Myocardial flow reserve recovery in patients with Takotsubo syndrome: Insights from positron emission tomography.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been implicated in the pathogenesis of Takotsubo syndrome (TTS). Positron emission tomography (PET) plays a key role in the assessment of CMD through myocardial flow reserve (MFR). However, there is limited information on the temporal progression of MFR and its relationship to coronary artery disease (CAD) in TTS patients. METHODS: This study evaluated patients with TTS who underwent cardiac catheterization and PET within one year of hospitalization. Patients were categorized into acute (≤10 days), subacute (11-30 days), and chronic (≥31 days) stages based on post-onset time of PET assessment. MFR values and prevalence of abnormal MFR (<2.0) were compared between stages. Temporal MFR changes in patients with obstructive CAD (≥70% stenosis by coronary angiography), non-obstructive CAD, and normal coronaries were compared. RESULTS: Of the 88 patients studied (mean age 70; 96% female), 52 (59%) were in the acute, 17 (19%) in the subacute, and 19 (22%) in the chronic stage. Median MFR in the acute stage was 2.0 (1.5-2.3), with 58% of patients showing abnormal MFR. A significant time-dependent improvement in MFR was observed (P = 0.002), accompanied by a decreased prevalence of abnormal MFR (P = 0.016). While patients with normal coronaries showed significant MFR improvement over time (P = 0.045), patients with obstructive or non-obstructive CAD demonstrated no improvement across three stages (P = 0.346 and 0.174, respectively). CONCLUSION: PET-derived MFR was impaired in TTS patients during the acute phase, with improvement suggesting potential recovery from CMD over time. The concurrent presence of obstructive CAD might impede this recovery process.

Interpretation of SPECT wall motion with deep learning.

OBJECTIVES: We sought to develop a novel deep learning (DL) workflow to interpret single-photon emission computed tomography (SPECT) wall motion. BACKGROUND: Wall motion assessment with SPECT is limited by image temporal and spatial resolution. Visual interpretation of wall motion can be subjective and prone to error. Artificial intelligence (AI) may improve accuracy of wall motion assessment. METHODS: A total of 1038 patients undergoing rest electrocardiogram (ECG)-gated SPECT and echocardiography were included. Using echocardiography as truth, a DL-model (DL-model 1) was trained to predict the probability of abnormal wall motion. Of the 1038 patients, 317 were used to train a DL-model (DL-model 2) to assess regional wall motion. A 10-fold cross-validation was adopted. Diagnostic performance of DL was compared with human readers and quantitative parameters. RESULTS: The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of DL model (AUC: .82 [95% CI: .79-.85]; ACC: .88) were higher than human (AUC: .77 [95% CI: .73-.81]; ACC: .82; P < .001) and quantitative parameter (AUC: .74 [95% CI: .66-.81]; ACC: .78; P < .05). The net reclassification index (NRI) was 7.7%. The AUC and accuracy of DL model for per-segment and per-vessel territory diagnosis were also higher than human reader. The DL model generated results within 30 seconds with operable guided user interface (GUI) and therefore could provide preliminary interpretation. CONCLUSIONS: DL can be used to improve interpretation of rest SPECT wall motion as compared with current human readers and quantitative parameter diagnosis.

An endogenous inhibitor of angiogenesis downregulated by hypoxia in human aortic valve stenosis promotes disease pathogenesis.

Aortic valve stenosis is the most common valve disease in the western world. Central to the pathogenesis of this disease is the growth of new blood vessels (angiogenesis) within the aortic valve allowing infiltration of immune cells and development of intra-valve inflammation. Identifying the cellular mediators involved in this angiogenesis is important as this may reveal new therapeutic targets which could ultimately prevent the progression of aortic valve stenosis. Aortic valves from patients undergoing surgery for aortic valve replacement or dilation of the aortic arch were examined both ex vivo and in vitro. We now demonstrate that the anti-angiogenic protein, soluble fms-like tyrosine kinase 1 (sFlt1), a non-signalling soluble receptor for vascular endothelial growth factor, is constitutively expressed in non-diseased valves. sFlt-1 expression was, however, significantly reduced in aortic valve tissue from patients with aortic valve stenosis while protein markers of hypoxia were simultaneously increased. Exposure of primary-cultured valve interstitial cells to hypoxia resulted in a decrease in the expression of sFlt-1. We further reveal using a bioassay that siRNA knock-down of sFlt1 in valve interstitial cells directly results in a pro-angiogenic environment. Finally, incubation of aortic valves with sphingosine 1-phosphate, a bioactive lipid-mediator, increased sFlt-1 expression and inhibited angiogenesis within valve tissue. In conclusion, this study demonstrates that sFlt1 expression is directly correlated with angiogenesis in aortic valves and the observed decrease in sFlt-1 expression in aortic valve stenosis could increase valve inflammation, promoting disease progression. This could be a viable therapeutic target in treating this disease.

Utility of FFRCT in Patients with Chest Pain.

PURPOSE OF REVIEW: The goal of this article is to review the data supporting the use of fractional flow reserve derived from coronary computed tomography angiography (FFRCT) in patients with chest pain. REVIEW FINDINGS: Numerous clinical trials have demonstrated that the diagnostic accuracy of coronary computed tomography angiography (CCTA) can be improved with the use of FFRCT, primarily due to its superior specificity when compared to CCTA alone. This promising development may help reduce the need for invasive angiography in patients presenting with chest pain. Furthermore, some studies have indicated that incorporating FFRCT into decision-making is safe, with an FFRCT value of ≥ 0.8 being associated with favorable outcomes. While FFRCT has been shown to be feasible in patients with acute chest pain, further large-scale studies are warranted to confirm its utility. The emergence of FFRCT as a tool for the management of patients with chest pain is promising. However, potential limitations require the interpretation of FFRCT in conjunction with clinical context.

Results and insights from a phase I clinical trial of Lomecel-B for Alzheimer's disease.

HYPOTHESIS: We hypothesized that Lomecel-B, an allogeneic medicinal signaling cell (MSC) therapeutic candidate for Alzheimer's disease (AD), is safe and potentially disease-modifying via pleiotropic mechanisms of action. KEY PREDICTIONS: We prospectively tested the predictions that Lomecel-B administration to mild AD patients is safe (primary endpoint) and would provide multiple exploratory indications of potential efficacy in clinical and biomarker domains (prespecified secondary/exploratory endpoints). STRATEGY AND KEY RESULTS: Mild AD patient received a single infusion of low- or high-dose Lomecel-B, or placebo, in a double-blind, randomized, phase I trial. The primary safety endpoint was met. Fluid-based and imaging biomarkers indicated significant improvement in the Lomecel-B arms versus placebo. The low-dose Lomecel-B arm showed significant improvements versus placebo on neurocognitive and other assessments. INTERPRETATION: Our results support the safety of Lomecel-B for AD, suggest clinical potential, and provide mechanistic insights. This early-stage study provides important exploratory information for larger efficacy-powered clinical trials.

Unmet needs in the diagnosis and treatment of Parkinson's disease psychosis and dementia-related psychosis.

Dementia due to Parkinson's disease and Alzheimer's disease are associated with behavioural and psychological symptoms, including psychosis. Long-term management presents a challenge for health care providers and caregivers. Symptoms of psychosis include hallucinations and delusions; if untreated, these can lead to institutionalisation, decreased quality of life, and significant patient and caregiver distress. A critical step in the effective management of dementia-related psychosis (DRP) is the identification and diagnosis of affected patients. The lack of a standardised diagnostic approach presents a barrier to treatment and there are no consensus guidelines for DRP. Furthermore, there are no approved therapies for the treatment of DRP. Antipsychotic medications are often prescribed off-label, even though some are associated with an increased risk of adverse events or mortality. We present currently available screening tools and guidelines for the diagnosis and treatment of Parkinson's disease psychosis and DRP in the context of what is needed for effective management of psychosis.KEY POINTSWe present currently available screening tools and guidelines for Parkinson's disease psychosis and dementia-related psychosis, and discuss the unmet need for simple clinical diagnostic tools and treatment guidelines.The identification of psychosis is variable across different settings and specialties, without a unified approach to screening, definition, or diagnosis.Currently used tools for defining and assessing psychosis in a research setting are usually too cumbersome for everyday clinical practice.The development of a standardised set of diagnostic criteria would provide clinicians the opportunity to improve the detection, treatment, and quality of life of patients and their caregivers.

Pattern recognition analysis of marine oil spills in airborne passive infrared multispectral remote sensing images.

Pattern recognition methodology was developed for the automated detection of marine oil spills in passive infrared multispectral remote sensing images. The images employed in this work were collected from the Deepwater Horizon oil spill accident in 2010. The imaging instrument for data collection was a downward-looking infrared line scanner equipped with eight optical bandpass filters in the spectral range of 8-12 µm on a fixed-wing aircraft. Oil slicks may show either positive or negative thermal contrast against the surrounding sea water, depending on the sun glint conditions or the oil thickness. Classifiers were developed separately to detect oil with different contrasts by the application of backpropagation neural networks to the preprocessed radiances. Preprocessing strategies included: (1) assembly of training data through k-means clustering analysis; (2) elimination of variation in radiance magnitudes by a customized temperature correction method; (3) removal of sun glint artifacts in images by polynomial correction; and (4) extraction of the most representative features as inputs for the neural networks by a subset selection approach. The classifiers designed to detect oil with positive and negative thermal contrast relative to water achieved overall classification accuracies of 88.7 and 92.2%, respectively. Composite classification images were generated by integrating classification scores produced by the two classifiers. The prediction performance of the classification system was demonstrated through its application to images not involved during the training of the networks.

Anti-inflammatory effect of rosuvastatin in patients with HIV infection: An FDG-PET pilot study.

AIMS: This study aimed to evaluate markers of systemic as well as imaging markers of inflammation in the ascending aorta, bone marrow, and spleen measured by 18F-FDG PET/CT, in HIV+ patients at baseline and following therapy with rosuvastatin. METHODS AND RESULTS: Of the 35 HIV+ patients enrolled, 17 were randomized to treatment with 10 mg/day rosuvastatin and 18 to usual care for 6 months. An HIV- control cohort was selected for baseline comparison of serum inflammatory markers and monocyte markers of inflammation. 18F-FDG-PET/CT imaging of bone marrow, spleen, and thoracic aorta was performed in the HIV+ cohort at baseline and 6 months. While CD14++CD16- and CCR2 expressions were reduced, serum levels of IL-7, IL-8, and MCP-1 were elevated in the HIV+ population compared to the controls. There was a significant drop in FDG uptake in the bone marrow (TBRmax), spleen (SUVmax) and thoracic aortic (TBRmax) in the statin-treated group compared to the control group (bone marrow: - 10.3 ± 16.9% versus 5.0 ± 18.9%, p = .0262; spleen: - 9.8 ± 20.3% versus 11.3 ± 28.8%, p = .0497; thoracic aorta: - 19.1 ± 24.2% versus 4.3 ± 15.4%, p = .003). CONCLUSIONS: HIV+ patients had significantly markers of systemic inflammation including monocyte activation. Treatment with low-dose rosuvastatin in the HIV+ cohort significantly reduced bone marrow, spleen and thoracic aortic FDG uptake.

Radiolabeled Thioflavin-T Derivative PET Imaging for the Assessment of Cardiac Amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) is an often under-recognized cause of heart failure with preserved ejection fraction. The goal of the current paper was to review imaging modalities available for detecting cardiac amyloidosis. We wished to determine what modalities are available for the diagnosis of cardiac amyloidosis and what modalities could be utilized in the future. RECENT FINDINGS: Early and delayed planar imaging of the chest currently plays a central role in the workup and diagnosis of CA. However, novel positron emission tomography (PET) tracers could play a large role in CA imaging in the future. There is an increasing body of literature supporting the use of targeted amyloid-binding PET radiotracers such as 11C-Pittsburgh compound B (11C-PIB), 18F-florbetapir, -flutemetamol, and -florbetaben for the detection of cardiac amyloid. While planar imaging currently plays a large role in the workup of CA, PET imaging could play an increasing important role in the future. The quantitative abilities of novel PET tracers could theoretically allow for the serial monitoring of patients and detection of response to therapy, and the sensitive nature of the tracers could allow for even earlier disease detection. Further work with large randomized controlled trial data is needed in the development and validation of PET tracers for cardiac amyloid and represents an exciting development within the realm of nuclear cardiology.

Coronary artery disease in patients with human immunodeficiency virus infection.

The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug-drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.