multicenter study involving 90 adults with a one-year follow-up. Results: A total of 10 patients (11.1%) died due to worsening heart failure before heart transplantation, 50 underwent a heart transplant (55.6%), and 9 died in the first year after the transplant. The patients with and without events (mortality or heart failure-induced hospitalization) had similar data regarding echocardiography, right heart catheterization, and pulmonary OCT (with a median estimated pulmonary artery systolic pressure of 42.0 mmHg, interquartile range (IQR) of 30.3-50.0 vs. 47.0 mmHg, IQR 34.6-59.5 and p = 0.79, median pulmonary vascular resistance of 2.2 Wood units, IQR 1.3-3.7 vs. 2.0 Wood units, IQR 1.4-3.2 and p = 0.99, and a median pulmonary artery wall thickness of 0.2 ± 0.5 mm vs. 0.2 ± 0.6 mm and p = 0.87). Conclusion: Pulmonary vascular remodeling (evaluated with echocardiography, right heart catheterization, and pulmonary OCT) was not associated with prognosis in a selected sample of adults evaluated for elective heart transplants. Pulmonary OCT is safe and feasible for the evaluation of these patients.Instituto de Salud Carlos III; PI18/00254European Regional Development Fund; CB16/11/0050