Deuterium metabolic imaging of the human brain in vivo at 7 T.

PURPOSE: To explore the potential of deuterium metabolic imaging (DMI) in the human brain in vivo at 7 T, using a multi-element deuterium (2 H) RF coil for 3D volume coverage. METHODS: 1 H-MR images and localized 2 H MR spectra were acquired in vivo in the human brain of 3 healthy subjects to generate DMI maps of 2 H-labeled water, glucose, and glutamate/glutamine (Glx). In addition, non-localized 2 H-MR spectra were acquired both in vivo and in vitro to determine T1 and T2 relaxation times of deuterated metabolites at 7 T. The performance of the 2 H coil was assessed through numeric simulations and experimentally acquired B1 + maps. RESULTS: 3D DMI maps covering the entire human brain in vivo were obtained from well-resolved deuterated (2 H) metabolite resonances of water, glucose, and Glx. The T1 and T2 relaxation times were consistent with those reported at adjacent field strengths. Experimental B1 + maps were in good agreement with simulations, indicating efficient and homogeneous B1 + transmission and low RF power deposition for 2 H, consistent with a similar array coil design reported at 9.4 T. CONCLUSION: Here, we have demonstrated the successful implementation of 3D DMI in the human brain in vivo at 7 T. The spatial and temporal nominal resolutions achieved at 7 T (i.e., 2.7 mL in 28 min, respectively) were close to those achieved at 9.4 T and greatly outperformed DMI at lower magnetic fields. DMI at 7 T and beyond has clear potential in applications dealing with small brain lesions.

New factors in heart failure pathophysiology: Immunity cells release of extracellular vesicles.

Leukocyte-shed extracellular vesicles (EVs) can play effector roles in the pathophysiological mechanisms of different diseases. These EVs released by membrane budding of leukocytes have been found in high amounts locally in inflamed tissues and in the circulation, indicating immunity cell activation. These EVs secreted by immune cell subsets have been minimally explored and deserve further investigation in many areas of disease. In this study we have investigated whether in heart failure there is innate and adaptive immune cell release of EVs. Patients with chronic heart failure (cHF) (n = 119) and in sex- and age-matched controls without this chronic condition (n = 60). Specifically, EVs were quantified and phenotypically characterized by flow cytometry and cell-specific monoclonal antibodies. We observed that even in well medically controlled cHF patients (with guideline-directed medical therapy) there are higher number of blood annexin-V+ (phosphatidylserine+)-EVs carrying activated immunity cell-epitopes in the circulation than in controls (p < 0.04 for all cell types). Particularly, EVs shed by monocytes and neutrophils (innate immunity) and by T-lymphocytes and natural-killer cells (adaptive immunity) are significantly higher in cHF patients. Additionally, EVs-shed by activated leukocytes/neutrophils (CD11b+, p = 0.006; CD29+/CD15+, p = 0.048), and T-lymphocytes (CD3+/CD45+, p < 0.02) were positively correlated with cHF disease severity (NYHA classification). Interestingly, cHF patients with ischemic etiology had the highest levels of EVs shed by lymphocytes and neutrophils (p < 0.045, all). In summary, in cHF patients there is a significant immune cell activation shown by high-release of EVs that is accentuated by clinical severity of cHF. These activated innate and adaptive immunity cell messengers may contribute by intercellular communication to the progression of the disease and to the common affectation of distant organs in heart failure (paracrine regulation) that contribute to the clinical deterioration of cHF patients.

Incremental prognostic value of lung ultrasound on contemporary heart failure risk scores.

Introduction: Over the last decades, several scores have been developed to aid clinicians in assessing prognosis in patients with heart failure (HF) based on clinical data, medications and, ultimately, biomarkers. Lung ultrasound (LUS) has emerged as a promising prognostic tool for patients when assessed at discharge after a HF hospitalization. We hypothesized that contemporary HF risk scores can be improved upon by the inclusion of the number of B-lines detected by LUS at discharge to predict death, urgent visit, or HF readmission at 6- month follow-up. Methods: We evaluated the discrimination improvement of adding the number of B-lines to 4 contemporary HF risk scores (Get with the Guidelines -GWTG-, MAGGIC, Redin-SCORE, and BCN Bio-HF) by comparing the change in the area under the receiver operating curve (AUC), the net reclassification index (NRI), and the integrated discrimination improvement (IDI). The population of the study was constituted by the 123 patients enrolled in the LUS-HF trial, adjusting the analyses by the intervention. Results: The AUC of the GWTG score increased from 0.682 to 0.789 (p = 0.02), resulting in a NRI of 0.608 and an IDI of 0.136 (p < 0.05). Similar results were observed when adding the number of B-lines to the MAGGIC score, with an AUC that increased from 0.705 to 0.787 (p < 0.05). This increase translated into a NRI of 0.608 and an IDI of 0.038 (p < 0.05). Regarding Redin-SCORE at 1-month and 1-year, the AUC increased from 0.714 to 0.773 and from 0.681 to 0.757, although it did not reach statistical significance (p = 0.08 and p = 0.06 respectively). Both IDI and NRI were significantly improved (0.093 and 0.509 in the 1-month score, p < 0.05; 0.056 and 0.111 in the 1-year score, p < 0.05). Lastly, the AUC for the BCN Bio-HF score increased from 0.733 to 0.772, which was statistically non-significant, with a NRI value of 0.363 (p = 0.06) and an IDI of 0.092 (p < 0.05). Conclusion: Adding the results of LUS evaluated at discharge improved the predictive value of most of the contemporary HF risk scores. As it is a simple, fast, and non-invasive test it may be recommended to assess prognosis at discharge in HF patients.

A Simple Score to Identify Super-Responders to Sacubitril/Valsartan in Ambulatory Patients With Heart Failure.

INTRODUCTION: Sacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients. METHODS: This is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method. RESULTS: Out of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (<25%), intermediate- (∼46%), and high-probability (>80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64-0.80), remaining consistent after internal validation. CONCLUSION: One-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice.

Interdisciplinary Mobile Health Model to Improve Clinical Care After Heart Transplantation: Implementation Strategy Study.

BACKGROUND: Solid organ transplantation could be the only life-saving treatment for end-stage heart failure. Nevertheless, multimorbidity and polypharmacy remain major problems after heart transplant. A technology-based behavioral intervention model was established to improve clinical practice in a heart transplant outpatient setting. To support the new strategy, the mHeart app, a mobile health (mHealth) tool, was developed for use by patients and providers. OBJECTIVE: The primary objective of this study was to describe the implementation of the mHeart model and to outline the main facilitators identified when conceiving an mHealth approach. The secondary objectives were to evaluate the barriers, benefits, and willingness to use mHealth services reported by heart transplant recipients and cardiology providers. METHODS: This was an implementation strategy study directed by a multidisciplinary cardiology team conducted in four stages: design of the model and the software, development of the mHeart tool, interoperability among systems, and quality and security requirements. A mixed methods study design was applied combining a literature review, several surveys, interviews, and focus groups. The approach involved merging engineering and behavioral theory science. Participants were chronic-stage heart transplant recipients, patient associations, health providers, stakeholders, and diverse experts from the legal, data protection, and interoperability fields. RESULTS: An interdisciplinary and patient-centered process was applied to obtain a comprehensive care model. The heart transplant recipients (N=135) included in the study confirmed they had access to smartphones (132/135, 97.7%) and were willing to use the mHeart system (132/135, 97.7%). Based on stakeholder agreement (>75%, N=26), the major priorities identified of the mHealth approach were to improve therapy management, patient empowerment, and patient-provider interactions. Stakeholder agreement on the barriers to implementing the system was weak (<75%). Establishing the new model posed several challenges to the multidisciplinary team in charge. The main factors that needed to be overcome were ensuring data confidentiality, reducing workload, minimizing the digital divide, and increasing interoperability. Experts from various fields, scientific societies, and patient associations were essential to meet the quality requirements and the model scalability. CONCLUSIONS: The mHeart model will be applicable in distinct clinical and research contexts, and may inspire other cardiology health providers to create innovative ways to deal with therapeutic complexity and multimorbidity through health care systems. Professionals and patients are willing to use such innovative mHealth programs. The facilitators and key strategies described were needed for success in the implementation of the new holistic theory-based mHealth strategy.

Prevalence and prognostic impact of subclinical pulmonary congestion at discharge in patients with acute heart failure.

AIMS: Residual pulmonary congestion at hospital discharge can worsen the outcomes in patients with heart failure (HF) and can be detected by lung ultrasound (LUS). The aim of this study was to analyse the prevalence of subclinical pulmonary congestion at discharge and its impact on prognosis in patients admitted for acute HF. METHODS AND RESULTS: This is a post-hoc analysis of the LUS-HF trial. LUS was performed by the investigators in eight chest zones with a pocket device. Physical exam was subsequently performed by the treating physicians. Primary outcome was a combined endpoint of rehospitalization, unexpected visit for HF worsening or death at 6- month follow-up. Subclinical pulmonary congestion at discharge was defined as the presence of ≥5 B-lines in LUS in absence of rales in the auscultation employing the area under the ROC curve. At discharge, 100 patients (81%) did not show clinical signs of pulmonary congestion. Of these, 41 had ≥5 B-lines. Independent factors related with the presence of subclinical pulmonary congestion were anaemia, higher New York Heart Association (NYHA) class, and N terminal pro brain natriuretic peptide (NT-proBNP). After adjusting by propensity score analysis including age, renal insufficiency, atrial fibrillation, NYHA class, NT-proBNP levels, clinical congestion, and the trial intervention, the presence of subclinical pulmonary congestion at discharge was a risk factor for the occurrence of the primary outcome (hazard ratio 2.63; 95% confidence interval: 1.08-6.41; P = 0.033). CONCLUSIONS: Up to 40% of patients considered 'dry' according to pulmonary auscultation presents subclinical congestion at hospital discharge that can be detected by LUS and implies a worse prognosis at 6- month follow-up. Comorbidities, high values of natriuretic peptides, and higher NYHA class are the factors related with its presence.

Design of the ß3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial.

Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (ß3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available ß3AR agonist) in patients with CpcPH due to HF. The effect of ß3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539).

A Mobile App (mHeart) to Detect Medication Nonadherence in the Heart Transplant Population: Validation Study.

BACKGROUND: Medication nonadherence in heart transplant recipients (HTxR) is related to graft loss and death. mHeart is a mobile app that uses electronic patient-reported outcome measures (ePROMs) to identify and manage medication nonadherence in the outpatient heart transplant (HTx) population. OBJECTIVE: The study primarily aimed to validate mHeart to measure medication nonadherence in early stage HTxR by assessing the psychometric properties of ePROMs. The secondary aims were to (1) measure patient satisfaction with the mHeart tool and its usability and (2) explore the impact of a theory-based treatment on medication nonadherence rates to determine its scalability to larger research. METHODS: A prospective study was conducted in the outpatient clinic of a tertiary hospital. All consecutive early stage HTxR (<1.5 years from HTx) were included. The ePROM psychometric properties assessed were validity, reliability, responsiveness, interpretability, and burden. ePROMs comprised the 4-item Morisky-Green-Levine questionnaire and an adapted version of the Haynes-Sackett questionnaire. The Simplified Medication Adherence Questionnaire (SMAQ) was also applied on-site. Three consecutive medication nonadherence assessments were performed by a transplant pharmacist. To improve medication nonadherence, theory-based interventions were delivered in a 1-month period. Patient satisfaction was assessed by a semiquantitative Web-based survey at the end of the study. RESULTS: We included 31 early stage HTxR (age: mean 54 years, SD 12 years), and 71% (22/31) of them were men. The HTxR were taking a mean 13 (SD 4; range 7-18) drugs per day. A total of 42% (13/31) of patients were unaware of the consequences of medication nonadherence, and 39% (12/31) of patients were nonadherent to immunosuppressive treatment. The content validity measure showed excellent levels of expert panel agreement for the Haynes-Sacket (14/14, 100%) and Morisky-Green-Levine (13/14, 93%) questionnaires. SMAQ and Morisky-Green-Levine ePROMs showed similar measurement domains (convergent validity, phi=0.6, P<.001), which, as expected, differed from Haynes-Sackett ePROMs (divergent validity, phi=0.3, P=.12). Reliability assessment revealed a very strong association between ePROM and on-site PROMs (phi>0.7, P<.001). Reproducibility was moderate (Haynes-Sackett κ=0.6, P<.002) or poor (Morisky-Green-Levine κ=0.3, P=.11) because of unexpected improved medication adherence rates during the test-retest period. According to responsiveness, the theory-based multifaceted intervention program improved medication nonadherence by 16% to 26% (P<.05). A burden analysis showed that ePROMs could potentially overcome traditional on-site limitations (eg, automatic recording of ePROM responses in the hospital information system). The mean score for overall patient satisfaction with the mHeart approach was 9 (SD 2; score range: 0-10). All 100% (29/29) of patients surveyed reported that they would recommend the mHeart platform to other HTxR. CONCLUSIONS: ePROMs adhered to the quality standards and successfully identified medication nonadherence in the HTx population, supporting their widespread use. The theory-based intervention program showed a promising improvement in medication adherence rates and produced excellent patient satisfaction and usability scores in HTxR.

Lung ultrasound-guided treatment in ambulatory patients with heart failure: a randomized controlled clinical trial (LUS-HF study).

AIMS: Lung ultrasound (LUS) is a useful tool with which to assess subclinical pulmonary congestion and to stratify the prognosis of patients with heart failure (HF). The aim of this study was to evaluate whether an LUS-guided follow-up protocol improves the outcomes of patients with HF. METHODS AND RESULTS: In this single-blind clinical trial, 123 patients admitted for HF were randomized to either a standard follow-up (n = 62, control group) or a LUS-guided follow-up (n = 61, LUS group). The primary endpoint was a composite of urgent visit, hospitalization for worsening HF and death during follow-up. Visits were scheduled at 14, 30, 90 and 180 days after discharge. Treating physicians were encouraged to modify diuretic therapy in accordance with the number of B-lines recorded by LUS. The mean ± standard deviation (SD) age of the patients was 69 ± 12 years and 72% were male. The mean ± SD left ventricular ejection fraction was 39 ± 14%. The hazard ratio for the primary outcome in the LUS group was 0.518 [95% confidence interval (CI) 0.268-0.998; P = 0.049], mainly resulting from a decrease in the number of urgent visits for worsening HF. The number of patients needed to treat to avoid an event was 5 (95% CI 3-62). Other secondary endpoints such as N-terminal pro-B-type natriuretic peptide reduction were not achieved. The safety parameters were similar in the two groups. Patients in the LUS group received more loop diuretics [51 (91%) vs. 42 (75%); P = 0.02] and showed an improvement in the distance achieved in the 6-min walking test [60 m (interquartile range: 29-125 m) vs. 37 m (interquartile range: 5-70 m); P = 0.023]. CONCLUSIONS: Tailored LUS-guided diuretic treatment of pulmonary congestion in this proof-of-concept study reduced the number of decompensations and improved walking capacity in patients with HF. LUS is a non-invasive, safe and easy-to-use technique with potential clinical applicability to guide pulmonary congestion treatment in patients with HF.

Perspectiva de género en el estudio OFRECE: diferencias en la atención entre pacientes que consultan por dolor torácico o por palpitaciones / The gender perspective within the OFRECE study: differences in health care among patients consulting for chest pain and/or palpitations

Introducción y objetivos: En un estudio de base poblacional, se analizaron las posibles diferencias en función del sexo en la atención al dolor torácico o las palpitaciones como motivo de consulta. Métodos: El estudio OFRECE incluyó una muestra aleatoria de la población española de 8.400 participantes de edad ≥ 40 años, de los que 1.132 (13,5%) tenían antecedentes de consulta por dolor en el pecho y 1.267 (15,1%), por palpitaciones y se incluyen en este estudio. Se calculó la odds ratio (OR) de que se practicaran determinadas pruebas y se comunicaran los resultados de las consultas en relación con el hecho de ser mujer, tanto brutas como ajustadas por los factores de riesgo cardiovascular clásicos, antecedentes de enfermedad cardiovascular y diagnóstico de angina estable o fibrilación auricular confirmado en este estudio en cada caso. Resultados: No se observaron diferencias en los antecedentes de consulta por dolor torácico entre mujeres y varones (el 13 y el 14,1%; p=0,159) y sí en las consultas por palpitaciones (el 19,0 y el 10,4% respectivamente; p <0,001). A las mujeres con antecedentes de consulta por dolor torácico, en comparación con los varones, se les realizaron menos ecocardiogramas (el 32,5 y el 45,3%; p <0,001), se las remitió con menor frecuencia al cardiólogo (el 49,1 y el 60,1%; p <0,001), ingresaron menos (el 20,1 y el 39,4%; p <0,001) y se alcanzó un diagnóstico en menor proporción de casos (el 60,9 y el 71,9%; p <0,001). Al ajustar, disminuyen las diferencias y dejan de ser significativas en todos los casos: para ecocardiogramas, OR ajustada=0,81 (IC95%, 0,60-1,09); para remisión al cardiólogo, OR ajustada=0,86 (IC95%, 0,63-1,16), y para ingreso, OR ajustada=0,76 (IC95%, 0,54-1,09). En el caso de las palpitaciones, las diferencias no ajustadas son menores y todas desaparecen al ajustar. Conclusiones: Este trabajo no confirma un sesgo en razón del sexo en la atención a estos síntomas, aunque no es descartable completamente un sesgo de género en el diagnóstico confirmado en el estudio que limite su capacidad para identificar diferencias en la atención a las pacientes

Introduction and objectives: To analyze differences between sexes in the clinical management of patients presenting with symptoms of chest pain and/or palpitations within a population-based study. Methods: The OFRECE study included a random sample of 8400 individuals from the Spanish population aged 40 years and older; 1132 (13.5%) had previously consulted for chest pain and 1267 (15.1%) had consulted for palpitations and were included in the present study. We calculated both the crude and adjusted odds ratios (OR) of undergoing certain tests and the results of consultations by sex. Adjustment was performed by classic cardiovascular risk factors, a personal history of cardiovascular disease, and a diagnosis of stable angina or atrial fibrillation confirmed in the OFRECE study in each case. Results: No differences were observed in history of consultation for chest pain between women and men (13% vs 14.1%; P=.159) but differences were found in palpitations (19% vs 10.4%, respectively; P <.001). Women who had previously consulted for chest pain underwent fewer echocardiograms (32.5% vs 45.3%, respectively; P <.001), were less frequently referred to a cardiologist (49.1% vs 60.1%; P <.001), were less often admitted to hospital (20.1% vs 39.4%; P <.001), and less frequently received a confirmed diagnosis (60.9 vs 71, 9; P <.001). After full adjustment, all differences decreased and become nonsignificant echocardiograms: adjusted OR, 0.81; 95%CI, 0.60-1.09; referral to a cardiologist: adjusted OR, 0.86; 95%CI, 0.63-1.16; hospital admission: adjusted OR, 0.76; 95%CI, 0.54-1.09). For palpitations, crude differences were smaller and all became nonsignificant after adjustment. Conclusions: This study does not confirm the existence of sex-related bias in the management of chest pain and palpitations. However, such bias cannot be completely ruled out in diagnoses confirmed within the OFRECE study, which might limit its ability to detect sex-related differences in health care

Hallazgos electrocardiográficos anormales en la población mayor de 40 años. Prevalencia y significación clínica. Resultados del estudio OFRECE / Abnormal electrocardiographic findings in the population older than 40 years. Prevalence and clinical significance. Results of the OFRECE study

Introducción y objetivos: Las anomalías electrocardiográficas son muy comunes. El propósito de este estudio es analizar la prevalencia de hallazgos electrocardiográficos anormales y su significado clínico en la población general española de 40 o más años. Métodos: Subanálisis del estudio OFRECE; se seleccionó una muestra representativa de la población española de 40 o más años. Se dispuso de datos clínicos y electrocardiograma de todos los participantes. La lectura de los electrocardiogramas fue centralizada, los evaluaron de manera independiente 2 cardiólogos expertos y se consultó con un tercero en caso de desacuerdo, para llegar al diagnóstico final por consenso. Antes de iniciarse la lectura de los electrocardiogramas, se establecieron estrictamente los criterios diagnósticos de cada una de las anomalías analizadas. Se estudiaron la prevalencia y los factores clínicos asociados con: crecimiento de cavidades, trastornos de conducción, anomalías de la repolarización, ondas Q patológicas, extrasistolia auricular y ventricular y preexcitación. Resultados: Se evaluó a 8.343 individuos (media de edad, 59,2 años; el 52,4% mujeres). Solo 4.074 (51,2%) presentaron un electrocardiograma rigurosamente normal. Las anomalías más frecuentes fueron las alteraciones inespecíficas de la repolarización (16%) asociadas con enfermedad coronaria y fibrilación auricular; el bloqueo de rama derecha (8,1%) asociado con enfermedad pulmonar obstructiva crónica; el hemibloqueo anterosuperior izquierdo (6,5%) relacionado con la hipertensión y la insuficiencia cardiaca y el intervalo PR largo (3,7%) se asociaron con enfermedad coronaria. Conclusiones: Las anomalías electrocardiográficas son muy comunes en la población general de 40 o más años. Tan solo la mitad de la población tenía un electrocardiograma rigurosamente normal

Introduction and objectives: Abnormal electrocardiographic findings are highly common. The aim of this study was to analyze the prevalence of abnormal electrocardiographic patterns in the general Spanish population aged 40 years or older. Methods: This subanalysis of the OFRECE study selected a representative sample of the Spanish population aged 40 years or older. Clinical data and electrocardiograms were available in all participants. The electrocardiograms were read centrally. Each electrocardiogram was independently assessed by 2 trained cardiologists and, if there was disagreement, a third was consulted to reach a consensus-based diagnosis. Prior to reading the electrocardiograms, diagnostic criteria were strictly defined for each of the abnormalities analyzed. We analyzed the prevalence and clinical factors associated with cavity enlargement, conduction disorders, repolarization abnormalities, pathological Q waves, atrial and ventricular premature beats, and pre-excitation. Results: A total of 8343 individuals were evaluated, (mean age, 59.2 years; 52.4% women). Only 4074 (51.2%) participants had a completely normal electrocardiogram. The most frequent abnormalities were nonspecific repolarization abnormalities (16%) associated with coronary heart disease and atrial fibrillation; right bundle-branch block (8.1%) associated with chronic pulmonary obstructive disease; left anterior hemiblock (6.5%) related to hypertension and congestive heart failure; and long PR interval (3.7%), which was associated with coronary heart disease. Conclusions: Electrocardiographic abnormalities are very common in the general population aged 40 years or older. Only about half of the population had a completely normal electrocardiogram

Improved off-resonance phase behavior using a phase-inverted adiabatic half-passage pulse for 13 C MRS in humans at 7 T.

In vivo 13 C MRS at high field benefits from an improved SNR and spectral resolution especially when using surface coils in combination with adiabatic pulses, such as the adiabatic half-passage (AHP) pulse for 13 C excitation. However, the excitation profile of the AHP pulse is asymmetric relative to the carrier frequency, which could lead to asymmetric excitation of the spectral lines relative to the center of the spectrum. In this study, a pulse-acquire sequence was designed for adiabatic 13 C excitation with a symmetric bandwidth, utilizing a combination of two AHP pulses with inverted phases in alternate scans. Magnetization and phase behavior as a function of frequency offset and RF amplitude of the B1 field, as well as the steady-state transverse magnetization response to off-resonance, were simulated. Excitation properties of the combined pulse sequence were studied by 23 Na imaging and 13 C spectroscopy in vitro on a phantom and in vivo on the human calf at 7 T. Simulations demonstrated symmetric transverse magnetization and phase with respect to positive and negative frequency offsets when using two AHP pulses with inverted phases in alternate scans, thereby minimizing baseline distortion and achieving symmetric T1 weighting, as confirmed by in vitro measurements. The intensities of the lipid peaks at 15, 30, 62, 73, and 130 ppm were in agreement with those theoretically predicted using two AHP pulses with inverted phases in alternate scans. We conclude that using two phase-inverted AHP pulses improves the symmetry of the 13 C excitation profile and phase response to off-resonance effects at 7 T in comparison with using a single AHP pulse.

The Gender Perspective Within the OFRECE Study: Differences in Health Care Among Patients Consulting for Chest Pain and/or Palpitations.

INTRODUCTION AND OBJECTIVES: To analyze differences between sexes in the clinical management of patients presenting with symptoms of chest pain and/or palpitations within a population-based study. METHODS: The OFRECE study included a random sample of 8400 individuals from the Spanish population aged 40 years and older; 1132 (13.5%) had previously consulted for chest pain and 1267 (15.1%) had consulted for palpitations and were included in the present study. We calculated both the crude and adjusted odds ratios (OR) of undergoing certain tests and the results of consultations by sex. Adjustment was performed by classic cardiovascular risk factors, a personal history of cardiovascular disease, and a diagnosis of stable angina or atrial fibrillation confirmed in the OFRECE study in each case. RESULTS: No differences were observed in history of consultation for chest pain between women and men (13% vs 14.1%; P=.159) but differences were found in palpitations (19% vs 10.4%, respectively; P <.001). Women who had previously consulted for chest pain underwent fewer echocardiograms (32.5% vs 45.3%, respectively; P <.001), were less frequently referred to a cardiologist (49.1% vs 60.1%; P <.001), were less often admitted to hospital (20.1% vs 39.4%; P <.001), and less frequently received a confirmed diagnosis (60.9 vs 71, 9; P <.001). After full adjustment, all differences decreased and become nonsignificant echocardiograms: adjusted OR, 0.81; 95%CI, 0.60-1.09; referral to a cardiologist: adjusted OR, 0.86; 95%CI, 0.63-1.16; hospital admission: adjusted OR, 0.76; 95%CI, 0.54-1.09). For palpitations, crude differences were smaller and all became nonsignificant after adjustment. CONCLUSIONS: This study does not confirm the existence of sex-related bias in the management of chest pain and palpitations. However, such bias cannot be completely ruled out in diagnoses confirmed within the OFRECE study, which might limit its ability to detect sex-related differences in health care.

Sacubitril/Valsartan in Real-Life Practice: Experience in Patients with Advanced Heart Failure and Systematic Review.

PURPOSE: Sacubitril/valsartan reduced heart failure (HF) admissions and cardiovascular mortality in the PARADIGM-HF trial. However, real-life studies are scarce comparing daily practice patients with those of the trial. The aim of our study was to analyze the efficacy and safety of the drug in an advanced heart failure cohort and to review systematically the previous real-life studies published to date. METHODS: We performed a retrospective analysis of consecutive patients prescribed sacubitril/valsartan in a single tertiary HF clinic between September 2016 and February 2018. HF admissions before and after the initiation of the drug were assessed in a paired fashion. A systematic review of real-life studies published to date was also conducted. RESULTS: Sacubitril/valsartan was started in 108 patients who were in a more advanced NYHA class and more frequently treated with mineral receptor antagonists, internal cardiac defibrillator, and cardiac resynchronization therapy than in the PARADIGM-HF trial. After a 6-month follow-up, we observed a significant reduction in the HF hospitalizations, median levels of NT-proBNP, and need for levosimendan ambulatory perfusion. Likewise, we found a significant improvement in mean LVEF and end diastolic left ventricle diameter. Regarding safety, sacubitril/valsartan was well-tolerated without any severe adverse effect. CONCLUSION: Sacubitril/valsartan in real-life is prescribed to a more advanced HF population, which could be responsible for the difficulties in reaching high doses of the drug. However, after a 6-month follow-up, sacubitril/valsartan significantly reduces HF hospitalization and induces cardiac reverse remodeling, without remarkable adverse events.

Abnormal Electrocardiographic Findings in the Population Older Than 40 Years. Prevalence and Clinical Significance. Results of the OFRECE Study.

INTRODUCTION AND OBJECTIVES: Abnormal electrocardiographic findings are highly common. The aim of this study was to analyze the prevalence of abnormal electrocardiographic patterns in the general Spanish population aged 40 years or older. METHODS: This subanalysis of the OFRECE study selected a representative sample of the Spanish population aged 40 years or older. Clinical data and electrocardiograms were available in all participants. The electrocardiograms were read centrally. Each electrocardiogram was independently assessed by 2 trained cardiologists and, if there was disagreement, a third was consulted to reach a consensus-based diagnosis. Prior to reading the electrocardiograms, diagnostic criteria were strictly defined for each of the abnormalities analyzed. We analyzed the prevalence and clinical factors associated with cavity enlargement, conduction disorders, repolarization abnormalities, pathological Q waves, atrial and ventricular premature beats, and pre-excitation. RESULTS: A total of 8343 individuals were evaluated, (mean age, 59.2 years; 52.4% women). Only 4074 (51.2%) participants had a completely normal electrocardiogram. The most frequent abnormalities were nonspecific repolarization abnormalities (16%) associated with coronary heart disease and atrial fibrillation; right bundle-branch block (8.1%) associated with chronic pulmonary obstructive disease; left anterior hemiblock (6.5%) related to hypertension and congestive heart failure; and long PR interval (3.7%), which was associated with coronary heart disease. CONCLUSIONS: Electrocardiographic abnormalities are very common in the general population aged 40 years or older. Only about half of the population had a completely normal electrocardiogram.

High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation.

ANTECEDENTS: Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. AIM: Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. METHODS: 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction < 50%, or heart failure not due to an acute rejection. RESULTS: 51 patients (53%) presented CAV at evaluation; 21 of them had CV events. Hs-cTnT (56 ± 45 versus 20 ± 18 ng/L; p = 0.04) and sAXL concentrations (98 ± 51 versus 26 ± 26 ng/L; p = 0.01) were significantly higher in patients with CV events. Hs-cTnT (HR 1.03; 95% CI 1.015-1.042, p = 0.0001) and sAXL (HR 1.01; 95% CI 1.001-1.019, p = 0.02) were independent predictors of CV events. A hs-cTnT concentration < 21 ng/L, detected by AUC ROC, predicted the absence of CV events with a predictive value of 91%; sAXL did not add more predictive value to hs-cTnT. Survival free of CV events was 92% in patients with hs-cTnT < 21 ng/L and 57% in those with hs-cTnT > 21 ng/L (p < 0.001). CONCLUSION: Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.