Investigación (FEP)

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A Systematic Review of the Claw Toe Deformity: What Is Known and What Is Needed Apart From Surgical Procedures
(John Wiley & Sons Ltd., 2024-10-08) López-López, Daniel; Becerro-de-Bengoa-Vallejo, Ricardo; Losa-Iglesias, Marta; Mayagoitia-Vázquez, José de Jesús; Miguel-Andrés, Israel; Gómez-Salgado, Juan; Ortiz-Lango, Luis Ángel
[Abstract] The claw toe deformity is a painful condition that mainly affects the adult population. Although there are many different treatments to solve the deformity, there is no optimal procedure to restore the normal foot mechanics. The objective of this review was to identify the technical features of the kinematic evaluation methods used in patients with claw toes. Furthermore, the aim of this review was to clarify what is known and what is needed apart from the surgical procedures to correct the claw toe deformity, with the purpose of reducing risk factors of falling in elderly people. A search in electronic databases, such as Scopus (n = 78), Google Scholar (n = 705) and ScienceDirect (n = 290) was conducted. There were seven articles (43.75%) related to the fixation (arthrodesis) of proximal and distal interphalangeal joints, one article (6.25%) describes the correction of the claw toe through plantar plate tenodesis and release of collateral ligaments, four articles (25%) describe the procedure of tendon transfer, one article (6.25%) describes flexor digitorum brevis tenotomy and a proximal interphalangeal joint arthrolysis, and another article (6.25%) presented the impact of partial phalanx osteotomy to treat the claw toe deformity. In conclusion, the review indicates that there are several studies related to the treatment or correction of claw toe deformity. However, there is a lack of knowledge of the postsurgical effects of treating claw toe condition, especially in the structural mechanics (plantar pressure distribution, stability, gait, foot mechanics and so on) of the foot after the correction of the claw toe deformity. The analysis of the foot mechanics after the correction of the claw toes has to be paramount to determine the benefits of the correction.
Relationship of Foot Pain With the Increased Risk of Falls in Patients With Parkinson’s Disease
(John Wiley & Sons Australia, 2024-12-12) López-López, Daniel; Labra, Carmen de; Saavedra-García, Miguel Á.; Navarro-Flores, Emmanuel; Losa-Iglesias, Marta; Becerro-de-Bengoa-Vallejo, Ricardo; Ruiz-Sánchez, Francisco Javier; Montiel-Luque, Alonso
[Abstract] Introduction Falls are one of the most frequent difficulties in patients with Parkinson's disease. The objective of this study was to determine the relationship between foot pain and the risk of falls in participants with Parkinson’s disease compared to a group of participants without Parkinson’s disease. Materials and Methods The subjects (124) were divided into two groups, cases (n = 62) and controls (n = 62). They completed the Downton scale that collects the following 5 dimensions: previous falls, medications, sensory deficit, mental state, and ambulation. Results Analyzing the Downton scale using dimensions, a significant difference was observed between both groups in all dimensions except mental state. Regarding the global result of risk of falls, the participants who had a diagnosis of Parkinson’s disease presented a high risk of falls, 40.3% compared to 3.2% of the non-Parkinson’s disease group, with statistically significant differences (p < 0.05). For the numerical value of the Downton scale, there was a clear statistically significant difference between groups (2.65 ± 0.96 vs. 1.31 ± 1.19). Conclusion This research confirms further evidence that people with Parkinson’s disease who suffer from foot pain are at high risk of falling, regardless of gender.
An Overview of the Risk Factors for Producing Fifth Metatarsal Fracture in Sports Activities: A Systematic Review
(John Wiley & Sons Australia, 2024-10-18) López-López, Daniel; Saavedra-García, Miguel Á.; Becerro-de-Bengoa-Vallejo, Ricardo; Losa-Iglesias, Marta; Ortiz-Lango, Luis Ángel; Miguel-Andrés, Israel; Mayagoitiza-Vázquez, José de Jesús; Gómez-Salgado, Juan
[Abstract] Introduction The fifth metatarsal fracture is a foot injury that occurs in sports activities. This fracture has been associated with risk factors based on intrinsic variables such as type of feet (flatfoot or cavus foot), foot pathologies, and bone density among others. Extrinsic variables associated with fifth metatarsal fractures include sports maneuvers, the type of sports practice, and contact surface. Although this injury has been investigated over the years, there is no consensus on the most relevant risk factors that cause this injury. An increase in the number of people with fractures makes it a relevant topic of research. The objective of this review was to identify an overview of the risk factors for producing the fifth metatarsal fracture based on intrinsic and extrinsic variables in sports activities. Furthermore, this review aimed to clarify what is known and what is needed on the risk factors that can influence the appearance of the fracture. Methods A search in electronic databases, such as Scopus (n = 87), PubMed (n = 187), and Web of Science (n = 173) was conducted. The initial search yielded 447 titles and abstracts, from which 31 papers were selected for detailed analysis after screening all citations against the eligibility criteria. Results After screening the manuscripts, it was found that the fifth metatarsal fracture can be produced by multiple factors. However, most of the studies focus on one or two specific risk factors. It was found that soccer (38.7%) is the sports activity that presents a higher risk of getting a fifth metatarsal fracture compared to other sports activities. The second risk factor was the performance of critical maneuvers (22.5%) and the third one was the biomechanics of the foot (22.5%). Conclusion It is paramount to identify the most critical risk factors linked to the fifth metatarsal fracture to be able to implement effective treatments and prevention strategies.
Influence of the Biomechanical Evaluation of Rupture Using Two Shapes of Same Intramedullary Implant After Proximal Interphalangeal Joint Arthrodesis to Correct the Claw/ Hammer Pathology: A Finite Element Study
(John Wiley & Sons Ltd., 2024-08) López-López, Daniel; Becerro-de-Bengoa-Vallejo, Ricardo; Bayod-López, Javier; Prados-Frutos, Juan Carlos; Losa-Iglesias, Marta Elena; Prados-Privado, María
[Abstract] We used finite element analysis to study the mechanical stress distribution of a new intramedullary implant used for proximal interphalangeal joint (PIPJ) arthrodesis (PIPJA) to surgically correct the claw-hammer toe deformity that affects 20% of the population. After geometric reconstruction of the foot skeleton from claw toe images of a 36-year-old male patient, two implants were positioned, in the virtual model, one neutral implant (NI) and another one 10° angled (10°AI) within the PIPJ of the second through fourth HT during the toe-off phase of gait and results were compared to those derived for the non-surgical foot (NSF). A PIPJA was performed on the second toe using a NI reduced tensile stress at the proximal phalanx (PP) (45.83 MPa) compared to the NSF (59.44 MPa; p < 0.001). When using the 10°AI, the tensile stress was much higher at PP and middle phalanges (MP) of the same toe, measuring 147.58 and 160.58 MPa, respectively, versus 59.44 and 74.95 MPa at corresponding joints in the NSF (all p < 0.001). Similar results were found for compressive stresses. The NI reduced compressive stress at the second PP (-65.12 MPa) compared to the NSF (-113.23 MPa) and the 10°AI (-142 MPa) (all p < 0.001). The von Mises stresses within the implant were also significantly lower when using NI versus 10°AI (p < 0.001). Therefore, we do not recommend performing a PIPJA using the 10°AI due to the increase in stress concentration primarily at the second PP and MP, which could promote implant breakage.
Health Outcomes Reported by Patients with Heart Failure: HF-OUTCOMES-Spain Study
(Elsevier, 2026-10) Crespo-Leiro, María Generosa; Díaz-Molina, Beatriz; García-Pinilla, José Manuel; Goirigolzarri-Artaza, Josebe; Lozano-Bahamonde, Ainara; Núñez, Julio; Movilla Fernández, María Jesús; Blanco-Canosa, Paula; Grille-Cancela, Zulaika; McDonagh, Theresa; Muñiz, Javier
[Abstract] Introduction and objectives. The feasibility of application and usefulness in daily clinical practice of the International Consortium for Health Outcomes Measurement-Heart Failure (ICHOM-HF) set is unknown. The objective of this study was to evaluate the feasibility of implementation and compliance at one year of the ICHOM-HF set in Spanish public hospitals after an episode of heart failure or a scheduled outpatient visit for HF. Methods. HF-OUTCOMES-Spain is a longitudinal study of patients with HF recruited from the cardiology departments of 6 hospitals followed up according to adapted ICHOM-HF recommendations. Success was defined as the proportion of follow-up visits performed as planned >70% and the proportion of missing data <10%. Results. A total of 581 consecutive patients (mean age 68.8 years, 36% women) participated, 73 after hospitalization and 508 as outpatients. A total of 97.3% (248/255) of visits were performed at 30 days according to protocol, as were 97% (532/548) at 6 months and 95.4% (473/496) at 1 year. The results reported by physicians met the target of <10% missing data, while some patient reported outcome measures fell just short, with significant differences between hospitals. Patient reported outcome measures detected common conditions that would otherwise go unnoticed (e.g., suspected depression). Women reported more symptoms, poorer functional status, and more disease-related limitations than men. Conclusions. Implementing the ICHOM-HF set in Spanish public hospitals is feasible and can help identify patients with special treatment needs.
Titin-Related Familial Dilated Cardiomyopathy: Factors Associated with Disease Onset
(Oxford University Press, 2025-08-11) Johnson, Renee; Fletcher, Robert A.; Peters, Stacey; Ohanian, Monique; Soka, Magdalena; Smolnikov, Andrei; Abihider, Katherine E.; Ackerman, Michael J.; Ader, Flavie; Akhtar, Mohammed M.; Amin, Ahmad S.; Ashley, Euan A.; Atherton, John J.; Austin, Rachel; Baas, Annette F.; Bagnall, Richard D.; Ross, Samantha Barratt; Blouin, Jean-Louis; Brown, Emily E.; Bundgaard, Henning; Cannie, Douglas E.; Chmielewski, Przemyslaw; Correnti, Gemma; Crespo-Leiro, María Generosa; Dal Ferro, Matteo; Dellefave-Castillo,. Lisa M.; Domínguez, Fernando; Dooijes, Dennis; Dybro, Anne M.; Ed Demri, Youssef; El Hachmi, Mohamed; Escobar-López, Luis; Foye, Sarah Jajesnica; Franaszczyk, Maria; Gigli, Marta; González-López, Esther; Goudal, Adeline; Graw, Sharon; Guipponi, Michel; Haan, Eric; Haas, Jan; Hammersley, Daniel J.; Hansen, Frederikke G.; Hayward, Christopher S.; Hey, Thomas M.; Heymans, Stephane; Ho, Carolyn Y.; Houweling, Arjan C.; Ingles, Jodie; Ingrey, Angela; Jabbour, Andrew; James, Paul A.; Jansweijer, Joeri A.; Jongbloed, Jan D.H.; Keogh, Anne M.; Larrañaga Moreira, José María; Deprez, Ronald H. Lekanne; Macciocca, Ivan; Macdonald, Peter; Mansencal, Nicolas; Mansour, Julia; Martínez-Veira, Cristina; McDonough, Barbara; McGaughran, Julie; Medo, Kristen; Merlo, Marco; Michalak, Ewa; Monserrat, Lorenzo; Mountain, Helen; Muller, Stephen A.; Murphy, Anne M.; Murray, Brittney; Oates, Emily C.; Ormondroyd, Elizabeth; Pachter, Nicholas; Paldino, Alessia; Palmyre, Aurélien; Pereira, Naveen L.; Picard, Kermshlise C.; Poplawski, Nicola; Prasad, Sanjay; Proukhnitzky, Julie; Pruny, Jean-François; Reant, Patricia; Richard, Pascale; Ronan, Anne; Sedaghat-Hamedani, Farbod; Semsarian, Christopher; Storm, Garrett; Stroeks, Sophie; Syrris, Petros; Taylor, Matthew R.G.; Thomson, Kate
[Abstract] Background and aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results: A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80-30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06-5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27-3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35-9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08-.23). Conclusions: Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.
Implementación de equipos de shock (shock teams) e impacto en el abordaje terapéutico y el pronóstico del shock cardiogénico en España
(Sociedad Española de Medicina de Urgencias y Emergencias (SEMES), 2026-04-27) Marcos-Mangas, Marta; Jorge Pérez, Pablo; Comín-Colet, Josep; Prado, Náyade del; Amado Fernández, Cristina; Viana Tejedor, Ana; Bernal, José Luis; Andrea, Rut; Sionis, Alessandro; Segovia Cubero, Javier; Bañeras, Jordi; Barrionuevo Sánchez, María Isabel; Sánchez-Salado, José Carlos; González-Costello, José; Alegre, Oriol; Martínez-Sellés, Manuel; Martín-Asenjo, Roberto; Crespo-Leiro, María Generosa; Gómez Hospital, Joan Antoni; Elola, Francisco J.; Ariza-Solé, Albert
[Resumen] Objetivos. No existen datos sobre la implementación de equipos de shock (shock teams, ST) ni su impacto en el shock cardiogénico (SC) en España. Métodos. Se realizó un estudio observacional retrospectivo que incluyó episodios de SC (2016-2022) de hospitales del Sistema Nacional de Salud con disponibilidad de unidad de cardiología Intervencionista. La población se dividió en: a) pacientes hospitalizados en centros con ST (SC-ST) y b) pacientes hospitalizados en centros sin ST (SC-NST). También se registró la disponibilidad de unidad de cuidados intensivos cardiológicos (UCIC), cirugía cardiaca, programa de trasplante cardiaco y volumen de casos de SC de cada centro. La variable de resultado fue la mortalidad hospitalaria. Resultados. Se analizaron 15.879 episodios, de los que el 32% (5.095) correspondían al grupo SC-ST. El porcentaje de centros con disponibilidad de ST aumentó de forma progresiva desde el 7% en 2016 al 39% en 2022. Los pacientes del grupo SC-ST eran más jóvenes (68 vs 71 años, p < 0,001), y fueron tratados con mayor frecuencia con ventilación mecánica, depuración extrarrenal y soporte circulatorio (p < 0,001), presentaron mayor incidencia de fracaso renal agudo e ictus y tuvieron una mayor estancia hospitalaria (12 vs 9 días, p < 0,001). La asistencia en centros con ST (OR: 0,86; IC 95%: 0,77-0,96; p = 0,005) y UCIC (OR: 0,82; IC 95%: 0,69-0,98; p < 0,033) se asoció de forma significativa con una menor mortalidad. Conclusiones. La disponibilidad de ST se ha extendido en España. Los pacientes ingresados en centros con ST se manejan de forma más invasiva, y tienen menor mortalidad hospitalaria a pesar de una mayor incidencia de complicaciones.
Natural Missplicing Events Amplified by an Elusive Deep-Intronic MYBPC3 Variant Cause Hypertrophic Cardiomyopathy
(American Heart Association, 2026-09-15) Gallego-Delgado, María; Lorenzo Hernández, Sandra Milagros; García-Hernández, Soledad; Rodríguez Diego, Sara; Heredero-Jung, David Hansoe; Maneiro, Emilia; Pérez-Barbeito, Marlene; García Monsalvo, Mónica; García-Berrocal, Belén; Rincón-Díaz, Luis M.; García-Salgado, María Jesús; Arnáiz-García, María Elena; Álvarez Martínez, Cristina; Díaz-Peláez, Elena; Merino, Ana; Roldán-Sevilla, Álvaro; Mayorga, Alfonso; Martínez-Paz, E.; Ruiz Olgado, María José; Rodríguez Estévez, Lucía; Perdiguero, Pedro D.; Voces, Roberto; Cruz-González, Ignacio; Sánchez, Pedro L; Isidoro-García, María; Ochoa, Juan Pablo; Villacorta, Eduardo; Torrado, Mario
[Abstract] Background: Disruption of MYBPC3 precursor mRNA splicing is a frequent genetic cause of hypertrophic cardiomyopathy (HCM). Most often, it reflects changes at canonical sites or the creation of novel splice sites. Prediction tools usually prioritize splice variants with lower efficiency when they are distant from canonical sites. These elusive variants may explain HCM in patients considered genotype-negative after DNA testing. Methods: Massively parallel sequencing identified the previously unreported deep-intronic variant MYBPC3 c.2308+227G>A in a cohort of genotype-negative patients with HCM from Salamanca, Spain. SpliceAI predicted a benign effect (Δ score, 0.03). However, its recurrent detection prompted us to conduct extensive analyses to investigate its pathogenicity, including genetic testing, clinical assessment, family studies, splicing assays, and haplotype reconstruction. Results: We identified 35 unrelated HCM probands carrying c.2308+227G>A, plus 46 relatives from 27 families, yielding 81 confirmed carriers. Of these, 56 (69%) met diagnostic criteria for HCM (66% male; mean age, 53±15 years). By age 60 years, cumulative penetrance was estimated to be 81% in women and 96% in men. The combined logarithm of the odds score of 5.51 across 20 informative families provided strong evidence of cosegregation. During follow-up of probands, no significant differences were observed in heart failure, arrhythmic events, atrial fibrillation, or mortality when compared with cohorts carrying other pathogenic MYBPC3 variants. Blood splicing assays, confirmed in cardiac tissue, showed that c.2308+227G>A disrupts splicing by the use of pre-existing cryptic donor (c.2308+299) and acceptor (c.2309-580) splice sites, generating 2 misspliced mRNAs with partial intron retention or cryptic exon inclusion, which encode truncated proteins. These cryptic sites are the leading natural, unannotated missplicing events in intron 23, and some of the most frequent across the whole MYBPC3 precursor mRNA, as revealed by SpliceVault analysis of RNA sequencing databases. This deep-intronic variant does not alter essential splice motifs but promotes the use of pre-existing cryptic sites, likely through gain of splicing regulatory enhancer elements. The identification of a shared haplotype among HCM probands carrying this variant explains its recurrent detection, consistent with an ancient founder effect. Conclusions: MYBPC3 c.2308+227G>A is a pathogenic splice-altering variant that causes HCM by amplifying natural missplicing events. These background splicing errors help explain how this elusive variant disrupts splicing without creating novel essential splice sites, thereby expanding the known mechanisms by which deep-intronic variants alter MYBPC3 splicing and ultimately contribute to HCM pathogenesis. Elusive MYBPC3 splice-altering variants should be considered in HCM patients with an unresolved genetic origin of disease.
Sex Differences in a Contemporary, Real-World Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis
(Springer Nature, 2026-09-04) Fontana, Marianna; Aimo, Alberto; Grogan, Martha; Crespo-Leiro, María Generosa; Maurer, Mathew S.; Siepen, Fabian aus dem; Hanna, Mazen; Delgado, Diego; Carlsson, Martin; Damy, Thibaud; Davis, Margot K.
[Abstract] Introduction: Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) versus placebo. ATTR-CM has historically been considered a predominantly male disease, and women are underrepresented in prior studies. Sex-specific data in contemporary patients treated with tafamidis remain limited. Methods: Data from two cohorts were pooled: an early-access cohort (NCT02791230) and patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS; NCT00628745) in 2019-2023. This analysis evaluated sex-related differences in clinical characteristics and all-cause mortality, adjusting for age, cohort, baseline New York Heart Association (NYHA) class, and wild-type (ATTRwt-CM) versus variant (ATTRv-CM) disease. Results: Overall, 1924 patients treated with tafamidis were included (1476 from the early-access cohort and 448 from THAOS), of whom 214 (11.1%) were women. A smaller proportion of women than men had ATTRwt-CM (59.8% vs. 88.9%), whereas a greater proportion had ATTRv-CM (40.2% vs. 11.1%; p < 0.0001). Women were more frequently of African descent (23.9% vs. 7.4%; overall p < 0.001). Age at enrollment, age at symptom onset, and time from symptom onset to diagnosis were similar between sexes (p > 0.05). Women appeared more symptomatic at baseline, with a higher proportion in NYHA class III/IV (37.7% vs. 29.4%; overall p = 0.036) and classified as National Amyloidosis Centre stage II/III (68.1% vs. 47.7%; overall p = 0.023), despite similar N-terminal pro-B-type natriuretic peptide levels (p > 0.05). In adjusted analyses, women had a higher estimated glomerular filtration rate than men (β [men vs. women] = - 10.61; p < 0.001). Over a mean follow-up of 1.5 years, men had a higher risk of all-cause mortality than women (adjusted hazard ratio [men vs. women], 1.60, 95% CI 1.12-2.30). Conclusions: In this analysis of contemporary patients with ATTR-CM treated with tafamidis, women represented a small proportion of the overall population, and a greater proportion had ATTRv-CM compared with men. Although women appeared more symptomatic at presentation, men had a higher risk of all-cause mortality.
From Rescue to Interception: The PREVENT 2-LATE (PReserve Eligibility Via Early, Necessary Transfer) Framework for Advanced Heart Failure
(Elsevier, 2026-08-27) Mehra, Mandeep R.; Nayak, Aditi; Savarese, Gianluigi; Kanwar, Manreet K.; Hall, Shelley A.; Kinugawa, Koichiro; Vukicevic, Milica; Cikes, Maja; Desai, Akshay S.; Molina, Ezequiel J.; Givertz, Michael M.; Crespo-Leiro, María Generosa; Goldstein, Daniel J.; Kormos, Robert L.
[Abstract] The management of advanced heart failure has been transformed by 2 parallel developments that have not yet been fully translated into clinical practice. Heart transplantation and durable left ventricular assist device (LVAD) support confer contemporary 1-year survival approaching 90%; yet, these therapies frequently are deployed only after the onset of progressive right ventricular dysfunction, cardiorenal injury, severe frailty, and hemodynamic instability, which are conditions that elevate procedural risk, impair long-term outcomes, and may ultimately preclude candidacy for advanced therapies altogether. The central limitation in advanced heart failure is therefore no longer the absence of effective therapies but the failure to identify and refer patients during the therapeutic window when physiologic reserve remains intact. This special communication advances 2 related but distinct objectives. First, we propose PREVENT 2-LATE (PReserve Eligibility Via Early, Necessary Transfer), a pragmatic referral framework in which the presence of any 2 of 4 early signals including escalating Loop diuretic requirements, recurrent Admissions, Therapy intolerance, and Early electrical, echocardiographic, or end-organ deterioration supplemented by persistently elevated natriuretic peptides-should prompt consideration for referral through shared care to an advanced heart failure program. These LATE criteria are designed to identify patients earlier in the disease trajectory than existing frameworks, when the full breadth of advanced therapy options is still intact. We further propose a multidisciplinary in-reach model, embedding advanced heart failure expertise within high-risk cardiovascular programs, including electrophysiology, structural heart, cardiogenic shock, cardiac surgery, and specialized cardiomyopathy services, to proactively identify and intercept residual risk before conventional referral triggers emerge. Second, and equally important, this communication provides a consolidated framework for contemporary LVAD best practices, an area in which clinical evidence has advanced rapidly but awareness and adoption remain inconsistent. We synthesize current evidence on morbidity decompression, pharmacologic optimization including renin-angiotensin-aldosterone system inhibition, myocardial recovery, frailty reversibility, and therapeutic sequencing including LVAD-first strategies, with the explicit goal of equipping clinicians to deploy these therapies earlier and more confidently. Critically, PREVENT 2-LATE is not designed to increase use of any single modality. Both heart transplantation and LVAD support are effective, and the framework exists precisely to preserve optionality across the full spectrum of advanced heart failure therapies, enabling expert multidisciplinary teams to match the right intervention to the right patient at the right time. The future of advanced heart failure lies not in increasingly urgent rescue after irreversible decline but in systematic interception while options remain.
Short-Term Mechanical Circulatory Support Before Heart Transplantation and Early Outcomes: Insights From the International Primary Graft Dysfunction Consortium
(Elsevier, 2026-09) Rivas-Lasarte, Mercedes; Ródenas-Alesina, Eduard; Moayedi, Yasbanoo; Truby, Lauren K.; Foroutan, Farid; Henricksen, Erik J.; Signorile, Marisa; Dhingra, Nitish K.; Hastenteufel, Laura; Fan, Chum-Po S.; Guzmán-Bofarull, Joan; Farrero-Torres, Marta; Khush, Kiran K.; Couto-Mallón, David; Moayedifar, Roxana; Kim, G.; Crespo-Leiro, María Generosa; Chih, Sharon; DeVore, Adam D.; Takeda, Koji; Lerman, Joseph B.; Sabatino, Mario; Potena, Luciano; Tremblay-Gravel, Maxime; Noly, Pierre Emmanuel; Miller, Robert J.H.; Zuckermann, Andreas; Farr, Maryjane A.; Ross, Heather; Martin, Archer K.; Segovia Cubero, Javier; Hall, Shelley A.
[Abstract] Background: Heart transplantation (HT) remains the gold-standard therapy for selected patients with advanced heart failure. Increasing recipient complexity and donor organ scarcity have led to the increased use of short-term mechanical circulatory support (ST-MCS) as a bridge to HT. The prognostic impact of ST-MCS on primary graft dysfunction (PGD) and other early outcomes remains limited. Methods: We analyzed data from the Primary Graft Dysfunction Consortium, a retrospective registry including 3800 adult HTs at 14 centers in the United States, Canada, and Europe between 2010 and 2020. Primary outcomes were severe PGD (according to International Society for Heart and Lung Transplantation criteria) and 1-year mortality. Multivariable logistic regression and Cox models were used, with multiple imputation for missingness. Results: Overall, 669 patients (17.6%) received pre-HT ST-MCS. Among them, 16.9% were supported with extracorporeal membrane oxygenation (ECMO), 60.4% with an intra-aortic balloon pump, 9.1% with a percutaneous left ventricular assist device, 9.1% with surgical ventricular assist devices, and 4.5% with other devices. ST-MCS use increased over time and varied by region, with the intra-aortic balloon pump predominating in the United States and ECMO more frequently used in Canada and Europe. Overall, ST-MCS was not associated with severe PGD after adjustment; however, ECMO was independently associated with greater PGD risk (adjusted odds ratio 3.28, 95% confidence interval 1.90-5.66). One-year mortality was 11.0% and did not differ significantly according to ST-MCS use after multivariable adjustment. Conclusions: In this large contemporary multinational cohort, pretransplant ST-MCS use has increased, with geographic heterogeneity observed. Although ECMO is associated with a greater risk of severe PGD, ST-MCS does not independently increase 1-year mortality after HT, supporting its use as a bridge in high-risk patients.
Old Donors for Young Heart Transplant Recipients: Clinical Implications of an Emerging Phenomenon
(Elsevier, 2026-10) Vilches-Miguel, Lidia; Almenar-Bonet, Luis; Crespo-Leiro, María Generosa; Hernández-Pérez, Francisco José; González-Vílchez, Francisco; García-Cosío, María Dolores; Sobrino-Márquez, José Manuel; Farrero-Torres, Marta; González-Costello, José; Martínez-Sellés, Manuel; Arizón-Del Prado, José L.; Mirabet, Sonia; Díaz-Molina, Beatriz; De la Fuente-Galán, Luis; Blasco-Peiró, Teresa; Garrido-Bravo, Iris P.; Rábago Juan-Aracil, Gregorio; García-Quintana, Antonio; Alfonso-Manterola, Fernando; Segovia Cubero, Javier
[Abstract] Background: Historically, heart transplantation (HTx) has focused on matching recipients with organs from donors of similar or younger age. However, due to the growing shortage of donors, especially in Europe, organs from older donors are being used more frequently. Objective: We aimed to evaluate whether transplant matchings with donor older than recipient allocation (DORA) have become more frequent in recent years, if they involved different donor/recipient characteristics, and whether this age mismatch might be associated with less favorable outcomes. Methods: The temporal evolution of the DORA rate in the Spanish HTx Registry (years 1984-2019, N = 8782) was analyzed, and survival was compared in each age-discrepancy group. The effect of DORA on various post-HTx complications was also evaluated. Results: The prevalence of DORA increased from 7% in 1995-1999 to 29% in 2015-2019 (p < 0.001). Both donor and recipient ages were significant predictors of increased mortality when considered individually. DORA mismatch was more frequent in urgent than in elective heart transplants, and recipients in the DORA cohort had more favorable characteristics. Even after adjusting for these variables, most DORA mismatch grades were not associated with reduced survival; only extreme mismatches (≥20 years) were associated with increased mortality. The incidence of primary graft failure, acute rejection, infection, or allograft vasculopathy did not differ between groups. Conclusions: In this extensive real-life registry, receiving a heart from an older donor was generally not associated with increased mortality or complications, although an extreme disparity (≥20 years) might be associated with lower survival.
Clinical Outcomes According to Age and Atrial Fibrillation Type: Insights from the Multicentre REGUEIFA Registry
(MDPI, 2026-09-19) López-Pena, Alejandro Manuel; Elices-Teja, Juliana; Durán-Bobín, Olga; González-Melchor, Laila; Vázquez Caamaño, María; Fernández-Obanza Windcheid, Emiliano; González-Babarro, Eva; Cabanas-Grandío, Pilar; Piñeiro-Portela, Miriam; Prada-Delgado, Óscar; Gutiérrez-Feijoo, Mario; Freire, Evaristo; Díaz-Castro, Óscar; Muñiz, Javier; Barge-Caballero, Eduardo; García-Seara, Javier; González-Juataney, Carlos
[Abstract] Background/Objectives: Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia, and its incidence rises markedly with advancing age. The relative prognostic impact of age compared with AF type remains uncertain. This study assessed the association between age, AF type, and clinical outcomes in a large real-world AF cohort. Methods: This study was based on data from the prospective, observational, multicentre REGUEIFA registry, which includes consecutive patients with AF treated at eight hospitals in northwestern Spain. Patients were stratified by age and AF type. Baseline characteristics, comorbidities, treatments, and risk scores were collected. Patients were followed for at least 2 years, and outcomes included all-cause mortality, heart failure (HF) worsening, stroke, and a composite endpoint. Results: A total of 997 patients were included. Increasing age was associated with a worse clinical profile, with higher comorbidity burden and increased thromboembolic and bleeding risk. During follow-up, adverse events increased stepwise with age, including mortality, HF worsening, and the composite endpoint. AF type was not independently associated with outcomes after multivariable adjustment. Rhythm-control strategy was independently associated with a lower risk of the composite endpoint. Age remained an independent predictor of all outcomes. Risk of the composite endpoint increased across age groups (HR 2.01 for 75-84 years; 2.34 for 85-89 years; 6.50 for ≥90 years vs. <75 years). Each additional year of age was associated with a 9% higher mortality risk (HR 1.09; 95% CI 1.06-1.13). Conclusions: In this prospective real-world cohort of patients with AF, age was the strongest and most consistent predictor of adverse clinical outcomes, whereas AF type lost prognostic significance after adjustment. These findings support age and overall clinical burden as key determinants of prognosis, favouring a patient-centred approach over AF subtype classification.
Neurohormonal therapy in patients with transthyretin cardiac amyloidosis: is it an option?
(Elsevier, 2026-09-23) Enríquez-Vázquez, Daniel; Antúnez-Ballesteros, Milena; Barge-Caballero, Gonzalo; Paniagua-Martín, María J.; Padilla-Bautista, María; González-Montes, Miguel; Couto-Mallón, David; Vázquez-Rodríguez, José Manuel; Barge-Caballero, Eduardo; Crespo-Leiro, María Generosa
[Abstract] Background: Neurohormonal therapy is strongly recommended for heart failure with reduced left ventricular ejection fraction (LVEF). However, its role in transthyretin cardiac amyloidosis remains uncertain given concerns regarding tolerability and the perception that systolic dysfunction reflects an irreversible situation. Cases summary: We report 3 patients with wild-type transthyretin cardiac amyloidosis (wtATTR-CA) who initially presented with heart failure and reduced LVEF (≤35%). Guideline-directed medical therapy was initiated and was carefully titrated. During follow-up, these patients experienced clinical improvement and recovery of LVEF to ≥50%, allowing subsequent initiation of tafamidis, which is only approved for LVEF ≥50% in our country. Discussion: These cases suggest that neurohormonal therapy may be feasible and beneficial in selected patients with wtATTR-CA and reduced LVEF, challenging the traditional paradigm of irreversible systolic dysfunction. Take-home messages: Guideline-directed medical therapy may be considered on an individualized basis in patients with wtATTR-CA and reduced LVEF. Some patients may tolerate treatment and experience improvement.
Role of Cardiopulmonary Exercise Testing in Clinical Stratification in Heart Failure. A Position Paper From the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology
(Oxford University Press, 2017-09-18) Corrá, Ugo; Agostoni, Piergiuseppe; Anker, Stefan; Coats, Andrew J.S.; Crespo-Leiro, María Generosa; De Boer, Rudolf A.; Harjola, Veli-Pekka; Hill, Loreena; Lainscak, Mitja; Lund, Lars H.; Metra, Marco; Ponikowski, Piotr; Riley, Jillian P.; Seferovic, Petar M.; Piepoli, Massimo
[Abstract] Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed.
Cardiac donation in Europe: emerging strategies in a changing landscape
(Elsevier, 2026-09) Crespo-Leiro, María Generosa; Zuckermann, Andreas; Ruschitzka, Frank
Validity of clinic blood pressure compared to ambulatory monitoring in hypertensive patients in a primary care setting
(Taylor & Francis, 2015-01-14) Reino-González, Sergio; Pita-Fernández, Salvador; Cibiriain-Sola, Margarita; Seoane-Pillado, Teresa; López-Calviño, Beatriz; Pértega-Díaz, Sonia
[Abstract] Aims: To determine the validity of the blood pressure (BP) measurement in a primary care setting in comparison with the measurement obtained from 24-h ambulatory blood pressure monitoring (ABPM). Methods: Patients with hypertension (n = 137) were studied in primary care. Immediately after a nurse took two measurements of each patient's BP, the ABPM device was attached. Agreement was determined using the Bland-Altman method and the Kappa index. The sensitivity, specificity, predictive values and likelihood ratios were calculated for the manual BP measurement in comparison with ABPM for the purpose of diagnosing uncontrolled BP. Results: The BP values from ABPM were lower than those obtained in the examination room. The difference between the clinic measurement and the ABPM was 18.07 ± 14.6 mmHg (systolic blood pressure, SBP) and 6.3 ± 9.2 mmHg (diastolic blood pressure, DBP). The agreement between the clinic measurement and 24h-ABPM for the purpose of classifying control or uncontrolled BP was 64.2% (Kappa = 0.311). In the case of ABPM, the sensitivity of the measurement in the examination room for diagnosing uncontrolled BP was 80.36%, specificity was 53.09%, positive predictive value 54.22% and negative predictive value 70.63%. Conclusions: Clinic measurements do not have sufficient sensitivity/specificity to be recommended as a single method of BP control in primary care.
Intensive follow-up strategies improve outcomes in nonmetastatic colorectal cancer patients after curative surgery: a systematic review and meta-analysis
(Elsevier, 2014-11-19) Pita-Fernández, Salvador; Alhayek, Mohammed; González-Martín, Cristina; López-Calviño, Beatriz; Seoane-Pillado, Teresa; Pértega-Díaz, Sonia
[Abstract] Background: A wide variety of follow-up strategies are used for patients with colorectal cancer (CRC) after curative surgery. The aim of this study is to review the evidence of the impact of different follow-up strategies in patients with nonmetastatic CRC after curative surgery, in relation to overall survival and other outcomes. Patients and methods: A systematic search of PubMed, EMBASE, SCOPUS and ISI Web of Knowledge up to June 2014 was carried out. Eligible studies were all randomized clinical trials comparing the effectiveness of different follow-up strategies after curative resection in nonmetastatic CRC. Results: Eleven studies with n = 4055 participants were included in a meta-analysis. A significant improvement in overall survival was observed in patients with more intensive follow-up strategies [hazard ratio = 0.75; 95% confidence interval (CI) 0.66-0.86]. A higher probability of detection of asymptomatic recurrences [relative risk (RR) = 2.59; 95% CI 1.66-4.06], curative surgery attempted at recurrences (RR = 1.98; 95% CI 1.51-2.60), survival after recurrences (RR = 2.13; 95% CI 1.24-3.69), and a shorter time in detecting recurrences (mean difference = -5.23 months; 95% CI -9.58 to -0.88) was observed in the intervention group. There were no significant differences in the total tumor recurrences, nor in the mortality related to disease. Conclusion: Intensive follow-up strategies improve overall survival, increase the detection of asymptomatic recurrences and curative surgery attempted at recurrence, and are associated with a shorter time in detecting recurrences. This more intensive follow-up could not be associated with an improvement in cancer-specific survival nor with an increased detection of total tumor recurrences. Follow-up with serum carcinoembryonic antigen and colonoscopies are related to an increase in overall survival.
Is the ORBIT bleeding risk score superior to the HAS-BLED score in anticoagulated atrial fibrillation patients?
(Japanese Circulation Society, 2016-08-24) Esteve-Pastor, María Asunción; García-Fernández, Amaya; Macías, Manuel; Segorb, Francisco; Valdés, Mariano; Roldán, Vanessa; Muñiz, Javier; Badimón, Lina; Roldán Rabadán, Inmaculada; Bertomeu-Martínez, Vicente; Cequier, Ángel; Lip, Gregory Y.H.; Anguita, Manuel; Marín, Francisco
[Abstract] Background: Several bleeding risk scores have been validated in patients with atrial fibrillation (AF). The ORBIT score has been recently proposed as a simple score with the best ability to predict major bleeding. The present study aimed to test the hypothesis that the ORBIT score was superior to the HAS-BLED score for predicting major bleeding and death in "real world" anticoagulated AF patients. Methods and results: We analyzed the predictive performance for bleeding and death of 406 AF patients who underwent 571 electrical cardioversion procedures and 1,276 patients with permanent/persistent AF from the FANTASIIA registry. In the cardioversion population, 21 patients had major bleeding events and 26 patients died. The predictive performance for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.77 (95% CI 0.66-0.88) and 0.82 (95% CI 0.77-0.93), respectively; P=0.080). For the FANTASIIA population, 46 patients had major bleeding events and 50 patients died. The predictive performances for major bleeding of HAS-BLED and ORBIT were not significantly different (c-statistics 0.63 (95% CI 0.56-0.71) and 0.70 (95% CI 0.62-0.77), respectively; P=0.116). For death, the predictive performances of HAS-BLED and ORBIT were not significantly different in both populations. The ORBIT score categorized most patients as "low risk". Conclusions: Despite the original claims in its derivation paper, the ORBIT score was not superior to HAS-BLED for predicting major bleeding and death in a "real world" oral anticoagulated AF population. (Circ J 2016; 80: 2102-2108).
Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management: position statement on behalf of the Heart Failure Association of the European Society of Cardiology
(Oxford University Press, 2017-10-16) Gorter, Thomas M.; van Veldhuisen, Dirk J.; Bauersachs, Johann; Borlaug, Barry A.; Celutkiene, Jelena; Coats, Andrew J.S.; Crespo-Leiro, María Generosa; Guazzi, Marco; Harjola, Veli-Pekka; Heymans, Stephane; Hill, Loreena; Lainscak, Mitja; Lam, Carolyn S.P.; Lund, Lars H.; Lyon, Alexander R.; Mebazaa, Alexandre; Mueller, Christian; Paulus, Walter J.; Pieske, Burkert Mathias; Piepoli, Massimo; Ruschitzka, Frank; Rutten, Frans H.; Seferovic, Petar M.; Solomon, Scott D.; Shah, Sanjiv J.; Triposkiadis, Filippos; Wachter, Rolf; Tschöpe, Carsten; De Boer, Rudolf A.
[Abstract] There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

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