High resolution 3-Dimensional imaging of the human cardiac conduction system from microanatomy to mathematical modeling

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees

What is the Clinical Significance of Ventricular Mural Antagonism?

Recent morphological studies provide evidence that the ventricular walls are arranged as a 3D meshwork of aggregated cardiomyocyte chains, exhibiting marked local structural variations. In contrary to previous findings, up to two-fifths of the chains are found to have a partially transmural alignment, thus deviating from the prevailing tangential orientation. Upon contraction, they produce, in addition to a tangential force, a radial force component that counteracts ventricular constriction and aids widening of the ventricular cavity. In experimental studies, we have provided evidence for the existence of such forces, which are auxotonic in nature. This is in contrast to the tangentially aligned myocytes that produce constrictive forces, which are unloading in nature. The ventricular myocardium is, therefore, able to function in an antagonistic fashion, with the prevailing constrictive forces acting simultaneously with a dilatory force component. The ratio of constrictive to dilating force varies locally according to the specific mural architecture. Such antagonism acts according to local demands to preserve the ventricular shape, store the elastic energy that drives the fast late systolic dilation and apportion mural motion to facilitate the spiralling nature of intracavitary flow. Intracavitary pressure and flow dynamics are thus governed concurrently by ventricular constrictive and dilative force components. Antagonistic activity, however, increases deleteriously in states of cardiac disease, such as hypertrophy and fibrosis. ß-blockade at low dosage acts selectively to temper the auxotonic forces

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology. The giraffe heart, for example, appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)-a leading form of hypertension-associated cardiovascular disease in humans. Here, we postulate that the physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlying this cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap for preventive and therapeutic strategies for human HFpEF

Aortic valve-sparing root replacement and composite root replacement:a Danish multicentre nationwide study

AIMS: Aortic valve-sparing root replacement is recommended over composite root replacement for aortic root aneurysms, especially in younger patients, but long-term outcomes in low-volume nationwide settings remain unclear. The objectives are to compare long-term survival, stroke, and reoperation rates between the two procedures in a low-volume national setting.METHODS AND RESULTS: Patients were identified from the Western Danish Heart Registry and the Danish Heart Registry. Cases were validated by review of operative descriptions. The primary outcome was long-term survival from all-cause mortality; secondary outcomes included stroke, reoperation, recurrent aortic regurgitation, and aortic stenosis. Groups were balanced using propensity score matching. Echocardiographic data were provided for the matched cohort. We identified 760 patients treated with composite root replacement and 179 patients with aortic valve-sparing root replacement between January 2010 and April 2022. Mean follow-up was 6.5 years. Composite root replacement patients were younger [50.7 years (SD 14.1) vs. 55.2 (SD 13.5), P &lt; 0.001], but more comorbid with a median EuroSCOREII of 5.5 [interquartile range (IQR): 3.3-11.7] vs. 3.4 (IQR: 2.6-5.0) ( P &lt; 0.001). After matching 157 patients per group, aortic valve-sparing root replacement showed improved 10-year survival [91.2%, 95% confidence interval (CI) 82.3-95.8 vs. 80.4%, 95% CI 70.0-87.5, log-rank P = 0.026], with lower 10-year stroke risk (4.9%, 95% CI 1.8-13.0 vs. 18.9%, 95% CI 11.7-29.9, log-rank P = 0.007). Risk of reoperation was nonsignificant (log-rank P = 0.12), which was consistent in the crude population when accounting for competing risk of death (log-rank P = 0.09). CONCLUSION: In this nationwide study, aortic valve-sparing root replacement was associated with better long-term survival and lower stroke risk, supporting its role as a durable surgical option for selected patients.</p

Sex difference in aortic root replacement with a stentless bioprosthesis

OBJECTIVES To investigate and quantify differences in survival and reinterventions between sexes after aortic root replacement with a stentless bioprosthesis, stratified for preoperative valve lesion.METHODS Elective adults undergoing aortic root replacement with the Freestyle bioprosthesis at six North-Atlantic centres were included. Survival analyses were performed using the Kaplan-Meier method or Aalen-Johansen with death as competing risk as relevant. Results were quantified using uni- and multivariable Cox regression tested using a log-rank likelihood ratio test.RESULTS In total, 884 patients were analysed for a median follow-up time of 10 years. Females were 4 years older. Survival was significantly worse in females operated for aortic valve insufficiency [60.7% and 72.2% for females and males at 14 years, respectively (P = 0.001)], but not for the other indications, even after correction for age. There were no differences in early outcomes or need for reoperation between the sexes and between the different aortic valve pathologies.CONCLUSIONS Sex difference in survival outcomes depends on pathology, and females have, compared to males, more symptoms preoperatively regardless of type of valve lesion and worse outcome after aortic root replacement due to aortic insufficiency. Updated surgical risk scores should account for interaction between sex and pathology, and the surgical community must raise awareness on risk of patient's or doctors delay to surgery.Cardiovascular disease presents differently in females and males regarding symptoms, pathophysiology, natural history and treatment [1-3].Thoracic Surger