Two-Hour Post-Load Plasma Glucose, a Biomarker to Improve the GRACE Score in Patients without Known Diabetes.

OBJECTIVE: To assess improvement in predictive performance of Global Registry of Acute Coronary Events risk score (GRS) by addition of a glucose matrix. METHODS: 1,056 acute coronary syndrome (ACS) survivors without known diabetes had pre-discharge fasting (FPG) and 2-h post-load plasma glucose (2h-PG) measured. GRS was calculated. Major adverse cardiac events (MACE; death and non-fatal myocardial infarction) were recorded during follow-up. Cox proportional hazard regression predicted event-free survival. Likelihood ratio test, Akaike's information criteria, continuous net reclassification index (NRI>0), and integrated discrimination improvement (IDI) were used to test the additional prognostic value of glycaemic indices over GRS. RESULTS: During a median follow-up of 36.5 months, 211 MACEs (20.0%), 96 deaths (9.1%), and 115 non-fatal re-infarctions (10.9%), occurred. 2h-PG, but not FPG, independently predicted MACE-free survival at all time points (HR 1.08, 95% CI 1.03-1.13, p = 0.002, at 3 years). Risk of MACE increased by 8-11% with every 1 mmol/L rise in 2h-PG. 2h-PG significantly improved the prognostic models containing GRS. Models containing GRS and 2h-PG yielded lowest corrected Akaike's information criteria compared to that with only GRS. 2h-PG, but not FPG, improved NRI>0 (NRI>0 0.169, p = 0.028 at 3 years) and IDI (IDI of 0.66%, p = 0.018 at 3 years) significantly at all time points during the follow-up. CONCLUSIONS: 2h-PG, but not FPG, improves performance of GRS-containing models in predicting post-ACS prognosis in the short to medium term.

Adjustment of the GRACE score by 2-hour post-load glucose improves prediction of long-term major adverse cardiac events in acute coronary syndrome in patients without known diabetes.

Aims: Global Registry of Acute Coronary Events (GRACE) risk score (GRS), a powerful predictor of prognosis after acute coronary event (ACE), does not include a glucometabolic measure. We investigate whether 2 h post-load plasma glucose (2h-PG) could improve GRS based prognostic models in ACE patients without known diabetes mellitus (DM). Methods and results: A retrospective cohort study of 1056 ACE survivors without known DM who had fasting plasma glucose (FPG) and 2h-PG measured pre-discharge. Death and non-fatal myocardial infarction were recorded as major adverse cardiac events (MACE) during follow-up. GRS for discharge to 6 months was calculated. Cox proportional-hazards regression was used to identify predictors of event free survival. The predictive value of 2h-PG alone and combined with GRS was estimated using likelihood ratio test, Akaike's information criteria, continuous net reclassification improvement (NRI>0), and integrated discrimination improvement (IDI). During 40.8 months follow-up 235 MACEs (22.3%) occurred, more frequently in the upper 2h-PG quartiles. Two-hour PG, but not FPG, adjusted for GRS independently predicted MACE (hazard ratio 1.091, 95% confidence interval 1.043-1.142; P = 0.0002). likelihood ratio test showed that 2h-PG significantly improved the prognostic models including GRS (χ2 = 20.56, 1 df; P = 0.000). Models containing GRS and 2h-PG yielded lowest corrected Akaike's information criteria, compared to that with only GRS. 2h-PG, when added to GRS, improved net reclassification significantly (NRIe>0 6.4%, NRIne>0 24%, NRI>0 0.176; P = 0.017 at final follow-up). Two-hour PG, improved integrated discrimination of models containing GRS (IDI of 0.87%, P = 0.008 at final follow-up). Conclusion: Two-hour PG, but not FPG, is an independent predictor of adverse outcome after ACE even after adjusting for the GRS. Two-hour PG, but not FPG, improves the predictability of prognostic models containing GRS.

Changes in Cardiac Electrical Biomarker in Response to Coronary Arterial Occlusion: An Experimental Observation.

Cardiac electrical biomarker (CEB), an indicator of ischaemia-induced change in myocyte polarity, has been proposed for diagnosis of acute coronary syndrome. However, effect of coronary occlusion on CEB has not been demonstrated. CEB was acquired before (CEB0), during maximal adenosine hyperaemia (CEBhyp), balloon inflations (CEBmax) and 1 (CEB1h), 2 (CEB2h) and 3 (CEB3h) h after percutaneous coronary intervention along with pre- and post-procedural troponin-I. CEB of subjects with non-cardiac chest pain without risk factors was used as controls (CEBc). "Late recovery" (LR) of CEB was defined as CEB3h > median-CEB0. CEB was recorded in 75 patients undergoing stenting (group 1) including 8 with FFR < 0.8 (group 1a), 25 with FFR ≥ 0.8 (group 2) and 49 controls. In group 1, CEB0 (median, IQR) was higher than CEBc (48.0; 29.5-88.3 vs 30.0; 17.0-44.0; p < 0.001). CEBmax (185; 105.0-331.0) was higher than CEB0 (p < 0.0001). CEB1h (78.0; 31.5-143.8; p < 0.0001) and CEB2h (63.0; 31.5-114.3; p = 0.039) were higher than CEB0 while CEB3h (54.0; 24.3-94.8, p = 0.152) was similar. LR occurred in 50.7% patients. CEBmax predicted LR (OR 1.01, 95% CI 1.00-1.01, p < 0.001) (AUC 0.759, p < 0.001). CEB0 in group 1a and group 2 were similar (p = 0.524). CEBhyp was higher than CEB0 in group 1a (126.0, 109.5-266.0 vs 47.5, 20.5-73.5; p = 0.016) and group 2 (44.0, 27.8-104.8 vs 39.0, 24.0-90.3; p = 0.014). CEBhyp was higher in group 1a than 2 (p = 0.039). CEBhyp (AUC 0.75, p = 0.017) accurately predicted FFR < 0.8. Coronary arterial occlusion increases CEB that retains a "memory" of the ischaemic event. CEBhyp was higher only when FFR was ischaemic and accurately identified FFR < 0.8.

Double jeopardy.

Torsades de pointes ("twisting of points") (TdP) is a broad complex tachyarrhythmia which was first described in 1966 by Francois Dessertenne and usually results from prolongation of the QT interval.(1) A wide variety of drugs have been shown to prolong the QT interval in susceptible individuals.(2) We present the case of a former intravenous heroin user presenting with several episodes of TdP which were caused by QT prolongation due to methadone treatment and exacerbated by hepatitis B/C infection. Despite aggressive medical treatment and withdrawal of methadone, he had recurrent episodes of TdP which required continuous temporary cardiac pacing for six days. He was found to have moderate LV dysfunction on his echocardiogram and unobstructed coronary arteries on coronary angiography. He underwent implantation of a defibrillator due to concerns about further episodes of ventricular arrhythmias which could recur even in the absence of further methadone use.

Arterial vascular access complication in osteogenesis imperfecta.

We present a case of the catastrophic bleeding from the femoral access site after an uncomplicated puncture in a patient with Type 1 osteogenesis imperfecta (OI) undergoing coronary angiogram via the femoral route. This had to be treated with a covered stent at the puncture site. This is an extremely rare complication in OI. The potential pathological mechanisms of this complication are discussed. An interventionist will rarely encounter such a patient in the catheterisation laboratory but would do well to be aware of this potential complication.

Aortic regurgitation and coronary microfistulae: double jeopardy causing myonecrosis.

We describe a 3-case series of patients with a rare combination of mild-to-moderate aortic regurgitation and coronary microfistulae but nonobstructed epicardial coronary arteries who presented with symptoms of unstable angina and had confirmed myonecrosis. A plausible pathophysiological mechanism for this phenomenon and its clinical implication are discussed.

Postload glucose spike but not fasting glucose determines prognosis after myocardial infarction in patients without known or newly diagnosed diabetes.

BACKGROUND: The effect of postload glucose spikes (PGS), the difference between 2 hour post-load plasma glucose (2hPLPG) and fasting plasma glucose (FPG), on post-myocardial infarction (post-MI) prognosis in nondiabetic patients is unexplored. METHODS: This is a retrospective cohort analysis of 847 nondiabetic post-MI survivors who underwent a predischarge oral glucose tolerance test (median PGS: 2.4 mmol/L). Patients were divided into the unmatched groups 1 and 2 (PGS ≤ and > 2.4 mmol/L) and the propensity score-matched groups 1M and 2M (355 pairs assembled from the overall cohort), and these groups were compared. Major adverse cardiac events (MACE: death and nonfatal reinfarction) were recorded during follow-up (median: 3.4 years). Event-free survival was compared by the Kaplan-Meier method. Multivariate Cox proportional hazards regression determined the predictors of MACE. C-statistics (change in area under the curve, δAUC), continuous net reclassification improvement (NRI>0 ), and integrated discrimination improvement (IDI) were used to compare models. RESULTS: The number of MACE was higher in groups 2 (27.3% vs 14.2%, P < .001) and 2M (24.5% vs 15.5%, P < .001). Event-free survival was worse in groups 2 (hazard ratio [HR] 2.01; 95% CI, 1.49-2.71; P < .001) and 2M (HR 1.63; 95% CI, 1.17-2.27; P = .004). PGS independently predicted MACE-free survival in the whole (HR 1.16; 95% CI, 1.06-1.26; P = .002) and matched cohort (HR 1.12; 95% CI, 1.02-1.24; P = .021). PGS, but not FPG or 2hPPG, improved the predictive performance of the base model (δAUC 0.013, P = .046), with greater improvement seen when PGS was added and compared to 2hPPG (δAUC 0.005, P = .034; NRI>0 0.2107, P = .013; IDI 0.0042, P = .046). CONCLUSION: PGS is a better predictor of post-MI prognosis than 2hPPG in nondiabetic patients.

Newly diagnosed abnormal glucose tolerance determines post-MI prognosis in patients with hospital related hyperglycaemia but without known diabetes.

AIMS: Investigate if abnormal glucose tolerance (AGT) affects post-myocardial infarction (MI) prognosis in patients with hospital-related hyperglycaemia (HRH) but without known diabetes mellitus (KDM). METHODS: Post-MI survivors without KDM underwent pre-discharge oral glucose tolerance test. Cardiovascular death and non-fatal re-infarction (MACE) were recorded. We compare the ability of admission (APG), fasting (FPG) and 2 h post-load (2 h-PG) plasma glucose to predict MACE in patients with (HRH) and without HRH (NoHRH). RESULTS: 50.2% and 73% of NoHRH and HRH had AGT respectively. MACE occurred in 19.5% and 18.1% in HRH and NoHRH groups. MACE-free survival was lower in patient with AGT in both groups (NoHRH: HR 1.82, 95% CI 1.19-2.78, p = 0.005; HRH: HR 2.48, 95% CI 1.24-4.96, p = 0.010). AGT predicted MACE-free survival (NoHRH: HR 1.60, 95% CI 1.02-2.51, p = 0.042; HRH: HR 3.09, 95% CI 1.07-8.94, p = 0.037). 2 h-PG, but not FPG or APG, independently predicted MACE free survival (NoHRH: HR 1.17, 95% CI 1.07-1.27, p ≤0.001 and HRH: HR 1.18, 95% CI 1.03-1.37, p = 0.020). Addition of AGT and 2 h-PG, not FPG or APG, improved net reclassification of events in both groups. CONCLUSION: Post-MI prognosis is worse with AGT irrespective of presence of HRH. 2 h-PG, predicts prognosis in HRH and NoHRH groups.

Pre-diabetes mellitus newly diagnosed after myocardial infarction adversely affects prognosis in patients without known diabetes.

BACKGROUND: Effect of pre-diabetes mellitus on post-myocardial infarction prognosis is unclear. METHODS: Retrospective cohort analysis of 1056 myocardial infarction survivors with fasting plasma glucose and 2-h post-load plasma glucose measured. Major adverse cardiovascular events included death, non-fatal reinfarction and ischaemic stroke. Cox proportional hazard regression identified predictors of event-free survival. Continuous net reclassification improvement and integrated discrimination improvement determined the added predictive value of glycaemic indices. RESULTS: Major adverse cardiovascular events occurred in 25.1% and 16.4% patients with and without pre-diabetes mellitus (hazard ratio with pre-diabetes mellitus: 1.56; 95% confidence interval: 1.17-2.08; p = 0.003) in the whole cohort and in 24.1% and 17.2% patients (hazard ratio with pre-diabetes mellitus, 1.43; 95% confidence interval: 1.03-1.98; p = 0.033) in the matched cohort, respectively. Pre-diabetes mellitus predicted major adverse cardiovascular events-free survival in whole (hazard ratio: 1.39; 95% confidence interval: 1.03-1.89; p = 0.033) and matched cohorts (hazard ratio: 1.42; 95% confidence interval: 1.01-1.99; p = 0.043). The 2-h post-load plasma glucose, but not fasting plasma glucose, predicted major adverse cardiovascular events-free survival in the whole (hazard ratio: 1.16; 95% confidence interval: 1.07-1.26; p < 0.0001) and matched cohorts (hazard ratio: 1.20; 95% confidence interval: 1.09-1.31; p < 0.0001). Adding 2-h post-load plasma glucose to models containing fasting plasma glucose, significantly improved net reclassification improvement and integrated discrimination improvement for both cohorts, but not vice versa. CONCLUSION: Pre-diabetes mellitus predicts major adverse cardiovascular events after myocardial infarction. The 2-h post-load plasma glucose predicts prognosis better than fasting plasma glucose in these patients.

Prospective evaluation of an ultrathin strut biodegradable polymer-coated sirolimus-eluting stent: 12 months' results from the S-FLEX UK registry.

OBJECTIVE: To prospectively evaluate safety and efficacy of the ultrathin strut biodegradable polymer-coated Supraflex sirolimus-eluting stent (S-SES) in 'real world' patient population requiring percutaneous coronary intervention (PCI). METHODS: National, prospective, multicentre, single-arm, all-comers, observational registry of 469 patients treated with S-SES from July 2015 and November 2016 in 11 centres in UK. Primary endpoint was target lesion failure (TLF) at 12 months (cardiac death, target vessel myocardial infarction (MI) or clinically driven target lesion revascularisation (TLR)). Secondary endpoints included safety and performance outcomes at 12 months-overall stent thrombosis (ST), all-cause mortality, any MI, target vessel failure (TVF) and major adverse cardiac events (MACE-composite of cardiac death, MI, emergent or repeat revascularisation). RESULTS: At 12 months, the primary endpoint occurred in 11 (2.4%) of 466 patients, consisting of 4 (0.9%) cardiac deaths, 3 (0.6%) target vessel MI and 7 (1.5%) TLR. Secondary endpoints findings included all-cause mortality in 6 (1.3%), TVF of 14 (3%), no definite ST, 1 (0.2%) probable ST and 3 (0.6%) possible ST. Overall MACE was observed in 18 (3.9%). CONCLUSIONS: The S-FLEX UK registry showed that the S-SES is safe with a low incidence of TLF in routine clinical practise in patients with coronary artery disease being treated by PCI.

The effect of pharmacological stress on intraventricular dyssynchrony in left ventricular systolic dysfunction.

BACKGROUND: Cardiac resynchronisation therapy (CRT) improves symptoms and exercise capacity in many patients with heart failure (HF) who have left ventricular systolic dysfunction (LVSD) and markers of dyssynchrony. LV dyssynchrony is conventionally measured at rest but the symptoms of heart failure occur predominantly on exercise. Induction or exacerbation of dyssynchrony during stress might identify additional patients who could benefit from CRT. METHODS AND RESULTS: Seventy-seven patients (47 with QRSd<120 ms and 30 with QRSd>120 ms) with heart failure due to left ventricular systolic dysfunction and 22 normal subjects underwent dobutamine stress echocardiography using colour tissue Doppler imaging. Left intraventricular dyssynchrony was measured as the standard deviation of the time to peak velocity from the onset of the QRS (Ts-SD) and the difference between the maximum and minimum time to peak velocity (Tscor-diff) in the 12 non-apical segments at rest and during peak stress. Timings were corrected for heart rate. The mean values of these indices increased with stress in both groups of patients but not in control subjects (p<0.001). The prevalence of conventionally-defined dyssynchrony also increased with stress. CONCLUSION: In patients with heart failure, the severity and the prevalence of intraventricular dyssynchrony increase with stress. Whether stress-induced dyssynchrony will identify patients who might benefit from CRT awaits further research.

Two-hour post-challenge glucose is a better predictor of adverse outcome after myocardial infarction than fasting or admission glucose in patients without diabetes.

AIMS: We evaluate prevalence of new abnormal glucose tolerance (AGT) in post-MI survivors without known diabetes (DM) if guidelines are followed and compare the ability of admission (APG), fasting (FPG) and 2-h post-load plasma glucose (2h-PG) to predict prognosis. METHODS: A total of 674 patients were followed up for 4 years for incidence of major adverse cardiovascular events (MACE) of cardiovascular death, non-fatal re-infarction or non-haemorrhagic stroke. Ability of models including APG, FPG and 2h-PG to predict MACE was compared. RESULTS: Of the total, 93-96% of impaired glucose tolerance and 64-75% of DM would be missed with current guidelines. MACE was higher in the upper quartiles of 2h-PG. When 2h-PG and FPG were included simultaneously in models, only 2h-PG predicted MACE (HR 1.12, CI 1.04-1.20, p = 0.0012), all cause mortality (HR 1.17, CI 1.05-1.30, p = 0.0039), cardiovascular mortality (HR 1.17, CI 1.02-1.33, p = 0.0205) and non-fatal MI (HR 1.10, CI 1.01-1.20, p = 0.0291). Adding 2h-PG significantly improved ability of models including FPG (χ2 = 16.01, df = 1, p = 0.0001) or FPG and APG (χ2 = 17.36, df = 1, p = 0.000) to predict MACE. Model including 2h-PG only had the lowest Akaike's information criteria and highest Akaike weights suggesting that this was the best in predicting events. Adding 2h-PG to models including FPG or APG with other co-variates yielded continuous net reclassification improvement (NRI) of 0.22 (p = 0.026) and 0.27 (p = 0.005) and categorical NRI of 0.09 (p = 0.032) and 0.12 (p = 0.014), respectively. Adding 2 h-PG to models including only FPG, only APG and both yielded integrated discrimination improvement of 0.012 (p = 0.015), 0.022 (p = 0.001) and 0.013 (p = 0.014), respectively. CONCLUSIONS: AGT is under-diagnosed on current guidelines. 2h-PG is a better predictor of prognosis compared to APG and FPG.

Correction to: Two-hour post-challenge glucose is a better predictor of adverse outcome after myocardial infarction than fasting or admission glucose in patients without diabetes.

Unfortunately, name of co-author "Thozhukat" was misspelled in the original publication and the same is corrected here. The original article has been corrected.

Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study.

OBJECTIVE: To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). RESEARCH DESIGN AND METHODS: Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. RESULTS: Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06-2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42-3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. CONCLUSION: Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention.

Are hematinic deficiencies the cause of anemia in chronic heart failure?

BACKGROUND: Anemia in chronic heart failure (CHF) is common, varying in prevalence between 14.4% and 55%, and is more frequent in patients with more severe heart failure. Patients with CHF who have anemia have a poorer quality of life, higher hospital admission rates, and reduced exercise tolerance. We explored the relation between hematinic levels and hemoglobin (Hb) levels and exercise tolerance in a group of patients with CHF. METHODS: We analyzed data from 173 patients with left ventricular systolic dysfunction (LVSD), 123 patients with symptoms of heart failure, but preserved left ventricular (LV) systolic function ("diastolic dysfunction"), and 58 control subjects of similar age. Each underwent echocardiography, a 6-minute walk test, and blood tests for renal function and Hb and hematinic levels (vitamin B12, iron, and folate). We classified patients as having no anemia (Hb level >12.5 g/dL), mild anemia (Hb level from 11.5-12.5 g/dL), or moderate anemia (Hb level <11.5 g/dL). RESULTS: Of patients with LVSD, 16% had moderate anemia and 19% had mild anemia. Of patients with preserved LV function, 16% had moderate anemia and 17% had mild anemia. Four control subjects had a Hb level <12.5 g/dL. Of all patients, 6% were vitamin B12 deficient, 13% were iron deficient, and 8% were folate deficient. There was no difference between patients with LVSD and the diastolic dysfunction group. In patients with LVSDS, the average Hb level was lower in New York Heart Association class III than classes II and I. The distance walked in 6 minutes correlated with Hb level in both groups of patients with CHF (r = 0.29; P <.0001). Patients with anemia achieved a lower pVO2 (15.0 [2.3] vs 19.5 [4.4], P <.05). Peak oxygen consumption correlated with Hb level (r = 0.21, P <.05) in the patients, but not in the control subjects. In patients with anemia, the mean creatinine level was higher than in patients with a Hb level >12.5 g/dL, but there was no clear relationship with simple regression. Hematocrit level and mean corpuscular volume were not different in the patients with diastolic dysfunction, patients with LV dysfunction, or the control subjects. Hematocrit levels were not influenced by diuretic dose. Patients with anemia were not more likely to be hematinic deficient than patients without anemia. CONCLUSIONS: Patients with symptoms and signs of CHF have a high prevalence of anemia (34%) whether they have LV dysfunction or diastolic dysfunction, but few patients have hematinic deficiency. Hemoglobin levels correlate with subjective and objective measures of severity and renal function.