Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Noninvasive Techniques for Tracking Biological Aging of the Cardiovascular System: JACC Family Series.

Population aging is one of the most important demographic transformations of our time. Increasing the "health span"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.

Cardiovascular Magnetic Resonance Reference Ranges From the Healthy Hearts Consortium.

BACKGROUND: The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care. OBJECTIVES: This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date. METHODS: CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals. RESULTS: The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 ± 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n = 8,779; 96.6%) and 3.0-T (n = 309; 3.4%) scanners from Siemens (n = 8,299; 91.3%), Philips (n = 498; 5.5%), and GE (n = 291, 3.2%). CONCLUSIONS: This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.

Global longitudinal strain and plasma biomarkers for prognosis in heart failure complicated by diabetes: a prospective observational study.

BACKGROUND: Heart failure (HF) and diabetes are associated with increased incidence and worse prognosis of each other. The prognostic value of global longitudinal strain (GLS) measured by cardiovascular magnetic resonance (CMR) has not been established in HF patients with diabetes. METHODS: In this prospective, observational study, consecutive patients (n = 315) with HF underwent CMR at 3T, including GLS, late gadolinium enhancement (LGE), native T1, and extracellular volume fraction (ECV) mapping. Plasma biomarker concentrations were measured including: N-terminal pro B-type natriuretic peptide(NT-proBNP), high-sensitivity troponin T(hs-TnT), growth differentiation factor 15(GDF-15), soluble ST2(sST2), and galectin 3(Gal-3). The primary outcome was a composite of all-cause mortality or HF hospitalisation. RESULTS: Compared to those without diabetes (n = 156), the diabetes group (n = 159) had a higher LGE prevalence (76 vs. 60%, p < 0.05), higher T1 (1285±42 vs. 1269±42ms, p < 0.001), and higher ECV (30.5±3.5 vs. 28.8±4.1%, p < 0.001). The diabetes group had higher NT-pro-BNP, hs-TnT, GDF-15, sST2, and Gal-3. Diabetes conferred worse prognosis (hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.43-3.79], p < 0.001). In multivariable Cox regression analysis including clinical markers and plasma biomarkers, sST2 alone remained independently associated with the primary outcome (HR per 1 ng/mL 1.04 [95% CI 1.02-1.07], p = 0.001). In multivariable Cox regression models in the diabetes group, both GLS and sST2 remained prognostic (GLS: HR 1.12 [95% CI 1.03-1.21], p = 0.01; sST2: HR per 1 ng/mL 1.03 [95% CI 1.00-1.06], p = 0.02). CONCLUSIONS: Compared to HF patients without diabetes, those with diabetes have worse plasma and CMR markers of fibrosis and a more adverse prognosis. GLS by CMR is a powerful and independent prognostic marker in HF patients with diabetes.

Unique characteristics of Asians with hypertension: what is known and what can be done?

Hypertension remains the leading modifiable risk factor for cardiovascular disease worldwide. Over the past 30 years, the prevalence of hypertension has been increasing in East and Southeast Asia to a greater extent as compared with other Western countries. Asians with hypertension have unique characteristics. This can be attributed to increased impact of obesity on Asians with hypertension, excessive salt intake and increased salt sensitivity, loss of diurnal rhythm in blood pressure and primary aldosteronism. The impact of hypertension on cardiovascular (particularly strokes) and chronic kidney disease is greater in Asians. These unique characteristics underpinned by the diverse socioeconomic backgrounds pose its own challenges in the diagnosis and management of hypertension in Asia.

Pilot Implementation of a Nutrition-Focused Community-Health-Worker Intervention among Formerly Chronically Homeless Adults in Permanent Supportive Housing.

Food insecurity is a known health equity threat for formerly chronically homeless populations even after they transition into permanent housing. This project utilized a human-centered design methodology to plan and implement a nutrition-focused community-health-worker (CHW) intervention in permanent supportive housing (PSH). The project aimed to increase access to healthy foods, improve nutritional literacy, healthy cooking/eating practices, and build community/social connectedness among 140 PSH residents. Validated food-security screening conducted by CHWs identified low or very low food security among 64% of 83 residents who completed the baseline survey, which is similar to rates found in a previous study among formerly homeless populations placed in PSH. Major themes identified through an analysis of resident feedback include (1) lack of needed kitchenware/appliances for food preparation, (2) knowledge gaps on how to purchase and prepare healthier food, (3) positive perceptions of healthy food options, (4) expanded preferences for healthy, easy-to-prepare foods, (5) regaining cooking skills lost during homelessness, (6) positive experiences participating in group activities, (7) community re-entry, and (8) resident ownership. Preliminary findings suggest the use of a human-centered design methodology for planning and implementing this multi-level CHW intervention helped reduce food insecurity, engaged participants in learning and adopting healthy and safe cooking and eating practices, and fostered social connectedness and feelings of community among formerly chronically homeless PSH residents.

Lesion voxels to lesion networks: The enduring value of the Vietnam Head Injury Study.

The Vietnam Head Injury Study has been curated by Dr Jordan Grafman since the 1980s in an effort to study patients with penetrating traumatic brain injuries suffered during the Vietnam War. Unlike many datasets of ischemic stroke lesions, the VHIS collected extraordinarily deep phenotyping and was able to sample lesion locations that are not constrained to typical vascular territories. For decades, this dataset has helped researchers draw causal links between neuroanatomical regions and neuropsychiatric symptoms. The value of the VHIS has only increased over time as techniques for analyzing the dataset have developed and evolved. Tools such as voxel lesion symptom mapping allowed one to relate symptoms to individual brain voxels. With the advent of the human connectome, tools such as lesion network mapping allow one to relate symptoms to connected brain networks by combining lesion datasets with new atlases of human brain connectivity. In a series of recent studies, lesion network mapping has been combined with the Vietnam Head Injury dataset to identify brain networks associated with spirituality, religiosity, consciousness, memory, emotion regulation, addiction, depression, and even transdiagnostic mental illness. These findings are enhancing our ability to make diagnoses, identify potential treatment targets for focal brain stimulation, and understand the human brain generally. Our techniques for studying brain lesions will continue to improve, as will our tools for modulating brain circuits. As these advances occur, the value of well characterized lesion datasets such as the Vietnam Head Injury Study will continue to grow. This study aims to review the history of the Vietnam Head Injury Study and contextualize its role in modern-day localization of neurological symptoms.

Is there an OAHI or O2 nadir that predicts the need for preoperative echocardiogram prior to adenotonsillectomy for children with severe obstructive sleep apnea?

PURPOSE: To investigate threshold values for obstructive apnea-hypopnea index (OAHI) and nadir oxygen saturation (NspO2) in children with severe obstructive sleep apnea (OSA) to identify children most appropriate for preoperative echocardiography. METHODS: A multi-institutional retrospective chart review was performed on children who underwent echocardiography and polysomnogram within a year. Children with severe OSA as defined by OAHI > 10 or NspO2 < 80% were included. Receiver operator curves and Youden's J index were used to assess the discriminatory ability and threshold values of OAHI and NspO2 for right heart strain (RHS) on echocardiography. RESULTS: A total of 173 prepubertal (< 10 years) children and 71 postpubertal (≥ 10 years) children of age were included. RHS was seen in 9 (5%) prepubertal children and 4 (6%) postpubertal children. In prepubertal children, OAHI and NspO2 were poor predictors of RHS (area under the curve [AUC] 0.53 [95%CI 0.45-0.61], p = 0.748; AUC 0.56 [95%CI 0.48-0.64], p = 0.609). In postpubertal children, threshold values of 55 events/hour and 69% were strong predictors for RHS (AUC 0.88 [95%CI 0.78-0.95], p < 0.001; AUC 0.92 [95%CI 0.83-0.97], p < 0.001). CONCLUSION: In children with severe OSA, evidence of RHS is low. Postpubertal children with OAHI > 55 and NspO2 < 69% appear most appropriate for echocardiography. Clinicians should weigh the risks and benefits of preoperative echocardiography for each child with these threshold values in mind.

Determination of Behavioral Changes Associated with Bovine Respiratory Disease in Australian Feedlots.

Accurately identifying bovine respiratory disease is challenging in feedlots, and previous studies suggest behavioral monitoring is important. The study objective was to describe individual differences in physical activity (distance traveled), feeding/watering patterns (proximity to feed and water), and social behavior (average cattle within 3 m) when associated with health status in commercially raised beef cattle during the first 28 days on feed. Data from a previous Australian feedlot study monitoring cattle behavior and associated health outcomes were analyzed. Health status categories were generated for all cattle, and each animal was categorized as known healthy (HLTH), known diseased (SICK), or intermediate/uncertain (INTR). The INTR animals were excluded from the final analysis. Key findings included: differentiation in activity between SICK (n = 138) and HLTH (n = 1508) cattle dependent on time of day, SICK cattle spending more time in water and feeding zones early in the feeding phase (<6 days on feed), SICK cattle spending more time in the water and feeding zone during the overnight hours, and SICK cattle spending more time in groups early in the feeding phase but more time in isolation after the first week on feed. Results illustrate behavioral data were associated with important health outcomes.

Genotype-Phenotype Taxonomy of Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression. METHODS: We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree. RESULTS: Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96]; P<0.002). Four main phenotypic branches were identified using unsupervised learning of 3-dimensional shape: (1) nonsarcomeric hypertrophy with coexisting hypertension; (2) diffuse and basal asymmetrical hypertrophy associated with outflow tract obstruction; (3) isolated basal hypertrophy; and (4) milder nonobstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for pathogenic or likely pathogenic variants, 2.18 [95% CI, 1.93-2.28]; P=0.0001). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalizable to an independent cohort (trustworthiness, M1: 0.86-0.88). CONCLUSIONS: We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.

Exaggerated elastin turnover in young individuals with Marfan syndrome: new insights from the AIMS trial.

Aims: The fragmentation and loss of elastic fibre in the tunica media of the aorta are pathological hallmarks of Marfan syndrome (MFS) but the dynamics of elastin degradation and its relationship to aortic size and physiological growth remain poorly understood. Methods and results: In this post hoc analysis of the AIMS randomized controlled trial, the association of plasma desmosine (pDES)-a specific biomarker of mature elastin degradation-with age and aortic size was analysed in 113 patients with MFS and compared to 109 healthy controls. There was a strong association between age and pDES in both groups, with higher pDES levels in the lower age groups compared to adults. During childhood, pDES increased and peaked during early adolescence, and thereafter decreased to lower adult levels. This trend was exaggerated in young individuals with MFS but in those above 25 years of age, pDES levels were comparable to controls despite the presence of aortic root dilation. In MFS children, increased aortic diameter relative to controls was seen at an early age and although the increase in diameter was less after adolescence, aortic root size continued to increase steadily with age. In MFS participants, there was an indication of a positive association between baseline pDES levels and aortic root dilatation during up to 5 years of follow-up. Conclusion: This study has shown that developmental age has a significant effect on levels of elastin turnover as measured by pDES in MFS individuals as well as healthy controls. This effect is exaggerated in those with MFS with increased levels seen during the period of physiologic development that plateaus towards adulthood. This suggests an early onset of pathophysiology that may present an important opportunity for disease-modifying intervention.

Implementing the human right to science in the regulatory governance of artificial intelligence in healthcare.

Artificial intelligence (AI) enables a medical device to optimize its performance through machine learning (ML), including the ability to learn from past experiences. In healthcare, ML is currently applied within controlled settings in devices to diagnose conditions like diabetic retinopathy without clinician input, for instance. In order to allow AI-based medical devices (AIMDs) to adapt actively to its data environment through ML, the current risk-based regulatory approaches are inadequate in facilitating this technological progression. Recent and innovative regulatory changes introduced to regulate AIMDs as a software, or 'software as a medical device' (SaMD), and the adoption of a total device/product-specific lifecycle approach (rather than one that is point-in-time) reflect a shift away from the strictly risk-based approach to one that is more collaborative and participatory in nature, and anticipatory in character. These features are better explained by a rights-based approach and consistent with the human right to science (HRS). With reference to the recent explication of the normative content of HRS by the Committee on Economic, Social and Cultural Rights of the United Nations, this paper explains why a rights-based approach that is centred on HRS could be a more effective response to the regulatory challenges posed by AIMDs. The paper also considers how such a rights-based approach could be implemented in the form of a regulatory network that draws on a 'common fund of knowledges' to formulate anticipatory responses to adaptive AIMDs. In essence, the HRS provides both the mandate and the obligation for states to ensure that regulatory governance of high connectivity AIMDs become increasingly collaborative and participatory in approach and pluralistic in substance.

Topical Spironolactone in the Treatment of Ocular Graft-Versus-Host Disease.

INTRODUCTION: This two-part study aimed to investigate the therapeutic potential of topical spironolactone in ocular graft-versus-host disease (oGVHD). While off-label use of topical spironolactone has been described in dry eye, its efficacy in managing signs and symptoms of oGVHD remains unstudied. Preclinically, we tested the hypothesis that spironolactone induces corneal lipid synthesis in a mouse model. Clinically, we assessed patient response to spironolactone with a retrospective observational design. METHODS: Both immortalized and primary human corneal epithelial cells were stained with oil red O after 9 days of treatment with spironolactone. C57BL/6 mice were dosed thrice daily with one drop in each eye for 18 days. Corneal tissue was stained with oil red O and BODIPY™. Twenty eyes with oGVHD, as defined by the International Chronic oGVHD Consensus Group, were studied. Corneal fluorescein staining, lid margin vascularity, meibomian gland obstruction, meibum turbidity, zone A posterior lid margin vascularity, and oGVHD diagnostic criteria severity grading were compared in a pre-post study. Follow-up times ranged from 7 to 21 weeks, with a median time of 12 weeks. Statistical analysis was done with STATA 17 by fitting data to a non-parametric model. RESULTS:  In vitro results showed an increased number and density of oil red O staining granules in the treatment group versus control in both primary and immortalized human corneal epithelium. In vivo, results showed translation to the mouse model with increased corneal epithelial BODIPY™ signal compared to untreated control. oGVHD patients had improved lid margin vascularity (p = 0.046), corneal fluorescein staining (p = 0.021), and International oGVHD Consensus Group severity scores (p = 0.011) after treatment with topical spironolactone. Minimal adverse effects were noted, the most common being mild stinging lasting less than a minute after instillation. CONCLUSION: The improved severity scores, lid margin inflammation, and corneal fluorescein staining after weeks of treatment support the rationale that topical spironolactone may benefit oGVHD. The observed lipid production by the corneal epithelium is thought to contribute to this protective effect against ocular surface erosive disease in oGVHD. A mineralocorticoid receptor antagonist, spironolactone may offer therapeutic benefits in oGVHD while avoiding undesirable side effects of topical or systemic glucocorticoids.

Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol.

Background: Diffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD. Methods: Role of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan. Discussion: REVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

Paracentral Bitemporal Hemianopsia and Acquired Supranuclear Ocular Motor Paresis Following Cardiac Surgery.

Acquired supranuclear ocular motor paresis (ASOMP) is a rare complication following cardiac surgery, characterized by limited voluntary eye motility. The exact cause and development of ASOMP after cardiac surgery remain unclear. We report a case of ASOMP with paracentral bitemporal hemianopsia with optic atrophy after cardiac surgery, which, to our knowledge, is novel. The patient demonstrated bilateral ophthalmoplegia, with gradual improvement in voluntary smooth pursuit but persistent impairment in saccadic eye movements. Interestingly, the patient showed improved proprioceptive-driven pursuit of their own hand compared to pursuit or saccades following an examiner's hand. The visual field examination revealed a bilateral paracentral temporal hemianopic field defect. The underlying mechanisms of ASOMP and potential chiasmal ischemia in this case remain unknown. Clinicians should be aware of the possibility of ASOMP following cardiac surgery, with potential slow improvement over time.

Impact of Diabetes on Myocardial Fibrosis in Patients With Hypertension: The REMODEL Study.

BACKGROUND: Compared with patients with hypertension only, those with hypertension and diabetes (HTN/DM) have worse prognosis. We aimed to characterize morphological differences between hypertension and HTN/DM using cardiovascular magnetic resonance; and compare differentially expressed proteins associated with myocardial fibrosis using high throughput multiplex assays. METHODS: Asymptomatic patients underwent cardiovascular magnetic resonance: 438 patients with hypertension (60±8 years; 59% males) and 167 age- and sex-matched patients with HTN/DM (60±10 years; 64% males). Replacement myocardial fibrosis was defined as nonischemic late gadolinium enhancement on cardiovascular magnetic resonance. Extracellular volume fraction was used as a marker of diffuse myocardial fibrosis. A total of 184 serum proteins (Olink Target Cardiovascular Disease II and III panels) were measured to identify unique signatures associated with myocardial fibrosis in all patients. RESULTS: Despite similar left ventricular mass (P=0.344) and systolic blood pressure (P=0.086), patients with HTN/DM had increased concentricity and worse multidirectional strain (P<0.001 for comparison of all strain measures) compared to hypertension only. Replacement myocardial fibrosis was present in 28% of patients with HTN/DM compared to 16% of those with hypertension (P<0.001). NT-proBNP (N-terminal pro-B-type natriuretic peptide) was the only protein differentially upregulated in hypertension patients with replacement myocardial fibrosis and independently associated with extracellular volume. In patients with HTN/DM, GDF-15 (growth differentiation factor 15) was independently associated with replacement myocardial fibrosis and extracellular volume. Ingenuity Pathway Analysis demonstrated a strong association between increased inflammatory response/immune cell trafficking and myocardial fibrosis in patients with HTN/DM. CONCLUSIONS: Adverse cardiac remodeling was observed in patients with HTN/DM. The novel proteomic signatures and associated biological activities of increased immune and inflammatory response may partly explain these observations.

Modelling the role of energy price movements toward economic stability in Malaysia: new evidence from wavelet-based analysis.

Energy is one of the prime factors in influencing the sustainable development of a country. Different energy sources play important roles in driving the income growth of different economic sectors such as industrial, agricultural, and services. Fossil fuels, however, have come under strong criticism for actively accelerating climate change. As such, it is imperative to investigate the contributions of various energy sources toward sustainable growth. With Malaysia as the test-bed, the present study analyzes the impact of energy prices on economic stability using the novel wavelet-based analysis. Specifically, the study analyzed the impact of crude oil, natural gas, and gasoline prices on the economic (brown) and green growth from 1995 to 2020. The results show that in continuous wavelet transform, the cone of influence of all five factors exhibits strong short-run variance and fluctuations from 2005 to 2013. However, the intensity of brown growth is more influential than green growth. Similarly, in wavelet coherence graphs, the downward right arrows indicate positively significant associations between crude oil prices, natural gas prices, and gasoline prices with brown and green growth. Additionally, wavelet-based Granger causality reveals a bidirectional causal relationship between all variables. The results thus strongly suggest that energy prices predominantly affect the economic (brown) and green growth progression of the Malaysian economy. The study concludes with some suggested implications to augment the country's sustainable growth.