Colchicine in acute heart failure: Rationale and design of a randomized double-blind placebo-controlled trial (COLICA).

AIMS: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. METHODS: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. CONCLUSION: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

Pronóstico del trasplante cardiaco en pacientes con miocardiopatía hipertrófica y restrictiva. Análisis de un registro nacional / Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis

Introducción y objetivos: Existe controversia acerca de los resultados del trasplante cardiaco en pacientes con miocardiopatía hipertrófica (MCH) o restrictiva (MCR). Métodos: Análisis retrospectivo de receptores adultos de un primer trasplante cardiaco entre 1984 y 2021 incluidos en un registro nacional. La mortalidad al primer y quinto año postrasplante en receptores con MCH y MCR se comparó con la de receptores con miocardiopatía dilatada (MCD). Resultados: Se incluyó a 3.703 pacientes (3.112 MCD; 331 MCH y 260 MCR) con seguimiento mediano de 5,0 años (3,1-5,0). En comparación con la MCD, el riesgo ajustado de mortalidad a 1 año fue: MCH: hazard ratio (HR)=1,38; intervalo de confianza del 95% (IC95%), 1,07-1,78; p=0,01, MCR: HR=1,48; IC95%, 1,14-1,93; p=0,003. El riesgo ajustado a 5 años fue: MCH: HR=1,17; IC95%, 0,93-1,47; p=0,18; MCR: HR=1,52; IC95%, 1,22-1,89; p<0,001. En los últimos 20 años, la MCR mejoró significativamente la supervivencia a 1 año (R2 ajustada=0,95) y a 5 años (R2=0,88); la MCH mejoró la supervivencia a 5 años (R2=0,59) y a 1 año permaneció estable (R2=0,16). Conclusiones: Se asoció la MCR y la MCH a peor pronóstico precoz postrasplante que la MCD. La diferencia desfavorable se mantuvo para la supervivencia a 5 años solo para la MCR. Se observa una tendencia temporal a mejor pronóstico precoz y tardío para la MCR, y solo para el tardío en la MCH. (AU)

Introduction and objectives: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. Methods: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). Results: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). Conclusions: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality. (AU)

Review of the allocation criteria for heart transplant in Spain in 2023. SEC-Heart Failure Association/ONT/SECCE consensus document.

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.

Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis.

INTRODUCTION AND OBJECTIVES: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. METHODS: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). RESULTS: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). CONCLUSIONS: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality.

Impact of SARS-CoV-2 Infection on Humoral and Cellular Immunity in a Cohort of Vaccinated Solid Organ Transplant Recipients.

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.

Red Blood Cells and Endothelium Derived Circulating Extracellular Vesicles in Health and Chronic Heart Failure: A Focus on Phosphatidylserine Dynamics in Vesiculation.

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; n = 119) and a reference non-HF group (n = 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.

Platelet-Released Extracellular Vesicle Characteristics Differ in Chronic and in Acute Heart Disease.

BACKGROUND: Extracellular vesicles (EVs), shed in response to cell activation, stress, or injury, are increased in the blood of patients with cardiovascular disease. EVs are characterized by expressing parental-cell antigens, allowing the determination of their cellular origin. Platelet-derived EVs (pEVs) are the most abundant in blood. Although not universally given, EVs generally express phosphatidylserine (PS) in their membrane. OBJECTIVES: To investigate pEVs in chronic and acute conditions, such as chronic heart failure (CHF) and first-onset acute coronary syndrome (ACS), in patients treated as per guidelines. METHODS: EVs in CHF patients (n = 119), ACS patients (n = 58), their respective controls (non-CHF [n = 21] and non-ACS [n = 24], respectively), and a reference control group (n = 31) were characterized and quantified by flow cytometry, using monoclonal antibodies against platelet antigens, and annexin V (AV) to determine PS exposure. RESULTS: CHF patients had higher EVs-PS- numbers, while ACS had predominantly EVs-PS+. In contrast to ACS, CHF patients had significantly reduced numbers of pEVs carrying PECAM and αIIb-integrin epitopes (CD31+/AV+, CD41a+/AV+, and CD31+/CD41a+/AV+), while no differences were observed in P-selectin-rich pEVs (CD62P+/AV+) compared with controls. Additionally, background etiology of CHF (ischemic vs. nonischemic) or ACS type (ST-elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]) did not affect pEV levels. CONCLUSION: PS exposure in EV and pEV-release differ between CHF and ACS patients, with tentatively different functional capacities beyond coagulation to inflammation and cross-talk with other cell types.

Identifying the patient with heart failure to be treated with vericiguat.

The pathophysiology of heart failure with reduced ejection fraction (HFrEF) is a complex process in which a number of neurohormonal systems are involved. Targeting only some of these systems, but not all, translates into a partial benefit of HF treatment. The nitric oxide-soluble guanylate cyclase (sGC)-cGMP pathway is impaired in HF, leading to cardiac, vascular and renal disturbances. Vericiguat is a once-daily oral stimulator of sGC that restores this system. No other disease-modifying HF drugs act on this system. Despite guidelines recommendations, a substantial proportion of patients are not taking all recommended drugs or when taking them, they do so at low doses, limiting their potential benefits. In this context, treatment should be optimized considering different parameters, such as blood pressure, heart rate, renal function, or potassium, as they may interfere with their implementation at the recommended doses. The VICTORIA trial showed that adding vericiguat to standard therapy in patients with HFrEF significantly reduced the risk of cardiovascular death or HF hospitalization by 10% (NNT 24). Furthermore, vericiguat does not interfere with heart rate, renal function or potassium, making it particularly useful for improving the prognosis of patients with HFrEF in specific settings and clinical profiles.

Optimizing the management of patients with worsening heart failure: beyond heart failure hospitalization.

INTRODUCTION: Worsening heart failure (HF) is associated with a high risk of death and HF hospitalization. AREAS COVERED: A systematic search was conducted on PubMed (MEDLINE), using the MeSH terms [Heart failure] + [Worsening] + [Treatment] + [Vulnerable period] up to February 2023. Original data from clinical trials, and observational studies were critically analyzed. EXPERT OPINION: Although the vulnerable period has been traditionally limited to the first 6 months after HF hospitalization, the fact is that there are other clinical scenarios in which the patient is particularly vulnerable. These vulnerable patients may also include those that require parenteral administration of diuretics in the day hospital or emergency department, those in which the increase of oral diuretic dose in an outpatient setting is needed to relief congestive symptoms, as well as those that remain symptomatic despite treatment. On the other hand, HF is a complex disease in which different neurohormonal systems are involved. Therefore, to actually reduce the HF burden, a comprehensive management, targeting all the neurohormonal systems that are involved in the pathogenesis of HF, through the use of those drugs that have demonstrated to positively modify the clinical course of HF, is needed.

ß3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.

AIMS: Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective ß3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). METHODS AND RESULTS: The ß3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. CONCLUSIONS: SPHERE-HF is the first clinical trial to assess the potential benefit of ß3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.

Systems Biology in Chronic Heart Failure-Identification of Potential miRNA Regulators.

Heart failure (HF) is a complex disease entity with high clinical impact, poorly understood pathophysiology and scantly known miRNA-mediated epigenetic regulation. We have analysed miRNA patterns in patients with chronic HF (cHF) and a sex- and age-matched reference group and pursued an in silico system biology analysis to discern pathways involved in cHF pathophysiology. Twenty-eight miRNAs were identified in cHF that were up-regulated in the reference group, and eight of them were validated by RT-qPCR. In silico analysis of predicted targets by STRING protein-protein interaction networks revealed eight cluster networks (involving seven of the identified miRNAs) enriched in pathways related to cell cycle, Ras, chemokine, PI3K-AKT and TGF-ß signaling. By ROC curve analysis, combined probabilities of these seven miRNAs (let-7a-5p, miR-107, miR-125a-5p, miR-139-5p, miR-150-5p, miR-30b-5p and miR-342-3p; clusters 1-4 [C:1-4]), discriminated between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), and ischaemic and non-ischaemic aetiology. A combination of miR-107, miR-139-5p and miR-150-5p, involved in clusters 5 and 7 (C:5+7), discriminated HFpEF from HFrEF. Pathway enrichment analysis of miRNAs present in C:1-4 (let-7a-5p, miR-125a-5p, miR-30b-5p and miR-342-3p) revealed pathways related to HF pathogenesis. In conclusion, we have identified a differential signature of down-regulated miRNAs in the plasma of HF patients and propose novel cellular mechanisms involved in cHF pathogenesis.

New factors in heart failure pathophysiology: Immunity cells release of extracellular vesicles.

Leukocyte-shed extracellular vesicles (EVs) can play effector roles in the pathophysiological mechanisms of different diseases. These EVs released by membrane budding of leukocytes have been found in high amounts locally in inflamed tissues and in the circulation, indicating immunity cell activation. These EVs secreted by immune cell subsets have been minimally explored and deserve further investigation in many areas of disease. In this study we have investigated whether in heart failure there is innate and adaptive immune cell release of EVs. Patients with chronic heart failure (cHF) (n = 119) and in sex- and age-matched controls without this chronic condition (n = 60). Specifically, EVs were quantified and phenotypically characterized by flow cytometry and cell-specific monoclonal antibodies. We observed that even in well medically controlled cHF patients (with guideline-directed medical therapy) there are higher number of blood annexin-V+ (phosphatidylserine+)-EVs carrying activated immunity cell-epitopes in the circulation than in controls (p < 0.04 for all cell types). Particularly, EVs shed by monocytes and neutrophils (innate immunity) and by T-lymphocytes and natural-killer cells (adaptive immunity) are significantly higher in cHF patients. Additionally, EVs-shed by activated leukocytes/neutrophils (CD11b+, p = 0.006; CD29+/CD15+, p = 0.048), and T-lymphocytes (CD3+/CD45+, p < 0.02) were positively correlated with cHF disease severity (NYHA classification). Interestingly, cHF patients with ischemic etiology had the highest levels of EVs shed by lymphocytes and neutrophils (p < 0.045, all). In summary, in cHF patients there is a significant immune cell activation shown by high-release of EVs that is accentuated by clinical severity of cHF. These activated innate and adaptive immunity cell messengers may contribute by intercellular communication to the progression of the disease and to the common affectation of distant organs in heart failure (paracrine regulation) that contribute to the clinical deterioration of cHF patients.

Incremental prognostic value of lung ultrasound on contemporary heart failure risk scores.

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.

Role of Quantitative Flow Ratio in Predicting Future Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

BACKGROUND: Coronary angiography is the gold standard for cardiac allograft vasculopathy (CAV) diagnosis, but it usually detects the disease at an advanced stage. We investigated the role of quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, in predicting CAV development in heart transplant recipients. METHODS: Consecutive heart transplant recipients with no evidence of angiographic CAV at baseline coronary angiography were retrospectively included between January 2010 and December 2015, and QFR computation was performed. The relationship between vessel QFR and the occurrence of angiographic vessel-related CAV (≥50% stenosis) was assessed. RESULTS: One hundred forty-three patients were included and QFR computation was feasible in 241 vessels. The median value of QFR at baseline coronary angiography was 0.98 (interquartile range, 0.94-1.00). During a median follow-up of 6.0 years (interquartile range, 4.6-7.8 years), vessel-related CAV occurred in 25 (10.4%) vessels. Receiver-operating characteristic curve analysis identified a QFR best cutoff of ≤0.95 (area under the curve, 0.81 [95% CI, 0.71-0.90]; P<0.001). QFR≤0.95 was associated with an increased risk of vessel-related CAV (adjusted hazard ratio, 20.87 [95% CI, 5.35-81.43]; P<0.001). In an exploratory analysis, QFR≤0.95 in at least 2 vessels was associated with higher incidence of cardiovascular death or late graft dysfunction (71.4% in recipients with 2-3 vessels affected versus 5.1% in recipients with 0-1 vessels affected, P<0.001). CONCLUSIONS: In a cohort of heart transplant recipients, QFR computation at baseline coronary angiography may be a safe and reliable tool to predict vessel-related CAV and clinical outcomes at long-term follow-up.

A Simple Score to Identify Super-Responders to Sacubitril/Valsartan in Ambulatory Patients With Heart Failure.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Influence of Gender in Advanced Heart Failure Therapies and Outcome Following Transplantation.

Biological differences between males and females change the course of different diseases and affect therapeutic measures' responses. Heart failure is not an exception to these differences. Women account for a minority of patients on the waiting list for heart transplantation or other advanced heart failure therapies. The reason for this under-representation is unknown. Men have a worse cardiovascular risk profile and suffer more often from ischemic heart disease. Conversely, transplanted women are younger and more frequently have non-ischemic cardiac disorders. Women's poorer survival on the waiting list for heart transplantation has been previously described, but this trend has been corrected in recent years. The use of ventricular assist devices in women is progressively increasing, with comparable results than in men. The indication rate for a heart transplant in women (number of women on the waiting list for millions of habitants) has remained unchanged over the past 25 years. Long-term results of heart transplants are equal for both men and women. We have analyzed the data of a national registry of heart transplant patients to look for possible future directions for a more in-depth study of sex differences in this area. We have analyzed 1-year outcomes of heart transplant recipients. We found similar results in men and women and no sex-related interactions with any of the factors related to survival or differences in death causes between men and women. We should keep trying to approach sex differences in prospective studies to confirm if they deserve a different approach, which is not supported by current evidence.

Differentiation of athlete's heart and hypertrophic cardiomyopathy by the fractal dimension of left ventricular trabeculae.

BACKGROUND: Differentiation between exercise induced adaptive myocardial hypertrophy (athlete's heart) and hypertrophic cardiomyopathy (HCM) is currently based on echocardiographic and cardiac magnetic resonance (CMR) criteria, but these may be insufficient in patients with subtle phenotype expression. This study aimed to assess whether left ventricular (LV) fractal pattern could permit to differentiate athlete's heart from HCM. METHODS: We recruited retrospectively 61 elite marathon runners, 67 patients with HCM, and 33 healthy subjects. A CMR study was performed in all subjects and the LV trabeculae fractal dimension (FD) was measured in end-diastolic frames of each short-axis cine sequence. For group comparison, the ratio of maximal myocardial wall thickness (mMWT)/indexed LV end-diastolic volume (LVED) was determined. RESULTS: As compared with athletes, patients with HCM had significantly (p < 0.001) greater FD in the LV basal (1.30 ± 0.07 vs. 1.23 ± 0.05) and apical (1.38 ± 0.06 vs. 1.30 ± 0.07) regions and in the whole heart (1.34 ± 0.05 vs. 1.27 ± 0.05). FD increased with age, left atrial area and indexed left ventricular mass (p < 0.05 for all) and correlated negatively with LV and RV end-diastolic volumes (p < 0.05 each). The addition of whole heart FD to the ratio of maximal myocardial wall thickness/indexed LVEDV lead to an improvement in the ability to discriminate HCM with a net reclassification index (NRI) of 71%. CONCLUSIONS: The FD regional distribution of the LV trabeculae differentiates patients with athlete's heart from patients with HCM. The addition of whole heart FD to the mMWT/indexed LVEDV ratio improves the predictive capacity of the model to differentiate both entities.

Validation of the usefulness of 2-dimensional strain parameters to exclude acute rejection after heart transplantation: a multicenter study.

INTRODUCTION AND OBJECTIVES: Two-dimensional speckle-tracking echocardiography has emerged as a promising alternative to endomyocardial biopsy to rule out acute cellular rejection after orthotopic heart transplantation (OHT) in single center studies. In an original cohort, 15.5% and 17% of cutoff points for left ventricular global longitudinal strain (LVGLS) and free-wall right ventricular longitudinal strain, respectively, achieved 100% negative predictive value to exclude moderate or severe acute cellular rejection (ACR ≥ 2R). Our objective was to demonstrate the usefulness of speckle-tracking and validate these cutoff points in an external cohort. METHODS: A prospective, multicenter study that included patients who were monitored during their first year after OHT was conducted. Echocardiographic studies analyzed by local investigators were compared with simultaneous paired endomyocardial biopsies samples. RESULTS: A total of 501 endomyocardial biopsy-echocardiographic studies were included in 99 patients. ACR≥2R was present in 7.4% of samples. LVGLS and free-wall right ventricular longitudinal strain were significantly reduced during ACR≥2R on univariate analysis. On multivariate analysis, LVGLS was independently associated with the presence of ACR≥2R. The original cutoff points demonstrated a negative predictive value of 94.3% to exclude ACR≥2R. CONCLUSIONS: This study maintained a strong negative predictive value to exclude ACR≥2R after OHT and LVGLS was independently associated with the presence of ACR≥2R. We propose the use of speckle-tracking, especially LVGLS, as part of the noninvasive diagnosis and management of ACR.

Interdisciplinary Mobile Health Model to Improve Clinical Care After Heart Transplantation: Implementation Strategy Study.

BACKGROUND: Solid organ transplantation could be the only life-saving treatment for end-stage heart failure. Nevertheless, multimorbidity and polypharmacy remain major problems after heart transplant. A technology-based behavioral intervention model was established to improve clinical practice in a heart transplant outpatient setting. To support the new strategy, the mHeart app, a mobile health (mHealth) tool, was developed for use by patients and providers. OBJECTIVE: The primary objective of this study was to describe the implementation of the mHeart model and to outline the main facilitators identified when conceiving an mHealth approach. The secondary objectives were to evaluate the barriers, benefits, and willingness to use mHealth services reported by heart transplant recipients and cardiology providers. METHODS: This was an implementation strategy study directed by a multidisciplinary cardiology team conducted in four stages: design of the model and the software, development of the mHeart tool, interoperability among systems, and quality and security requirements. A mixed methods study design was applied combining a literature review, several surveys, interviews, and focus groups. The approach involved merging engineering and behavioral theory science. Participants were chronic-stage heart transplant recipients, patient associations, health providers, stakeholders, and diverse experts from the legal, data protection, and interoperability fields. RESULTS: An interdisciplinary and patient-centered process was applied to obtain a comprehensive care model. The heart transplant recipients (N=135) included in the study confirmed they had access to smartphones (132/135, 97.7%) and were willing to use the mHeart system (132/135, 97.7%). Based on stakeholder agreement (>75%, N=26), the major priorities identified of the mHealth approach were to improve therapy management, patient empowerment, and patient-provider interactions. Stakeholder agreement on the barriers to implementing the system was weak (<75%). Establishing the new model posed several challenges to the multidisciplinary team in charge. The main factors that needed to be overcome were ensuring data confidentiality, reducing workload, minimizing the digital divide, and increasing interoperability. Experts from various fields, scientific societies, and patient associations were essential to meet the quality requirements and the model scalability. CONCLUSIONS: The mHeart model will be applicable in distinct clinical and research contexts, and may inspire other cardiology health providers to create innovative ways to deal with therapeutic complexity and multimorbidity through health care systems. Professionals and patients are willing to use such innovative mHealth programs. The facilitators and key strategies described were needed for success in the implementation of the new holistic theory-based mHealth strategy.