Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography.

BACKGROUND: Composite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference "truth" to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS. RESULTS: Median rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52-1.02] and 0.16 with 4DM; 0.41 [0.34-0.54] and 0.10 with 4DM-FVD; 0.66 [0.51-0.85] and 0.11 with Cedars; 0.51 [0.43-0.61] and 0.08 with Emory-Votaw; 0.37 [0.30-0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23-0.32], COV 0.07 with HeartSee. CONCLUSIONS: SWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively). TRIAL REGISTRATION: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593 .

The Effects of Exercise on Lipid Biomarkers.

The World Health Organization has declared obesity to be a global epidemic that increases cardiovascular disease (CVD) mortality risk factors, such as hypertension, diabetes, dyslipidemia, and atherosclerosis. The increasing ratio of time spent in sedentary activities to that spent performing physically demanding tasks increases the trends to obesity and susceptibility to these risk factors. Dyslipidemia is the foundation of atherosclerotic buildup and lipoproteins serve as cofactors to the inflammatory processes that destabilize plaques. Increasing cardiorespiratory fitness and muscular strength helps attenuate concentrations of low-density lipoproteins (LDLs), such as LDL cholesterol, and increase levels of high-density lipoprotein cholesterol, as well as reduce proprotein convertase subtilisin kexin type 9 expression. Effects of physical activity on the inflammatory pathways of atherosclerosis, specifically C-reactive protein, are more closely related to reducing the levels of adiposity in tandem with increasing fitness, than with exercise training alone. The purpose of this review is to describe the physiology of dyslipidemia and relate it to CVD and exercise therapies.

Development and Validation of a Multivariable Risk Prediction Model for COVID-19 Mortality in the Southern United States.

OBJECTIVE: To evaluate clinical characteristics of patients admitted to the hospital with coronavirus disease 2019 (COVID-19) in Southern United States and development as well as validation of a mortality risk prediction model. PATIENTS AND METHODS: Southern Louisiana was an early hotspot during the pandemic, which provided a large collection of clinical data on inpatients with COVID-19. We designed a risk stratification model to assess the mortality risk for patients admitted to the hospital with COVID-19. Data from 1673 consecutive patients diagnosed with COVID-19 infection and hospitalized between March 1, 2020, and April 30, 2020, was used to create an 11-factor mortality risk model based on baseline comorbidity, organ injury, and laboratory results. The risk model was validated using a subsequent cohort of 2067 consecutive hospitalized patients admitted between June 1, 2020, and December 31, 2020. RESULTS: The resultant model has an area under the curve of 0.783 (95% CI, 0.76 to 0.81), with an optimal sensitivity of 0.74 and specificity of 0.69 for predicting mortality. Validation of this model in a subsequent cohort of 2067 consecutively hospitalized patients yielded comparable prognostic performance. CONCLUSION: We have developed an easy-to-use, robust model for systematically evaluating patients presenting to acute care settings with COVID-19 infection.

Tailoring the management of hypertension to comorbidities.

PURPOSE OF REVIEW: In this article, we review the most current evidence for initiation and maintenance of various antihypertension (HTN) drug classes, including other misconceptions with respect to common comorbidities in patients with HTN. RECENT FINDINGS: Although the currently available anti-HTN agents have broad applicability in treating HTN, additional agents, such as angiotensin receptor-neprilysin inhibitors and novel nonsteroidal mineralocorticoid antagonists, have recently gained clinical significance. In addition, there have been some anecdotal concerns regarding the adverse effects, indications, and risks of COVID-19 infection/mortality when using certain anti-HTN agents. SUMMARY: Current guidelines currently address the treatment of primary HTN. However, isolated HTN is uncommon and often involves comorbid diseases that require specific regimentation. Several experimental medications are currently in late-stage trials showing potential superiority over current drugs that are available in the market.

Hypertension in obesity.

PURPOSE OF REVIEW: The obesity epidemic is progressively affecting majority of individuals worldwide leading to many adverse metabolic and cardiovascular outcomes. Increasingly concerning among them is obesity hypertension (HTN). In this review, we delve into the physiology and therapeutic options in obesity HTN as we discuss the implications of obesity HTN on society. RECENT FINDINGS: Obesity is the most common cause of primary HTN and is directly proportional to increases BMI. The significance of adiposity in obesity HTN centers on humoral mechanisms via stimulation of the renal-angiotensin system, leptin activity, sympathetic overdrive, and proinflammatory processes that potentiate vascular remodeling, which results in a higher incidence of the progression of many known serious cardiovascular diseases. Although lifestyle and medical therapies have been recommended for obesity and its sequelae, continued global progression of this disease has driven the development of newer therapies such as carotid baroreflex activation therapy, renal denervation, and selective leptin receptor antagonism. SUMMARY: The pathophysiology of obesity HTN has not yet been fully elucidated despite it being one of the oldest known diseases to mankind. Major efforts to understand obesity HTN endures, paving opportunities for newer and possibly superior therapeutic options.

Global genetic population structure of Bacillus anthracis.

Anthrax, caused by the bacterium Bacillus anthracis, is a disease of historical and current importance that is found throughout the world. The basis of its historical transmission is anecdotal and its true global population structure has remained largely cryptic. Seven diverse B. anthracis strains were whole-genome sequenced to identify rare single nucleotide polymorphisms (SNPs), followed by phylogenetic reconstruction of these characters onto an evolutionary model. This analysis identified SNPs that define the major clonal lineages within the species. These SNPs, in concert with 15 variable number tandem repeat (VNTR) markers, were used to subtype a collection of 1,033 B. anthracis isolates from 42 countries to create an extensive genotype data set. These analyses subdivided the isolates into three previously recognized major lineages (A, B, and C), with further subdivision into 12 clonal sub-lineages or sub-groups and, finally, 221 unique MLVA15 genotypes. This rare genomic variation was used to document the evolutionary progression of B. anthracis and to establish global patterns of diversity. Isolates in the A lineage are widely dispersed globally, whereas the B and C lineages occur on more restricted spatial scales. Molecular clock models based upon genome-wide synonymous substitutions indicate there was a massive radiation of the A lineage that occurred in the mid-Holocene (3,064-6,127 ybp). On more recent temporal scales, the global population structure of B. anthracis reflects colonial-era importation of specific genotypes from the Old World into the New World, as well as the repeated industrial importation of diverse genotypes into developed countries via spore-contaminated animal products. These findings indicate humans have played an important role in the evolution of anthrax by increasing the proliferation and dispersal of this now global disease. Finally, the value of global genotypic analysis for investigating bioterrorist-mediated outbreaks of anthrax is demonstrated.

Phylogenetic discovery bias in Bacillus anthracis using single-nucleotide polymorphisms from whole-genome sequencing.

Phylogenetic reconstruction using molecular data is often subject to homoplasy, leading to inaccurate conclusions about phylogenetic relationships among operational taxonomic units. Compared with other molecular markers, single-nucleotide polymorphisms (SNPs) exhibit extremely low mutation rates, making them rare in recently emerged pathogens, but they are less prone to homoplasy and thus extremely valuable for phylogenetic analyses. Despite their phylogenetic potential, ascertainment bias occurs when SNP characters are discovered through biased taxonomic sampling; by using whole-genome comparisons of five diverse strains of Bacillus anthracis to facilitate SNP discovery, we show that only polymorphisms lying along the evolutionary pathway between reference strains will be observed. We illustrate this in theoretical and simulated data sets in which complex phylogenetic topologies are reduced to linear evolutionary models. Using a set of 990 SNP markers, we also show how divergent branches in our topologies collapse to single points but provide accurate information on internodal distances and points of origin for ancestral clades. These data allowed us to determine the ancestral root of B. anthracis, showing that it lies closer to a newly described "C" branch than to either of two previously described "A" or "B" branches. In addition, subclade rooting of the C branch revealed unequal evolutionary rates that seem to be correlated with ecological parameters and strain attributes. Our use of nonhomoplastic whole-genome SNP characters allows branch points and clade membership to be estimated with great precision, providing greater insight into epidemiological, ecological, and forensic questions.