Vaccine-carditis study: Spanish multicenter registry of inflammatory heart disease after COVID-19 vaccination.

INTRODUCTION AND OBJECTIVES: Vaccines against SARS-CoV-2 have been a major scientific and medical achievement in the control of the COVID-19 pandemic. However, very infrequent cases of inflammatory heart disease have been described as adverse events, leading to uncertainty in the scientific community and in the general population. METHODS: The Vaccine-Carditis Registry has included all cases of myocarditis and pericarditis diagnosed within 30 days after COVID-19 vaccination since August 1, 2021 in 29 centers throughout the Spanish territory. The definitions of myocarditis (probable or confirmed) and pericarditis followed the consensus of the Centers for Disease Control and the Clinical Practice Guidelines of the European Society of Cardiology. A comprehensive analysis of clinical characteristics and 3-month evolution is presented. RESULTS: From August 1, 2021, to March 10, 2022, 139 cases of myocarditis or pericarditis were recorded (81.3% male, median age 28 years). Most cases were detected in the 1st week after administration of an mRNA vaccine, the majority after the second dose. The most common presentation was mixed inflammatory disease (myocarditis and pericarditis). 11% had left ventricular systolic dysfunction, 4% had right ventricular systolic dysfunction, and 21% had pericardial effusion. In cardiac magnetic resonance studies, left ventricular inferolateral involvement was the most frequent pattern (58%). More than 90% of cases had a benign clinical course. After a 3-month follow-up, the incidence of adverse events was 12.78% (1.44% mortality). CONCLUSIONS: In our setting, inflammatory heart disease after vaccination against SARS-CoV-2 predominantly affects young men in the 1st week after the second dose of RNA-m vaccine and presents a favorable clinical course in most cases.

Prevalence and clinical profile of kidney disease in patients with chronic heart failure. Insights from the Spanish cardiorenal registry.

INTRODUCTION AND OBJECTIVES: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF. METHODS: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain. RESULTS: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i. CONCLUSIONS: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.

La reducción temprana del filtrado glomerular se asocia con aumento de la hemoglobina tras el inicio de dapagliflozina en la insuficiencia cardiaca con fracción de eyección reducida / Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction

Introducción y objetivos: Los inhibidores del cotransportador 2 de sodio-glucosa (iSGLT2) inducen cambios a corto plazo en la función renal y la hemoglobina y su fisiopatología se comprende de manera incompleta. Nuestro objetivo es evaluar la relación entre los cambios de la tasa de filtrago glomerular estimado (TFGre) y la hemoglobina tras el inicio de dapagliflozina en pacientes estables con insuficiencia cardiaca y fracción de eyección reducida (IC-FEr). Métodos: Este análisis post hoc de un ensayo clínico aleatorizado evaluó el efecto de la dapagliflozina sobre el consumo máximo de oxígeno a 1 y 3 meses en pacientes ambulatorios con IC-FEr estable (ensayo DAPA-VO2, NCT04197635). Se utilizó un análisis de regresión lineal mixta para evaluar la relación entre los cambios en la TFGe y la hemoglobina a 1 y 3 meses. Resultados: Se evaluó a 87 pacientes. La media de edad era 67,0±10,5 años, y 21 pacientes (24,1%) eran mujeres. Las medias basales de TFGe y hemoglobina fueron de 66,9±20,7ml/min/1,73 m2 y 14,3±1,7g/dl respectivamente. En comparación con el placebo, la TFGe no cambió significativamente en el grupo de dapagliflozina, pero la hemoglobina aumentó significativamente a 1 y 3 meses. A 1 mes, el aumento de la hemoglobina se relacionó con la disminución de la TFGe solo en el grupo de dapagliflozina (p <0,001). A los 3 meses no había asociación significativa (p=0,123). Los cambios de la TFGe a 1 y 3 meses no se asociaron con cambios en el consumo pico de oxígeno, la calidad de vida o los péptidos natriuréticos. Conclusiones: En pacientes con IC-FEr estable, los cambios en la TFGe a 1 mes inducidos por la dapagliflozina están en relación inversa con cambios en la hemoglobina. Esta asociación no se observa a los 3 meses. (AU)

Introduction and objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF). Methods: This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO2 trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms. Results: A total of 87 patients were evaluated in this substudy. The mean age was 67.0± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9±20.7mL/min/1.73m2 and 14.3±1.7g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P <.001). At 3 months, there was no significant association in either treatment arms (P=.123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides. Conclusions: In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months. (AU)

The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. METHODS: A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p.(Glu259Glyfs*77) variant in the PKP2 gene. The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. RESULTS: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 [24-59] months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed. CONCLUSIONS: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry.

PURPOSE OF THE WORK: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF. FINDINGS: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.

Análisis de la actividad de la consulta de enfermería telefónica a demanda para pacientes con insuficiencia cardíaca / Analysis of the activity of the telephone nursing consultation on demand for patients with heart failure

Objetivo: Analizar los motivos más frecuentes de demanda telefónica en la consulta de la enfermera de insuficiencia cardiaca y evaluar la capacidad de resolución de respuesta tras la llamada. Método: Estudio descriptivo, retrospectivo, de todas las llamadas telefónicas registradas entre junio de 2020 y abril de 2021 en una consulta específica de enfermería para la atención a la insuficiencia cardiaca. De las historias clínicas electrónicas se extrajeron las principales variables sociodemográficas y clínicas, el motivo de llamada y la acción realizada por la enfermera, para su posterior análisis descriptivo. Resultados: Se analizaron 643 llamadas, 354 (55,1%) de las cuales fueron realizadas por los pacientes. El motivo de llamada más frecuente fue para consultar síntomas: 45,8% (n=162). El 71,6% (n=116) de las consultas se solucionaron ajustando el tratamiento farmacológico por teléfono, el 24,7% (n=40) precisaron una visita presencial en la consulta de la enfermera, necesitaron atención en urgencias 22 (13,6%) pacientes: 5 por empeoramiento de la insuficiencia cardiaca. Los pacientes que consultaron por síntomas presentaban peor clase funcional (p=0,007) y habían sido derivados desde hospitalización (p=0,023). Conclusiones: La consulta telefónica se mostró útil para pacientes con insuficiencia cardiaca, siendo principalmente demandada por usuarios que presentan síntomas de empeoramiento de su enfermedad.(AU)

Objective: Analyzing the most frequent reasons for telephone demand in the heart failure nurse's consultation and to evaluate the response resolution capacity after the call. Method: Descriptive, retrospective study of all telephone calls recorded between June 2020 and April 2021 in a specific nursing consultation for heart failure care. The main sociodemographic and clinical variables, reason for calling and action carried out by the nurse were extracted from the electronic medical records, for its subsequent descriptive analysis. Results: A total of 643 calls were analyzed, 354 (55.1%) were made by the patients. The most frequent reason for calling was to consult symptoms: 45.8% (n=162). 71.6% (n=116) of the consultations were resolved by adjusting the pharmacological treatment by telephone, 24.7% (n=40) required a face-to-face visit in the nurse's consultation, 22 (13.6%) needed emergency care: 5 due to worsening heart failure. The patients who consulted for symptoms had a worse functional class (P=.007) and had been referred from hospitalization (P=.023). Conclusions: The telephone consultation was shown to be useful for patients with heart failure, being mainly demanded by users who present symptoms of worsening of their disease.(AU)

Early glomerular filtration rate decline is associated with hemoglobin rise following dapagliflozin initiation in heart failure with reduced ejection fraction.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce short-term changes in renal function and hemoglobin. Their pathophysiology is incompletely understood. We aimed to evaluate the relationship between 1- and 3-month estimated glomerular filtration rate (eGFR) and hemoglobin changes following initiation of dapagliflozin in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS: This is a post hoc analysis of a randomized clinical trial that evaluated the effect of dapagliflozin on 1- and 3-month peak oxygen consumption in outpatients with stable HFrEF (DAPA-VO2 trial, NCT04197635). We used linear mixed regression analysis to assess the relationship between eGFR and hemoglobin changes across treatment arms. RESULTS: A total of 87 patients were evaluated in this substudy. The mean age was 67.0± 10.5 years, and 21 (24.1%) were women. The mean baseline eGFR and hemoglobin were 66.9±20.7mL/min/1.73m2 and 14.3±1.7g/dL, respectively. Compared with placebo, eGFR did not significantly change at either time points in the dapagliflozin group, but hemoglobin significantly increased at 1 and 3 months. At 1 month, the hemoglobin increase was related to decreases in eGFR only in the dapagliflozin arm (P <.001). At 3 months, there was no significant association in either treatment arms (P=.123). Changes in eGFR were not associated with changes in peak oxygen consumption, quality of life, or natriuretic peptides. CONCLUSIONS: In patients with stable HFrEF, 1-month changes in eGFR induced by dapagliflozin are inversely related to changes in hemoglobin. This association was no longer significant at 3 months.

Short-term Changes in Hemoglobin and Changes in Functional Status, Quality of Life and Natriuretic Peptides After Initiation of Dapagliflozin in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels. METHODS: This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels. RESULTS: At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; P = 0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; P = 0.048 and -62.7%; P = 0.029, respectively). CONCLUSIONS: In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.

Analysis of the activity of the telephone nursing consultation on demand for patients with heart failure.

OBJECTIVE: Analyzing the most frequent reasons for telephone demand in the heart failure nurse's consultation and to evaluate the response resolution capacity after the call. METHOD: Descriptive, retrospective study of all telephone calls recorded between June 2020 and April 2021 in a specific nursing consultation for heart failure care. The main sociodemographic and clinical variables, reason for calling and action carried out by the nurse were extracted from the electronic medical records. For its subsequent descriptive análisis. RESULTS: 643 calls were analyzed, 354 (55.1%) were made by the patients. The most frequent reason for calling was to consult symptoms 45.8% (n = 162). 71.6% (n = 116) of the consultations were resolved by adjusting the pharmacological treatment by telephone, 24.7% (n = 40) required a face-to-face visit in the nurse's consultation, 22 (13.6%) needed emergency care. 5 due to worsening heart failure. The patients who consulted for symptoms had a worse functional class (p = 0.007) and had been referred from hospitalization (p = 0.023). CONCLUSIONS: The telephone consultation was shown to be useful for patients with heart failure, being mainly demanded by users who present symptoms of worsening of their disease.

The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants.

BACKGROUND: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. RESULTS: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). CONCLUSIONS: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry.

AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.

Pharmacotherapy for stroke prevention in nonvalvular atrial fibrillation: current strategies and future directions.

INTRODUCTION: Cardioembolic stroke, associated to nonvalvular atrial fibrillation (NVAF), accounts for approximately one in every four strokes. Cardioembolic stroke has a bad prognosis and is associated with a significant rate of recurrence. AREAS COVERED: This article reviews current pharmacotherapeutic options for prevention of stroke in NVAF, paying special attention to their use in particular clinical settings (e.g. cardioversion, catheter ablation). We also aim to review new drug candidates that have entered clinical studies in this indication. EXPERT OPINION: Oral anticoagulant therapy (OAT) remains the mainstay for ischemic stroke prophylaxis in NVAF in patients at risk. Several oral (asundexian, milvexian) and parenteral (abelacimab, osocimab, xisomab, IONIS-FXIRX, fesomersen) factor XIa inhibitors are under development. These new compounds appear to be associated with a low bleeding tendency and have the potential to complement current existing alternatives for anticoagulation. However, it is also of paramount importance to implement interventions to improve adherence to available anticoagulants, which is currently suboptimal. Non-anticoagulant drugs, such as colchicine, metformin and dronedarone, also being investigated to reduce the burden of NVAF and cardioembolic stroke. Additional clinical data are needed to more clearly define the role of these drugs for stroke prevention in NVAF.

Case report on ambulatory pulmonary pressure monitoring: an attempt to reduce readmissions for heart failure with preserved ejection fraction.

Background: Despite many recent advances in heart failure (HF) therapies, there remains an unmet need in patients with HF with preserved ejection fraction (HFpEF) for adequate treatment and follow-up, with the potential to reduce associated mortality and morbidity. Increased intracardiac and intrapulmonary pressures have been shown to precede the onset of symptoms of decompensated HF by several days or even weeks, so there have been several attempts to influence the prognosis of HF by monitoring through various methods. One of these is ambulatory pulmonary pressure monitoring to guide treatment in anticipation of decompensation. Case summary: We present the case of a 65-year-old woman with rheumatic valve disease and mechanical aortic and mitral prosthesis since 2003 and pacemaker since 2014, with development of severe tricuspid regurgitation in 2018 and with new valve implantation and multiple decompensations of HFpEF despite optimal medical treatment. Under follow-up in the Heart Failure Unit and after multiple unsuccessful treatment adjustments, it was decided to implant a pulmonary artery pressure monitoring device-CardioMEMS®-in order to optimize patient follow-up and treatment. The procedure was carried out without complications and early optimization of treatment was possible, resulting in a significant reduction in decompensations and admissions for HF. Discussion: Ambulatory pulmonary pressure monitoring is shown to be a safe and effective option to anticipate treatment of heart failure decompensation even with preserved left ventricular ejection fraction, with a significantly positive impact on hospital readmissions and consequent benefit on morbidity and mortality.

Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator.

AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.

Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2 ): a randomized clinical trial.

AIMS: This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n = 45) or placebo (n = 45). The primary outcome was a change in peak oxygen consumption (peakVO2 ) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO2 , 6MWT and MLHFQ were 13.2 ± 3.5 ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th-75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889-2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO2 significantly increased in patients on treatment with dapagliflozin (1 month: +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14-2.04; p = 0.021, and 3 months: +Δ 1.06 ml/kg/min, 95% CI 0.07-2.04; p = 0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints. CONCLUSIONS: Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO2 at 1 and 3 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04197635.

Prevalence, Incidence, and Outcomes of Hyperkalaemia in Patients with Chronic Heart Failure and Reduced Ejection Fraction from a Spanish Multicentre Study: SPANIK-HF Design and Baseline Characteristics.

Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m2, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1−5.4 mEq/L = 13.8%, 5.5−5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment.