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The prognostic impact of non-obstructive coronary artery disease (CAD) remains controversial. Therefore, the objective of this study is to assess the long-term prognostic significance of non-obstructive CAD using machine learning models. We designed a multicenter retrospective, longitudinal, and observational study that included 3265 patients classified into three groups: 1426 patients with lesions < 20%, 643 patients with non-obstructive CAD (lesions 20–50%), and 1196 patients with obstructive CAD (lesions > 70%). A composite cardiovascular event (acute myocardial infarction, stroke, hospitalization due to heart failure, or cardiovascular-related death) was assessed after a mean follow-up of 43 months. To achieve this, various machine learning models were constructed. The model with the highest accuracy was selected to perform a Shapley Additive Explanations (SHAP) analysis, revealing the contribution of different variables in predicting an event. The SHAP analysis suggested that the percentage of coronary lesion was the most significant predictor of cardiovascular events. None of the models demonstrated adequate capability in predicting the event, showing only a good predictive ability for the absence of an endpoint. In conclusions, this study demonstrates how machine learning techniques may facilitate the development of high-performing models for predicting long-term cardiovascular events in patients undergoing coronary angiography.

RESUMEN Introducción y objetivos: Se debate la necesidad de realizar revascularización coronaria completa tras un síndrome coronario agudo en pacientes diabéticos con enfermedad coronaria multivaso, y más aún si estos son reflejo de los pacientes de la práctica clínica habitual (mundo real). Por ello, el objetivo de este trabajo es analizar las complicaciones cardiovasculares en pacientes diabéticos con y sin revascularización completa incluibles en ensayos clínicos como de la práctica clínica habitual. Métodos: Estudio unicéntrico retrospectivo de pacientes diabéticos con enfermedad coronaria multivaso. Se analizaron 733 pacientes diabéticos: 299 (40,8%) con criterios compatibles de inclusión de ensayos clínicos y 434 (59,2%) del mundo real. Resultados: Los pacientes del mundo real constituyen el 59,2% de la muestra. Se caracterizan por presentar mayor porcentaje de factores de riesgo, mayor edad media y comorbilidad. Los diabéticos con enfermedad coronaria multivaso incluibles en ensayos tienen menor riesgo de mortalidad total (HR = 0,30; IC95%, 0,16-0,57; p < 0,001), de mortalidad de causa cardiaca (HR = 0,33; IC95%, 0,15-0,71; p = 0,03) y de sufrir eventos cardiovasculares adversos mayores (HR = 0,58; IC95%, 0,38-0,86; p = 0,008). Por otro lado, recibir revascularización completa desciende el riesgo de mortalidad de causa cardiaca (HR = 0,32; IC95%, 0,13-0,83; p = 0,019) y de eventos cardiacos adversos mayores (HR = 0,50; IC95%, 0,29-0,89; p = 0,017) en los pacientes diabéticos del mundo real. Conclusiones: Se sugiere que revascularizar completamente a los pacientes del mundo real mejoraría el pronóstico en cuanto a supervivencia. Asimismo, los diabéticos incluibles en ensayos clínicos presentan menos complicaciones que los diabéticos no incluibles.

ABSTRACT Introduction and objectives: The need for complete coronary artery revascularization after acute coronary syndrome in diabetic patients with multivessel coronary artery disease was discussed, even more so if they reflect the routine clinical practice (“real world”). Therefore, the objective of this study is to analyze cardiovascular complications in diabetics with and without complete revascularization included in clinical trials and in the routine clinical practice. Methods: This was a single-center retrospective study of diabetic patients with multivessel coronary artery disease. We analyzed 733 diabetic patients: 299 (40.8%) with compatible criteria to be included in clinical trials, and 434 real-world patients (59.2%). Results: Real-world patients make up 59.2% of the sample. They are characterized by a higher percentage of risk factors, older mean age, and more comorbidities. Diabetics with multivessel coronary artery disease included in the trials have a lower risk of overall mortality (HR, 0.30; 95%CI, 0.16-0.57; P < .001), cardiac death (HR, 0.33; 95%CI, 0.15-0.71; P = .03), and major adverse cardiovascular events (HR, 0.58; 95%CI, 0.38-0.86; P = .008). On the other hand, receiving complete revascularization reduces the risk of cardiac death (HR, 0.32; 95%CI, 0.13-0.83; P = .019), and major adverse cardiovascular events (HR, 0.50; 95%CI, 0.29-0.89; P = .017) in real-world diabetic patients. Conclusions: It is suggested that fully revascularizing real-world patients would improve survival prognosis. In addition, diabetics included in clinical trials present fewer complications compared to those not included.

The COVID-19 pandemic has caused a challenge for our society due to the post-acute sequelae of the disease. Persistent symptoms and long-term multiorgan complications, known as post-acute COVID-19 syndrome, can occur beyond 4 weeks from the onset of the COVID-19 infection. Postural orthostatic tachycardia syndrome (POTS) is considered a variety of dysautonomia, which is characterized by chronic symptoms that occur with standing and a sustained increase in heart rate, without orthostatic hypotension. POTS can lead to debilitating symptoms, significant disability, and impaired quality of life. In this narrative review, the etiopathogenic basis, epidemiology, clinical manifestations, diagnosis, treatment, prognosis, and socioeconomic impact of POTS, as well as other related dysautonomic disorders, after COVID-19 infection and SARS-CoV-2 postvaccination, were discussed. After a search conducted in March 2023, a total of 89 relevant articles were selected from the PubMed, Google Scholar, and Web of Science databases. The review highlights the importance of recognizing and managing POTS after COVID-19 infection and vaccination, and the approach to autonomic disorders should be known by all specialists in different medical areas. The diagnosis of POTS requires a comprehensive clinical assessment, including a detailed medical history, physical examination, orthostatic vital signs, and autonomic function tests. The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. Further research is needed to understand the underlying mechanisms, risk factors, and optimal treatment strategies for this complication.

Abstract Patient-centred medicine is a healthcare approach that focuses on patients’ wants, needs and preferences. An obstacle to implement patient-centred medicine is the difficulty of obtaining data that is relevant and representative of the whole society. In 2019, the Spanish Society of Cardiology highlighted eight trends that would exert a determining influence on the future of cardiology: “demographics”, “economic environment”, “political environment”, “citizens’ expectations”, “incorporation of women”, “technological innovation”, “health levels and cardiovascular risk factors” and “healthcare organisation and management”. In order to assess these trends from a pacient-centred approach, the aim of this study is to evaluate the opinions of the individuals who are part of Spanish society, regarding the eight trends identified by the Spanish Society of Cardiology, using natural language processing tools to analyse the communications expressed by citizens in digital ecosystems and official channels of communication. We analysed communications published between 2007 and 2019. Natural language processing identified 17 areas of opinion that support the eight trends. We evaluated the impact of each area of opinion based on the standard metrics of online reputation: presence, emotion and reach. Thus, 257,456 communications were analysed. The most relevant trend was “healthcare organisation and management” (54% of the total impact), followed by “health levels and cardiovascular risk factors” and “demographics” (14% and 10%, respectively). The least relevant trend was “citizens’ expectations” (1%). Within the areas of opinion identified, the one with greatest impact was “the cardiologist” (16% of the total impact). In conclusion, the results of this research show that natural language processing tools are a useful tool for patient-centred medicine. The high impact associated with the cardiologist’s role, together with the low impact observed for “citizen’s expectations” show that Spanish citizens identify the cardiologist as the leading figure regarding their cardiovascular health.

Sr. Editor: La angiotomografía computarizada de arterias coronarias (TCAC) es ya una de las principales herramientas para la exclusión de enfermedad coronaria en pacientes con síntomas estables; permite, con un excelente valor predictivo negativo, caracterizar las placas ateromatosas y el grado de estenosis que estas producen1. En algunos laboratorios de imagen la TCAC se realiza después de medir la puntuación (score) de calcio coronario (SCC), en general mediante la escala de Agatston, lo que no requiere inicialmente inyección de contraste. Los estudios sugieren que los pacientes con síntomas estables y ausencia de calcio coronario, es decir, con SCC nula o Agatston igual a 0, no suelen tener estenosis coronarias significativas y presentan un marcado mejor pronóstico, de lo que se deduce que una TCAC con la consiguiente inyección de contraste podría no aportar información relevante en la mayoría de los casos2-4. Así, nuestros objetivos fueron describir la prevalencia y las características de los pacientes con SCC igual a 0; evaluar en ellos los hallazgos obtenidos en el posterior estudio con contraste y, en caso de realizarse, en la coronariografía invasiva; y estudiar los eventos en el seguimiento a largo plazo en este grupo. Para ello realizamos un estudio de cohortes observacional que...

To the Editor, Coronary computed tomography angiography (CCTA) is one of the main imaging modalities used to discard coronary artery disease in patients with stable symptoms; thanks to its excellent negative predictive value, it can characterize atheromatous plaques and the degree of stenosis they cause.1 In some imaging facilities, the CCTA is used after measuring the coronary calcium score often through the Agatston score that does not require initially the injection of contrast. Studies suggest that patients with stable symptoms and lack of coronary calcium (CCS = 0 or Agatston = 0) don’t usually have significant coronary stenoses but a have better prognosis. This is indicative that a CCTA with the corresponding injection of contrast would not provide relevant information in most of the cases.2-4 Therefore, our objectives were to describe the prevalence and characteristic of patients with CCS = 0; also, to assess the findings obtained in the subsequent contrast study and invasive coronary angiography if any; finally, we studied the events occurring at the long-term follow-up in this group of patients. Therefore, we conducted an observational cohort study that included all procedures (CCS and subsequent CCTA) performed in a tertiary center between 2008 and 2016. The authors declare that they acted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients. All patients were referred with chest pain and a past medical history of ischemic heart disease. The Philips CT Brillance 64-multislice detector computed tomography scanner and Heartbeat-CS software (Philips Medical Systems, United States) were used. The CCS was assessed using the Agatston score. Stenoses that were > 70% quantitatively were considered significant coronary lesions.

Abstract Background Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables. Methods We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM. Results LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6–6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98–4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors. Conclusions SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

Expression of Wilms’ tumor suppressor transcription factor (WT1) in the embryonic epicardium is essential for cardiac development, but its myocardial expression is little known. We have found that WT1 is expressed at low levels in 20–25% of the embryonic cardiomyocytes. Conditional ablation of WT1 using a cardiac troponin T driver (Tnnt2Cre) caused abnormal sinus venosus and atrium development, lack of pectinate muscles, thin ventricular myocardium and, in some cases, interventricular septum and cardiac wall defects, ventricular diverticula and aneurisms. Coronary development was normal and there was not embryonic lethality, although survival of adult mutant mice was reduced probably due to perinatal mortality. Adult mutant mice showed electrocardiographic anomalies, including increased RR and QRS intervals, and decreased PR intervals. RNASeq analysis identified differential expression of 137 genes in the E13.5 mutant heart as compared to controls. GO functional enrichment analysis suggested that both calcium ion regulation and modulation of potassium channels are deeply altered in the mutant myocardium. In summary, together with its essential function in the embryonic epicardium, myocardial WT1 expression is also required for normal cardiac development.

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long‐term follow‐up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32–44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18–26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow‐up of 4.5 years, 91 deaths accounted for 4.21 higher‐than‐expected mortality in the age‐matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance—either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six‐month changes in the composite clinical score and in the 6‐minute walk test distance were related to survival. Conclusions Persistent valvular heart disease–pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.

Abstract Background During the last decade, the use of ministernotomy in cardiac surgery has increased. Quality of life and patient satisfaction after ministernotomy have never been compared to conventional full sternotomy in randomised trials. The aim of the study is to determine if this minimally invasive approach improves quality of life, satisfaction and clinical morbimortality outcomes. Methods/design The QUALITY-AVR trial is a single-blind, single-centre, independent, and pragmatic randomised clinical trial comparing ministernotomy (“J” shaped upper hemisternotomy toward right 4th intercostal space) to full sternotomy in patients with isolated severe aortic stenosis scheduled for elective aortic valve replacement. One hundred patients will be randomised in a 1:1 computational fashion. Sample size was determined for the primary end point with alpha error of 0.05 and with power of 90% in detecting differences between intervention groups of ≥ 0.10 points in change from baseline quality of life Questionnaire EuroQOL-index (EQ-5D-5 L®), measured at 1, 6 or 12 months. Secondary endpoints are: the differences in change from other baseline EQ-5D-5 L® utilities (visual analogue scale, Health Index and Severity Index), cardiac surgery specific satisfaction questionnaire (SATISCORE®), a combined safety endpoint of four major adverse complications at 1 month (all-cause mortality, acute myocardial infarction, neurologic events and acute renal failure), bleeding through drains within the first 24 h, intubation time, postoperative hospital and intensive care unit length of stay, transfusion needs during the first 72 h and 1-year survival rates. Clinical follow up is scheduled at baseline, 1, 6, and 12 months after randomization. All clinical outcomes are recorded following the Valve Academic Research Consortium 2 criteria. Discussion The QUALITY-AVR trial aims to test the hypothesis that ministernotomy improves quality of life, satisfaction and clinical outcomes in patients referred for isolated aortic valve replacement. Statistically significant differences favouring ministernotomy could modify the surgical “gold standard” for aortic stenosis surgery, and subsequently the need to change the control group in transcatheter aortic valve implantation trials. Recruitment started on 18 March 2016. In November 2017, 75 patients were enrolled. Trial registration ClinicalTrials.gov, NCT02726087. Registered on 13 March 2016.

Abstract Background Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS. Material and methods This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016. Results The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p

Introducción y objetivos: La utilización de la arteria mamaria izquierda u otros injertos arteriales, sobre territorios diferentes de la descendente anterior son objeto de debate actualmente. El objetivo de este estudio fue evaluar la permeabilidad a medio-largo plazo, de los injertos arteriales compuestos y factores de riesgo relacionados. Métodos: Estudio retrospectivo; se incluyó a pacientes sometidos a cirugía de revascularización cardíaca, utilizando para ello 2 o más anastomosis arteriales. La estenosis coronaria previa a la intervención fue evaluada con el uso de angiografía coronaria cuantitativa y la permeabilidad del injerto con angio-TAC coronaria. Resultados: La media de edad fue de 55,8 ± 8,7 años, con alta comorbilidad. El porcentaje medio de lesión de tronco coronario izquierdo fue del 60,1%. El resto de las lesiones coronarias en otros territorios superaban el 70%. Todos los vasos revascularizados con arterial radial presentaban estenosis superiores al 80%. No encontramos relación entre la permeabilidad de los injertos arteriales compuestos de arteria radial o arteria mamaria derecha y los factores de riesgo cardiovascular, así como tampoco encontramos diferencias entre el uso de arteria radial o arteria mamaria derecha con respecto a la permeabilidad del injerto. Conclusiones: Existe una alta permeabilidad a medio-largo plazo en los injertos arteriales compuestos. No encontramos diferencias entre la utilización de arteria mamaria derecha y la arteria radial en términos de permeabilidad. La angio-TAC coronaria es una técnica segura y factible, permitiendo el estudio de la permeabilidad del injerto de forma no invasiva.

Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180-240 days old) and 56 old (300-440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.