Cardiovascular and Renal Treatment in Heart Failure Patients with Hyperkalemia or High Risk of Hyperkalemia: Rationale and Design of the CARE-HK in HF Registry.

BACKGROUND: Despite guideline recommendations, many patients with heart failure (HF) do not receive target doses of renin-angiotensin-aldosterone system inhibitors (RAASis) in clinical practice due, in part, to concerns about hyperkalemia (HK). METHODS AND RESULTS: This non-interventional, multinational, multicenter registry (NCT04864795; 111 sites in Europe and the USA) enrolled 2,558 eligible adults with chronic HF (mostly with reduced ejection fraction [HFrEF]). Eligibility criteria included use of angiotensin-converting-enzyme inhibitor / angiotensin-II receptor blocker / angiotensin-receptor-neprilysin inhibitor, candidate for or treatment with mineralocorticoid receptor antagonist, and increased risk of HK (eg, current serum potassium >5.0 mmol/L], history of HK in the previous 24 months, or estimated glomerular filtration rate <45 mL/min/1.73 m2). Information on RAASi and other guideline-recommended therapies was collected retrospectively and prospectively (≥6 months). Patients were followed according to local clinical practice, without study-specific visits or interventions. The main objectives were to characterize RAASi treatment patterns compared with guideline recommendations, describe RAASi modifications following episodes of HK, and describe RAASi treatment in patients treated with patiromer. Baseline characteristics for the first 1,000 patients are presented. CONCLUSIONS: CARE-HK is a multinational prospective HF registry designed to report on the management and outcomes of patients with HF at high risk for HK in routine clinical practice.

The effect of long-term tafamidis treatment on quality of life in people with transthyretin amyloid cardiomyopathy (ATTR-CM): A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary explains some results of a study called ATTR-ACT and its ongoing long-term extension study that were published in the European Journal of Heart Failure. The purpose of ATTR-ACT was to find out if a drug called tafamidis is an effective treatment for people with a heart condition called transthyretin amyloid cardiomyopathy (ATTR-CM). People took tafamidis or placebo for up to 2.5 years in ATTR-ACT (the initial study). A placebo looks like the study medicine but does not contain any active ingredients. After people completed the initial study, they could take part in the extension study. An extension study allows people to continue receiving treatment after the original clinical study ends and helps researchers understand how well a treatment works over a longer time period. This extension study allows people to receive tafamidis for up to an additional 5 years. People who took placebo in the initial study now receive tafamidis. People who took tafamidis in the initial study continue tafamidis treatment. Researchers looked at changes in peoples' ability to enjoy life ('quality of life') and heart failure symptoms since they started ATTR-ACT. Results are available for the first 2.5 years of the extension study. WHAT ARE THE KEY TAKEAWAYS?: During the initial study, there was less worsening of quality of life and heart failure symptoms in people who took tafamidis compared to people who took placebo. In the extension study, quality of life and heart failure symptoms were maintained or nearly maintained in people who took tafamidis in the initial study. In people who started tafamidis in the extension study, quality of life and heart failure symptoms continued to worsen, but the worsening slowed down. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Tafamidis slows the worsening of quality of life and heart failure symptoms in people with ATTR-CM. People with ATTR-CM should start treatment early to receive the most benefit.Clinical Trial Registration: NCT01994889 (ATTR-ACT) (ClinicalTrials.gov).

Connective tissue amyloidosis in patients referred for orthopedic surgery. CONNECT-AMY study. / Amiloidosis del tejido conectivo en pacientes referidos a cirugía ortopédica. Estudio CONNECT-AMY.

INTRODUCTION AND OBJECTIVE: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement. MATERIAL AND METHODS: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement. RESULTS: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement. CONCLUSIONS: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue.

Spanish heart transplant registry. 35th official report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: Our aim was to describe the characteristics and outcomes of heart transplants in Spain. METHODS: We analyzed trends in recipient and donor characteristics, recipient-donor interaction, surgical procedures, immunosuppression, and outcomes of patients included in the Spanish heart transplant registry from 2014 to 2023. Changes in survival were analyzed using the Kaplan-Meier method. RESULTS: In 2023, 325 cardiac transplants were performed (4.5% more than in the previous year), with a total of 2987 procedures from 2014 to 2023. There was a trend toward performing more transplants in women (29.2%), with etiologies other than cardiomyopathy (32.6%), and with better pretransplant status (less hepatic [12.5%], renal [glomerular filtration rate, 81.5mL/min/1.73 m2], and respiratory [8.7%] involvement). In 2023, the number of urgent transplants increased (44% of the total), especially those performed after circulatory support with extracorporeal membrane oxygenation (36% of total assistance), and transplants performed with donation after circulatory death (17.9%). Survival improved in the triennium from 2020 to 2022 compared with 2014 to 2016 (83.0% at 1 year from 2020-2022 vs 79.0% from 2014-2016). CONCLUSIONS: The number of transplants performed in Spain showed an upward trend, with recipients with better clinical status and an increasing use of donation after circulatory death. Survival improved in the last triennium.

Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL) / Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introducción y objetivos: La amiloidosis cardiaca (AC) es una patología asociada a un elevado número de ingresos hospitalarios. Dada la escasa información disponible al respecto, planteamos un análisis de la incidencia y las causas de hospitalización en esta enfermedad.Material y métodosSe evaluaron 143 pacientes (128 por transtiretina [AC-ATTR] y 15 por cadenas ligeras [AC-AL]) incluidos en el Registro de Amiloidosis Cardiaca de Galicia (AMIGAL), recogiendo todas sus hospitalizaciones.ResultadosDurante un seguimiento mediano de 959 días se produjeron 179 hospitalizaciones no programadas (tasa de incidencia [TI] 512,6 ingresos hospitalarios por 1.000 pacientes-año), siendo las más habituales las de causa cardiovascular (n=109, TI 312,2). El motivo individual de ingreso hospitalario más frecuente fue la insuficiencia cardiaca (IC) (n=87, TI 249,2).La AC-AL se asoció con una TI de hospitalizaciones no programadas más elevada que la AC-ATTR (TI 781 vs. 483,2; HR 1,62; p=0,029) a expensas de las de causa no cardiovascular (TI 376 vs. 181,2; HR 2,07; p=0,027). La supervivencia libre de hospitalización no programada al año y a los tres años en la AC-AL fue menor que en la AC-ATTR (46,7 y 20,0% vs. 73,4 y 35,2%, respectivamente; p=0,021). (AU)

Introduction and objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease.Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations.ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). (AU)

Effect of long-term tafamidis treatment on health-related quality of life in patients with transthyretin amyloid cardiomyopathy.

AIMS: To evaluate the effect of long-term tafamidis treatment on health-related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension (LTE) study. METHODS AND RESULTS: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) and clinical summary (KCCQ-CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR-ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR-ACT and tafamidis for 30 months in the LTE study. In ATTR-ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6- to 7-point reduction in least squares (LS) mean (standard error) KCCQ-OS and KCCQ-CS scores at month 30 (-6.25 [1.53] and -7.48 [1.39]), with little or no further decline over the next 30 months (-5.92 [1.77] and -9.21 [1.88] at month 60). Patients who received placebo in ATTR-ACT had a 20-point reduction in LS mean KCCQ-OS and KCCQ-CS scores at month 30 (-19.60 [1.94] and -19.90 [2.01]), but the decline slowed after initiating tafamidis (-24.70 [3.04] and -25.30 [3.36] at month 60). CONCLUSION: Tafamidis reduced HRQoL decline in patients with ATTR-CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR-ACT, tafamidis reduced the decline in HRQoL during the LTE study.

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Prognostic value of the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio in cardiac amyloidosis.

INTRODUCTION AND OBJECTIVES: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis. METHODS: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days. RESULTS: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization. CONCLUSIONS: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis.

Use of a surgically implanted, nondischargeable, extracorporeal continuous flow circulatory support system as a bridge to heart transplant.

INTRODUCTION AND OBJECTIVES: We aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx). METHODS: We conducted a descriptive analysis of the clinical outcomes of consecutive HTx candidates included in a multicenter retrospective registry who were treated with the CentriMag device, configured either for left ventricular support (LVS) or biventricular support (BVS). All patients were listed for high-priority HTx. The study assessed the period 2010 to 2020 and involved 16 transplant centers around Spain. We excluded patients treated with isolated right ventricular support or venoarterial extracorporeal membrane oxygenation without LVS. The primary endpoint was 1-year post-HTx survival. RESULTS: The study population comprised 213 emergency HTx candidates bridged on CentriMag LVS and 145 on CentriMag BVS. Overall, 303 (84.6%) patients received a transplant and 53 (14.8%) died without having an organ donor during the index hospitalization. Median time on the device was 15 days, with 66 (18.6%) patients being supported for> 30 days. One-year posttransplant survival was 77.6%. Univariable and multivariable analyses showed no statistically significant differences in pre- or post-HTx survival in patients managed with BVS vs LVS. Patients managed with BVS had higher rates of bleeding, need for transfusion, hemolysis and renal failure than patients managed with LVS, while the latter group showed a higher incidence of ischemic stroke. CONCLUSIONS: In a setting of candidate prioritization with short waiting list times, bridging to HTx with the CentriMag system was feasible and resulted in acceptable on-support and posttransplant outcomes.

Left ventricular ejection fraction digit bias and reclassification of heart failure with mildly reduced vs reduced ejection fraction based on the 2021 definition and classification of heart failure.

AIMS: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. METHODS AND RESULTS: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. CONCLUSIONS: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

Registro español de trasplante cardiaco. XXXIV informe oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología / Spanish heart transplant registry. 34th official report of the Heart Failure Association of the Spanish Society of Cardiology

Introducción y objetivos: El Registro español de trasplante cardiaco actualiza sus datos anualmente. En este artículo se presentan los datos correspondientes al año 2022.Métodos: Se describen las principales características clínicas, del tratamiento recibido y de los resultados en términos de supervivencia de los procedimientos realizados en 2022, así como las tendencias de estos desde el año 2013.Resultados: En 2022 se han realizado 311 trasplantes cardiacos (un 3,0% más que el año anterior). No se han observado cambios relevantes en las características demográficas y clínicas en 2022 respecto a los años inmediatamente anteriores, lo que confirma las tendencias ya descritas en la última década a una disminución de los procedimientos urgentes y el uso de asistencia circulatoria, sobre todo de dispositivos de asistencia ventricular. En el último decenio, las supervivencias son del 81,4 y el 73,4% a 1 año y a los 3 años, con una mejoría numérica que no ha alcanzado significación estadística.Conclusiones: En la última década se observa una estabilización en las características de los procedimientos de trasplante cardiaco y de sus resultados. Registrado en ClinicalTrial.gov (Identificador: NCT03015311).(AU)

Introduction and objectives: The Spanish heart transplant registry updates its data annually. The current update presents the data for the year 2022.Methods: We describe the main clinical characteristics, treatments received, and survival outcomes including procedures performed in 2022, along with their trends since 2013.Results: In 2022, 311 cardiac transplants were performed, representing a 3.0% increase compared with 2021. Compared with previous years, no significant changes in demographic and clinical characteristics were observed in 2022, confirming the trends identified in the last decade. These trends indicate a decrease in urgent procedures and the use of circulatory support, particularly ventricular assist devices. In the last decade, survival rates at 1 and 3 years were 81.4% and 73.4% respectively, with a slight, nonsignificant improvement.Conclusions: In the last decade, there has been a stabilization in the characteristics of heart transplant procedures and their outcomes. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).(AU)

Spanish heart transplant registry. 34th official report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: The Spanish heart transplant registry updates its data annually. The current update presents the data for the year 2022. METHODS: We describe the main clinical characteristics, treatments received, and survival outcomes including procedures performed in 2022, along with their trends since 2013. RESULTS: In 2022, 311 cardiac transplants were performed, representing a 3.0% increase compared with 2021. Compared with previous years, no significant changes in demographic and clinical characteristics were observed in 2022, confirming the trends identified in the last decade. These trends indicate a decrease in urgent procedures and the use of circulatory support, particularly ventricular assist devices. In the last decade, survival rates at 1 and 3 years were 81.4% and 73.4% respectively, with a slight, nonsignificant improvement. CONCLUSIONS: In the last decade, there has been a stabilization in the characteristics of heart transplant procedures and their outcomes. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice.

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.