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IntroductionCardiac troponin levels below the 99th percentile improve the predictive efficacy for cardiovascular events when associated with relevant clinical variables. However, whether ultra-sensitive analytical methods improve this predictive efficacy over less sensitive or contemporary analytical methods remains unknown.MethodsThis retrospective observational study involved consecutive patients who presented to the emergency department for suspected acute coronary syndrome and underwent measurement of ultra-sensitive cardiac troponin I (Singulex) and contemporary cardiac troponin I (Siemens) with levels below the 99th percentile. The clinical characteristics of these patients were analysed, and the efficacy of both analytical methods for predicting cardiovascular events over a 4-year follow-up period was compared.ResultsIn total, 838 patients were analysed (mean age, 62.9 ± 16.6 years; 42.2% women). Their cumulative incidence of the composite cardiovascular event (death, readmission for myocardial infarction, and readmission for heart failure) was 25.9% over the 4-year follow-up. Both Singulex cardiac troponin I (analysed by quartiles) and Siemens cardiac troponin (analysed as detectable/undetectable) improved the predictive efficacy for the combined event over clinical variables [Harrell's C-index (95% confidence interval): 0.77 (0.74–0.80) vs. 0.79 (0.76–0.81) and 0.77 (0.74–0.80) vs. 0.78 (0.75–0.81), respectively; p = 0.018]. However, there were no statistically significant difference between the two predictive models that included the aforementioned troponin assays.ConclusionsDetectable levels of cardiac troponin using a contemporary analytical method or those near the 99th percentile using an ultra-sensitive analytical method improve the predictive efficacy for cardiovascular events, with no differences between the two methods

Abstract Aims The criteria for patients with heart failure (HF) and improved ejection fraction (HFimpEF) are a baseline left ventricular ejection fraction (LVEF) ≤40%, a ≥10‐point increase from baseline LVEF, and a second LVEF measurement >40%. We aimed to (i) assess patients with HF and reduced LVEF (HFrEF) at baseline and compare quality of life (QoL) changes between those that fulfilled and those that did not fulfil the HFimpEF criteria 1 year later and (ii) assess the prognostic role of QoL in patients with HFimpEF. Methods We reviewed data from a prospective registry of real‐world outpatients with HF that were assessed for LVEF and QoL at a first visit to the HF clinic and 1 year later. QoL was evaluated with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). The primary prognostic endpoint was the composite of all‐cause death or HF hospitalization. Results Baseline and 1‐year LVEF and MLWFQ scores were available for 1040 patients with an initial LVEF ≤40% (mean age, 65.2 ± 11.7 years; 75.9% men). The main aetiology was ischaemic heart disease (52.9%), and patients were mostly in New York heart Association Classes II (71.1%) and III (21.6%). At baseline, the mean LVEF was 28.5% ± 7.3, and the mean MLWHFQ score was 30.2 ± 19.5. After 1 year, the mean LVEF increased to 38.0% ± 12.2, and the MLWHFQ scores improved to 17.4 ± 16.0. In 361 patients that fulfilled the HFimpEF criteria (34.7%), significant improvements were observed in both LVEF (from 28.7% ± 6.6 to 50.9% ± 7.6, P

Abstract Aims Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF–PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS‐HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF–PH treated with sacubitril/valsartan. Methods and results This single‐arm, investigator‐initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF–PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre‐ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B‐line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre‐ARNI vs. ARNI ON, mPAP significantly declined by −4.99 mmHg [95% confidence interval (CI) −5.55 to −4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre‐ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B‐lines, and QoL. Mean loop diuretic management did not differ between periods. Conclusions Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF–PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF–PH.

Abstract Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case–control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini–Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

ObjectivesHeart failure (HF) management has significantly improved over the past two decades, leading to better survival. This study aimed to assess changes in predicted mortality risk after 12 months of management in a multidisciplinary HF clinic.Materials and MethodsOut of 1,032 consecutive HF outpatients admitted from March-2012 to November-2018, 357 completed the 12-months follow-up and had N-terminal pro-B-type natriuretic peptide (NTproBNP), high sensitivity troponin T (hs-TnT), and interleukin-1 receptor-like-1 (known as ST2) measurements available both at baseline and follow-up. Three contemporary risk scores were used: MAGGIC-HF, Seattle HF Model (SHFM), and the Barcelona Bio-HF (BCN Bio-HF) calculator, which incorporates the three above mentioned biomarkers. The predicted risk of all-cause death at 1 and 3 years was calculated at baseline and re-evaluated after 12 months.ResultsA significant decline in predicted 1-and 3-year mortality risk was observed at 12 months: MAGGIC ~16%, SHFM ~22% and BCN Bio-HF ~15%. In the HF with reduced ejection fraction (HFrEF) subgroup guideline-directed medical therapy led to a complete normalization of left ventricular ejection fraction (≥50%) in almost a third of the patients and to a partial normalization (41–49%) in 30% of them. Repeated risk assessment after 12 months with SHFM and BCN Bio-HF provided adequate discrimination for all-cause 3-year mortality (C-Index: MAGGIC-HF 0.762, SHFM 0.781 and BCN Bio-HF 0.791).ConclusionMortality risk declines in patients with HF managed for 12 months in a multidisciplinary HF clinic. Repeating the mortality risk assessment after optimizing the HF treatment is recommended, particularly in the HFrEF subgroup.

Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9–3440.5) pg/mL vs. 1396.05 (820.3–2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6–79.8) ng/mL vs. 34.1 (24.09–55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09–1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12–4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09–1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21–7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11–3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D.

Abstract Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril–valsartan, beta‐blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.

Summary: Background: In preclinical studies, the use of double allogeneic grafts has shown promising results in promoting tissue revascularization, reducing infarct size, preventing adverse remodelling and fibrosis, and ultimately enhancing cardiac function. Building upon these findings, the safety of PeriCord, an engineered tissue graft consisting of a decellularised pericardial matrix and umbilical cord Wharton's jelly mesenchymal stromal cells, was evaluated in the PERISCOPE Phase I clinical trial (NCT03798353), marking its first application in human subjects. Methods: This was a double-blind, single-centre trial that enrolled patients with non-acute myocardial infarction eligible for surgical revascularization. Seven patients were implanted with PeriCord while five served as controls. Findings: Patients who received PeriCord showed no adverse effects during post-operative phase and one-year follow-up. No significant changes in secondary outcomes, such as quality of life or cardiac function, were found in patients who received PeriCord. However, PeriCord did modulate the kinetics of circulating monocytes involved in post-infarction myocardial repair towards non-classical inflammation-resolving macrophages, as well as levels of monocyte chemoattractants and the prognostic marker Meteorin-like in plasma following treatment. Interpretation: In summary, the PeriCord graft has exhibited a safe profile and notable immunomodulatory properties. Nevertheless, further research is required to fully unlock its potential as a platform for managing inflammatory-related pathologies. Funding: This work was supported in part by grants from MICINN (SAF2017-84324-C2-1-R); Instituto de Salud Carlos III (ICI19/00039 and Red RICORS-TERAV RD21/0017/0022, and CIBER Cardiovascular CB16/11/00403) as a part of the Plan Nacional de I + D + I, and co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (2021-SGR-01437).

Resumen: Introducción: La reparación de la insuficiencia mitral por prolapso del velo posterior ha evolucionado en los últimos 20 años desde las técnicas clásicas de Carpentier hacia procedimientos menos agresivos con el tejido valvular. Nuestro objetivo es describir la evolución del tratamiento de esta patología en nuestro centro. Métodos: Estudio retrospectivo de pacientes con prolapso de velo posterior operados en nuestro centro desde 2001 a 2021. Recogida de datos intraoperatorios y datos ecocardiográficos y de seguimiento durante 20 años. Resultados: Se incluyeron 260 pacientes operados en dos períodos: hasta 2010, 84 pacientes (grupo A) y desde 2011, 176 pacientes (grupo B). Las técnicas más utilizadas en el grupo A fueron la resección cuadrangular (51 pacientes, 60,7%), la triangular (20 pacientes, 23,8%) y la implantación de neocuerdas (8 pacientes, 9,5%) siendo la tasa de reparabilidad del 98,8%, y en el grupo B fueron la resección triangular (86 pacientes, 48,9%), la implantación de neocuerdas (45 pacientes, 25,6%) y la resección cuadrangular (28 pacientes, 15,9%) con una reparabilidad del 96,6%. La mortalidad hospitalaria fue del 3,6% (n = 3) en el grupo A y del 0,6% (n = 1) en el B. Supervivencia actuarial 50% a los 20 años (A) y 81% a los 10 años (B). Tasa libre de reintervención del 98% (A) y del 97,2% (B). Teniendo en cuenta las técnicas más frecuentemente utilizadas, la recidiva de insuficiencia mitral ≥ II fue mayor en los pacientes con neocuerdas (n = 14, 26,4%) que en los casos de resección cuadrangular (n = 10, 13,2%) o triangular (n = 13, 12,4%). Conclusiones: Nuestro centro ha evolucionado hacia técnicas con menor resección tisular y mayor utilización de neocuerdas, aunque ambas técnicas han mostrado excelentes resultados a largo plazo. Las técnicas resectivas son más reproducibles y duraderas que la implantación de neocuerdas. Abstract: Introduction: Repair of mitral regurgitation due to posterior leaflet prolapse has evolved in the last 20 years from the classic Carpentier techniques towards less aggressive procedures with the valve tissue. The objective of this study is to describe the evolution of our center in the treatment of this pathology. Methods: Retrospective study of 260 patients with posterior leaflet prolapse operated on our center since 2001, including them into two groups: A (until 2010) and B (since 2011). We collected intraoperative data and echocardiographic and follow-up data for 20 years. Results: 260 patients operated on in two periods were included: until 2010, 84 patients (group A) and since 2011, 176 patients (group B). The most commonly used techniques in group A were quadrangular resection (51 patients, 60.7%), triangular resection (20 patients, 23.8%), and neochordal implantation (8 patients, 9.5%), with a reparability rate of 98.8% and in group B, triangular resection (86 patients, 48.9%), neochordal implantation (45 patients, 25.6%) and quadrangular resection (28 patients, 15.9%) with a reparability rate of 96.6%. Hospital mortality was 3.6% (n = 3) in group A and 0.6% (n = 1) in group B. Actuarial survival was 50% at 20 years (A) and 81% at 10 years (B). Reoperation-free rate was 98% (A) and 97.2% (B). Taking into account the most frequently used techniques, the recurrence of mitral regurgitation ≥ II was greater in patients with neochordae (n = 14, 26.4%) than in cases with quadrangular (n = 10, 13.2%) or triangular resection (n = 13, 12.4%). Conclusions: Our center has evolved towards techniques with less tissue resection and greater use of neochordae although both techniques have showed excellent long-term results. Resective techniques are more reproducible and durable than neochordal implantation.