Multiscale Structure and Function of the Aortic Valve Apparatus.

While studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, herein referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and supporting left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underly the simultaneous fulfilment of these functions. A brief overview of the tools used to investigate the AVA is included, such as: medical imaging modalities, experimental methods, and computational modelling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this paper support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.

Asymmetry of flow in aortic root and its application in hypertrophic obstructive cardiomyopathy.

The aortic root (AR) performs sophisticated functions regulating the blood dynamics during the cardiac cycle. Such complex function depends on the nature of flow in the AR. Here, we investigate the potential of new quantitative parameters of flow asymmetry that could have clinical implications. We developed a MATLAB program to study the AR hemodynamics in each sinus of Valsalva using two-dimensional (2-D) cardiac magnetic resonance imaging during systole and particularly at peak systolic flow in 13 healthy volunteers and compared with 10 patients with hypertrophic obstructive cardiomyopathy (HOCM). We show that the effective area of the aortic jet in healthy volunteers is significantly higher at peak systolic flow and on average during systole. The flow asymmetry index, indicating how the jet is skewed away from the left coronary sinus (LCS), is small in healthy volunteers and much larger in HOCM at peak systole. The average of this index over systole is significantly more different between cohorts. Looking in more detail at the flow in the sinuses during systole, we show that the AR jet in healthy volunteers is more symmetrical, affecting the three sinuses almost equally, unlike the asymmetric AR jet in patients with HOCM that has decreased flow rate in the LCS and increased fractional area of backward flow in the LCS. The percentage of backward flow in the sinuses of Valsalva calculated over systole is a potential indicator of perturbed AR hemodynamics and the distribution of vortical flow and could be used as a measure of flow asymmetry.NEW & NOTEWORTHY The aortic root is a vital organ responsible for performing sophisticated functions to regulate the blood flow dynamics during the cardiac cycle. Such synchronized complex performance affects and is affected by the flow symmetry and type of flow reaching the aorta. Here, we report flow asymmetry in the aortic root which could have clinical implications, and we investigate the potential of various quantitative parameters as measures of flow asymmetry in hypertrophic obstructive cardiomyopathy.

QTc prolongation during levofloxacin and triazole combination chemoprophylaxis: Prevalence and predisposing risk factors in a cohort of hematopoietic cell transplantation recipients.

BACKGROUND: QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase. METHODS: This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available. RESULTS: Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation (P = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease (P = 0.12), grade 2 vomiting and diarrhea (P = 0.16, P = 0.46, respectively), baseline hypokalemia (P = 0.18) and hypocalcemia (P = 0.3), hypomagnesemia on day-3 (P = 0.21) and day-6 hyponatremia (P = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval (P = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias. CONCLUSION: The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.

The Use of Maximum Entropy to Enhance Wave Intensity Analysis: An Application to Coronary Arteries in Hypertrophic Obstructive Cardiomyopathy.

Background: Wave intensity analysis is useful for analyzing coronary hemodynamics. Much of its clinical application involves the identification of waves indicated by peaks in the wave intensity and relating their presence or absence to different cardiovascular events. However, the analysis of wave intensity peaks can be problematic because of the associated noise in the measurements. This study shows how wave intensity analysis can be enhanced by using a Maximum Entropy Method (MEM). Methods: We introduce a MEM to differentiate between "peaks" and "background" in wave intensity waveforms. We apply the method to the wave intensity waveforms measured in the left anterior descending coronary artery from 10 Hypertrophic Obstructive Cardiomyopathy (HOCM) and 11 Controls with normal cardiac function. We propose a naming convention for the significant waves and compare them across the cohorts. Results: Using a MEM enhances wave intensity analysis by identifying twice as many significant waves as previous studies. The results are robust when MEM is applied to the log transformed wave intensity data and when all of the measured data are used. Comparing waves across cohorts, we suggest that the absence of a forward expansion wave in HOCM can be taken as an indication of HOCM. Our results also indicate that the backward compression waves in HOCM are significantly larger than in Controls; unlike the forward compression waves where the wave energy in Controls is significantly higher than in HOCM. Comparing the smaller secondary waves revealed by MEM, we find some waves that are present in the majority of Controls and absent in almost all HOCM, and other waves that are present in some HOCM patients but entirely absent in Controls. This suggests some diagnostic utility in the clinical measurement of these waves, which can be a positive sign of HOCM or a subgroup with a particular pathology. Conclusion: The MEM enhances wave intensity analysis by identifying many more significant waves. The method is novel and can be applied to wave intensity analysis in all arteries. As an example, we show how it can be useful in the clinical study of hemodynamics in the coronary arteries in HOCM.

A New Technique for Shaping the Aortic Sinuses and Conserving Dynamism in the Remodeling Operation.

BACKGROUND: Preserving dynamism and recreating the sinuses in the Dacron graft are thought to be important for optimizing results of aortic valve-conserving operations. METHODS: We describe a novel technique that preserves dynamism and recreates the sinotubular junction. In addition, it tailors 3 sinuses of defined longitudinal and transverse curvatures in a straight Dacron tube during the operation. The technique has been used in 6 patients with varied aortic root pathology. We performed preoperative and postoperative multimodality imaging using computerized image analysis as well as 3-dimensional models. RESULTS: There was no early or midterm death. Upon discharge, patients were clinically well, with echocardiographic evidence of minimal (3 patients) or mild (3 patients) aortic regurgitation. Computed tomography and cardiac magnetic resonance imaging with extensive image analysis of the aortic root size, shape, and function showed partial or complete normalization of these parameters. This included the shape and dynamism of the aortic annulus and the size and shape of the geometric (effective) orifice. The 4-dimensional magnetic resonance imaging pattern of flow in the sinuses and ascending aorta showed favorable vortices in the sinuses, right-handed helical flow, and marked diminution of energy loss in the ascending aorta. CONCLUSIONS: The novel technique described here is simple, practical, and cost-effective because it uses a widely available straight Dacron tube. The technique does not use rigid internal or external support. The early results are encouraging. Larger series with longer follow-up are required.