Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.

Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged adults.

AIMS: Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. METHODS: A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrollment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed, and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). RESULTS: On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 (OR for 3rd tertile, 8.31; 95% CI 2.85-24.2; p<0.001; and 2.77; 95% CI, 1.02-7.51; p=0.045, respectively) and provided significant incremental diagnostic value over SCORE2. CONCLUSIONS: In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures.

Monocyte distribution width (MDW): study of reference values in blood donors.

OBJECTIVES: Monocyte distribution width (MDW) is a new biomarker used as an early indicator of sepsis (ESId). It is often aids in the identification of patients who may develop sepsis. This study aims to establish the MDW reference interval (RI) within the healthy population of blood donors using EDTA-K2 as anticoagulant. Many hospitals use this biomarker as a means of identifying patients who present to the hospital with sepsis. METHODS: A total of 274 samples obtained from healthy donors were analyzed. MDW measurements were taken within 2 h post-extraction. The RI was estimated using various statistical methodologies, including the recommended CLSI EP28-A3c guideline, non-parametric and robust methods, along with the Harrell-Davis bootstrap method applied to the entire sample. RESULTS: The RI estimated through non-parametric method was 14.77 CI90 % (14.36-14.97)-21.13 CI90 % (20.89-21.68); RI using the robust method was 15.64-19.05 and RI using the Harrell-Davis bootstrap method was 14.73 CI90 % (14.53-14.92)-21.14 CI90 % (20.88-21.40). CONCLUSIONS: Based on clinical applicability, we recommend utilizing the RI derived from the non-parametric method, aligning with the CLSI recommendations. Furthermore, we consider that our results can be taken as a reference in other laboratories that serve a population similar to our study cohort.

Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife: The PESA Observational Study.

BACKGROUND: APOE is a known genetic contributor to cardiovascular disease, but the differential role APOE alleles play in subclinical atherosclerosis remains unclear. METHODS: The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were APOE-genotyped, and omics data were additionally evaluated. RESULTS: In the PESA study, the frequencies for APOE -ε2, -ε3, and -ε4 alleles were 0.060, 0.844, and 0.096, respectively. This study included a subcohort of 3887 participants (45.8±4.3 years of age; 62% males). As expected, APOE-ε4 carriers were at the highest risk for cardiovascular disease and had significantly greater odds of having subclinical atherosclerosis compared with ε3/ε3 carriers, which was mainly explained by their higher levels of low-density lipoprotein (LDL)-cholesterol. In turn, APOE-ε2 carriers were at the lowest risk for cardiovascular disease and had significantly lower odds of having subclinical atherosclerosis in several vascular territories (carotids: 0.62 [95% CI, 0.47-0.81]; P=0.00043; femorals: 0.60 [0.47-0.78]; P=9.96×10-5; coronaries: 0.53 [0.39-0.74]; P=0.00013; and increased PESA score: 0.58 [0.48-0.71]; P=3.16×10-8). This APOE-ε2 atheroprotective effect was mostly independent of the associated lower LDL-cholesterol levels and other cardiovascular risk factors. The protection conferred by the ε2 allele was greater with age (50-54 years: 0.49 [95% CI, 0.32-0.73]; P=0.00045), and normal (<150 mg/dL) levels of triglycerides (0.54 [0.44-0.66]; P=4.70×10-9 versus 0.90 [0.57-1.43]; P=0.67 if ≥150 mg/dL). Omics analysis revealed an enrichment of several canonical pathways associated with anti-inflammatory mechanisms together with the modulation of erythrocyte homeostasis, coagulation, and complement activation in ε2 carriers that might play a relevant role in the ε2's atheroprotective effect. CONCLUSIONS: This work sheds light on the role of APOE in cardiovascular disease development with important therapeutic and prevention implications on cardiovascular health, especially in early midlife. REGISTRATION: URL: https://www.clinicaltrials.gov: NCT01410318.

MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.

Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure. These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition.

GOLD COPD DOCUMENT 2023: a brief update for practicing cardiologists.

Many patients seen by cardiologists suffer chronic obstructive pulmonary disease (COPD) in addition to their primary cardiovascular problem. Yet, quite often COPD has not been diagnosed and, consequently, patients have not been treated of their pulmonary disease. Recognizing and treating COPD in patients with CVDs is important because optimal treatment of the COPD carries important benefits on cardiovascular outcomes. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) publishes an annual report that serves as a clinical guideline for the diagnosis and management of COPD around the world and has very recently released the 2023 annual report. Here, we provide a summary of the GOLD 2023 recommendations that highlights those aspects of more interest for practicing cardiologists dealing with patients with CVD who may suffer COPD.

Early insulin resistance in normoglycemic low-risk individuals is associated with subclinical atherosclerosis.

BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with a higher burden of subclinical atherosclerosis (SA). However, the association with SA of earlier insulin resistance markers is poorly understood. The study assessed the association between the homeostatic model assessment of insulin resistance index (HOMA-IR) and SA in addition to the effect of cardiovascular risk factors (CVRFs) in individuals with normal HbA1c. METHODS: A cohort of 3,741 middle-aged individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study with basal HbA1c < 6.0% (< 42 mmol/mol) and no known CV disease underwent extensive imaging (multiterritorial vascular ultrasound and coronary artery calcium score, CACS) to assess the presence, burden, and extent of SA. RESULTS: Individuals with higher HOMA-IR values had higher rates of CVRFs. HOMA-IR showed a direct association with the multiterritorial extent of SA and CACS (p < 0.001) and with global plaque volume measured by 3-dimensional vascular ultrasound (p < 0.001). After adjusting for key CVRFs and HbA1c, HOMA-IR values ≥ 3 were associated with both the multiterritorial extent of SA (odds ratio 1.41; 95%CI: 1.01 to 1.95, p = 0.041) and CACS > 0 (odds ratio 1.74; 95%CI: 1.20 to 2.54, p = 0.004), as compared with the HOMA-IR < 2 (the reference HOMA-IR category). In a stratified analysis, this association remained significant in individuals with a low-to-moderate SCORE2 risk estimate (75.6% of the cohort) but not in high-risk individuals. CONCLUSIONS: The use of HOMA-IR identified low-risk individuals with a higher burden of SA, after adjusting for the effects of key traditional CVRFs and HbA1c. HOMA-IR is a simple measure that could facilitate earlier implementation of primary CV prevention strategies in clinical practice.

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years.

BACKGROUND: Atherosclerosis is a systemic disease that frequently begins early in life. However, knowledge about the temporal disease dynamics (ie, progression or regression) of human subclinical atherosclerosis and their determinants is scarce. OBJECTIVES: This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals by using multiterritorial 3-dimensional vascular ultrasound (3DVUS) imaging. METHODS: A total of 3,471 participants from the PESA (Progression of Early Subclinical Atherosclerosis) cohort study (baseline age 40-55 years; 36% female) underwent 3 serial 3DVUS imaging assessments of peripheral arteries at 3-year intervals. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden). Multivariable logistic regression models for progression and regression were developed using stepwise forward variable selection. RESULTS: Baseline to 6-year subclinical atherosclerosis progression occurred in 32.7% of the cohort (17.5% presenting with incident disease and 15.2% progressing from prevalent disease at enrollment). Regression was observed in 8.0% of those patients with baseline disease. The effects of higher low-density lipoprotein cholesterol (LDL-C) and elevated systolic blood pressure (SBP) on 6-year subclinical atherosclerosis progression risk were more pronounced among participants in the youngest age stratum (Pinteraction = 0.04 and 0.02, respectively). CONCLUSIONS: Over 6 years, subclinical atherosclerosis progressed in one-third of middle-age asymptomatic subjects. Atherosclerosis regression is possible in early stages of the disease. The impact of LDL-C and SBP on subclinical atherosclerosis progression was more pronounced in younger participants, a finding suggesting that the prevention of atherosclerosis and its progression could be enhanced by tighter risk factor control at younger ages, with a likely long-term impact on reducing the risk of clinical events. (Progression of Early Subclinical Atherosclerosis [PESA; also PESA-CNIC-Santander]; NCT01410318).

A possible role for the venous-to-arterial CO2 difference in cardiogenic shock: an exploratory study. / Estudio exploratorio del rol de la diferencia venoarterial de dióxido de carbono en el shock cardiogénico.

OBJECTIVES: The venous-to-arterial CO2 partial pressure difference (CO2) is a marker of how adequately capillary blood flow is able to remove CO2 from tissues, but evidence regarding its usefulness in patients with cardiogenic shock (CS) is scarce The main objective of this study was to describe the changes in CO2 in patients with cardiogenic shock during the 48 hours after hospital admission. A secondary objective was to analyze the association between CO2 and in-hospital mortality due to cardiovascular disease (CVD) and cardiogenic shock refractory to treatment. MATERIAL AND METHODS: Prospective observational exploratory study in a single hospital. Patients in cardiogenic shock who were admitted to a cardiology critical care unit were included. We measured CO2 on inclusion and 6, 12, 24, and 48 hours after admission to the unit. Variables were explored with logistic regression analysis and areas under the receiver operating characteristic curves were calculated. RESULTS: A total of 50 patients were included. In-hospital mortality due to CVD was 20%. CO2 peaked initially and decreased gradually over the first 48 hours of care. In-hospital mortality tended to be higher in patients with the highest CO2 values, but the difference was not significant. High CO2 values at 24 hours were associated with refractory cardiogenic shock. The negative predictive value of a CO2 value lower than 6 mmHg at 12 hours was 87% for mortality due to CVD. CONCLUSION: This exploratory study suggests that CO2 could be a helpful additional marker to measure when managing cardiogenic shock. CO2 lower than 6 mmHg between 12 and 24 hours after admission may identify patients at low risk of death due to CVD or refractory cardiogenic shock.

OBJETIVO: La diferencia venoarterial de dióxido de carbono (CO2) representa la adecuación del flujo capilar para eliminar CO2 tisular, sin embargo, su evidencia en pacientes con shock cardiogénico (SC) es escasa. El objetivo primario fue caracterizar la cinética de la diferencia venoarterial de CO2 en pacientes con SC durante las primeras 48 horas de ingreso. El objetivo secundario fue analizar la asociación de la CO2 con la mortalidad intrahospitalaria de causa cardiovascular y el SC refractario. METODO: Estudio exploratorio, observacional, prospectivo y unicéntrico. Se incluyeron pacientes en SC ingresados en una unidad de cuidados críticos cardiológicos. Se determinó la CO2 a la inclusión, a las 6, 12, 24 y 48 horas y se realizó un análisis de regresión logística y curvas de la característica operativa del receptor. RESULTADOS: Se incluyeron 50 pacientes. La mortalidad cardiovascular intrahospitalaria fue del 20%. La cinética de la CO2 mostró un pico inicial y un progresivo descenso durante las primeras 48 horas. Los pacientes con valores más altos de CO2 tuvieron una mayor mortalidad cardiovascular intrahospitalaria, pero esta diferencia no fue significativa. A las 24 horas, valores elevados de CO2 se asociaron significativamente con SC refractario. Un valor inferior a 6 mmHg a las 12 horas mostró un valor predictivo negativo del 87% para mortalidad cardiovascular. CONCLUSIONES: Este estudio exploratorio sugiere la potencial utilidad de la CO2 como biomarcador adicional en el manejo del SC. La CO2 permite identificar pacientes con bajo riesgo de mortalidad cardiovascular y SC refractario cuando sus valores son inferiores a 6 mmHg a las 12-24 horas de evolución.

Estudio exploratorio del rol de la diferencia venoarterial de dióxido de carbono en el shock cardiogénico / A possible role for the venous-to-arterial CO2 difference in cardiogenic shock: an exploratory study

Introducción y objetivos: La diferencia venoarterial de dióxido de carbono (ΔCO2) representa la adecuación del flujo capilar para eliminar CO2 tisular, sin embargo, su evidencia en pacientes con shock cardiogénico (SC) es escasa”. El objetivo primario fue caracterizar la cinética de la diferencia venoarterial de ΔCO2 en pacientes con SC durante las primeras 48 horas de ingreso. El objetivo secundario fue analizar la asociación de la ΔCO2 con la mortalidad intrahospitalaria de causa cardiovascular y el SC refractario. Método: Estudio exploratorio, observacional, prospectivo y unicéntrico. Se incluyeron pacientes en SC ingresados en una unidad de cuidados críticos cardiológicos. Se determinó la ΔCO2 a la inclusión, a las 6, 12, 24 y 48 horas y se realizó un análisis de regresión logística y curvas de la característica operativa del receptor. Resultados: Se incluyeron 50 pacientes. La mortalidad cardiovascular intrahospitalaria fue del 20%. La cinética de la ΔCO2 mostró un pico inicial y un progresivo descenso durante las primeras 48 horas. Los pacientes con valores más altos de ΔCO2 tuvieron una mayor mortalidad cardiovascular intrahospitalaria, pero esta diferencia no fue significativa. A las 24 horas, valores elevados de ΔCO2 se asociaron significativamente con SC refractario. Un valor inferior a 6 mmHg a las 12 horas mostró un valor predictivo negativo del 87% para mortalidad cardiovascular. Conclusiones: Este estudio exploratorio sugiere la potencial utilidad de la ΔCO2 como biomarcador adicional en el manejo del SC. La ΔCO2 permite identificar pacientes con bajo riesgo de mortalidad cardiovascular y SC refractario cuando sus valores son inferiores a 6 mmHg a las 12-24 horas de evolución. (AU)

Background and objectives: The venous-to-arterial CO2 partial pressure difference ('CO2) is a marker of how adequately capillary blood flow is able to remove CO2 from tissues, but evidence regarding its usefulness in patients with cardiogenic shock (CS) is scarce The main objective of this study was to describe the changes in 'CO2 in patients with cardiogenic shock during the 48 hours after hospital admission. A secondary objective was to analyze the association between 'CO2 and in-hospital mortality due to cardiovascular disease (CVD) and cardiogenic shock refractory to treatment. Methods: Prospective observational exploratory study in a single hospital. Patients in cardiogenic shock who were admitted to a cardiology critical care unit were included. We measured 'CO2 on inclusion and 6, 12, 24, and 48 hours after admission to the unit. Variables were explored with logistic regression analysis and areas under the receiver operating characteristic curves were calculated. Results: A total of 50 patients were included. In-hospital mortality due to CVD was 20%. 'CO2 peaked initially and decreased gradually over the first 48 hours of care. In-hospital mortality tended to be higher in patients with the highest 'CO2 values, but the difference was not significant. High 'CO2 values at 24 hours were associated with refractory cardiogenic shock. The negative predictive value of a 'CO2 value lower than 6 mmHg at 12 hours was 87% for mortality due to CVD. Conclusions: This exploratory study suggests that 'CO2 could be a helpful additional marker to measure when managing cardiogenic shock. 'CO2 lower than 6 mmHg between 12 and 24 hours after admission may identify patients at low risk of death due to CVD or refractory cardiogenic shock. (AU)

Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study.

BACKGROUND: Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals. METHODS: The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood-based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach. FINDINGS: This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49·8 years [IQR 46·1-52·2]; 309 [84%] men, 61 [16%] women; median follow-up 4·7 years [IQR 4·2-5·2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (ß=-0·008 [95% CI -0·013 to -0·002]; pFDR=0·040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (ß=0·198 [0·008 to 0·740]; pFDR=0·050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (ß=-0·269 [95% CI -0·509 to -0·027]; p=0·029). INTERPRETATION: Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life. FUNDING: Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Santander Bank, Pro-CNIC Foundation, BrightFocus Foundation, BBVA Foundation, "la Caixa" Foundation.

Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis.

OBJECTIVE: Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown. RESEARCH DESIGN AND METHODS: 821 asymptomatic individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study (50.6 [46.9-53.6] years, 83.7% male) underwent two whole-body 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET-MR) 4.8 ± 0.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade 0, while positive uptake was classified in grades 1-3 according to target-to-background ratio tertiles. RESULTS: One hundred fifty-six participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs. 13.9%, P < 0.001), hypertension (29.0% vs. 18.0%, P = 0.002), and diabetes (11.0% vs. 3.2%, P < 0.001), and with higher insulin resistance index (HOMA-IR, 1.64% vs. 1.23%, P < 0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e., arterial 18F-FDG uptake, P = 0.004). On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (P < 0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (P < 0.001) increase in myocardial uptake. CONCLUSIONS: Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.

Late gadolinium enhancement distribution patterns in non-ischaemic dilated cardiomyopathy: genotype-phenotype correlation.

AIMS: Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM); there is little information about its frequency and distribution pattern according to the underlying genetic substrate. We sought to describe LGE patterns according to genotypes and to analyse the risk of major ventricular arrhythmias (MVA) according to patterns. METHODS AND RESULTS: Cardiac magnetic resonance findings and LGE distribution according to genetics were performed in a cohort of 600 DCM patients followed at 20 Spanish centres. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, left ventricular ejection fraction 36.9 ± 13.9%) conformed to the final cohort. A causative genetic variant was identified in 219 (38%) patients, and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20, and MYH7 (0, 5, and 20%, respectively). Patients with variants in DMD, DSP, and FLNC showed a predominance of LGE subepicardial patterns (50, 41, and 18%, respectively), whereas patients with variants in TTN, BAG3, LMNA, and MYBPC3 showed unspecific LGE patterns. The genetic yield differed according to LGE patterns. Patients with subepicardial, lineal midwall, transmural, and right ventricular insertion points or with combinations of LGE patterns showed an increased risk of MVA compared with patients without LGE. CONCLUSION: LGE patterns in DCM have a specific distribution according to the affected gene. Certain LGE patterns are associated with an increased risk of MVA and with an increased yield of genetic testing.

Repair of mitral prolapse: comparison of thoracoscopic minimally invasive and conventional approaches.

OBJECTIVES: Surgical repair remains the best treatment for severe primary mitral regurgitation (MR). Minimally invasive mitral valve surgery is being increasingly performed, but there is a lack of solid evidence comparing thoracoscopic with conventional surgery. Our objective was to compare outcomes of both approaches for repair of leaflet prolapse. METHODS: All consecutive patients undergoing surgery for severe MR due to mitral prolapse from 2012 to 2020 were evaluated according to the approach used. Freedom from mortality, reoperation and recurrent severe MR were evaluated by Kaplan-Meier method. Differences in baseline characteristics were adjusted with propensity score-matched analysis (1:1, nearest neighbour). RESULTS: Three hundred patients met inclusion criteria and were divided into thoracoscopic (N = 188) and conventional (sternotomy; N = 112) groups. Unmatched patients in the thoracoscopic group were younger and had lower body mass index, New York Heart Association class and EuroSCORE II preoperatively. After matching, thoracoscopic group presented significantly shorter mechanical ventilation (9 vs 15 h), shorter intensive care unit stay (41 vs 65 h) and higher postoperative haemoglobin levels (11 vs 10.2 mg/dl) despite longer bypass and cross-clamp times (+30 and +17 min). There were no differences in mortality or MR grade at discharge between groups nor differences in survival, repair failures and reinterventions during follow-up. CONCLUSIONS: Minimally invasive mitral repair can be performed in the majority of patients with mitral prolapse, without compromising outcomes, repair rate or durability, while providing shorter mechanical ventilation and intensive care unit stay and less blood loss.

Multimodal Prehabilitation in Heart Transplant Recipients Improves Short-Term Post-Transplant Outcomes without Increasing Costs.

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.

Monocyte distribution width (MDW) as an infection indicator in severe patients attending in the Emergency Department: a pilot study / Ancho de distribución de los monocitos como indicador de infección en pacientes graves atendidos en Urgencias: estudio piloto

Background. The aim of the present study was to evaluate the diagnostic performance of monocyte distribution width (MDW) as a biomarker for sepsis diagnosis in severe patients attended in the Emergency Department for different conditions and not only infections. Methods. We performed an observational study in a consecutive prospective cohort including severe patients attending the Emergency Department with different conditions. MDW and other biomarkers were determined from samples obtained during the first care of patients. The diagnostic performance of the different biomarkers was determined based on the final diagnosis at patient discharge. Results: One hundred two patients, with a mean age of 76.7 (SD 16.5) years were included, 53 being (51.9%) male. Among the patients included, 65 (63.7%) had an infectious disease while the remaining had other different conditions. A MDW cut-off of 20.115 provided the best accuracy to identify infected patients, with a sensitivity of 89.2 (95% CI 79.4-94.7), a specificity of 89.2 (95% CI 75.3-95.7), a positive predictive value of 93.5 (95% CI 84.6-97.5), a negative predictive value of 82.5% (95% CI 68.0-91.3), a positive likelihood ratio of 8.25 (3.26-20.91), and a negative likelihood ratio of 0.12 (0.06-0.24). The area under the receiver operating characteristic curve for infection according to MDW was 0.943 (95% CI 0.897-0.989; p<0.001). Conclusions: A MDW > 20.115 may be associated with infection and could help to distinguish between infected and non-infected patients in severe patients. These results must be confirmed in new studies due to the limited patient sample included. (AU)

Introducción: El objetivo del presente estudio fue evaluar el desempeño diagnóstico del ancho de distribución de monocitos (MDW) como biomarcador para el diagnóstico desepsis entre pacientes graves atendidos en el servicio de urgencias por diferentes afecciones y no solo por infecciones. Métodos: Realizamos un estudio observacional en una cohorte prospectiva consecutiva que incluyó pacientes graves desde el punto de vista clínico que acudían a urgencias con diferentes patologías. El MDW y otros biomarcadores se determinaron a partir de muestras obtenidas durante la primera atención de los pacientes. Se estudio la precisión de los diferentes biomarcadores para apoyar el diagnósticode infección, basándonos en el diagnóstico final al alta del paciente. Resultados: Se incluyeron 102 pacientes, con una edad media de 76,7 (DE 16,5) años, siendo 53 (51,9%) del sexo masculino. Entre los pacientes incluidos, 65 (63,7%) pacientes tenían una enfermedad infecciosa y el resto otras condiciones diferentes. Un punto de corte MDW de 20,115proporcionó la mejor precisión para identificar pacientes infectados, con un sensibilidad de 89,2 (IC 95 % 79,4-94,7), una especificidad de 89,2 (IC 95 % 75,3-95,7), un valor predictivo positivo de 93,5 (IC 95 % 84,6-97,5), un valor predictivo negativo de 82,5% (IC 95% 68,0-91,3), un coeficiente de probabilidad positivo de 8,25 (3,26-20,91), y uncoeficiente de probabilidad negativo de 0,12 (0,06-0,24). El área bajo la curva característica operativa del receptor para la infección del MDW fue de 0,943 (IC del 95 %: 0,897-0,989; p<0,001). Conclusiones: Un MDW > 20.115 se asocia a padecer una enfermedad infecciosa en un paciente grave y podría ayudar a distinguir entre pacientes infectados y no infectados. Estos resultados deben ser confirmados en nuevos estudios debido a la muestra limitada de pacientes incluidos. (AU)