Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from ...the inner to the outer leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study, we have phenotypically and quantitatively characterised cEVs by flow cytometry, paying special attention to the proportions of PS in chronic heart failure patients (cHF;
= 119) and a reference non-HF group (
= 21). PS
-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on the PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS
-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS
and were increased in the non-HF group. We observed similar levels of PS
- and PS
-cEVs in non-HF subjects when analysing immune cell-derived Evs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45
, CD29
, CD11b
, and CD15
were mainly PS
-cEVs, while those carrying CD14
, CD3
, and CD56
were mainly PS
-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients, as detected by a high shedding of cEVs. Despite PS
-cEVs and PS
-cEVs representing two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to their PS content.
The lengthy waiting time for heart transplantation is associated with high mortality. To increase the number of donors, new strategies have emerged, including the use of hearts from donors ≥50 years ...old. However, this practice remains controversial. The aim of this study was to evaluate outcomes of patients receiving heart transplants from older donors.
We retrospectively analyzed 2,102 consecutive heart transplants in 8 Spanish hospitals from 1998 to 2010. Acute and overall mortality were compared in patients with grafts from donors ≥50 years old versus grafts from younger donors.
There were 1,758 (84%) transplanted grafts from donors < 50 years old (Group I) and 344 (16%) from donors ≥50 years old (Group II). Group I had more male donors than Group II (71% vs. 57%, p = 0.0001). The incidence of cardiovascular risk factors was higher in older donors. There were no differences in acute mortality or acute rejection episodes between the 2 groups. Global mortality was higher in Group II (rate ratio, 1.40; 95% confidence interval, 1.18-1.67; p = 0.001) than in Group I. After adjusting for donor cause of death, donor smoking history, recipient age, induction therapy, and cyclosporine therapy, the differences lost significance. Group II had a higher incidence of coronary allograft vasculopathy at 5 years (rate ratio, 1.67; 95% confidence interval, 1.22-2.27; p = 0.001).
There were no differences in acute and overall mortality after adjusting for confounding factors. However, there was a midterm increased risk of coronary allograft vasculopathy with the use of older donors. Careful selection of recipients and close monitoring of coronary allograft vasculopathy are warranted in these patients.
Non-adherence after heart transplantation (HTx) is a significant problem. The main objective of this study was to evaluate if a mHealth strategy is more effective than standard care in improving ...adherence and patients' experience in heart transplant recipients. Methods: This was a single-center, randomized controlled trial (RCT) in adult recipients >1.5 years post-HTx. Participants were randomized to standard care (control group) or to the mHeart Strategy (intervention group). For patients randomized to the mHeart strategy, multifaceted theory-based interventions were provided during the study period to optimize therapy management using the mHeart mobile application. Patient experience regarding their medication regimens were evaluated in a face-to-face interview. Medication adherence was assessed by performing self-reported questionnaires. A composite adherence score that included the SMAQ questionnaire, the coefficient of variation of drug levels and missing visits was also reported.
: A total of 134 HTx recipients were randomized (intervention N = 71; control N = 63). Mean follow-up was 1.6 (SD 0.6) years. Improvement in adherence from baseline was significantly higher in the intervention group versus the control group according to the SMAQ questionnaire (85% vs. 46%, OR = 6.7 (2.9; 15.8),
-value < 0.001) and the composite score (51% vs. 23%, OR = 0.3 (0.1; 0.6),
-value = 0.001). Patients' experiences with their drug therapy including knowledge of their medication timing intakes (
-value = 0.019) and the drug indications or uses that they remembered (
-value = 0.003) significantly improved in the intervention versus the control group.
: In our study, the mHealth-based strategy significantly improved adherence and patient beliefs regarding their medication regimens among the HTx population. The mHeart mobile application was used as a feasible tool for providing long-term, tailor-made interventions to HTx recipients to improve the goals assessed.
Aims
The prognostic value of biomarkers in patients with heart failure (HF) and mid‐range (HFmrEF) or preserved ejection fraction (HFpEF) has not been widely addressed. The aim of this study was to ...assess whether the prognostic value of growth differentiation factor 15 (GDF‐15) is superior to that of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in patients with HFmrEF or HFpEF.
Methods and results
Heart failure patients with either HFpEF or HFmrEF were included in the study. During their first visit to the HF unit, serum samples were obtained and stored for later assessment of GDF‐15 and NT‐proBNP concentrations. Patients were followed up by the HF unit. The main endpoint was all‐cause mortality. A total of 311 patients, 90 (29%) HFmrEF and 221 (71%) HFpEF, were included. Mean age was 72 ± 13 years, and 136 (44%) were women. No differences were found in GDF‐15 or NT‐proBNP concentrations between both HF groups. During a median follow‐up of 15 months (Q1–Q3: 9–30 months), 98 patients (32%) died, most (71%) of cardiovascular causes. Patients who died had higher median concentrations of GDF‐15 (4085 vs. 2270 ng/L, P < 0.0001) and NT‐proBNP (1984 vs. 1095 ng/L, P < 0.0001). A Cox multivariable model identified New York Heart Association Functional Class III (P = 0.04), systolic blood pressure (P = 0.01), left atrial diameter (P = 0.03), age >65 years (P < 0.0001), and GDF‐15 concentrations (P = 0.01) but not NT‐proBNP as independent predictors of all‐cause mortality. The area under the curve was 0.797 for the basic model including NT‐proBNP, and the area under the curve comparing the overall model was 0.819, P = 0.016 (DeLong's test). Integrated discrimination improvement index after the inclusion of GDF‐15 in the model with the mortality risk factors was 0.033; that is, the ability to predict death increased by 3.3% (P = 0.004). Net reclassification improvement was 0.548 (P < 0.001); that is, the capacity to improve the classification of the event (mortality) was 54.8%. GDF‐15 concentrations were divided in tertiles (<1625, 1625–4330, and >4330 ng/L), and survival curves were evaluated using the Kaplan–Meier technique. Patients in the highest tertile had the poorest 5 year survival, at 16%, whereas the lowest tertile had the best survival, of 78% (P < 0.001).
Conclusions
Growth differentiation factor 15 was superior to NT‐proBNP for assessing prognosis in patients with HFpEF and HFmrEF. GDF‐15 emerges as a strong, independent biomarker for identifying HFmrEF and HFpEF patients with worse prognosis.
Introduction:
Over the last decades, several scores have been developed to aid clinicians in assessing prognosis in patients with heart failure (HF) based on clinical data, medications and, ...ultimately, biomarkers. Lung ultrasound (LUS) has emerged as a promising prognostic tool for patients when assessed at discharge after a HF hospitalization. We hypothesized that contemporary HF risk scores can be improved upon by the inclusion of the number of B-lines detected by LUS at discharge to predict death, urgent visit, or HF readmission at 6- month follow-up.
Methods:
We evaluated the discrimination improvement of adding the number of B-lines to 4 contemporary HF risk scores (Get with the Guidelines -GWTG-, MAGGIC, Redin-SCORE, and BCN Bio-HF) by comparing the change in the area under the receiver operating curve (AUC), the net reclassification index (NRI), and the integrated discrimination improvement (IDI). The population of the study was constituted by the 123 patients enrolled in the LUS-HF trial, adjusting the analyses by the intervention.
Results:
The AUC of the GWTG score increased from 0.682 to 0.789 (
p
= 0.02), resulting in a NRI of 0.608 and an IDI of 0.136 (
p
< 0.05). Similar results were observed when adding the number of B-lines to the MAGGIC score, with an AUC that increased from 0.705 to 0.787 (
p
< 0.05). This increase translated into a NRI of 0.608 and an IDI of 0.038 (
p
< 0.05). Regarding Redin-SCORE at 1-month and 1-year, the AUC increased from 0.714 to 0.773 and from 0.681 to 0.757, although it did not reach statistical significance (
p
= 0.08 and
p
= 0.06 respectively). Both IDI and NRI were significantly improved (0.093 and 0.509 in the 1-month score,
p
< 0.05; 0.056 and 0.111 in the 1-year score,
p
< 0.05). Lastly, the AUC for the BCN Bio-HF score increased from 0.733 to 0.772, which was statistically non-significant, with a NRI value of 0.363 (
p
= 0.06) and an IDI of 0.092 (
p
< 0.05).
Conclusion:
Adding the results of LUS evaluated at discharge improved the predictive value of most of the contemporary HF risk scores. As it is a simple, fast, and non-invasive test it may be recommended to assess prognosis at discharge in HF patients.
Summary
Male patients are at increased risk for developing malignancy postheart transplantation (HT); however, real incidence and prognosis in both genders remain unknown. The aim of this study was ...to assess differences in incidence and mortality related to malignancy between genders in a large cohort of HT patients. Incidence and mortality rates were calculated for all tumors, skin cancers (SCs), lymphoma, and nonskin solid cancers (NSSCs) as well as survival since first diagnosis of neoplasia. 5865 patients (81.6% male) were included. Total incidence rates for all tumors, SCs, and NSSCs were lower in females all tumors: 25.7 vs. 44.8 per 1000 person‐years; rate ratio (RR) 0.68, (0.60–0.78), P < 0.001. Mortality rates were also lower in females for all tumors 94.0 (77.3–114.3) vs. 129.6 (120.9–138.9) per 1000 person‐years; RR 0.76, (0.62–0.94), P = 0.01 and for NSSCs 125.0 (95.2–164.0) vs 234.7 (214.0–257.5) per 1000 person‐years; RR 0.60 (0.44–0.80), P = 0.001, albeit not for SCs or lymphoma. Female sex was associated with a better survival after diagnosis of malignancy log‐rank p test = 0.0037; HR 0.74 (0.60–0.91), P = 0.004. In conclusion, incidence of malignancies post‐HT is higher in males than in females, especially for SCs and NSSCs. Prognosis after cancer diagnosis is also worse in males.
Background
Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin ...inhibitor, is increasingly used for anticoagulation in patients with non‐valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab.
Aim
To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT.
Methods
Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery.
Results
Fifty‐three patients were included (81.1% male). 7.5% required re‐operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30‐day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post‐HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post‐HT death was associated with bleeding.
Conclusions
These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.
Aims
Residual pulmonary congestion at hospital discharge can worsen the outcomes in patients with heart failure (HF) and can be detected by lung ultrasound (LUS). The aim of this study was to analyse ...the prevalence of subclinical pulmonary congestion at discharge and its impact on prognosis in patients admitted for acute HF.
Methods and results
This is a post‐hoc analysis of the LUS‐HF trial. LUS was performed by the investigators in eight chest zones with a pocket device. Physical exam was subsequently performed by the treating physicians. Primary outcome was a combined endpoint of rehospitalization, unexpected visit for HF worsening or death at 6‐ month follow‐up. Subclinical pulmonary congestion at discharge was defined as the presence of ≥5 B‐lines in LUS in absence of rales in the auscultation employing the area under the ROC curve. At discharge, 100 patients (81%) did not show clinical signs of pulmonary congestion. Of these, 41 had ≥5 B‐lines. Independent factors related with the presence of subclinical pulmonary congestion were anaemia, higher New York Heart Association (NYHA) class, and N terminal pro brain natriuretic peptide (NT‐proBNP). After adjusting by propensity score analysis including age, renal insufficiency, atrial fibrillation, NYHA class, NT‐proBNP levels, clinical congestion, and the trial intervention, the presence of subclinical pulmonary congestion at discharge was a risk factor for the occurrence of the primary outcome (hazard ratio 2.63; 95% confidence interval: 1.08–6.41; P = 0.033).
Conclusions
Up to 40% of patients considered ‘dry’ according to pulmonary auscultation presents subclinical congestion at hospital discharge that can be detected by LUS and implies a worse prognosis at 6‐ month follow‐up. Comorbidities, high values of natriuretic peptides, and higher NYHA class are the factors related with its presence.
The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, ...including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination.
Sacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in ...daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients.
This is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method.
Out of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (<25%), intermediate- (∼46%), and high-probability (>80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64-0.80), remaining consistent after internal validation.
One-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice.
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