Simulating impaired left ventricular-arterial coupling in aging and disease: a systematic review.

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.

Non-invasive parameters of autonomic function using beat-to-beat cardiovascular variations and arterial stiffness in hypertensive individuals: a systematic review.

PURPOSE: Non-invasive, beat-to-beat variations in physiological indices provide an opportunity for more accessible assessment of autonomic dysfunction. The potential association between the changes in these parameters and arterial stiffness in hypertension remains poorly understood. This systematic review aims to investigate the association between non-invasive indicators of autonomic function based on beat-to-beat cardiovascular signals with arterial stiffness in individuals with hypertension. METHODS: Four electronic databases were searched from inception to June 2022. Studies that investigated non-invasive parameters of arterial stiffness and autonomic function using beat-to-beat cardiovascular signals over a period of > 5min were included. Study quality was assessed using the STROBE criteria. Two authors screened the titles, abstracts, and full texts independently. RESULTS: Nineteen studies met the inclusion criteria. A comprehensive overview of experimental design for assessing autonomic function in terms of baroreflex sensitivity and beat-to-beat cardiovascular variabilities, as well as arterial stiffness, was presented. Alterations in non-invasive indicators of autonomic function, which included baroreflex sensitivity, beat-to-beat cardiovascular variabilities and hemodynamic changes in response to autonomic challenges, as well as arterial stiffness, were identified in individuals with hypertension. A mixed result was found in terms of the association between non-invasive quantitative autonomic indices and arterial stiffness in hypertensive individuals. Nine out of 12 studies which quantified baroreflex sensitivity revealed a significant association with arterial stiffness parameters. Three studies estimated beat-to-beat heart rate variability and only one study reported a significant relationship with arterial stiffness indices. Three out of five studies which studied beat-to-beat blood pressure variability showed a significant association with arterial structural changes. One study revealed that hemodynamic changes in response to autonomic challenges were significantly correlated with arterial stiffness parameters. CONCLUSIONS: The current review demonstrated alteration in autonomic function, which encompasses both the sympathetic and parasympathetic modulation of sinus node function and vasomotor tone (derived from beat-to-beat cardiovascular signals) in hypertension, and a significant association between some of these parameters with arterial stiffness. By employing non-invasive measurements to monitor changes in autonomic function and arterial remodeling in individuals with hypertension, we would be able to enhance our ability to identify individuals at high risk of cardiovascular disease. Understanding the intricate relationships among these cardiovascular variability measures and arterial stiffness could contribute toward better individualized treatment for hypertension in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID: CRD42022336703. Date of registration: 12/06/2022.

Remodeling in Aortic Stenosis With Reduced and Preserved Ejection Fraction: Insight on Motion Abnormality Via 3D + Time Personalized LV Modeling in Cardiac MRI.

BACKGROUND: Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration. PURPOSE: To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS. STUDY TYPE: Retrospective. POPULATION: A total of 31 AS patients with reduced and preserved ejection fraction (14 AS_rEF: 7 male, 66.5 [7.8] years old; 17 AS_pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old). FIELD STRENGTH/SEQUENCE: 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences. ASSESSMENT: Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling. STATISTICAL TESTS: Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P < 0.05); ICC and CV: variability; Mann-Whitney: effect size. RESULTS: AS_rEF group shows distinct deterioration of cardiac motions compared to AS_pEF and healthy groups (TIAS_rEF : 0.92 [0.85] mm, TIAS_pEF : 5.13 [1.99] mm, TIhealthy : 3.61 [1.09] mm, ES: 0.48-0.83; DIAS_rEF : 17.11 [7.89]%, DIAS_pEF : 6.39 [4.04]%, DIhealthy : 5.71 [1.87]%, ES: 0.32-0.85; CRAS_rEF : 8.69 [6.11] mm/second, CRAS_pEF : 16.48 [6.70] mm/second, CRhealthy : 10.82 [4.57] mm/second, ES: 0.29-0.60; RRAS_rEF : 8.45 [4.84] mm/second; RRAS_pEF : 13.49 [8.56] mm/second, RRhealthy : 9.31 [2.48] mm/second, ES: 0.14-0.43). The difference in the motion metrics between healthy and AS_pEF groups were insignificant (P-value = 0.16-0.72). AS_rEF group was dominated by eccentric hypertrophy (47.1%) with concomitant scarring. Conversely, AS_pEF group was dominated by concentric remodeling and hypertrophy (71.4%), which could demonstrate hyperkinesia with slight wall dyssynchrony than healthy. Dysfunction of LV mechanics corresponded to the presence of myocardial scarring (54.9% in AS), which reverted the compensatory mechanisms initiated and performed by LV remodeling. DATA CONCLUSION: The proposed 3D + time modeling technique may distinguish regional motion abnormalities between AS_pEF, AS_rEF, and healthy cohorts, aiding clinical diagnosis and monitoring of AS progression. Subclinical myocardial dysfunction is evident in early AS despite of normal EF. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Assessing Complex Left Ventricular Adaptations in Aortic Stenosis Using Personalized 3D + time Cardiac MRI Modeling.

Left ventricular adaptations can be a complex process under the influence of aortic stenosis (AS) and comorbidities. This study proposed and assessed the feasibility of using a motion-corrected personalized 3D + time LV modeling technique to evaluate the adaptive and maladaptive LV response to aid treatment decision-making. A total of 22 AS patients were analyzed and compared against 10 healthy subjects. The 3D + time analysis showed a highly distinct and personalized pattern of remodeling in individual AS patients which is associated with comorbidities and fibrosis. Patients with AS alone showed better wall thickening and synchrony than those comorbid with hypertension. Ischemic heart disease in AS caused impaired wall thickening and synchrony and systolic function. Apart from showing significant correlations to echocardiography and clinical MRI measurements (r: 0.70-0.95; p < 0.01), the proposed technique helped in detecting subclinical and subtle LV dysfunction, providing a better approach to evaluate AS patients for specific treatment, surgical planning, and follow-up recovery.

Hereditary transthyretin amyloidosis in multi-ethnic Malaysians.

We report the clinical and genetic characteristics of hereditary transthyretin amyloidosis in the multi-ethnic Malaysian population. Subjects with genetically confirmed transthyretin amyloidosis seen between 2001 till August 2020 were included. There were 30 patients and 14 asymptomatic carriers, of which 26 (59.1%) were men. The majority (86.7%) were ethnic Chinese while two (6.7%) each were Malay and Sri Lankan Tamil ethnicity respectively. Among patients, mean age of symptom-onset was 55.9 ±â€¯9.8 years with mean duration from symptom-onset to diagnosis of 3.2 ±â€¯2.5 years. Common presenting symptoms were sensory symptoms of upper limbs (43.3%), symmetric sensory symptoms of both lower limbs (16.7%) and autonomic symptoms (16.7%). Nerve conduction studies showed sensorimotor polyneuropathy in 25 (83.3%) patients (22, axonal). Abnormal echocardiograms were seen in 24 (80%) patients, although 15 were asymptomatic. Of six different TTR mutations found, Ala97Ser was the commonest, and found exclusively in 84.6% of Chinese patients. Other mutations among Chinese patients were Val30Met, Ala25Thr and Asp39Val. Our Malay and Tamil patients had Glu54Lys and Gly47Val mutations respectively. In conclusion, TTR Ala97Ser is the commonest mutation among ethnic Chinese Malaysians which presented with late-onset progressive sensorimotor polyneuropathy, autonomic dysfunction and subclinical cardiac involvement.

Phenotyping of hypertensive heart disease and hypertrophic cardiomyopathy using personalized 3D modelling and cardiac cine MRI.

Differential diagnosis of hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) is clinically challenging but important for treatment management. This study aims to phenotype HHD and HCM in 3D + time domain by using a multiparametric motion-corrected personalized modeling algorithm and cardiac magnetic resonance (CMR). 44 CMR data, including 12 healthy, 16 HHD and 16 HCM cases, were examined. Multiple CMR phenotype data consisting of geometric and dynamic variables were extracted globally and regionally from the models over a full cardiac cycle for comparison against healthy models and clinical reports. Statistical classifications were used to identify the distinctive characteristics and disease subtypes with overlapping functional data, providing insights into the challenges for differential diagnosis of both types of disease. While HCM is characterized by localized extreme hypertrophy of the LV, wall thickening/contraction/strain was found to be normal and in sync, though it was occasionally exaggerated at normotrophic/less severely hypertrophic regions during systole to preserve the overall ejection fraction (EF) and systolic functionality. Additionally, we observed that hypertrophy in HHD could also be localized, although at less extreme conditions (i.e. more concentric). While fibrosis occurs mostly in those HCM cases with aortic obstruction, only minority of HHD patients were found affected by fibrosis. We demonstrate that subgroups of HHD (i.e. preserved and reduced EF: HHDpEF & HHDrEF) have different 3D + time CMR characteristics. While HHDpEF has cardiac functions in normal range, dilation and heart failure are indicated in HHDrEF as reflected by low LV wall thickening/contraction/strain and synchrony, as well as much reduced EF.

Quantitative and qualitative comparison of low- and high-cost 3D-printed heart models.

Current visualization techniques of complex congenital heart disease (CHD) are unable to provide comprehensive visualization of the anomalous cardiac anatomy as the medical datasets can essentially only be viewed from a flat, two-dimensional (2D) screen. Three-dimensional (3D) printing has therefore been used to replicate patient-specific hearts in 3D views based on medical imaging datasets. This technique has been shown to have a positive impact on the preoperative planning of corrective surgery, patient-doctor communication, and the learning experience of medical students. However, 3D printing is often costly, and this impedes the routine application of this technology in clinical practice. This technical note aims to investigate whether reducing 3D printing costs can have any impact on the clinical value of the 3D-printed heart models. Low-cost and a high-cost 3D-printed models based on a selected case of CHD were generated with materials of differing cost. Quantitative assessment of dimensional accuracy of the cardiac anatomy and pathology was compared between the 3D-printed models and the original cardiac computed tomography (CT) images with excellent correlation (r=0.99). Qualitative evaluation of model usefulness showed no difference between the two models in medical applications.