Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a frequent complication caused by cardiac and non-cardiac pathophysiological mechanisms, but often it is subclinical. MINS is associated with increased morbidity and mortality, justifying the need to its diagnose and the investigation of their causes for its potential prevention. METHODS: Prospective, observational, pilot study, aiming to detect MINS, its relationship with silent coronary artery disease and its effect on future adverse outcomes in patients undergoing major non-cardiac surgery and without postoperative signs or symptoms of myocardial ischemia. MINS was defined by a high-sensitive cardiac troponin T (hs-cTnT) concentration > 14 ng/L at 48-72 h after surgery and exceeding by 50% the preoperative value; controls were the operated patients without MINS. Within 1-month after discharge, cardiac computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) studies were performed in MINS and control subjects. Significant coronary artery disease (CAD) was defined by a CAD-RADS category ≥ 3. The primary outcomes were prevalence of CAD among MINS and controls and incidence of major cardiovascular events (MACE) at 1-year after surgery. Secondary outcomes were the incidence of individual MACE components and mortality. RESULTS: We included 52 MINS and 12 controls. The small number of included patients could be attributed to the study design complexity and the dates of later follow-ups (amid COVID-19 waves). Significant CAD by CCTA was equally found in 20 MINS and controls (30% vs 33%, respectively). Ischemic patterns (n = 5) and ischemic segments (n = 2) depicted by cardiac MRI were only observed in patients with MINS. One-year MACE were also only observed in MINS patients (15.4%). CONCLUSION: This study with advanced imaging methods found a similar CAD frequency in MINS and control patients, but that cardiac ischemic findings by MRI and worse prognosis were only observed in MINS patients. Our results, obtained in a pilot study, suggest the need of further, extended studies that screened systematically MINS and evaluated its relationship with cardiac ischemia and poor outcomes. Trial registration Clinicaltrials.gov identifier: NCT03438448 (19/02/2018).

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol.

BACKGROUND: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. METHODS: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. DISCUSSION: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. TRIAL REGISTRATION: NCT04162236.

Reliability of a new method for coronary artery calcium or metal subtraction by 320-row cardiac CT.

PURPOSE: To investigate the feasibility and diagnostic accuracy of subtraction CTA on patients with highly calcified coronary artery disease (CAD) or previous implanted stents, in comparison with invasive coronary angiography (ICA). MATERIALS AND METHODS: Twenty-three patients were recruited. All conventional and subtraction CTA exams were performed using a 320-row CT. Subjective image quality score was assessed for each segment using a 4-point scale: 1-uninterpretable to 4-good image quality. RESULTS: A total of 129 calcified or stented coronary segments were studied. Mean coronary image quality with conventional CTA was 2.73 ± 0.97 and in subtracted CTA 3.3 ± 0.92 (p < 0.01). After metal subtraction, image quality in stented coronary segments with >3 mm of diameter improved from 2.69 ± 0.97 to 3.34 ± 0.89 (p = 0.01) and in those with <3 mm of diameter from 2.11 ± 0.78 to 2.67 ± 0.87 (p = 0.17). There was an improvement in diagnostic accuracy to detect ICA stenosis >50 % by subtraction CTA compared with conventional CTA (AUC 0.93 to 0.87; p = 0.02). CONCLUSION: Subtraction CTA is promising in overcoming limitations of conventional CTA due to calcium or metal artefacts, especially if no motion artefact is present or when stents > 3 mm are studied. KEY POINTS: • Calcium and metal artefacts are still a limitation for conventional coronary CTA • Diagnostic accuracy is improved by subtraction as compared with conventional CTA • Subtraction CTA is a promising tool to overcome limitations of conventional CTA.

Usefulness of Cardiac Computed Tomography in Coronary Risk Prediction: A Five-Year Follow-Up of the SPICA Study (Secure Prevention with Imaging of the Coronary Arteries).

Accurate identification of individuals at high coronary risk would reduce acute coronary syndrome incidence and morbi-mortality. We analyzed the effect on coronary risk prediction of adding coronary artery calcification (CAC) and Segment Involvement Score (SIS) to cardiovascular risk factors. This was a prospective cohort study of asymptomatic patients recruited between 2013-2017. All participants underwent a coronary computed tomography angiography to determine CAC and SIS. The cohort was followed-up for a composite endpoint of myocardial infarction, coronary angiography and/or revascularization (median = five years). Discrimination and reclassification of the REGICOR function with CAC/SIS were examined with the Sommer's D index and with the Net reclassification index (NRI). Nine of the 251 individuals included had an event. Of the included participants, 94 had a CAC = 0 and 85 a SIS = 0, none of them had an event. The addition of SIS or of SIS and CAC to the REGICOR risk function significantly increased the discrimination capacity from 0.74 to 0.89. Reclassification improved significantly when SIS or both scores were included. CAC and SIS were associated with five-year coronary event incidence, independently of cardiovascular risk factors. Discrimination and reclassification of the REGICOR risk function were significantly improved by both indexes, but SIS overrode the effect of CAC.

A different type of acute myocarditis: a case report of acute autoimmune myocarditis mediated by anti-PD-1 T lymphocyte receptor (pembrolizumab).

BACKGROUND: Pembrolizumab is an immune check-point inhibitor (ICI), which acts by blocking the T lymphocyte PD-1 inhibitor receptor. It has been increasingly used in advanced or non-responsive tumours with promising results. However, acute myocarditis is an infrequent but potentially life-threatening autoimmune adverse effect related to ICIs. CASE SUMMARY: This case deals with a 69-year-old gentleman on second-line therapy with pembrolizumab for advanced non-small cell lung cancer. Three weeks after first dose, the patient was diagnosed with an autoimmune hepatitis, treated with decreasing corticoid dosage, followed by acute heart failure. On admission, his electrocardiogram (ECG) showed diffuse repolarization changes and a transthoracic echocardiography revealed severe left ventricle impairment (left ventricular ejection fraction 32%). High-sensitivity cardiac troponin was elevated and a coronary angiogram was performed showing non-significant obstructive disease. An autoimmune myocarditis was suspected, and high-dose intravenous corticoid, intravenous vasodilators, and loop diuretics were started with favourable response. Cardiac magnetic resonance (CMR) imaging, performed 2 weeks after clinical onset, revealed extracellular oedema in the anteroseptal-apical left ventricle segments. A new transthoracic echocardiography, performed after 3 months, showed preserved left ventricle ejection fraction. Finally, the patient was readmitted due to an autoimmune myasthenia-like syndrome. DISCUSSION: Acute autoimmune myocarditis related to ICIs is a challenging diagnosis and its incidence has been underestimated in early studies. Endomyocardial biopsy (EMB) is the gold standard test for its diagnosis. Nevertheless, a definite myocarditis diagnosis is possible without EMB when characteristic clinical syndrome, elevated myonecrosis markers, and electrocardiographic, echocardiographic, and CMR changes are present together.

Field dynamics in atrioventricular activation. Clinical evidence of a specific field-to-protein interaction.

The atrioventricular node (AV) is considered the electrical connection between the atria and ventricles. There is an electrical pause between activation of the atria and the ventricles (PR segment), but to date the mechanism responsible for this interruption remains unclear. The present communication focuses on the hypothesis that magnetic field dynamics could provide the answer. Proof of this hypothesis is that in Wolff-Parkinson-White syndrome, where there is physical connection between the atria and ventricles (bundle of Kent), there is electrical AV continuity, no PR segment is detected, and catheter ablation of the abnormal bundle restores AV discontinuity. Spontaneous initiation of the heart at the level of the sinus node, the pacemaker of the heart, could also be explained via field dynamics. The known transmembrane pacemaker protein CHN4, present in both sinoatrial and AV nodal cells, could interact with field information to provide specificity in an electronic key-to-lock mechanism interaction.

Investigación anatómica del ápex cardíaco / Anatomical investigation of the cardiac ápex

RESUMEN Objetivo: Comprender la anatomía cardíaca es la clave para resolver incógnitas sobre su función. La estructura miocárdica continua y helicoidal desempeña un papel fundamental en los movimientos de torsión-detorsión. El ápex, parte constitutiva del ventrículo, ¿tiene relevancia en la dinámica cardíaca o es simplemente un fondo de saco? El objetivo del presente trabajo fue responder este interrogante. Material y métodos: Se utilizaron para los estudios anátomo-histológicos cuatro corazones de bovinos jóvenes y cuatro corazones humanos (dos embriones y dos adultos). Para esta investigación se realizaron dos procedimientos: a) desplegamiento del miocardio continuo para observar la disposición de las fibras en la punta del ventrículo izquierdo, denominada zona apexiana; b) cortes horizontales y longitudinales para estudiar la estructura del ápex. Los primeros se realizaron entre los 2/3 medio y apexiano, y los longitudinales seccionando la punta ventricular izquierda con una orientación ápex-base. Resultados: Hemos encontrado en todos los corazones humanos y bovinos estudiados que el ápex corresponde únicamente al ventrículo izquierdo, en donde se ubica el giro del segmento descendente en la continuidad ascendente del miocardio continuo. El fondo de saco apexiano no posee prácticamente plano muscular en su extremo final. Está tapizado por dentro por el endocardio y por fuera por el epicardio. El plano muscular es apenas un 10% en espesor del miocardio contiguo. La transiluminación reafirma este concepto estructural. Conclusiones: El ápex es un fondo de saco prácticamente sin músculo, en el que el endocardio y el epicardio se hallan adosados, pero que cumple funciones del soporte de las presiones intraventriculares y es parte constitutiva de los movimientos de torsión y detorsión.

ABSTRACT Objective: Understanding cardiac anatomy is the key to solve unknown issues about its function. The continuous and helical myocardial structure plays a fundamental role in its torsion-detorsion motions. Does the apex, a constitutive part of the ventricle, have relevance in cardiac dynamics or is it simply a cul-de-sac? The aim of this study was to answer this question. Methods: Four young bovine and four human hearts (two embryos and two adults) were used for the anatomo-histological studies. Two procedures were carried out for this investigation: a) the continuous myocardium unfolding to observe the fiber arrangement at the tip of the left ventricle, called the apical zone; and b) horizontal and longitudinal sections to study the structure of the apex. The horizontal sections were performed between the middle 2/3 and the apex, and the longitudinal ones, sectioning left ventricular apex, with an apex-base orientation. Results: In all the human and bovine hearts studied we found that the apex corresponds only to the left ventricle, where the twist of the descending segment is located, in the ascending continuity of the myocardium. The apical cul-de-sac has practically no muscular plane at its end. It is internally lined by the endocardium and externally by the epicardium. The muscular plane has only 10% thickness of the adjacent myocardium, a structural concept confirmed by transillumination. Conclusions: The apex is a cul-de-sac practically devoid of muscle, in which the endocardium and epicardium are attached, but which performs the functions of supporting intraventricular pressures and being a constitutive part of the torsion and detorsion motions.

The helical ventricular myocardial band: global, three-dimensional, functional architecture of the ventricular myocardium.

We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.

Towards new understanding of the heart structure and function.

Structure and function in any organ are inseparable categories, both in health and disease. Whether we are ready to accept, or not, many questions in cardiovascular medicine are still pending, due to our insufficient insight in the basic science. Even so, any new concept encounters difficulties, mainly arising from our inert attitude, which may result either in unjustified acceptance or denial. The ventricular myocardial band concept, developed over the last 50 years, has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium. After more than five centuries long debate on macroscopic structure of the ventricular myocardium, this concept has provided a promising ground for its final understanding. Recent validations of the ventricular myocardial band, reviewed here, as well as future research directions that are pointed out, should initiate much wider scientific interest, which would, in turn, lead to reconciliation of some exceeded concepts about developmental, electrical, mechanical and energetical events in human heart. The benefit of this, of course, would be the most evident in the clinical arena.

Systolic ventricular filling.

The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles involved in this action. This contraction occurs during the last part of classical systole and the first part of diastole. Therefore, the most important part of ventricular diastole (i.e. the rapid filling phase), in which it receives >70% of the stroke volume, belongs to the active muscular contraction of the ascendent segment. We hope that these facts will give rise to new understanding of the principal mechanisms involved in normal and abnormal diastolic heart function.

Coronary computed tomographic angiographic findings in asymptomatic patients with heterozygous familial hypercholesterolemia and null allele low-density lipoprotein receptor mutations.

Heterozygous familial hypercholesterolemia (HeFH) can be associated with early coronary artery disease (CAD) in asymptomatic patients. The objectives of the present study were to assess the prevalence and magnitude of subclinical CAD in patients with HeFH using coronary computed tomographic angiography (CCTA) and to determine the clinical and genetic profile of those at the greatest risk of CAD. The study included 50 consecutive patients with HeFH diagnosed according to the Dutch Lipid Clinic Network criteria and a control group of 70 healthy subjects. The findings from CCTA for the patients with HeFH were compared with those from the control group, who had been referred for CCTA as a part of a preventive medical examination. In 82% of the patients with HeFH, genetic DNA was screened for low-density lipoprotein receptor (LDLR) gene mutations using a microarray. CCTA revealed a significantly greater Agatston calcium score in the study group than in the control group (260 vs 46; p = 0.002). The prevalence of CAD in the patients with HeFH was 48%. It was significant in 26%, involving mainly the proximal segments of the coronary arteries. In the control group, the prevalence of CAD was 33% and was significant in 5% (p <0.05 for prevalence and severity of CAD compared to patients with HeFH). In those with HeFH, increased age, null allele LDLR mutations, and low high-density lipoprotein blood levels at diagnosis showed a statistically significant association with CAD (p <0.05). In conclusion, patients with HeFH present with a greater prevalence, extension, and severity of subclinical CAD than the general population. Increased age, low high-density lipoprotein levels, and LDLR null allele mutations are related to the occurrence of CAD. CCTA has emerged as a useful technique for the screening of subclinical CAD in patients with HeFH.