Effects of catheter-based renal denervation in hypertension: a systematic review and meta-analysis.

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. Aim: To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. Methods: We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Results: Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials. Conclusions: RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication. Clinical Perspective: What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

Fully Automated Construction of Three-dimensional Finite Element Simulations from Optical Coherence Tomography.

Despite recent advances in diagnosis and treatment, atherosclerotic coronary artery diseases remain a leading cause of death worldwide. Various imaging modalities and metrics can detect lesions and predict patients at risk; however, identifying unstable lesions is still difficult. Current techniques cannot fully capture the complex morphology-modulated mechanical responses that affect plaque stability, leading to catastrophic failure and mute the benefit of device and drug interventions. Finite Element (FE) simulations utilizing intravascular imaging OCT (Optical Coherence Tomography) are effective in defining physiological stress distributions. However, creating 3D FE simulations of coronary arteries from OCT images is challenging to fully automate given OCT frame sparsity, limited material contrast, and restricted penetration depth. To address such limitations, we developed an algorithmic approach to automatically produce 3D FE-ready digital twins from labeled OCT images. The 3D models are anatomically faithful and recapitulate mechanically relevant tissue lesion components, automatically producing morphologies structurally similar to manually constructed models whilst including more minute details. A mesh convergence study highlighted the ability to reach stress and strain convergence with average errors of just 5.9% and 1.6% respectively in comparison to FE models with approximately twice the number of elements in areas of refinement. Such an automated procedure will enable analysis of large clinical cohorts at a previously unattainable scale and opens the possibility for in-silico methods for patient specific diagnoses and treatment planning for coronary artery disease.

Differential Effects of Pharmacologic and Mechanical Support on Right-Left Ventricular Coupling.

BACKGROUND: Percutaneous ventricular assist devices are increasingly relied on to maintain perfusion for cardiogenic shock patients. Optimal medical management strategies however remain uncertain from limited understanding of interventricular effects. This study analyzed the effects of pharmacologic and left-sided mechanical support on right ventricular function. METHODS: A porcine model was developed to assess biventricular function during bolus pharmacologic administration before and after left-sided percutaneous ventricular assist and in cardiogenic shock. RESULTS: The presence of mechanical support increased right ventricular load and stress with respect to the left ventricle. This shifted and exaggerated the relative effects of commonly used vasoactive agents. Furthermore, induction of cardiogenic shock led to differential pulmonary vascular and right ventricular responses. CONCLUSIONS: Left ventricular ischemia and mechanical support altered interventricular coupling. Resulting impacts of pharmacologic agents indicate differential right heart responses and sensitivity to treatments and the need for further study to optimize biventricular function in shock patients.

Ultrathin-strut versus thin-strut stent healing and outcomes in preclinical and clinical subjects.

BACKGROUND: Compared with thin-strut durable-polymer drug-eluting stents (DP-DES), ultrathin-strut biodegradable-polymer sirolimus-eluting stents (BP-SES) improve stent-related clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Reduced stent strut thickness is hypothesised to underlie these benefits, but this conjecture remains unproven. AIMS: We aimed to assess the impact of strut thickness on stent healing and clinical outcomes between ultrathin-strut and thin-strut BP-SES. METHODS: First, we performed a preclinical study of 8 rabbits implanted with non-overlapping thin-strut (diameter/thickness 3.5 mm/80 µm) and ultrathin-strut (diameter/thickness 3.0 mm/60 µm) BP-SES in the infrarenal aorta. On day 7, the rabbits underwent intravascular near-infrared fluorescence optical coherence tomography (NIRF-OCT) molecular-structural imaging of fibrin deposition and stent tissue coverage, followed by histopathological analysis. Second, we conducted an individual data pooled analysis of patients enrolled in the BIOSCIENCE and BIOSTEMI randomised PCI trials treated with ultrathin-strut (n=282) or thin-strut (n=222) BP-SES. The primary endpoint was target lesion failure (TLF) at 1-year follow-up, with a landmark analysis at 30 days. RESULTS: NIRF-OCT image analyses revealed that ultrathin-strut and thin-strut BP-SES exhibited similar stent fibrin deposition (p=0.49) and percentage of uncovered stent struts (p=0.63). Histopathological assessments corroÂborated these findings. In 504 pooled randomised trial patients, TLF rates were similar for those treated with ultrathin-strut or thin-strut BP-SES at 30-day (2.5% vs 1.8%; p=0.62) and 1-year follow-up (4.3% vs 4.7%; p=0.88). CONCLUSIONS: Ultrathin-strut and thin-strut BP-SES demonstrate similar early arterial healing profiles and 30-day and 1-year clinical outcomes.

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.

Multimodal Learning for Mapping the Genotype-Phenotype Dynamics.

How complex phenotypes emerge from intricate gene expression patterns is a fundamental question in biology. Quantitative characterization of this relationship, however, is challenging due to the vast combinatorial possibilities and dynamic interplay between genotype and phenotype landscapes. Integrating high-content genotyping approaches such as single-cell RNA sequencing and advanced learning methods such as language models offers an opportunity for dissecting this complex relationship. Here, we present a computational integrated genetics framework designed to analyze and interpret the high-dimensional landscape of genotypes and their associated phenotypes simultaneously. We applied this approach to develop a multimodal foundation model to explore the genotype-phenotype relationship manifold for human transcriptomics at the cellular level. Analyzing this joint manifold showed a refined resolution of cellular heterogeneity, enhanced precision in phenotype annotating, and uncovered potential cross-tissue biomarkers that are undetectable through conventional gene expression analysis alone. Moreover, our results revealed that the gene networks are characterized by scale-free patterns and show context-dependent gene-gene interactions, both of which result in significant variations in the topology of the gene network, particularly evident during aging. Finally, utilizing contextualized embeddings, we investigated gene polyfunctionality which illustrates the multifaceted roles that genes play in different biological processes, and demonstrated that for VWF gene in endothelial cells. Overall, this study advances our understanding of the dynamic interplay between gene expression and phenotypic manifestation and demonstrates the potential of integrated genetics in uncovering new dimensions of cellular function and complexity.

Steady Flow Left Ventricle Unloading Is Superior to Pulsatile Pressure Augmentation Venting During Venoarterial Extracorporeal Membrane Oxygenation Support.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) shunts venous blood to the systemic arterial circulation to provide end-organ perfusion while increasing afterload that may impede left ventricle (LV) ejection and impair cardiac recovery. To maintain flow across the aortic valve and reduce risk of lethal clot formation, secondary mechanical circulatory support (MCS) devices are increasingly used despite limited understanding of their effects on cardiac function. This study sought to quantify the effects of VA-ECMO and combined with either intraaortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD) on LV physiologic state and perfusion metrics in a porcine model of acute cardiogenic shock. Shock was induced through serial left anterior descending artery microbead embolization followed by initiation of VA-ECMO support and then placement of either IABP or pVAD. Hemodynamic measurements, LV pressure-volume loops, and carotid artery blood flow were evaluated before and after institution of combined MCS. The IABP decreased LV end-diastolic pressure by a peak of 15% while slightly increasing LV stroke work compared with decreases of more than 60% and 50% with the pVAD, respectively. The pVAD also demonstrated increased coronary perfusion and systemic pressure gradients in comparison to the IABP. Combined support with VA-ECMO and pVAD improves cardiovascular state in comparison to IABP.

A transformer-based pyramid network for coronary calcified plaque segmentation in intravascular optical coherence tomography images.

Characterizing coronary calcified plaque (CCP) provides essential insight into diagnosis and treatment of atherosclerosis. Intravascular optical coherence tomography (OCT) offers significant advantages for detecting CCP and even automated segmentation with recent advances in deep learning techniques. Most of current methods have achieved promising results by adopting existing convolution neural networks (CNNs) in computer vision domain. However, their performance can be detrimentally affected by unseen plaque patterns and artifacts due to inherent limitation of CNNs in contextual reasoning. To overcome this obstacle, we proposed a Transformer-based pyramid network called AFS-TPNet for robust, end-to-end segmentation of CCP from OCT images. Its encoder is built upon CSWin Transformer architecture, allowing for better perceptual understanding of calcified arteries at a higher semantic level. Specifically, an augmented feature split (AFS) module and residual convolutional position encoding (RCPE) mechanism are designed to effectively enhance the capability of Transformer in capturing both fine-grained features and global contexts. Extensive experiments showed that AFS-TPNet trained using Lovasz Loss achieved superior performance in segmentation CCP under various contexts, surpassing prior state-of-the-art CNN and Transformer architectures by more than 6.58% intersection over union (IoU) score. The application of this promising method to extract CCP features is expected to enhance clinical intervention and translational research using OCT.

Dynamic load modulation predicts right heart tolerance of left ventricular cardiovascular assist in a porcine model of cardiogenic shock.

Ventricular assist devices (VADs) offer mechanical support for patients with cardiogenic shock by unloading the impaired ventricle and increasing cardiac outflow and subsequent tissue perfusion. Their ability to adjust ventricular assistance allows for rapid and safe dynamic changes in cardiac load, which can be used with direct measures of chamber pressures to quantify cardiac pathophysiologic state, predict response to interventions, and unmask vulnerabilities such as limitations of left-sided support efficacy due to intolerance of the right heart. We defined hemodynamic metrics in five pigs with dynamic peripheral transvalvular VAD (pVAD) support to the left ventricle. Metrics were obtained across a spectrum of disease states, including left ventricular ischemia induced by titrated microembolization of a coronary artery and right ventricular strain induced by titrated microembolization of the pulmonary arteries. A sweep of different pVAD speeds confirmed mechanisms of right heart decompensation after left-sided support and revealed intolerance. In contrast to the systemic circulation, pulmonary vascular compliance dominated in the right heart and defined the ability of the right heart to adapt to left-sided pVAD unloading. We developed a clinically accessible metric to measure pulmonary vascular compliance at different pVAD speeds that could predict right heart efficiency and tolerance to left-sided pVAD support. Findings in swine were validated with retrospective hemodynamic data from eight patients on pVAD support. This methodology and metric could be used to track right heart tolerance, predict decompensation before right heart failure, and guide titration of device speed and the need for biventricular support.

A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions / Novo Algoritmo para Quantificar o Remodelamento Coronário Utilizando Dimensões Normais Preditas

Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH). Coronary vessel remodeling at cross-section (n = 27.639) and lesion (n = 618) levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI), which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

Fundamento:O remodelamento vascular, alteração dimensional dinâmica frente ao estresse, pode assumir diferentes direções e magnitudes na doença aterosclerótica. As medidas clássicas baseiam-se em referências a distância do segmento-alvo, com risco de comparação inadequada pela seleção de porções vasculares indesejáveis.Objetivo:Explorar um novo método para quantificar remodelamento vascular, baseado na comparação entre um determinado segmento-alvo e suas dimensões normais inferidas.Métodos:Parâmetros geométricos e a composição da placa foram determinados em 67 pacientes usando-se ultrassom intravascular de três vasos com histologia virtual (IVUS-VH). Avaliou-se o remodelamento coronário ao nível da seção transversal (n = 27.639) e da lesão (n = 618) usando-se métrica clássica e um novo algoritmo analítico baseado no índice de remodelamento vascular fracionado (FVRI) que quantifica a alteração total nas dimensões da parede arterial em relação a dimensão normal estimada do vaso. Construiu-se um modelo preditivo para estimar a dimensão normal do vaso para calcular o FVRI.Resultados:De acordo com o novo algoritmo, o padrão de remodelamento “ectásico” foi o menos comum, o remodelamento “completo compensatório” foi observado em metade dos casos, e os tipos “negativo” e “incompleto compensatório” foram detectados nos restantes. Comparada ao esquema tradicional diagnóstico, a classificação baseada no FVRI pareceu melhor discriminar a composição da placa através de IVUS-VH.Conclusão:A análise quantitativa do remodelamento coronário utilizando dimensões do segmento-alvo oferece uma abordagem promissora para avaliar a resposta vascular ao crescimento e à regressão da placa.