Evaluating the Prevalence of Maternal Health Indicators on Infant Mortality Rates in Florida.

Background The infant mortality rate is defined as the number of infant deaths for every 1000 live births. In 2020, the infant mortality rate was 5.8% in the state of Florida, compared to 7.0% in 2000. Although infant mortality rates have declined in the state of Florida, disparities influencing these rates exist across varying Florida counties, with the widest differences being compared between the healthiest versus unhealthiest counties in Florida. Many factors can contribute to high infant mortality rates in certain counties, including income inequality, access to and quality of healthcare, race/ethnicity, obesity, and disadvantaged socioeconomic status (SES). Methods This study utilized data from Florida Health Charts on infant mortality rates in the state of Florida and the Pregnancy and Young Child Profiles in 10 counties to examine how certain risk factors impact infant mortality outcomes in the state of Florida. These 10 counties consist of five healthiest and five unhealthiest counties, as determined by the 2022 County Health Rankings data. T-tests were used to evaluate the relationship between county health status and several county health indicators. Results The average infant mortality rate from 2011 to 2020 differed significantly among healthy and unhealthy counties (p-value=0.0000). Median household income, individuals below the poverty level, and those aged zero to 17 years old were found to differ significantly by county health status (p-values 0.0000, 0.001, and 0.009, respectively). However, mothers having no high school education, births with first-trimester care, births with adequate care, and births with late or no prenatal care were not statistically significant. Conclusion Our study suggests that counties more likely to have fewer resources than other counties, such as those considered unhealthy, are more impacted by a higher infant mortality rate. The unhealthy counties in this study were found to have lower average median household income, higher rates of no high school education among mothers, and less prenatal care in comparison to healthy counties.

Infant, Neonatal, and Post-neonatal Mortality in Greece: A Nationwide Time-Trend Analysis.

INTRODUCTION: Infant mortality is a crucial perinatal measure and is also regarded as an important public health indicator. This study aimed to comprehensively present time trends in infant, neonatal, and post-neonatal mortality in Greece. METHODS: The annual infant mortality rate (IMR), the neonatal mortality rate (NMR), and the post-neonatal mortality rate (PNMR) were calculated based on official national data obtained from the Hellenic Statistical Authority, spanning 67 years from 1956 to 2022. The time trends of the mortality rates were evaluated using joinpoint regression analysis, and the annual percent changes (APC) and the overall average annual percent change (AAPC) were calculated with a 95% confidence interval (95% CI). RESULTS: The IMR exhibited accelerating declines over more than 50 years, with an APC of -1.9 (-2.8 to -1.0) from 1956 to 1968, -5.4 (-5.6 to -5.2) from 1968 to 1999, and -7.3 (-8.9 to -5.7) between 1999 and 2008. In 2008, IMR reached its all-time low of 2.7 per 1,000 live births, down 16.6-fold from its peak at 44.1 per 1,000 live births in 1957. This improving trend was reversed following the onset of the economic crisis in the country, leading to a 57% increase in IMR from 2008 to 2016, with an upward trend APC of 3.4 (1.2 to 5.5). In the recent period 2016-2022, there was an improvement with an APC of -3.7 (-6.2 to -1.1), resulting in an IMR of 3.1 per 1,000 live births in 2022. The decrease in IMR was estimated to have prevented 209,109 infant deaths in the country from 1958 to 2022. From 1956 to 2022, the IMR decreased with an AAPC of -3.9 (-4.3 to -3.4), while the PNMR saw a decline with an AAPC of -4.5 (-5.1 to -3.9) and the NMR with an AAPC of -3.2 (-3.7 to -2.6). CONCLUSION: Greece achieved an impressive decrease in infant mortality rates, but this progress was halted and completely reversed during the economic crisis. Although there have been some recent improvements after the country's economic recovery, the rates have yet to reach pre-crisis levels.

Angiography-versus wire-based microvascular resistance index to detect coronary microvascular obstruction associated with ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) measured by cardiac magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) has important prognostic implications. While invasive index of microvascular resistance (IMR) have been shown to predict the occurrence and extent of MVO, the role of the angiography-based microvascular resistance (Angio-IMR) for this purpose remains unknown. The present study aims to perform a head-to-head comparison of wire-based and angiography-derived microcirculatory resistance (IMR and Angio-IMR, respectively) for the detection of MVO. METHODS: Patients with a first STEMI and multivessel disease underwent CMR for detection of MVO, and angio-IMR and IMR measurements during PPCI and at 30 day follow up, both in STEMI culprit and non-culprit vessels. RESULTS: 58 patients were included (mean age 60.7 ± 9.9 years, 82% male). At the time of PPCI, angio-IMR and IMR exhibited significant correlation (r = 0.70, P < 0.001), and agreement (coefficient of agreement 0.58). Both indices showed good predictive value of MVO [Angio IMR: AUC 0.79 (95% CI: 0.667-0.928); IMR: AUC 0.70 (95% CI: 0.539-0.853); p = 0.15]. Angio-IMR 40 U and IMR 34 U were identified as best cut-offs for prediction of MVO. In non-culprit vessels, angio-IMR and IMR also correlated well (rho = 0.59, p < 0.001), with overall lower mean values compared to culprit vessels (Angio-IMR: 36 vs. 23; IMR: 39 vs. 22, p < 0.001 for both comparisons). CONCLUSION: Angio-IMR constitutes a valid alternative to wire-based IMR in predicting MVO in STEMI. Angio-IMR and IMR show a good correlation in the acute and subacute STEMI phases, both in culprit and non-culprit vessels.

Coronary microvascular dysfunction in patients with Takotsubo syndrome.

BACKGROUND: The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. OBJECTIVES: We sought to evaluate CMD in patients with TTS. METHODS: Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. RESULTS: Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). CONCLUSION: CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

Impact of the use of plaque modification techniques on coronary microcirculation using an angiography-derived index of microcirculatory resistance.

Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve outcomes in this setting. However, their impact on coronary microcirculation remains unknown. The aim of this study is to evaluate the influence of plaque modification techniques on coronary microcirculation across patients with severely calcified coronary artery disease. In this multicenter retrospective study, consecutive patients undergoing PCI with either Rotablation (RA) or Shockwave-intravascular-lithotripsy (IVL) were included. Primary endpoint was the impairment of coronary microvascular resistances assessed by Δ angiography-derived index of microvascular resistance (ΔIMRangio) which was defined as the difference in IMRangio value post- and pre-PCI. Secondary endpoints included the development of peri procedural PCI complications (flow-limiting coronary dissection, slow-flow/no reflow during PCI, coronary perforation, branch occlusion, failed PCI, stroke and shock developed during PCI) and 12-month follow-up adverse events. 162 patients were included in the analysis. Almost 80% of patients were male and the left descending anterior artery was the most common treated vessel. Both RA and IVL led to an increase in ΔIMRangio (22.3 and 10.3; p = 0.038, respectively). A significantly higher rate of PCI complications was observed in patients with ΔIMRangio above the median of the cohort (21.0% vs. 6.2%; p = 0.006). PCI with RA was independently associated with higher ΔIMRangio values (OR 2.01, 95% CI: 1.01-4.03; p = 0.048). Plaque modification with IVL and RA during PCI increases microvascular resistance. Evaluating the microcirculatory status in this setting might help to predict clinical and procedural outcomes and to optimize clinical results.

Prognostic Value of Microvascular Resistance Reserve After Percutaneous Coronary Intervention in Patients With Myocardial Infarction.

BACKGROUND: The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. METHODS: From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n = 1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. RESULTS: Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95% CI: 2.31-7.50; P < 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. CONCLUSIONS: MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.

Engineered IgM and IgG cleaving enzymes for mitigating antibody neutralization and complement activation in AAV gene transfer.

Systemic dosing of adeno-associated viral (AAV) vectors poses potential risk of adverse side effects including complement activation triggered by anti-capsid immunity. Due to the multifactorial nature of toxicities observed in this setting, a wide spectrum of immune modulatory regimens are being investigated in the clinic. Here, we discover an IgM cleaving enzyme (IceM) that degrades human IgM, a key trigger in the anti-AAV immune cascade. We then engineer a fusion enzyme (IceMG) with dual proteolytic activity against human IgM and IgG. IceMG cleaves B cell surface antigen receptors and inactivates phospholipase gamma signaling in vitro. Importantly, IceMG is more effective at inhibiting complement activation compared with an IgG cleaving enzyme alone. Upon IV dosing, IceMG rapidly and reversibly clears circulating IgM and IgG in macaques. Antisera from these animals treated with IceMG shows decreased ability to neutralize AAV and activate complement. Consistently, pre-conditioning with IceMG restores AAV transduction in mice passively immunized with human antisera. Thus, IgM cleaving enzymes show promise in simultaneously addressing multiple aspects of anti-AAV immunity mediated by B cells, circulating antibodies and complement. These studies have implications for improving safety of AAV gene therapies and possibly broader applications including organ transplantation and autoimmune diseases.

The Role of Index of Microcirculatory Resistance in Left Anterior Descending Artery ST Segment Elevation Myocardial Infarction Patients after Primary Percutaneous Coronary Intervention.

Background: Our aim was to assess the relationship of the index of microvascular resistance (IMR) in left anterior descending (LAD) artery involved STEMI patients. Methods: Data of 316 STEMI patients who had undergone primary percutaneous coronary intervention (PCI) were collected from three cardiovascular centers from 2005 to 2015. In total, 246 patients with LAD STEMI were enrolled for IMR evaluation. Patients were divided into two groups respective of the cut-off IMR value of 30. All-cause mortality, left ventricular function, improvement of systolic function, and cardiac biomarkers were analyzed and compared. Results: A total of 246 patients were enrolled. The number of patients in the IMR above 30 group was 93 and below 30 was 153. The mean ages for each group were 57.91 ± 11.99 and 54 ± 10.63, respectively. The peak creatinine kinase (CK) (3936.85 ± 2827.32 IU/L vs. 2218.08 ± 2310.41 IU/L, p < 0.001) and CKmb (336.15 ± 195.08 mg/mL vs. 231.53 ± 179.53 mg/mL, p < 0.001) levels were higher for an IMR above the 30 group. The left ventricular ejection fraction (LVEF) (44.57 ± 6.685% vs. 47.35 ± 8.17%, p = 0.006) and improvement of LVEF (2.81 ± 7.135% vs. 5.88 ± 7.65%, p = 0.004) was lower in the IMR above 30 group. All-cause mortality (7.5% vs. 1.3%, p = 0.012) was higher in the IMR above 30 group, and a Cox regression analysis showed that an IMR above 30 was a poor prognostic factor regarding all-cause mortality (HR: 5.151, 95% CI 1.062-24.987, p = 0.042) even after adjusting for classical clinical risk factors. Conclusions: An elevated IMR value represented larger infarct size, more severe LV dysfunction, and higher mortality in LAD STEMI patients after successful PCI.

Assessing the Psychometric Properties of the Illness Management and Recovery Scale: A Systematic Review Using the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN).

The Illness Management and Recovery Scale (IMR-S) is based on the IMR program, developed to assess the recovery process for people with severe mental disorders by considering the perceptions of clients and clinicians involved in it. The aim of this study was to analyze the psychometric properties of the IMR-S so as to determine the reliability and suitability of its scores for evaluating recovery. Two coders searched five databases for studies, published between January 2004 and May 2023, that describe the psychometric assessment of the IMR-S. Studies were assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. Finally, 46 papers were included. Methodological quality was very good for most of the studies that provide information on internal validity, and limited for those that report on responsiveness. Measurement properties were positive for convergent validity and measurement error. The quality of evidence was high for structural validity studies. Although this study only includes research published in English and may have overlooked certain psychometric properties evaluated in studies published in other languages, our findings suggest that the IMR-S is a valid and reliable instrument, demonstrating its potential to offer guidance for clinical practice.

Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: A systematic review and meta-analysis.

BACKGROUND: Microvascular obstruction (MVO) is an independent predictor of adverse cardiac events after ST-elevation myocardial infarction (STEMI). The Index of Microcirculatory Resistance (IMR) may be a useful marker of MVO, which could simplify the care pathway without the need for Cardiac Magnetic Resonance (CMR). We assessed whether the IMR can predict MVO in STEMI patients. METHODS AND RESULTS: We conducted a systematic review and meta-analysis, including articles where invasive IMR was performed post primary percutaneous coronary intervention (PCI) in addition to MVO assessment with cardiac MRI. We searched PubMed, Scopus, Embase, and Cochrane databases from inception until January 2023. Baseline characteristics, coronary physiology and cardiac MRI data were extracted by two independent reviewers. The random-effects model was used to pool the data. Among 15 articles identified, nine articles (n = 728, mean age 61, 81% male) contained IMR data stratified by MVO. Patients with MVO had a mean IMR of 41.2 [95% CI 32.4-50.4], compared to 25.3 [18.3-32.2] for those without. The difference in IMR between those with and without MVO was 15.1 [9.7-20.6]. Meta-regression analyses demonstrated a linear relationship between IMR and TIMI grade (ß = 0.69 [0.13-1.26]), as well as infarct size (ß = 1.18 [0.24-2.11]) or ejection fraction at 6 months (ß = -0.18 [-0.35 to -0.01]). CONCLUSION: In STEMI, patients with MVO had 15-unit higher IMR than those without. IMR also predicts key prognostic endpoints such as infarct size, MVO, and long-term systolic function.

Toward quantitative intrafractional monitoring in paraspinal SBRT using a proprietary software application: clinical implementation and patient results.

Objective.We report on paraspinal motion and the clinical implementation of our proprietary software that leverages Varian's intrafraction motion review (IMR) capability for quantitative tracking of the spine during paraspinal SBRT. The work is based on our prior development and analysis on phantoms.Approach.To address complexities in patient anatomy, digitally reconstructed radiographs (DRR's) that highlight only the spine or hardware were constructed as tracking reference. Moreover, a high-pass filter and first-pass coarse search were implemented to enhance registration accuracy and stability. For evaluation, 84 paraspinal SBRT patients with sites spanning across the entire vertebral column were enrolled with prescriptions ranging from 24 to 40 Gy in one to five fractions. Treatments were planned and delivered with 9 IMRT beams roughly equally distributed posteriorly. IMR was triggered every 200 or 500 MU for each beam. During treatment, the software grabbed the IMR image, registered it with the corresponding DRR, and displayed the motion result in near real-time on auto-pilot mode. Four independent experts completed offline manual registrations as ground truth for tracking accuracy evaluation.Main results.Our software detected ≥1.5 mm and ≥2 mm motions among 17.1% and 6.6% of 1371 patient images, respectively, in either lateral or longitudinal direction. In the validation set of 637 patient images, 91.9% of the tracking errors compared to manual registration fell within ±0.5 mm in either direction. Given a motion threshold of 2 mm, the software accomplished a 98.7% specificity and a 93.9% sensitivity in deciding whether to interrupt treatment for patient re-setup.Significance.Significant intrafractional motion exists in certain paraspinal SBRT patients, supporting the need for quantitative motion monitoring during treatment. Our improved software achieves high motion tracking accuracy clinically and provides reliable guidance for treatment intervention. It offers a practical solution to ensure accurate delivery of paraspinal SBRT on a conventional Linac platform.

Temporal Quantitative Proteomic and Phosphoproteomic Profiling of SH-SY5Y and IMR-32 Neuroblastoma Cells during All-Trans-Retinoic Acid-Induced Neuronal Differentiation.

The human neuroblastoma cell lines SH-SY5Y and IMR-32 can be differentiated into neuron-like phenotypes through treatment with all-trans-retinoic acid (ATRA). After differentiation, these cell lines are extensively utilized as in vitro models to study various aspects of neuronal cell biology. However, temporal and quantitative profiling of the proteome and phosphoproteome of SH-SY5Y and IMR-32 cells throughout ATRA-induced differentiation has been limited. Here, we performed relative quantification of the proteomes and phosphoproteomes of SH-SY5Y and IMR-32 cells at multiple time points during ATRA-induced differentiation. Relative quantification of proteins and phosphopeptides with subsequent gene ontology analysis revealed that several biological processes, including cytoskeleton organization, cell division, chaperone function and protein folding, and one-carbon metabolism, were associated with ATRA-induced differentiation in both cell lines. Furthermore, kinase-substrate enrichment analysis predicted altered activities of several kinases during differentiation. Among these, CDK5 exhibited increased activity, while CDK2 displayed reduced activity. The data presented serve as a valuable resource for investigating temporal protein and phosphoprotein abundance changes in SH-SY5Y and IMR-32 cells during ATRA-induced differentiation.

Exploring the Therapeutic Potential: Malaysian Channa striatus Water Extract Enriched with Arachidonic Acid for Wound Healing in Human Foetal Lung Cells (IMR-90) (Meneroka Potensi Terapeutik: Ekstrak Air Channa striatus Malaysia yang Diperkaya dengan Asid Arachidonic untuk Penyembuhan Luka dalam Sel Paru-paru Janin Manusia (IMR-90)) / Jurnal Sains Kesihatan Malaysia

@#Channa striatus, also known as haruan, is traditionally used in Malaysia for its wound-healing properties. This study evaluated the wound healing potential of Channa striatus water extract (CSWE) and identified key compounds promoting fibroblast cell growth. Channa striatus were deboned to maximize fillet retention. CSWE was obtained through aqueous extraction, and its physicochemical properties were analyzed, including pH, rheological characteristics, moisture content, amino acid composition, and arachidonic acid presence. The effective concentration (EC50) of the sample was determined using a 2-D cell culture system with human fibroblast cells (IMR-90) over three days. Results showed CSWE had a near-neutral pH (6.34 ± 0.01) and high moisture content (97.3 ± 0.01%). The extract displayed Newtonian fluid behavior with a viscosity of 1.50 ± 0.31 mPa.s. CSWE contained essential amino acid glycine and arachidonic acid, important for wound healing, but in low concentrations. These low concentrations did not significantly promote IMR-90 cell growth (p>0.05) compared to the control. Consequently, EC50 values for CSWE were invalid due to over-dilution from a high fish weight-to-solvent ratio. Despite this, IMR-90 cell growth rates remained consistent across different CSWE concentrations, with no observed mortality during the three-day incubation. Overall, IMR-90 cells exhibited insignificant growth, even with arachidonic acid and glycine at low concentrations during treatment.

Coronary microvascular dysfunction in Takotsubo syndrome: an analysis using angiography-derived index of microcirculatory resistance.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been proposed as a crucial factor in the pathophysiology of Takotsubo syndrome (TTS). The angiography-derived index of microcirculatory resistance (caIMR) offers an alternative to conventional hyperemic wire-based IMR to assess CMD. We aimed to evaluate CMD's prevalence, transience, and impact on in-hospital outcomes in TTS. METHODS: All three coronary arteries of 96 patients with TTS were assessed for their coronary angiography derived Index of microcirculatory Resistance (caIMR) and compared to non-obstructed vessels of matched patients with ST-elevation myocardial infarction. Further, the association between caIMR and the TTS-specific combined in-hospital endpoint of death, cardiac arrest, ventricular arrhythmogenic events and cardiogenic shock was investigated. RESULTS: Elevated IMR was present in all TTS patients, with significantly elevated caIMR values in all coronary arteries compared to controls. CaIMR did not differ between apical and midventricular TTS types. CaIMR normalized in TTS patients with follow-up angiographies performed at a median of 28 months (median caIMR at event vs follow-up: LAD 34.8 [29.9-41.1] vs 20.3 [16.0-25.3], p < 0.001; LCX: 38.7 [32.9-50.1] vs 23.7 [19.4-30.5], p < 0.001; RCA: 31.7 [25.0-39.1] vs 19.6 [17.1-24.0], p < 0.001). The extent of caIMR elevation significantly correlated with the combined in-hospital endpoint (p = 0.036). CONCLUSION: TTS patients had evidence of elevated caIMR in at least one coronary artery with a trend towards higher LAD caIMR in apical type TTS and normalization after recovery. Furthermore, extent of caIMR elevation was associated with increased risk of in-hospital MACE of TTS patients.

The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data.

BACKGROUND: Despite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. OBJECTIVES: The aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. METHODS: In a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. RESULTS: In total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. CONCLUSIONS: In this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

Are baseline conditions of coronary arteries sufficient for calculating angio-based index of microcirculatory resistance and fractional flow reserve?

Background: Angio-based index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) have been developed, however, the differences between baseline and hyperemic data and their effects on their computation have not yet been discussed. This study aimed to compare the diagnostic performance of a novel method for calculating IMR and FFR from coronary angiography under baseline and hyperemic conditions. Methods: We performed a retrospective study to investigate the diagnostic performance of angiography-derived IMR (AccuIMR) and FFR (AccuFFRangio) computed from the hyperemic condition (AccuIMRhyp, AccuFFRangiohyp) and baseline condition (AccuIMRbase, AccuFFRangiobase) in 101 consecutive patients with chronic coronary syndrome (CCS) who underwent measurements of IMR and FFR at a single center, using wire-based IMR and FFR as the reference standard. Results: AccuIMRhyp showed much better correlation with IMR than AccuIMRbase (r=0.77 vs. 0.47, P<0.001). The diagnostic accuracy and area under the curve (AUC) for identifying significant microvascular dysfunction was higher for AccuIMRhyp than AccuIMRbase [92.1% (95% CI: 85.0-96.5%) vs. 83.2% (95% CI: 74.4-89.9%), P=0.012; 0.942 (95% CI: 0.877-0.979) vs. 0.815 (95% CI: 0.726-0.886), P=0.003]. The computed AccuFFRangio showed good correlations with FFR and good diagnostic performance under both hyperemic and baseline conditions [r=0.68 vs. 0.68, P>0.99; diagnostic accuracy =95.9% (95% CI: 89.8-98.9%) vs. 94.9% (95% CI: 88.4-98.3%), P=0.728; AUC =0.989 (95% CI: 0.942-1.000) vs. 0.973 (95% CI: 0.919-0.995), P=0.381]. The net reclassification index (NRI) demonstrated that hyperemic group had improved reclassification ability compared to the baseline group in identification of IMR >25 (NRI =0.20, P<0.001) and FFR ≤0.8 (NRI =0.11, P<0.001). Conclusions: By comparing the calculated angio-derived IMR and FFR under the baseline and hyperemic conditions, this study demonstrates that AccuIMR calculation is more accurate using the hyperemic condition, while AccuFFRangio calculation is accurate under both conditions.

Simultaneous Imaging of Ga-DOTA-TATE and Lu-DOTA-TATE in Murine Models of Neuroblastoma.

68Ga-DOTA-TATE and 177Lu-DOTA-TATE are radiolabeled somatostatin analogs used to detect or treat neuroendocrine tumors. They are administered separately for either diagnostic or therapeutic purposes but little experimental data for their biokinetics are measured simultaneously in the same biological model. By co-administering 68Ga-DOTA-TATE and 177Lu-DOTA-TATE in three laboratory mice bearing two IMR32 tumor xenografts expressing different levels of somatostatin receptors (SSTRs) on their shoulders and imaging both 68Ga and 177Lu simultaneously, we investigated the relationship between the uptake of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE in organs and tumors. In addition, using the percent of injected activity (%IA) values of 68Ga-DOTA-TATE at 0 hr and 4 hr, we investigated the correlation between 68Ga-DOTA-TATE %IA and the time-integrated activity coefficients (TIACs) of 177Lu-DOTA-TATE to estimate the organ-based and tumor-based doses of 177Lu-DOTA-TATE. The results showed that the extrapolated clearance time of 68Ga-DOTA-TATE linearly correlated with the TIACs of 177Lu-DOTA-TATE in the IMR32-SSTR2 tumor, kidneys, brain, heart, liver, stomach and remainder body. The extrapolated %IA value at 0 hr of 68Ga-DOTA-TATE linearly correlated with the TIACs of 177Lu-DOTA-TATE in the IMR32 tumor and lungs. In our murine study, both kidneys and lungs were organs that showed high absorbed doses of 177Lu-DOTA-TATE.

Microvascular function and inflammatory activation in Takotsubo cardiomyopathy.

AIMS: The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS-induced pathology. METHODS AND RESULTS: The study included 20 females [median age 65 years; interquarile range (IQR) = 58-70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, we determined the index of microvascular resistance (IMR) and drew blood samples almost simultaneously from the aorta and coronary sinus. Cardiac magnetic resonance imaging (MRI) was done in the acute phase. We present descriptive coronary physiology and cardiac MRI data and compare inflammatory biomarkers between samples from the aorta, coronary sinus, and venous samples after 3 months using the Wilcoxon signed-rank test. For comparison, we also analysed the actual biomarkers in venous blood from 15 healthy female controls. A supplementary analysis explored Spearman's rank correlation between the inflammatory biomarkers, IMR, MRI data, and cardiac biomarkers. The median IMR was 16.5 mmHg·s (IQR = 10.5-28.2 mmHg·s), which was only slightly higher than that in the reference populations. Seven (35%) of the study subjects had IMR > 25 mmHg·s, suggesting a microvascular dysfunction. IMR was not affected by time from symptom onset. According to MRI, the apical region of the left ventricle was affected in 65% of the subjects. The median ejection fraction was 41% (IQR = 31-48%). Biomarker analyses revealed elevation of markers for extracellular matrix remodelling and fibrosis, inflammation, immune activation, and upstream inflammation as compared with healthy controls. Only the levels of interleukin (IL)-1 receptor antagonist and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) were higher in the coronary sinus than in the aorta. No variable was significantly correlated with IMR. The IL-6 level in the aorta was inversely correlated with the left ventricular ejection fraction. Growth differentiation factor-15, osteoprotegerin, and von Willebrand factor levels in both aorta and coronary sinus were positively correlated with N-terminal-pro-brain-natriuretic peptide, while the correlations of IL-6 and sTIM-3 with N-terminal-pro-brain-natriuretic peptide were restricted to the aorta and coronary sinus, respectively. While most of the markers were within normal limits after 3 months, matrix metalloproteinase-9 increased during follow-up to reach levels higher than those in the healthy controls. CONCLUSION: The median IMR was only slightly elevated in this study, but about one-third of the patients had values indicating microvascular dysfunction. The present study supports the involvement of several inflammatory pathways in TTS, including monocyte/macrophage activation, with sTIM-3 as a potential novel marker.

The imPAct of Trimetazidine on MicrOcirculation after Stenting for stable coronary artery disease (PATMOS study).

Background: Myocardial ischemia is caused by epicardial coronary artery stenosis or atherosclerotic disease affecting microcirculation. Trimetazidine (TMZ), promotes glucose oxidation which optimizes cellular energy processes in ischemic conditions. Small studies demonstrated protective effects of TMZ in terms of reducing myocardial injury after percutaneous coronary intervention (PCI), its effect on microcirculation using contemporary investigative methods has not been studied. The aim of the study was to examine effects of trimetazidine, given before elective PCI, on microcirculation using invasively measured index of microcirculatory resistance (IMR). Methods: This was prospective, single blinded, randomized study performed in a single university hospital. It included consecutive patients with an indication for PCI of a single, de novo, native coronary artery lesion. Patients were randomly assigned to receive either TMZ plus standard therapy (TMZ group) or just standard therapy. Coronary physiology indices fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured before and after PCI using coronary pressure wire. Results: We randomized 71 patients with similar clinical characteristics and risk profile, previous medications and coronary angiograms. Patientshad similar values of Pd/Pa, FFR and CFR prior to PCI procedure. After PCI, FFR values were higher in TMZ group, while IMR values were lower in this group respectively (FFR TMZ + 0.89 ± 0.05 vs. TMZ - 0.85 ± 0.06, p = 0.007; CFR TMZ + 2.1 ± 0.8 vs. TMZ- 2.3 ± 1.3, p = 0.469; IMR TMZ + 18 ± 9 vs. TMZ- 24 ± 12, p = 0.028). In two-way repeated measures ANOVA PCI was associated with change in FFR values (TMZ p = 0.050; PCI p < 0.001; p for interaction 0.577) and TMZ with change in IMR values (TMZ p = 0.034, PCI p = 0.129, p for interaction 0.344). Conclusion: Adding trimetazidine on top of medical treatment prior to elective PCI reduces microvascular dysfunction by lowering postprocedural IMR values when compared to standard therapy alone.