Phytochemical profile and diverse pharmacology of Garcinia celebica L.

Garcinia celebica L. syn. Garcinia hombroniana Pierre belongs to the family Clusiaceae, is indigenous to Southeast Asian countries. This review aims to provide updated, comprehensive and categorized information on the phytoconstituents and pharmacological effects of this species. The data collection mainly involved searches through databases named Scopus, Google Scholar, Pubmed and Springer Link. Approximately 100 phytochemicals were recorded in this review, with various classes of compounds such as triterpenoids, flavonoids, benzophenones, xanthones, depsidones and sterols identified. The most abundant compounds isolated belong to two chemical classes: triterpenoids and xanthones. Their extracts and pure compounds have been reported for their antibacterial, antiparasitic, hepatoprotective, antioxidant, antidiabetic, antituberculosis, antiplatelet aggregation, anti-neuraminidase and cholinesterase inhibitory activities. This review will provide a comprehensive understanding between the phytochemical components and its medicinal uses that may serve as a valuable resource for future drug development.

Computed Tomography Pulmonary Angiography Prediction of Adverse Long-Term Outcomes in Chronic Thromboembolic Pulmonary Hypertension: Correlation with Hemodynamic Measurements Pre- and Post-Pulmonary Endarterectomy.

CT pulmonary angiography is commonly used in diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This work was conducted to determine if cardiac chamber size on CTPA may also be useful for predicting the outcome of CTEPH treatment. A retrospective analysis of paired CTPA and right heart hemodynamics in 33 consecutive CTEPH cases before and after pulmonary thromboendarterectomy (PTE) was performed. Semiautomated and manual CT biatrial and biventricular size quantifications were correlated with mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. The baseline indexed right atrioventricular volumes were twice the left atrioventricular volumes, with significant (p < 0.001) augmentation of left heart filling following PTE. Except for the left atrial volume to cardiac index, all other chamber ratios significantly correlated with hemodynamics. Left to right ventricular ratio cut point <0.82 has high sensitivity (91% and 97%) and specificity (88% and 85%) for identifying significant elevations of mPAP and PVR, respectively (AUC 0.90 and 0.95), outperforming atrial ratios (sensitivity 78% and 79%, specificity 82% and 92%, and AUC 0.86 and 0.91). Manual LV:RV basal dimension ratio correlates strongly with semiautomated volume ratio (r 0.77, 95% CI 0.64-0.85) and is an expeditious alternative with comparable prognostic utility (AUC 0.90 and 0.95). LV:RV dimension ratio of <1.03 and ≤0.99 (alternatively expressed as RV:LV ratio of >0.97 and ≥1.01) is a simple metric that can be used for CTEPH outcome prediction.

Pulmonary Vein Sign on Computed Tomography Pulmonary Angiography in Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension With Hemodynamic Correlation.

BACKGROUND: Pulmonary vein sign (PVS) indicates abnormal pulmonary venous flow on computed tomography pulmonary angiography (CTPA) is a frequent finding in proximal chronic thromboembolic pulmonary hypertension (CTEPH). PVS's occurrence in distal CTEPH and correlation to disease severity is unknown. Using right heart catheterization data, we evaluated the relationship between PVS and CTEPH disease distribution and severity. MATERIALS AND METHOD: A total of 93 consecutive CTEPH cases with both CTPA and right heart catheterization were identified in this retrospective multi-institutional study. After excluding 17 cases with suboptimal CTPA, there were 52 proximal and 24 distal CTEPH cases. Blood flow in the major pulmonary veins was graded qualitatively. Subgroup analysis of PVS was performed in 38 proximal CTEPH cases before and after pulmonary endarterectomy. RESULTS: PVS was more frequent in proximal (79%) than distal CTEPH (29%) ( P <0.001). No significant difference was noted in invasive mean pulmonary artery pressure (46±11 and 41±12 mm Hg) or pulmonary vascular resistance (9.4±4.5 and 8.4±4.8 WU) between the 2 groups. In the subgroup analysis, PVS was present in 29/38 patients (76%) before surgery. Postoperatively, 33/38 cases (87%, P <0.001) had normal venous flow (mean pulmonary artery pressure 46±11 and 25; pulmonary vascular resistance 9.2±4.3 and 2.6 WU preop and postop, respectively). CONCLUSION: PVS is a common feature in proximal but infrequent findings in distal CTEPH. PVS does not correlate with hemodynamic severity. PVS resolution was seen in the majority of patients following successful endarterectomy.

Utility of cardiac magnetic resonance feature tracking strain assessment in chronic thromboembolic pulmonary hypertension for prediction of REVEAL 2.0 high risk status.

Chronic thromboembolic pulmonary hypertension may be cured by pulmonary endarterectomy (PEA). Thromboembolic disease distribution/PEA success primarily determines prognosis but risk scoring criteria may be adjunctive. Right ventriculoarterial (RV-PA) and ventriculoatrial (RV-right atrium [RA]) coupling may be evaluated by cardiac MRI (CMR) feature tracking deformation/strain assessment. We characterized biatrial and biventricular CMR feature tracking (FT) strain parameters following PEA and tested the ability of CMR FT to identify REVEAL 2.0 high-risk status. We undertook a retrospective single-center cross-sectional study of patients (n = 57) who underwent PEA (2015-2020). All underwent pre and postoperative catheterization and CMR. Pulmonary arterial hypertension validated risk scores were calculated. Significant postoperative improvements were observed in mean pulmonary artery pressure (mPAP) (pre-op 45 ± 11 mmHg vs. post-op 26 ± 11 mmHg; p < 0.001) and PVR however a large proportion had residual pulmonary hypertension (45%; mPAP ≥25 mmHg). PEA augmented left heart filling with left ventricular end diastolic volume index and left atrial volume index increment. Left ventricular ejection fraction was unchanged postoperatively but LV global longitudinal strain improved (pre-op median -14.2% vs. post-op -16.0%; p < 0.001). Right ventricular (RV) geometry and function also improved with reduction in RV mass. Most had uncoupled RV-PA relationships which recovered (pre-op right ventricular free wall longitudinal strain -13.2 ± 4.8%, RV stroke volume/right ventricular end systolic volume ratio 0.78 ± 0.53 vs. post-op -16.8 ± 4.2%, 1.32 ± 0.55; both p < 0.001). Postoperatively, there were six REVEAL 2.0 high-risk patients, best predicted by impaired RA strain which was superior to traditional volumetric parameters (area under the curve [AUC] 0.99 vs. RVEF AUC 0.88). CMR deformation/strain evaluation can offer insights into coupling recovery; RA strain may be an expeditious surrogate for the more laborious REVEAL 2.0 score.

Biatrial Volumetric Assessment by Non-ECG-Gated CT Pulmonary Angiography Correlated with Transthoracic Echocardiography in Patients with Normal Diastology.

Atrial size is a predictor of cardiovascular mortality. Non-ECG-gated computed tomography pulmonary angiography (CTPA) is a common test for cardiopulmonary evaluation but normative values for biatrial volumes are lacking. We derived normal CT biatrial volumes using manual and semiautomated segmentation with contemporaneous transthoracic echocardiography (TTE) to confirm normal diastology. Thirty-five consecutive cases in sinus rhythm with no history of cardio-vascular, renal, or pulmonary disease and normal diastolic function were selected. Planimetric CTPA measurements were compared to TTE volumes measured using area length method. TTE and CTPA derived normal LAVi and RAVi were 27 + 5 and 20 + 6 mL/m2, and 30 + 8 and 29 + 9 mL/m2, respectively. Bland-Altman analysis revealed an underestimation of biatrial volumes by TTE. TTE-CT mean biases for LAV and RAV were -5.7 + 12.0 mL and -16.2 + 14.8 mL, respectively. The CT intraclass correlation coefficients (ICC 95% CI) for LA and RA volumes were 0.99 (0.96-1.00) and 0.96 (0.76-0.99), respectively. There was excellent correlation (p < 0.001) between the semiautomated and manual measurements for LA (r 0.99, 95% CI 0.98-0.99) and RA (r 0.99, 95% CI 0.99-1.00). Atrial volumetric assessment on CTPA is easy and reproducible and can provide additional metric in cardiopulmonary assessment.

MRI Feature Tracking Strain in Pulmonary Hypertension: Utility of Combined Left Atrial Volumetric and Deformation Assessment in Distinguishing Post- From Pre-capillary Physiology.

Aims: Pulmonary hypertension (PH) is dichotomized into pre- and post-capillary physiology by invasive catheterization. Imaging, particularly strain assessment, may aid in classification and be helpful with ambiguous hemodynamics. We sought to define cardiac MRI (CMR) feature tracking biatrial peak reservoir and biventricular peak systolic strain in pre- and post-capillary PH and examine the performance of peak left atrial strain in distinguishing the 2 groups compared to TTE. Methods and Results: Retrospective cross-sectional study from 1 Jan 2015 to 31 Dec 2020; 48 patients (22 pre- and 26 post-capillary) were included with contemporaneous TTE, CMR and catheterization. Mean pulmonary artery pressures were higher in the pre-capillary cohort (55 ± 14 vs. 42 ± 9 mmHg; p < 0.001) as was pulmonary vascular resistance (median 11.7 vs. 3.7 WU; p < 0.001). Post-capillary patients had significantly larger left atria (60 ± 22 vs. 25 ± 9 ml/m2; p < 0.001). There was no difference in right atrial volumes between groups (60 ± 21 vs. 61 ± 29 ml/m2; p = 0.694), however peak RA strain was lower in post-capillary PH patients (8.9 ± 5.5 vs. 18.8 ± 7.0%; p < 0.001). In the post-capillary group, there was commensurately severe peak strain impairment in both atria (LA strain 9.0 ± 5.8%, RA strain 8.9 ± 5.5%). CMR LAVi and peak LA strain had a multivariate AUC of 0.98 (95% CI 0.89-1.00; p < 0.001) for post-capillary PH diagnosis which was superior to TTE. Conclusion: CMR volumetric and deformation assessment of the left atrium can highly accurately distinguish post- from pre-capillary PH.

Totally Occluded Culprit Coronary Artery in Patients with Non-ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

The short- and long-term implications of identifying totally occluded culprit coronary arteries (TOCCA) in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) have not been well studied. This study compares clinical characteristics, short- and long-term outcomes of patients with NSTEMI identified with TOCCA to that of patients with non-TOCCA undergoing percutaneous coronary intervention (PCI). We analyzed data from patients with NSTEMI undergoing single-vessel PCI within the Melbourne Interventional Group multi-center registry between 2005 and 2017. Those with TOCCA were compared to those with non-TOCCA. The primary endpoint was 30-day major adverse cardiac events (MACE). Secondary endpoints included 12-month MACE and long-term mortality. A total of 6,829 patients with NSTEMI had single-vessel PCI of which 954 (14%) had TOCCA. Most TOCCA were non-left anterior descending (right coronary artery 39% versus circumflex 33% versus left anterior descending 26%; p <0.001). Cardiogenic shock and left ventricular dysfunction were higher in the TOCCA group, but non-TOCCA patients had more baseline comorbidities. Thirty-day MACE was higher in the TOCCA group (6.7% versus 3.8%; p <0.001). Long-term mortality with an average follow-up of 4.9 years was higher in the non-TOCCA group (12% versus 18%, p <0.01). Multivariable Cox-proportional hazards regression identified TOCCA as an independent predictor of 30-day MACE (HR = 1.93; 95%CI: 1.4-2.6), but not long-term mortality, which was predicted by baseline comorbidities. In conclusion, while patients with NSTEMI with TOCCA undergoing PCI represent a more unstable subgroup early on, long-term outcomes appear more dependent on baseline comorbidities.

Native aorto-ostial coronary lesions on CT coronary angiogram.

Aorto-ostial coronary lesions (AOLs) are important to detect due to the high risk of catastrophic consequences. Unfortunately, due to the complexities of these lesions, they may be missed on invasive coronary angiography. Computed tomography coronary angiogram (CTCA) is highly sensitive and specific in detecting AOLs, and has the additional advantage of demonstrating the surrounding anatomy. CTCA is particularly useful when assessing for AOL aetiologies in addition to atherosclerotic disease, e.g. Congenital anomalies, extrinsic Compression, Iatrogenic, Arteritis and Other, such as Thrombus, Embolism, Dissection and Spasm. This gives rise to "CIAO (TEDS)" as a proposed aide-mémoire and will form the structure of this pictorial review.

Aortic root measurement on CT: linear dimensions, aortic root area and comparison with echocardiography. A retrospective cross sectional study.

OBJECTIVE: We sought to assess the different CT aortic root measurements and determine their relationship to transthoracic echocardiography (TTE). METHODS: TTE and ECG-gated CT images were reviewed from 70 consecutive patients (mean age 54 ± 18 years; 67% male) with tricuspid aortic roots (trileaflet aortic valves) between Nov 2009 and Dec 2013. Three CT planes (coronal, short axis en face and three-chamber) were used for measurement of nine linear dimensions. TTE aortic root dimension was measured as per guidelines from the parasternal long axis view. RESULTS: All CT short axis measurements of the aortic root had excellent reproducibility (intraclass correlation coefficient, ICC 0.96-0.99), while coronal and three-chamber planes had lower reproducibility with ICC 0.90 (95% CI 0.84-0.94) and ICC 0.92 (0.87-0.95) respectively. CT coronal and short axis maximal dimensions were systematically larger than TTE (mean 2 mm larger, p < 0.001), while CT cusp to commissure measurements were systematically smaller (CT RCC-comm mean 2 mm smaller than TTE, p < 0.001). All CT short axis measurements had excellent correlation with aortic root area with CT short axis maximal dimension marginally better than the rest (Pearson's R 0.97). CONCLUSION: Systematic differences exist between CT and TTE dependent on the CT plane of measurement. All CT short axis measurements of the aortic root had excellent reproducibility and correlation with aortic root area with maximal dimension appearing marginally better than the rest. Our findings highlight the importance of specifying the chosen plane of aortic root measurement on CT. ADVANCES IN KNOWLEDGE: Systematic differences in aortic root dimension exist between TTE and the various CT measurement planes. CT coronal and short axis maximal dimensions were systematically larger than TTE, while CT cusp to commissure measurements were smaller. CT readers should indicate the plane of measurement and the specific linear dimension to avoid ambiguity in follow-up and comparison.

Troponin least significant change (z-score) is associated with poor clinical outcomes in patients presenting to the emergency department.

BACKGROUND: A rise and/or fall in high sensitivity cardiac troponin (hs-Tn) is critical in defining acute myocardial injury and therefore the diagnosis of acute myocardial infarction. A significant rise in hs-Tn is not well defined in current guidelines. Calculation of a z-score for two consecutive hs-Tn measurements is a method-independent measure of dynamic troponin elevation. However, the association of hs-Tn z-score with outcomes for unselected emergency department admissions is unknown. Moreover, the association of non-dynamic troponin elevations, as defined by a normal z-score, with clinical outcomes remains to be assessed. METHODS: We retrospectively calculated z-scores for patients presenting to emergency department over 18 months who had serial troponin measurements with at least one result >99th percentile using the Abbott hs-TnI assay. We assessed the association of z-score with discharge diagnosis, cardiac interventions, inpatient mortality, length of stay and readmission rates. RESULTS: There were 2062 presentations for 1830 patients where a z-score was calculated. Z-score was elevated in 1080 presentations. Dynamic troponin elevation (z-score ≥ 2) was associated with acute myocardial infarction (OR = 9.1, P < 0.01), admission to an inpatient unit (95 vs. 88%, P < 0.01), increased inpatient length of stay (97 vs. 65 days, P < 0.01), inpatient coronary intervention (21 vs. 6%, P < 0.01) and mortality (4.4 vs. 2.4%, P < 0.05) compared with myocardial injury with a static troponin elevation. CONCLUSIONS: Z-score is an assay-independent tool to alert clinicians of significant, dynamic troponin elevation and acute myocardial injury. It is associated with poorer clinical outcomes.

Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants.

INTRODUCTION: Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. METHODS AND RESULTS: We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extracardiac phenotypes, including contractures, scoliosis, cleft palate, and facial dysmorphisms. We observed no association between variant type or location, disease severity, and/or extracardiac manifestations. Myocardial histopathology showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis in patients under 4 years of age, and myofibrillar disarray in adults. Rare heterozygous ALPK3 variants were also assessed in adult-onset cardiomyopathy patients. Among 1548 Dutch patients referred for initial genetic analyses, we identified 39 individuals with rare heterozygous ALPK3 variants (2.5%; 95% CI: 1.8%-3.4%), including 26 missense and 10 LoF variants. Among 149 U.S. patients without pathogenic variants in 83 cardiomyopathy-related genes, we identified six missense and nine LoF ALPK3 variants (10.1%; 95% CI: 5.7%-16.1%). LoF ALPK3 variants were increased in comparison to matched controls (Dutch cohort, P = 1.6×10-5; U.S. cohort, P = 2.2×10-13). CONCLUSION: Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy.

Ticagrelor-associated ventricular pauses: a case report and literature review.

BACKGROUND: Ticagrelor is an oral anti-platelet agent that is a reversible and direct inhibitor of the adenosine diphosphate P2Y12 receptor. Ticagrelor's brady-arrhythmic potential was investigated in a sub-study of the PLATO trial, which concluded that the effects were transient and not clinically significant beyond the acute initiation phase. Since then, there have been emerging reports of ticagrelor-associated high-degree heart block, requiring drug discontinuation and pacemaker insertion. We present a case of symptomatic ventricular pauses in a patient loaded with ticagrelor post-percutaneous coronary intervention (PCI) for non-ST elevation acute coronary syndrome (NSTEACS) and review the literature relating to ticagrelor and its brady-arrhythmic potential. CASE SUMMARY: A 59-year-old female presented to our hospital with NSTEACS and received an oral load of ticagrelor 180 mg following PCI to her mid-left circumflex coronary artery. Three hours after, four pauses were observed on telemetry over a 20 min period, the longest being 18.5 s in duration. Ticagrelor was ceased and clopidogrel commenced in place. No arrhythmic events were recorded on loop recorder interrogation following ticagrelor discontinuation. DISCUSSION: The exact mechanism of ticagrelor-induced brady-arrhythmia is unclear, although inhibition of adenosine reuptake is proposed as likely due to structural similarities between ticagrelor and adenosine. In the setting of acute coronary syndrome treated with ticagrelor, extracellular adenosine concentrations are amplified by the ischaemic milieu with myocardial adenosine release and blunted cellular reuptake. This leads to enhanced agonism of adenosine A1 receptors, causing negative chronotropy and dromotropy. This case report highlights ticagrelor's brady-arrhythmic potential even in the absence of baseline conduction disease or concurrent confounding medications.

Exploring beliefs of the four major ethnic groups in Melbourne regarding healthcare and treatment.

OBJECTIVES: To explore and compare beliefs about healthcare and treatment of four ethnic groups attending a Melbourne emergency department (ED), and the corresponding perceptions held by emergency clinicians. METHOD: Prospective survey of ED doctors and patients from Greek, Italian, Vietnamese and Anglo-Saxon backgrounds. RESULTS: Vietnamese patients were least likely to believe their ethnic group received the best available care but less likely to believe in the existence of ethnic healthcare disparities. They were most likely to have an ethnically concordant GP and preferred most strongly to raise sensitive issues with an ethnically concordant doctor. Anglo-Saxon patients placed less importance on family support and older Anglo-Saxons were less likely than other groups to turn to God for comfort. Doctors perceived the existence of ethnic healthcare disparity, which was not perceived by the ethnic groups themselves. They underestimated the extent of patient-perceived disease control, external supports for coping, or use of complementary practitioners. Doctors overestimated patient perceived importance of doctor-patient ethnic concordance for Anglo-Saxons but underestimated the importance this has for Vietnamese patients. They also underestimated importance of clinician-demonstrated cultural understanding. CONCLUSIONS: Beliefs about healthcare and treatment differ across the four major ethnic groups attending a Melbourne ED. Doctors' misperceptions of patients' beliefs suggest that cultural competence amongst ED doctors could be improved.