Clinical and Angiographic Predictors of Mortality in Sudden Cardiac Arrest Patients Having Cardiac Catheterisation: A Single Centre Registry.

BACKGROUND: Immediate cardiac catheterisation (CC) is recommended in ST-elevation myocardial infarction (STEMI) following sudden cardiac arrest (SCA). Guidelines advise urgent CC for SCA patients without-STEMI, at clinician discretion. We examined the clinical and angiographic factors predicting mortality in SCA patients having CC. METHODS: Consecutive SCA patients having CC at Liverpool Hospital, Sydney (January 2011-September 2015) were retrospectively analysed. Patient data were retrieved from hospital records, and angiographic SYNTAX scores (SS) were quantified online. Independent predictors of mortality were derived using multivariate logistic analysis. RESULTS: The study cohort comprised 104 SCA patients; mean age 61±12years, and 79% male. Immediate CC (<2hours post-SCA) was performed in 35% overall. Compared to the without-STEMI subgroup, STEMI patients had more ventricular fibrillation (91 vs 50%; p<0.0001), and higher mean peak serum high-sensitivity troponin-T (8.25±14.7 vs 1.97±6.13 ug/L; p=0.006); in the context of higher median SS (18 vs 6.5; p=0.002) and target-lesion SS (tSS, 10 vs 0; p<0.001). Percutaneous coronary intervention (PCI; 75 vs 23%; p<0.0001) and target vessel revascularisation (11 vs 0%; p=0.005) were more frequent for STEMI. All-cause mortality was 39%, at 1.3±1.5years follow-up. Independent mortality predictors were: delayed CC (HR 4.08), serum lactate >7mmol/L (HR 3.47), and tSS (HR 1.05). CONCLUSIONS: Elevated serum lactate, tSS, and delayed CC, were predictive of longer-term mortality in SCA patients having CC. Late CC in patients without-STEMI suggest scope for improvement in real-world systems of care. Closer scrutiny of target lesion complexity may aid prognostication in SCA survivors.

Late clinical outcomes for SeQuent please paclitaxel-coated balloons in PCI of instent restenosis and de novo lesions: A single-center, real world registry.

OBJECTIVES: The aims of this study were to evaluate clinical outcomes following PCI using SeQuent Please paclitaxel-coated balloons (PCB) of ISR and denovo lesions (DNL), in all-comer patients at Liverpool Hospital, Sydney, Australia. BACKGROUND: There have been promising results for PCI using drug-coated balloons; however, long-term data for clinical outcomes are lacking. METHODS: Baseline patient demographics, PCI procedural details, and clinical outcomes were collected. The primary endpoint was the incidence of MACE, a composite of cardiac death, myocardial infarction (MI), and clinical-driven target lesion restenosis (TLR). The median follow-up for clinical events was 1.3 [0.6-1.9] years. RESULTS: A total of 188 lesions (n = 147 patients) were treated with PCB, comprising 118 (63%) ISR lesions and 70 (38%) DNL. Patient mean age was 67 ± 11years, 79% were male, and 54% had type 2 diabetes mellitus (DM). MACE was recorded in 17 patients (12%), with cardiac death confirmed in 1 patient (0.7%). MACE was significantly lower for DNL than ISR (1% vs. 15%, P = 0.03), and PCB had favourable TLR for DNL. Cox regression demonstrated that DM (HR 7.17, 0.92-55.6, P = 0.05) and prior CABG (HR 3.22, 1.17-8.83, P = 0.02) were independent predictors of MACE for ISR lesions. CONCLUSIONS: MACE rates were acceptable, with overall low incidence of cardiac death, MI, and TLR, for PCB treatment of ISR and DNL. Independent predictors of poor outcome in the ISR group were DM and prior CABG. The particularly low MACE for the DNL group supports direct PCB as a viable stent-sparing PCI strategy in challenging patients and lesion subsets. © 2016 Wiley Periodicals, Inc.

Adverse diastolic remodeling after reperfused ST-elevation myocardial infarction: An important prognostic indicator.

OBJECTIVES: We sought to determine the relationship of adverse diastolic remodeling (ie, worsening diastolic or persistent restrictive filling) with infarct scar characteristics, and to evaluate its prognostic value after ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Severe diastolic dysfunction (restrictive filling) has known prognostic value post STEMI. However, ongoing left ventricular (LV) remodeling post STEMI may alter diastolic function even if less severe. METHODS AND RESULTS: There were 218 prospectively recruited STEMI patients with serial echocardiograms (transthoracic echocardiography) and cardiac magnetic resonance imaging (CMR) performed, at a median of 4 days (early) and 55 days (follow-up). LV ejection fraction and infarct characteristics were assessed by CMR, and comprehensive diastolic function assessment including a diastolic grade was evaluated on transthoracic echocardiography. 'Adverse diastolic remodeling' occurred if diastolic function grade either worsened (≥1 grade) between early and follow-up imaging, or remained as persistent restrictive filling at follow-up. Follow-up infarct scar size (IS) predicted adverse diastolic remodeling (area under the curve 0.86) and persistent restrictive filling (area under the curve 0.89). The primary endpoint of major adverse cardiovascular events (MACE) occurred in 48 patients during follow-up (mean, 710±79 days). Kaplan-Meier analysis showed that adverse diastolic remodeling (n=50) and persistent restrictive filling alone (n=33) were significant predictors of MACE (both P<.001). Multivariate Cox analysis, when adjusted for TIMI risk score and CMR IS, microvascular obstruction, and LV ejection fraction, showed adverse diastolic remodeling (HR 3.79, P<.001) was an independent predictor of MACE, as was persistent restrictive filling alone (HR 2.61, P=.019). CONCLUSIONS: Larger IS is associated with adverse diastolic remodeling. Following STEMI, adverse diastolic remodeling is a powerful prognostic marker, and identifies a larger group of 'at-risk' patients, than does persistent restrictive filling alone.

High-sensitivity troponin T predicts infarct scar characteristics and adverse left ventricular function by cardiac magnetic resonance imaging early after reperfused acute myocardial infarction.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) is the current standard for evaluation of myocardial infarct scar size and characteristics. Because post-ST-segment elevation myocardial infarction (STEMI) troponin levels correlate with clinical outcomes, we sought to determine the sampling period for high-sensitivity troponin T (hs-TnT) that would best predict CMRI-measured infarct scar characteristics and left ventricular (LV) function. METHODS AND RESULTS: Among 201 patients with first presentation with STEMI who were prospectively recruited, we measured serial hs-TnT levels at admission, peak, 24 hours, 48 hours, and 72 hours after STEMI. Indexed LV volumes, LV ejection fraction (LVEF) and infarct scar characteristics (scar size, scar heterogeneity, myocardial salvage index, and microvascular obstruction) were evaluated by CMRI at a median of 4 days post-STEMI. Peak and serial hs-TnT levels correlated positively with early indexed LV volumes and infarct scar characteristics, and negatively correlated with myocardial salvage index and LVEF. Both 48- and 72-hour hs-TnT levels similarly predicted "large" total infarct scar size (odds ratios [ORs] 3.08 and 3.53, both P < .001), myocardial salvage index (ORs 1.68 and 2.30, both P < .001), and LVEF <40% (ORs 2.16 and 2.17, both P < .001) on univariate analyses. On multivariate analyses, 48- and 72-hour hs-TnT levels independently predicted large infarct scar size (ORs 2.05 and 2.31, both P < .001), reduced myocardial salvage index (OR 1.39 [P = .031] and OR 1.55 [P = .009]), and LVEF <40% (OR 1.47 [P = .018] and OR 1.43 [P = .026]). All measured hs-TnT levels had a modest association and similar capacity to predict microvascular obstruction. CONCLUSIONS: Levels of hs-TnT at 48 and 72 hours, measured during the "plateau phase" post-STEMI, predicted infarct scar size, poor myocardial salvage, and LVEF. These levels also correlated with scar heterogeneity and microvascular obstruction post-STEMI. Since ascertaining peak levels after STEMI is challenging in routine practice, based on the biphasic kinetics of hs-TnT, a measurement at 48 to 72 hours (during the plateau phase) provides a useful and simple method for early evaluation of LV function and infarct scar characteristics.

"Target-lesion" SYNTAX score (tSS) determines radiation dose in percutaneous coronary intervention.

OBJECTIVES: To investigate the correlation between "target-lesion" SYNTAX score (tSS) and radiation dose (RD) and examine the predictive value of tSS and other variables on RD from percutaneous coronary intervention (PCI). BACKGROUND: The complexity of PCI influences procedural RD. The novel tSS was utilized to quantify targeted-PCI complexity. METHODS: We studied 420 consecutive patients who had PCI in our hospital. Two investigators independently measured tSS using the SYNTAX scoring algorithm. Patients were divided into three BMI (kg/m(2) ) subgroups: <25 (normal), 25-30 (overweight), and >30 (obese); and tSS tertiles: <5.5 (simple), 5.5-9 (moderate), and >9 (complex). RESULTS: Obese patients were significantly younger and likely to have diabetes mellitus (DM). tSS positively correlated with RD for both genders, with median RD significantly higher in males (P < 0.0001). tSS correlated with RD in all three BMI subgroups (all P < 0.0001). Multivariate linear regression showed RD can be predicted by the formula: RD = -898 + 18 tSS + 49 BMI + 142 DM + 207 male. CONCLUSIONS: We report that tSS is a quantitative index of "target-lesion" PCI complexity, which is easy to measure with good reproducibility. tSS significantly and independently correlates with RD, although the strength of the association is less than for other predictors of RD (gender, diabetes, and BMI). tSS may be used to determine the RD from PCI and enhance patient risk-stratification when formulating a PCI strategy.

Chronic kidney disease is independently associated with alterations in left atrial function.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality; hence detection of early cardiovascular involvement in CKD is important to prevent future adverse cardiovascular events. Left atrial (LA) enlargement and dysfunction has been reported in end stage renal disease. However, there is a paucity of published data regarding the evaluation of LA function in CKD using noninvasive imaging parameters. In this study, we evaluated biplane LA volume as well as LA function (LA global systolic strain (GS) and strain rate [SR]) in stage 3 CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) to determine if LA function parameters are more significantly altered by the presence of CKD in addition to changes due to hypertension alone. METHODS: Thirty-three CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) with hypertension were compared to 33 normal controls and 34 hypertensive (HT) subjects with normal renal function; all participants underwent a detailed transthoracic echocardiogram. Indexed biplane LA volume (LAVI), LA segmental function, and GS and SR (systolic, early, and late diastole) derived from tissue Doppler imaging (TDI) were measured. Univariate predictors of LA strain were determined. Multiple logistic regression analysis was used to examine the effect of patient group (i.e. CKD) on GS and SR as well as LAVI. RESULTS: Left atrial volume indexed was significantly increased in both the HT and CKD with HT group compared to normal controls (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) vs. 23 ± 5 mL/m(2) , respectively, P = 0.02). However, LAVI was similar in the HT and CKD with HT group (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) ; P = NS). LA GS and SR were reduced in both the CKD with HT and HT group, compared to controls. However, a significantly lower LA GS was present in the CKD with HT group (Controls vs. HT vs. CKD with HT: 54.9 ± 14.5% vs. 34.5 ± 6.2% vs. 25.7 ± 9.3%, respectively; P = 0.001). To examine the effect of group, (i.e. presence of CKD) multiple logistic regression analysis was performed with univariate predictors including indexed left ventricular mass (LVMI), LV diastolic grade, LAVI, peak A-wave velocity, ß-blocker therapy, GS and SR; this demonstrated that CKD had an independent effect on LA GS and SR (systolic, early, and late diastole). GS demonstrated moderate correlation with systolic blood pressure (r = -0.5, P = 0.01), diastolic grade (r = -0.5, P = 0.01), E' velocity (r = 0.6, P = 0.0001), peak A velocity (r = -0.5, P = 0.004), and LAVI (r = -0.6, P = 0.002). CONCLUSIONS: Left atrial dysfunction is evident in stage 3 CKD with associated LA enlargement. This study demonstrates that LA GS and SR were reduced in the CKD group despite similar LAVI in the CKD with HT and HT group. Hence LA GS and SR may be a more sensitive noninvasive tool to detect cardiovascular involvement in CKD.

Bare-metal stenting of large coronary arteries in ST-elevation myocardial infarction is associated with low rates of target vessel revascularization.

BACKGROUND: During percutaneous coronary intervention (PCI) performed in the emergent setting of ST-segment elevation myocardial infarction (STEMI), uncertainty about patients' ability to comply with 12 months dual antiplatelet therapy after drug-eluting stenting is common, and thus, selective bare-metal stent (BMS) deployment could be an attractive strategy if this achieved low target vessel revascularization (TVR) rates in large infarct-related arteries (IRAs) (≥3.5 mm). METHODS AND RESULTS: To evaluate this hypothesis, among 1,282 patients with STEMI who underwent PCI during their initial hospitalization, we studied 1,059 patients (83%) who received BMS, of whom 512 (48%) had large IRAs ≥3.5 mm in diameter, 333 (31%) had IRAs 3 to 3.49 mm, and 214 (20%) had IRAs <3 mm. At 1 year, TVR rate in patients with BMS was 5.8% (2.2% with large BMS [≥3.5 mm], 9.2% with BMS 3-3.49 mm [intermediate], and 9.0% with BMS <3.0 mm [small], P < .001). The rates of death/reinfarction among patients with large BMS compared with intermediate BMS or small BMS were lower (6.6% vs 11.7% vs 9.0%, P = .042). Among patients who received BMS, the independent predictors of TVR at 1 year were the following: vessel diameter <3.5 mm (odds ratio [OR] 4.39 [95% CI 2.24-8.60], P < .001), proximal left anterior descending coronary artery lesions (OR 1.89 [95% CI 1.08-3.31], P = .027), hypertension (OR 2.01 [95% CI 1.17-3.438], P = .011), and prior PCI (OR 3.46 [95% CI 1.21-9.85], P = .02). The predictors of death/myocardial infarction at 1 year were pre-PCI cardiogenic shock (OR 8.16 [95% CI 4.16-16.01], P < .001), age ≥65 years (OR 2.63 [95% CI 1.58-4.39], P < .001), left anterior descending coronary artery culprit lesions (OR 1.95 [95% CI 1.19-3.21], P = .008), female gender (OR 1.93 [95% CI 1.12-3.32], P = .019), and American College of Cardiology/American Heart Association lesion classes B2 and C (OR 2.17 [95% CI 1.10-4.27], P = .026). CONCLUSION: Bare-metal stent deployment in STEMI patients with IRAs ≥3.5 mm was associated with low rates of TVR. Their use in this setting warrants comparison with second-generation drug-eluting stenting deployment in future randomized clinical trials.

Late clinical outcomes of unselected patients with diabetic mellitus and multi-vessel coronary artery disease.

BACKGROUND: The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-Vessel Disease (FREEDOM) clinical trial randomized only a proportion of screened patients with diabetes mellitus (DM) and multi-vessel disease (MVD). METHODS AND RESULTS: We determined late rates of death, non-fatal myocardial infarction (MI) and stroke in all 430 patients with DM who had MVD identified on angiographic screening for the FREEDOM Trial, which recruited from June 2006 -March 2010 at Liverpool Hospital, Sydney, Australia. Mortality at 6 years [median] was 23% among 192 FREEDOM-eligible patients and 26% among 238 FREEDOM-ineligible patients, of whom 139 [58%] had prior. CABG (mortality 31%). Overall, 196 (45%) had percutaneous coronary intervention (PCI), 127 (30%) underwent coronary artery bypass grafting (CABG) (who were 4 years younger; p = 0.003), and 107 (25%) had neither procedure of whom 80 were considered unsuitable for revascularization. Mortality was 26% post-PCI 16%, post-CABG and 33% among those who did not undergo revascularization (p = 0.01). On multivariable analyses, factors associated with late mortality were older age, hypertension and not undergoing CABG (all p < 0.05). Factors associated with late MI were presented with an acute coronary syndrome, whereas patients that underwent treatment with either PCI or CABG had less late MI (all p < 0.05). CONCLUSION: Among consecutive diabetic patients with MVD, at a median of 6-years CABG was associated with better survival and fewer non-fatal MI outcomes compared to PCI.

Real-world use of ticagrelor versus clopidogrel in percutaneous coronary intervention-treated ST-elevation myocardial infarction patients: A single-center registry study.

OBJECTIVES: The primary aim was to investigate the efficacy and safety of dual antiplatelet therapy (DAPT) using ticagrelor (T-DAPT) versus clopidogrel (C-DAPT) in a real-world ST-elevation myocardial infarction (STEMI) population. METHODS: We retrospectively analyzed 655 consecutive patients having primary percutaneous coronary intervention (PCI) for STEMI at Liverpool Hospital, Sydney, Australia (from January 2013 to April 2016). Medical and procedural therapies were at clinician discretion. Patient data were retrieved from hospital records and primary clinicians. RESULTS: T-DAPT (65%) was used more frequently, and in patients with lower mean CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) score, than C-DAPT (24.6 vs. 32.2; p < 0.0001, respectively). All-cause mortality was 9.0% at 2.7 years follow-up, with fewer deaths for T-DAPT (4.5% vs. 17.2%; p < 0.0001). T-DAPT incurred less BARC (Bleeding Academic Research Consortium) 3-5 major bleeding (5.0% vs. 12.4%; p < 0.0001). Multivariate regression showed that C-DAPT, GRACE (Global Registry of Acute Cardiac Events) score, and renal insufficiency were independently associated with mortality. Intra-aortic balloon pump (IABP) and GRACE score independently predicted BARC 3-5 bleeding. Early DAPT discontinuation (1.7%) and ticagrelor intolerance (7.6%) was rare. Switching DAPT regimen was infrequent (21.7%) and mostly attributed to clinician preference (73.2%). Independent determinants of C-DAPT selection were older age, diabetes, prior PCI, IABP, and higher CRUSADE score. CONCLUSION: Ticagrelor was preferred in low bleeding risk patients, which may have contributed to less BARC 3-5 bleeding and lower mortality for T-DAPT. Thus, bleeding mitigation is a clinical priority when selecting DAPT for PCI-treated STEMI patients. Continuation of initial DAPT regimen was typical, but early switching from clopidogrel to ticagrelor shows willingness to optimize DAPT. Patients with very low CRUSADE scores (<21.5) may be appropriate for switching to a potent P2Y12 inhibitor.

Strain Imaging Detects Dose-Dependent Segmental Cardiac Dysfunction in the Acute Phase After Breast Irradiation.

PURPOSE: We examined the utility of echocardiographic 2-dimensional speckle tracking strain imaging (SI) for the evaluation of segmental myocardial dysfunction before and after radiation therapy (RT) and the relationship to dose exposure. METHODS AND MATERIALS: We prospectively recruited 40 women with left-sided breast cancer, undergoing only adjuvant RT to the left chest. Comparisons of traditional echocardiographic parameters and SI parameters at baseline and 6 weeks after RT were analyzed. Regional strain and strain rate (SR) parameters were obtained from all 18 left ventricular segments. The correlation of change in strain parameters with segmental radiation dose was examined. RESULTS: We observed a significant reduction in global and segmental systolic strain parameters at 6 weeks after RT compared with baseline, with the largest decrement in the apical segments; this corresponded with the segments receiving the highest radiation dose exposure (apical peak systolic strain of -21.21% ± 3.49% before RT vs -18.69% ± 3.34% after RT, percentage change of 11.88%, P=.002; apical peak systolic SR of -1.17 ± 0.24 s-1 before RT vs -1.04 ± 0.19 s-1 after RT, percentage change of 11.11%, P=.008). There was a modest correlation between the apical segment systolic strain reduction and radiation dose exposure (apical segment Δ change and apical radiation dose, r=0.345, P=.031; apical segment percentage change and apical radiation dose, r=0.346, P=.031). A significant reduction in early diastolic SR was observed in the apical segments after treatment compared with baseline (apical early diastolic SR, 1.54 ± 0.45 s-1 before RT vs 1.35 ± 0.33 after RT s-1; percentage change, 12.34%; P=.034). CONCLUSIONS: Two-dimensional SI detected dose-related regional myocardial dysfunction in the acute phase after RT in chemotherapy-naive left-sided breast cancer patients. Although the long-term effects remain unknown, this imaging modality may have a potential role in the evaluation of irradiation-related cardiotoxicity.

The kynurenine pathway and parasitic infections that affect CNS function.

The kynurenine pathway of tryptophan metabolism has been implicated in brain function, immunoregulation, anti-microbial mechanisms and pregnancy. Some of these actions are due to depletion of tryptophan and others to the formation of biologically active metabolites. This review focuses on the roles of the kynurenine pathway in host responses during two parasitic diseases of major health and economic importance, malaria and toxoplasmosis, with an emphasis on their impacts on CNS function. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.

Electrocardiographic measurement of infarct size compared to cardiac MRI in reperfused first time ST-segment elevation myocardial infarction.

BACKGROUND: Myocardial infarct size (IS) following ST-segment elevation myocardial infarction (STEMI) is an important prognostic factor. We assessed the Selvester 32-point QRS score from the 12-lead ECG for measurement of IS in STEMI patients receiving reperfusion therapy compared to cardiac magnetic resonance imaging (CMRI). Furthermore we sought to explore the impact of microvascular obstruction (MVO) on the scoring system, and determine factors contributing to discrepancies between CMRI IS and Selvester score. METHODS: We examined 70 patients (55 men, 15 women), mean age 57±10years with a first time STEMI (46 anterior, 24 non-anterior). QRS scores were calculated early and at follow-up (mean 2±1 and 59±14days post-STEMI). Myocardial core scar size (5SD) was measured at 5.3±3.3 and 57.8±13.5days post-infarction by CMRI. MVO was determined on initial MRI. Logistic regression analysis was performed to determine factors contributing to discordant scores, defined as a difference between CMRI and Selvester IS of >6% myocardium. RESULTS: QRS scoring of anterior infarcts correlated with CMRI IS both early (r=0.734, p<0.0001) and at follow-up (r=0.716, p<0.0001); however no correlation was seen among non-anterior infarcts. QRS scoring overestimated IS at all time points. There was better agreement between ECG and CMRI measured IS in patients without MVO at both time points. Anterior infarction was inversely predictive of discordant IS estimation acutely, and larger Selvester scores were predictive of inaccurate scoring at both time periods. CONCLUSIONS: Selvester QRS score correlates well with CMRI IS for anterior infarcts. MVO did not independently affect the score.

Prognostic value of high sensitivity troponin T after ST-segment elevation myocardial infarction in the era of cardiac magnetic resonance imaging.

AIMS: To determine if high sensitivity troponin T (hs-TnT) measurements performed during the 'plateau phase' of troponin release (≥48 h) following ST-segment elevation myocardial infarction (STEMI) can predict major adverse cardiovascular endpoints (MACE), and to evaluate its prognostic value compared with cardiac magnetic resonance imaging (CMRI) parameters. METHODS AND RESULTS: We prospectively recruited 201 first presentation STEMI patients. Serial hs-TnT levels were measured at admission, peak (highest), 24, 48 and 72 h. CMRI and transthoracic echocardiography were performed (4 days median) post-STEMI, evaluating infarct scar characteristics and left ventricular ejection fraction (LVEF). Associations were determined between hs-TnT levels and CMRI parameters early after STEMI with MACE (comprising mortality, re-infarction, new or worsening of heart failure, cerebrovascular accident, and sustained ventricular arrhythmias) at medium-term follow-up. After 602 days (median), 33 (17%) patients had MACE. Upper tertile hs-TnT levels at 48 and 72 h were associated with MACE (Kaplan-Meier P = 0.002 and P = 0.012, respectively). Multivariate Cox analyses, incorporating diabetes, CMRI scar size, LVEF and hs-TnT levels (applied at a single hs-TnT time point) showed that 48 and 72 h hs-TnT levels were independent predictors for MACE (HR = 1.20, P = 0.002, and HR = 1.21, P = 0.035 respectively). CONCLUSION: Measurement of hs-TnT in the plateau phase after STEMI is an inexpensive method of prognostic risk assessment.

Subclinical cardiac dysfunction detected by strain imaging during breast irradiation with persistent changes 6 weeks after treatment.

PURPOSE: To evaluate 2-dimensional strain imaging (SI) for the detection of subclinical myocardial dysfunction during and after radiation therapy (RT). METHODS AND MATERIALS: Forty women with left-sided breast cancer, undergoing only adjuvant RT to the left chest, were prospectively recruited. Standard echocardiography and SI were performed at baseline, during RT, and 6 weeks after RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal, circumferential, and radial planes. Correlation of change in global longitudinal strain (GLS % and Δ change) and the volume of heart receiving 30 Gy (V30) and mean heart dose (MHD) were examined. RESULTS: Left ventricular ejection fraction was unchanged; however, longitudinal systolic S and Sr and radial S were significantly reduced during RT and remained reduced at 6 weeks after treatment [longitudinal S (%) -20.44 ± 2.66 baseline vs -18.60 ± 2.70* during RT vs -18.34 ± 2.86* at 6 weeks after RT; longitudinal Sr (s(-1)) -1.19 ± 0.21 vs -1.06 ± 0.18* vs -1.06 ± 0.16*; radial S (%) 56.66 ± 18.57 vs 46.93 ± 14.56* vs 49.22 ± 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6 weeks after RT [longitudinal E Sr (s(-1)) 1.47 ± 0.32 vs 1.29 ± 0.27*; longitudinal A Sr (s(-1)) 1.19 ± 0.31 vs 1.03 ± 0.24*; *P<.05 vs baseline], whereas circumferential strain was preserved throughout. A modest correlation between S and Sr and V30 and MHD was observed (GLS Δ change and V30 ρ = 0.314, P=.05; GLS % change and V30 ρ = 0.288, P=.076; GLS Δ change and MHD ρ = 0.348, P=.03; GLS % change and MHD ρ = 0.346, P=.031). CONCLUSIONS: Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT, with changes persisting 6 weeks after treatment, though long-term effects remain unknown. Additionally, a modest correlation between strain reduction and radiation dose was observed.

Left atrial volume and adverse cardiovascular outcomes in unselected patients with and without CKD.

BACKGROUND AND OBJECTIVES: Patients with CKD have increased cardiovascular morbidity and mortality. This study investigated the prognostic value of common clinical echocardiographic parameters. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: There were 289 unselected consecutive patients who had a transthoracic echocardiogram between January and June 2003. Patients with stage 3 or 4 CKD (n=49) were compared with those with eGFR≥60 ml/min per 1.73 m(2), n=240). Left ventricular volume, ejection fraction and mass, left atrial volume, and function parameters were measured. The primary endpoint, determined a priori, was a composite of cardiac death, myocardial infarction, and congestive cardiac failure. RESULTS: Patients were followed for a median 5.6 years. The incidence of the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001), who were older and had a higher prevalence of hypertension and ischemic heart disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m(2) had significantly lower event-free survival than patients with normal (<28 ml/m(2)) or mildly dilated LAVI (28-32 ml/m(2)) (P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31; P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently associated with LAVI>32 ml/m(2). Multivariate Cox regression analysis demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04), hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR, 1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary endpoint. CONCLUSIONS: Patients with CKD were at higher risk for cardiovascular events. LAVI was significantly larger in the CKD group and was a predictor of adverse cardiac events.

Risk factor modification in diabetic patients following angiographic identification of multi-vessel disease.

There is little information on whether identification of multi-vessel disease (MVD) in patients with diabetic mellitus (DM) affects risk factor management. From 1125 consecutively screened patients between June 2006 and March 2010, we examined 227 diabetic patients with MVD on coronary angiography. Diabetic control and cholesterol levels were assessed by glycated haemoglobin (HbA1c) and total cholesterol (TC) respectively which were evaluated at baseline and at 1-year follow-up. Patients were grouped by age into <55(n=33), 55-65(n=75), 66-75(n=75) and >75(n=44). Target levels were defined as HbA1c<7% and TC<4.0 mmol/L. Patients <55 years had the highest HbA1c at 9.1[7.6-11.2]% with the lowest proportion of patients (n=3; 11.1%) within target at baseline, while 66-75 years had the best HbA1c at 7.1[6.4-7.8]% with the highest proportion (n=28, 45.2%) reaching target (p<0.0001). At 1-year, the poorest HbA1c control was again observed in the age <55 with fewer patients achieving target compared to the 66-75 age group (HbA1c: 8.5% vs 6.9%; % of patients at target: 20.7% vs 54.5%; p<0.0001). Furthermore, the group <55 years demonstrated the worst TC control at 1-year with a significant increase compared to the baseline TC (p=0.01). Patients with a lower body mass index (BMI) were likely to have an improvement in HbA1c and reach target (p=0.01). Paradoxically, patients who were current smokers demonstrated a beneficial effect on optimal TC control (29.2% vs 15.4%, p=0.027). In younger diabetic patients, risk factor modification at 1-year was poor despite identification of MVD. Developing an effective education and monitoring programme to improve glycaemic control in this high risk group should be a priority.

Outcomes of coronary revascularization (percutaneous or bypass) in patients with diabetes mellitus and multivessel coronary disease.

Clinical outcomes in patients with diabetes mellitus and multivessel disease (MVD) undergoing coronary revascularization have not been extensively evaluated, we sought to examine outcomes in a diabetic cohort of 195 consecutive patients with MVD characterized by SYNTAX scores (SSs) undergoing nonrandomized revascularization, 102 (52%) by percutaneous intervention (PCI) and 93 (48%) by coronary artery bypass grafting (CABG) at Liverpool Hospital (Sydney, Australia) from June 2006 to March 2010. Clinical outcomes were assessed at a median term of 14 months. The overall median SS was 44, with significantly higher SSs in CABG- than PCI-treated patients (48 vs 39, p <0.0001). There was a similar incidence of all-cause death, nonfatal myocardial infarction and stroke in PCI- and CABG-treated patients (6.1% vs 8.3%, p = 0.383; 12% vs 4.9%, p = 0.152; 3.1% vs 3.5%, p = 0.680 respectively). However, the rates of target vessel revascularization and major adverse coronary and cerebral event were significantly higher in PCI-treated patients than in those undergoing CABG (20% vs 1.2%, p <0.0001; 29% vs 15%, p = 0.034). Despite a much higher SS, patients who underwent PCI achieved comparable outcomes at 1 year to those with diabetes mellitus and a SS ≥ 33 as reported in the SYNTAX trial. In conclusion, in this single-center nonrandomized observational study, coronary revascularization by PCI is associated with increased major adverse coronary and cerebral events at 1-year follow-up, predominantly driven by a high rate of target vessel revascularization. Thus, CABG should remain the revascularization procedure of choice for diabetic patients with MVD and high SSs.

Reduced activity of the epithelial sodium channel in malaria-induced pulmonary oedema in mice.

Lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ARDS). Infecting C57BL/6 mice with Plasmodium berghei K173 strain (PbK) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (iRBCs), and leukocyte infiltration into the lungs. This new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investigation of mechanisms leading to the lung disease. The activity of the amiloride-sensitive epithelial sodium channel (ENaC) in alveolar epithelial cells is decreased by several respiratory tract pathogens and this is suggested to contribute to pulmonary oedema. We show that PbK, a pathogen that remains in the circulation, also decreased the activity and expression of ENaC, suggesting that infectious agents can have indirect effects on ENaC activity in lung epithelial cells. The reduced ENaC activity may contribute to the pulmonary oedema induced by PbK malaria.

Early cytokine production is associated with protection from murine cerebral malaria.

Cerebral malaria (CM) is an infrequent but serious complication of Plasmodium falciparum infection in humans. Animal and human studies suggest that the pathogenesis of CM is immune mediated, but the precise mechanisms leading to cerebral pathology are unclear. In mice, infection with Plasmodium berghei ANKA results in CM on day 6 postinoculation (p.i.), while infection with the closely related strain P. berghei K173 does not result in CM. Infection with P. berghei K173 was associated with increased plasma gamma interferon (IFN-gamma) at 24 h p.i. and with increased splenic and hepatic mRNAs for a range of cytokines (IFN-gamma, interleukin-10 [IL-10], and IL-12) as well as the immunoregulatory enzyme indoleamine 2,3-dioxygenase. In contrast, P. berghei ANKA infection was associated with an absence of cytokine production at 24 h p.i. but a surge of IFN-gamma production at 3 to 4 days p.i. When mice were coinfected with both ANKA and K173, they produced an early cytokine response, including a burst of IFN-gamma at 24 h p.i., in a manner similar to animals infected with P. berghei K173 alone. These coinfected mice failed to develop CM. In addition, in a low-dose P. berghei K173 infection model, protection from CM was associated with early production of IFN-gamma. Early IFN-gamma production was present in NK-cell-depleted, gammadelta-cell-depleted, and Jalpha281(-/-) (NKT-cell-deficient) mice but absent from beta2-microglobulin mice that had been infected with P. berghei K173. Taken together, the results suggest that the absence of a regulatory pathway involving IFN-gamma and CD8(+) T cells in P. berghei ANKA infection allows the development of cerebral immunopathology.