Late gadolinium enhancement and outcome of cardiac resynchronization therapy in non-ischemic cardiomyopathy.

BACKGROUND: It is uncertain whether CRT with defibrillator (CRTD) is superior to CRT with pacemaker (CRTP) in NICM. Patients with low arrhythmic risk and high probability of response to CRT might be ideal candidates for CRTP. We aimed to evaluate predictors of ventricular arrhythmias and of echocardiographic response to cardiac resynchronization therapy (CRT) in non-ischemic cardiomyopathy (NICM). METHODS: Multicenter, retrospective observational study of NICM patients with left ventricular ejection fraction (LVEF) ≤35 %, cardiac magnetic resonance with analysis of late gadolinium enhancement (LGE) available and de-novo CRT implant. Echocardiographic response to CRT was defined as an improvement in LVEF ≥10 %. The combined arrhythmic endpoint included sustained ventricular tachycardia, appropriate ICD therapy, resuscitated cardiac arrest and sudden death. RESULTS: We included 167 patients, with a median follow-up of 63 months. LGE was present in 77 (46 %). Response to CRT occurred in 68 % of patients, more frequently in LGE- than in LGE+ (81 % vs 53 %, p < 0.001). Absence of LGE (OR 3.4, p = 0.002), was an independent predictor of response to CRT. The arrhythmic endpoint occurred in 19 patients (11 %). Among LGE- patients there were zero arrhythmic events as compared to a 25 % cumulative incidence in LGE+ (p < 0.001). Presence of LGE (HR 22.5, p < 0.001), was an independent predictor of the arrhythmic endpoint. CONCLUSION: Absence of LGE identifies patients at minimal arrhythmic risk and with high probability of response to CRT. Thus, they might be ideal candidates to CRT-P.

Prognostic Role of Tissue Iron Deficiency Measured by sTfR Levels in Heart Failure Patients without Systemic Iron Deficiency or Anemia.

Background. Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods. This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results. The sTfR level (HR 1.48, 95% CI 1.13-1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22-3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.

Serum potassium abnormalities, renin-angiotensin-aldosterone system inhibitor discontinuation, and clinical outcomes in patients with chronic cardiovascular, metabolic, and renal conditions: A population-based analysis.

BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASIs) play a crucial role in the treatment of several chronic cardiovascular conditions. Nonetheless, hyperkalemia, a frequent side effect, often leads to the discontinuation of RAASIs. The implications of hyperkalemia-driven changes in RAASI medications are poorly understood. METHODS: Population-based, observational, retrospective cohort study. Two large healthcare databases were utilized to identify 77,089 individuals aged 55 years and older with chronic conditions who were prescribed RAASIs between 2015 and 2017 in Southern Barcelona, Spain. We assessed the interplay between serum potassium abnormalities, RAASI management, and their associations with clinical outcomes, adjusting for potential confounders including socioeconomic factors, medical conditions, and potassium levels. RESULTS: The one-year prevalence of hyperkalemia (defined as serum potassium, K+ >5.0 mmol/L) was 17.8 %. RAASI were down-titrated in 16.1 % of these 13,673 patients with K+ levels. Factors linked to a higher likelihood of reducing/discontinuing RAASI after developing hyperkalemia included older age, impaired kidney function, higher potassium levels, and previous hospitalizations. Dose reduction/discontinuation of RAASI after developing hyperkalemia was associated with an increased risk of hospitalization (adjusted hazard ratio [HR] 1.16, 95 % confidence interval [CI] 1.10-1.21) and with increased mortality (HR 1.60, 95 % CI 1.56-1.84). CONCLUSION: In this large, observational study, hyperkalemia was linked to a greater likelihood of discontinuing RAASIs. Down-titration of RAASI was independently associated with unfavorable clinical outcomes such as hospitalization and specially mortality. Although the observational nature of the study, these findings underscore the importance of preventing circumstances that may lead to RAASI down-titration, such as hyperkalemia, as well as preventing hospitalizations and mortality, to ensure RAASI benefits.

Early Miocene remains of Melissiodon from Mokrá-Quarry (Moravia, Czech Republic) shed light on the evolutionary history of the rare cricetid genus.

Background: Melissiodon is a rare cricetid genus endemic to Europe, known from the Early Oligoceneto the Early Miocene. It is usually a very rare find, and even in the few localities where Melissiodon remains are found, those are scarce and fragmentary. Only a few Central European localities have yielded rich remains of the genus. Currently, two species are known from the Early Miocene: Melissiodon schlosseri, which is based on two teeth from the MN2 German locality of Haslach and only found in two other sites of similar age (Ulm-Uniklinik and La Chaux, from Germany and Switzerland respectively); and Melissiodon dominans, found in MN3 and MN4 localities across Europe, even though the scarce and fragmentary remains make some of these attributions dubious. For that reason, Melissiodon dominans has become a catch-all species. However, Mokrá-Quarry represents one of the best documented findings of Melissiodon remains from MN4 localities of Europe. Methods: The Melissiodon assemblage from Mokrá-Quarry has been studied thoroughly, providing metrics and detailed descriptions of all teeth positions, as well as complete comparisons with other MN3 and MN4 localities bearing Melissiodon remains. Results: In this work, new remains of Melissiodon have been identified as a new morphotype that clearly differs from Melissiodon dominans by its unique m1 morphology but still shows some resemblance with Melissiodon schlosseri. Based on that, we here propose the hypothesis of an evolutionary lineage starting from Melissiodon schlosseri, diverging from the lineage leading towards Melissiodon dominans. With this finding, there are at least two different taxa of Melissiodon known during the Early Miocene, prior to the genus extinction. This study arises the certainty that the evolution history of the genus is more complex than previously thought and that more studies are necessary to elucidate it, including a complete revision of the type material of Melissiodon dominans and Melissiodon schlosseri in the light of current knowledge of the genus, which will help to elucidate the attribution of the populations from Mokrá-Quarry. For the time being, the assemblage presented here is referred as Melissiodon aff. schlosseri.

Can Pallars i Llobateres: A new hominoid-bearing locality from the late Miocene of the Vallès-Penedès Basin (NE Iberian Peninsula).

In the Iberian Peninsula, Miocene apes (Hominoidea) are generally rare and mostly restricted to the Vallès-Penedès Basin. Here we report a new hominoid maxillary fragment with M2 from this basin. It was surface-collected in March 2017 from the site of Can Pallars i Llobateres (CPL, Sant Quirze del Vallès), where fossil apes had not been previously recorded. The locality of provenance (CPL-M), which has delivered no further fossil remains, is located very close (ca. 50 m) to previously known CPL outcrops, and not very far (ca. 500 m in NW direction) from the classical hominoid-bearing locality of Can Poncic 1. Here we describe the new fossil and, based on the size and proportions of the M2, justify its taxonomic attribution to Hispanopithecus cf. laietanus, a species previously recorded from several Vallesian sites of the Vallès-Penedès Basin. Based on the associated mammalian fauna from CPL, we also provide a biochronological dating and a paleoenvironmental reconstruction for the site. The associated fauna enables an unambiguous correlation to the Cricetulodon hartenbergeri - Progonomys hispanicus interval local subzone, with an estimated age of 9.98-9.73 Ma (late Vallesian, MN10). Therefore, CPL-M is roughly coeval with the Hispanopithecus laietanus-bearing localities of Can Llobateres 1 and Can Feu 1, and minimally older than those of La Tarumba 1 and Can Llobateres 2. In contrast, CPL-M is younger than the early Vallesian (MN9) localities of Can Poncic 1 (the type locality of Hispanopithecus crusafonti) as well as Polinyà 2 (Gabarró) and Estació Depuradora d'Aigües Residuals-Riu Ripoll 13, where Hispanopithecus sp. is recorded. The associated fauna from CPL indicates a densely forested and humid paleoenvironment with nearby freshwater. This supports the view that Hispanopithecus might have been restricted to dense wetland forests soon before its extinction during the late Vallesian, due to progressive climatic deterioration. Coupled with the existence of other fossiliferous outcrops in the area, this find is most promising for the prospect of discovering additional fossil hominoid remains in the future.