By multi-variate analysis, incretin-based agents were associated with improved PWV (p = 0.029), GLS (p = 0.037), PBR (p = 0.047), and FMD% (p = 0.034), in addition to a reduction of HbA1c. The patients with a final HbA1c ≤ 7% (≤ 53 mmol/mol) had greater reduction in PWV, PBR, and markers of oxidative stress, with a parallel increase in FMD and GLS, compared to those who had HbA1c > 7% (> 53 mmol/mol). Conclusions: Intensified glycaemic control, in addition to incretin-based treatment, improves arterial stiffness, endothelial glycocalyx, and myocardial deformation in type 2 diabetes after one year of treatment.Background: Poor glycaemic control affects myocardial function. We investigated changes in endothelial function and left ventricular (LV) myocardial deformation in poorly controlled type 2 diabetics before and after glycaemic control intensification. Methods: In 100 poorly-controlled diabetic patients (age: 51 ± 12 years), we measured at baseline and at 12 months after intensified glycaemic control: (a) Pulse wave velocity ; (b) flow-mediated dilatation  of the brachial artery; (c) perfused boundary region (PBR) of the sublingual arterial micro-vessels ; (d) LV global longitudinal strain (GLS), peak twisting (pTw), peak twisting velocity (pTwVel), and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, where the ratio of PWV/GLS was used as a marker of ventricular-arterial interaction; and (e) Malondialdehyde (MDA) and protein carbonyls (PCs) plasma levels. Results: Intensified 12-month antidiabetic treatment reduced HbA1c (8.9 ± 1.8% (74 ± 24 mmol/mol) versus 7.1 ± 1.2% (54 ± 14 mmol/mol),  Type 2 diabetes accelerates atherosclerosis and contributes to the development of diabetic cardiomyopathy ,2. ProspMarkers of vascular function ) have been found to be elevated and flow-mediated dilation (FMD) to be decreased in type 2 diabetes . AssessmThe endothelial glycocalyx forms a layer of glycoproteins and proteoglycans that prevents direct contact of blood cells with the endothelial vascular cells . Loss ofHowever, it is not clear whether glycaemic control can lead to the improvement of arterial wall properties, endothelial glycocalyx, and decrease oxidative stress, which is a widely accepted participant in the development and progression of diabetes and its complications .In the present study, we hypothesize that the intensification of glycaemic control, particularly by incretin-based treatment, may improve endothelial function, arterial elastic properties, LV myocardial strain, twisting–untwisting, and oxidative stress  and protein carbonyls (PCs) blood levels).A total of 100 patients with type 2 diabetes were prospectively screened and recruited. Eligible patients included adults with type 2 diabetes with sub-optimal glycaemic control (glycated haemoglobin (HbA1c) ≥ 7% (≥ 53mmol/mol)). Patients were recruited consecutively from the Diabetes Centre outpatient clinic. Exclusion criteria were type 1 diabetes, history or clinical evidence of coronary artery disease, valvular heart disease, congestive heart failure, peripheral vascular disease, and liver or kidney failure. All subjects had normal resting electrocardiograms. Good glycaemic control was defined as HbA1c ≤ 7% (≤ 53 mmol/mol). We defined dyslipidaemia as total cholesterol > 220 mg/dL (low-density lipoprotein (LDL) > 100 mg/dL and/or high-density lipoprotein (HDL) < 40 mg/dL in men and HDL < 50 mg/dL in women) and/or triglycerides > 150 mg/dL, and hypertension as clinic blood pressure > 140/90 mmHg. The choice of the antidiabetic treatment was made according to the American Diabetes Association/European Association for the Study of Diabetes 2018 guidelines. We took into account cardiovascular risk, the presence of multiple risk factors of or established cardiovascular disease, the presence of excess weight, patient preferences , fear of hypoglycaemia, and contra-indications . Thus, patients being overweight or obese, with non-alcoholic fatty liver disease (NAFLD), central obesity, dyslipidaemia, or hypertension were more likely to receive an incretin-based therapy. On the other hand, patients which presented catabolic symptoms, low weight, long-standing diabetes, or severe decompensation and profound hyperglycaemia were more likely to receive insulin.The investigation conformed to the principles outlined in the Declaration of Helsinki. The study protocol was approved by the institute’s ethics committee, and written informed consents were obtained from all patients.The primary endpoint was a change in arterial stiffness, as assessed by pulse wave velocity and augmentation index 12 months after intensified glycaemic control.Secondary endpoints were changes in endothelial function, as assessed by flow-mediated dilation and glycocalyx thickness, LV myocardial deformation, and oxidative stress 12 months after glycaemic control.75 was calculated to adjust the AI for a heart rate of 75 beats/min using the formula: AI75 = ((heart rate − 75) × 0.39) + AI [At baseline and after 12 months of intensive glycaemic control, we measured the carotid–femoral pulse wave velocity (PWV) and central aortic pressures using tonometry by Complior . Normal values were PWV < 10 m/s [39) + AI . Brachia2) = 8 × μ × mean flow velocity/resting diameter, where μ is the viscosity of blood, as previously described [2. All vasoactive medications  inhibitors, or angiotensin II receptor blockers (ARB)) were discontinued for four half-lives of the drug before the vascular studies. Advice was given to keep a similar low-carbohydrate diet (specific for diabetics) throughout the study.A linear array transducer (10 MHz) was used to measure the right brachial artery diameter at end diastole utilizing electronic calipers  and to record the baseline arterial blood flow velocity by color-coded Doppler ultrasonography (with an insonation angle of ≤60°). After a baseline assessment, a cuff fitted distally to the brachial artery was inflated (200–250 mmHg), altering arterial flow for 5 min. After cuff deflation, the hyperemic arterial blood flow velocity was recorded within the first 15 s and, afterwards, the brachial artery was scanned continuously for 90 s after cuff deflation, in order to define its maximal diameter (diameter during reactive hyperemia). Flow-mediated dilation (FMD) of the brachial artery was calculated as a percentage change of the arterial diameter after hyperemia from the baseline diameter . BrachiaWe measured the perfused boundary region (PBR) of the sublingual arterial micro-vessels (which ranged from 5–25 μm) using side-stream dark-field imaging by dedicated cameras . This method provides a non-invasive assessment of the endothelial glycocalyx . The PBRStudies were performed using a Vivid E95  ultrasound system. All studies were digitally stored in a computerized station  and were analyzed by two observers blind to the clinical and laboratory data.The E and A waves of the mitral inflow velocity were measured and the ratio E/A was calculated using pulse-wave Doppler .−1, utilizing a dedicated software  [Longitudinal systolic strain (LS) and systolic strain rate (LSR) were measured from 2-dimensional echocardiography images with a frame rate of 70–80 s Norway) . We calc Norway) . The nor Norway) .The ratio of carotid–femoral PWV to global longitudinal strain (m/s−%) was calculated as an index of ventricular–arterial interaction, as previously published ,17. The MVO), peak (UtwPEF), and at the end of left ventricular early filling (UtwEDF). LV untwisting during diastole was estimated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-UtwMVO), at the peak (%dpTw-UtwPEF), and at the end of early filling (%dpTw-UtwEDF) [The parasternal short axis views at basal and apical level were used to assess LV twisting and untwisting . Twistin-UtwEDF) . FurtherWe measured malondialdehyde (MDA) and protein carbonyls (PCs) spectrophotometrically  using a colorimetric assay for lipid peroxidation (measurement range 1–20 nmol/L) and assessment of the 2,4-dinitrophenylhydrazine derivatives of protein carbonyls (nmol/mg protein), respectively ,18.The SPSS 21.0 statistical software package was used for analysis. We compared the categorical variables by a standard chi-square test. We used the Kolmogorov–Smirnov test to examine the distribution of continuous variables. Normally distributed variables are expressed as mean ± standard deviation. Data with a non-Gaussian distribution are shown as median (interquartile range) and transformed into ranks for analysis. A t-test (or paired t-test) was used to compare differences in mean values of continuous variables. The Mann–Whitney U-test (or Wilcoxon signed-rank test) was applied for non-normally distributed variables. Cross-sectional associations were examined by parametric (Pearson r) or non-parametric (Spearman rho) correlation coefficients. Comparison of the measurements of the examined markers at baseline and 12 months after glycaemic control was performed by ANOVA, with adjustment for age, sex, and interactions. Post-hoc comparisons were performed by Bonferroni correction.p < 0.1 on univariable analysis were entered into the final multi-variable model as explanatory variables. Independent contributions were then assessed, and there was no evidence of significant multi-collinearity. The anthropometric and metabolic values at the 12-month follow-up were used for predicting GLS, PWV, PBR, and FMD on follow-up. Changes between baseline and 12-month follow-up (Δ parameters) for the continuous variables were used to predict ΔGLS and ΔPWV.Linear regression was used to investigate relations between improvement in GLS, PWV, PBR, and FMD with changes in HbA1c. Multiple linear regression was used to identify independent predictors of GLS, PWV, PBR, and FMD at follow-up and changes in these outcomes (Δ parameters) from their respective baseline values. Parameters with p > 0.05). In particular, 58% of the patients with HbA1c ≤ 7% and 42% with HbA1c > 7% were treated with statins (p = 0.76). Age was similar between patients with HbA1 < 7% and > 7% . The smoking status remained unchanged in the smoker patients at 1 year post treatment.The 100 patients (65 men and 35 women) had a mean age of 51 ± 12 years, and a mean duration of type 2 diabetes of 3.2 ± 1.5 years. Their baseline and 12-month follow-up clinical and metabolic characteristics are presented in p = 0.012) and negatively related with FMD% . Furthermore, HbA1c was related with GLS  and peak twisting , and reversely associated with %dpTw-UtwMVO . Additionally, HbA1c was correlated with the PWV/GLS ratio and MDA levels .At baseline, HbA1c was positively associated with PBR 20–25 μm . Moreover, PCs were reversely associated with GLSR E  and positively related with PBR 5–25 μm .MDA and PCs were related with PWV  and reversely associated with GLSR E . Furthermore, PWV was positively related with peak twisting .PWV was correlated with GLS . There were no significant changes in BMI, waist circumference, and lipid profile in the overall population. However, patients on incretin-based agents showed a significant reduction of BMI .HbA1c improved significantly post treatment (p > 0.05). There was a significantly greater improvement in PWV , as well as improved strain rate E at early diastole and reduced LA volume after a 12-month period, suggesting improved systolic and diastolic function (p < 0.05). There was a progressively greater improvement in GLS, GLSrE, LA volume, and PWV/GLS ratio as the patients achieved a lower final HbA1C, with the patients with final HbA1c ≤ 7% (≤53 mmol/mol) having the largest improvements . In addition, the percentage changes between peak twisting and untwisting at mitral valve opening (%dpTw-UtwMVO) and peak (%dpTw-UtwPEF) of early diastolic LV filling were increased  and protein carbonyls (PCs) concentrations . The patp = 0.043) and the percentage increases of GLS and GLSRE . Furthermore, the percentage improvement of HbA1c was significantly correlated with the percentage reduction of PWV and PWV/GLS ratio  after the 12-month follow-up. Furthermore, the percentage reduction of HbA1c was related with the reduction of MDA and PCs .After 12 months, the percentage reduction of HbA1c was related with the percentage decrease of PBR 5–25 μm . Furthermore, the reduction of MDA was positively associated with the reduction of cSBP . Moreover, the reduction of MDA was negatively correlated with increase of FMD% and %dpTw-UtwPEF . The percentage reduction of PCs was correlated with the percentage increase of GLS after the 12-month follow-up .The percentage improvement of MDA and PCs was significantly correlated with the percentage reduction of PWV . Moreover, the percentage reduction of PBR 5–25 μm was positively correlated with the PWV/GLS ratio  at follow-up.The percentage reduction of PBR 5–25 μm was negatively related with the percentage increase of FMD and GLS  .Lastly, the percentage reduction of PWV was significantly correlated with the percentage improvement of GLS and the percentage difference between peak twisting and untwisting at peak of early LV diastolic filling (%dpTw-Utwp > 0.05) after 1 year of treatment  were associated with improved PWV, GLS, and PBR, in addition to HbA1 value changes. Duration of type 2 diabetes, history of hypertension, baseline value, and change in HbA1c were independent predictors of change in GLS. Age, smoking, and change in HbA1c were independent predictors of change in PWV. Furthermore, BMI, history of hypertension and dyslipidemia, change in HbA1c, and treatment with basal insulin analogs were independent predictors of change in PBR. Additionally, independent predictors of change in FMD were age, duration of type 2 diabetes, treatment with basal insulin analogs, and treatment with DDP-4 inhibitors and GLP-1 receptor agonists (incretin-based agents), but not the change in HbA1c  was associated with the improvement of cardiovascular function markers, in addition to effective glycaemic control, as assessed by HbA1 value changes.Type 2 diabetes has been associated with increased arterial  and endoAcute and long-term hyperglycemia, oxidative stress, and inflammation have been associated with the loss of glycocalyx integrity ,24. In oAsymptomatic diabetic patients manifest complications that are closely associated with systolic dysfunction , despiteArterial stiffness is one of the determinants of LV longitudinal strain and twisting–untwisting by affecting perfusion of sub-endocardial myocardial fibers . FurtherLipid peroxidation and protein oxidation are commonly assessed by malondialdehyde and PCs levels, respectively . GlycatiIn our previous study, oxidative stress was reduced after 6 months of treatment with a GLP-1 analogue, while this improvement was not evident in the group treated with metformin, despite a similar change of HbA1 between the two treatment arms, suggesting an early improvement of oxidative stress by incretin-based treatment. In the current study, after 1 year of treatment both change of HbA1 and incretin-based treatment are independent determinants of improved GLS and PWV. Moreover, in this study, the percentage reduction of HbA1c was related with the reduction of MDA and PCs after 1 year of antidiabetic treatment; furthermore, the reduction of oxidative stress was associated with improved PWV and myocardial deformation after 1 year of treatment. Thus, incretin-based treatment for a longer period contributes to an optimal glucose control, as assessed by HbA1 changes, and thus to a further reduction of oxidative stress, resulting in a further improvement of vascular and myocardial function than the shorter term treatment period (6 months) used in our previous study.The present study was conducted as a single-arm interventional study, with each patient acting as their own control, and we compared those who improved glycaemic control with those who did not. Moreover, the effects of improved glycaemic control on endothelial and myocardial function observed in this study are only preliminary. Large-scale studies are needed to confirm the findings.Intensified glycaemic control over a 12-month period improved arterial stiffness, LV myocardial deformation, and, consequently, ventricular–arterial interaction, probably by reduction of oxidative stress and endothelial dysfunction, in initially poorly controlled type 2 diabetic patients. Glycaemic control may reverse early subclinical cardiac and vascular dysfunction and reduce the risk of heart failure. Incretin-based treatment has an additive value to effective glycaemic control, as assessed by HbA1c value, for the improvement of cardiovascular function after 1 year of treatment. Thus, incretin-based agents appear to produce favorable cardiovascular effects among individuals with diabetes and may reduce the risk of heart failure events.


To determine the relationship between plasminogen activator inhibitor-1 (PAI-1) activity rise during the first 24 hours of ST-elevation myocardial infarction (STEMI) treatment and death after 5 years.From May 1, 2009 to March 23, 2010, 87 STEMI patients treated with primary percutaneous coronary intervention (PCI) at the Sestre Milosrdnice University Hospital Center were consecutively enrolled in prospective single-center cohort study. PAI-1 activity was determined on admission and 24 hours later. The primary end-point was death after 5 years. The predictive value of PAI-1 activity variables as biomarkers of death was assessed using receiver operating characteristic (ROC) curve, independent predictors of death were assessed using multivariate Cox regression, and covariates independently related to higher PAI-1 activity rise were assessed using linear regression.P < 0.001). Kaplan-Meier survival curve diverged within the first year after STEMI. Independent predictors of death were PAI-1 rise and final TIMI flow. PAI-1 activity rise was independently related to heart failure, thrombus aspiration, and body weight.Two patients died during the hospital treatment and 11 during the follow-up. PAI-1 activity rise had the largest area under curve (0.748) for predicting death rate . Patients with PAI-1 activity rise higher than 3.7 U/mL had significantly higher mortality (PAI-1 activity rise higher than 3.7 U/mL is associated with higher 5-year death rate in STEMI patients treated with primary PCI.Oxford Centre for Evidence-based Medicine level of evidence: 3. Myocardial infarction (MI) is initiated by a coronary artery atherosclerotic plaque rupture or erosion, followed by a thrombotic event leading to a complete or partial occlusion . ThrombuPAI-1 role in acute MI has been studied only regarding short-term outcomes. Collet et al  reportedOne hundred consecutive acute STEMI patients treated with primary PCI within 12 hours from the symptoms onset at the Sestre Milosrdnice University Hospital Center from May 1, 2009 to March 23, 2010 were examined for eligibility to enter this prospective single-center cohort study. The only inclusion criterion was STEMI diagnosis, established if persistent ST-segment elevation ≥1 mm in at least 2 consecutive standard electrocardiogram (ECG) leads or persistent ST-segment elevation ≥2 mm in precordial ECG leads, or new onset complete left bundle branch block, was observed and accompanied by chest pain lasting more than 20 minutes. Inability or refusal to sign the informed consent was regarded as a non-inclusion criterion. Ethical approval was received from Sestre Milosrdnice Clinical Hospital Center Ethics Committee.The exclusion criteria were as follows: not available or deceased at 24 hours (1 patient), chronic corticosteroid or immunosuppressive therapy (4 patients), no significant coronary artery disease on angiogram (2 patients), diagnosis of acute infective or inflammatory disease established within the first 24 hours (5 patients), active malignant disease (1 patient), and chronic hepatic failure requiring treatment (0 patients). A total of 87 patients entered the study. The number of participants was restricted by available financial resources, which were used for laboratory analyses.Blood samples were collected in citrated tubes on admission (before PCI) in the catheterization laboratory and exactly 24 hours later in the Cardiac Intensive Care Unit. The samples were centrifuged for 10 minutes at 4000 rotations per minute, frozen at -20°C, and analyzed for PAI-1 activity after no more than 28 days  . After S2, Fisher exact, or Fisher-Halton-Freeman exact test, continuous by Mann-Whitney U test, and correlations by point-biserial correlation. Receiver operating characteristic (ROC) curves were used to determine variable’s predictive value and optimal cut-off points (using Youden index). Binary logistic and linear regression models were used to determine independent contribution of an individual variable to PAI-1 activity variability. Survival was analyzed using Cox regression and log-rank test, and presented as Kaplan-Meier curves. Two-tailed significance tests were performed, and P < 0.05 was considered significant. Statistical analyses were performed using SPSS for Windows, version 25 .Depending on the normality of distribution, tested by Kolmogorov-Smirnov test, descriptive data are presented as means and standard deviations (SD) or medians and interquartile ranges (IQR). Categorical variables are presented as counts and frequencies. The difference between PAI-1 activity values on admission and after 24 hours was tested using Wilcoxon signed-rank test. PAI-1 activity rise was defined as the value on admission subtracted from the value obtained 24 hours later. Categorical variables were analyzed with χP < 0.001, Wilcoxon signed-rank test). PAI-1 activity rise correlated with heart failure occurrence , thrombus aspiration , pulmonary edema , and final TIMI flow lower than 3 .Study population was predominantly male, aged 61.1 ± 12.2 years, with a high prevalence of patients with hypertension and active smokers . Low admPAI-1 rise was then expressed as a binary variable with the cut-off point of 3.7 U/mL, as determined by ROC analysis of long-term survival. Variables related to PAI-1 activity rise higher than 3.7 U/mL were heart failure, anterior wall myocardial infarction, left anterior descending artery as an infarction-related artery, use of thrombus aspiration, no-reflow phenomenon, worse final TIMI flow, and female sex among categorical variables , and higb] = 35.3; P = 0.004), thrombus aspiration , female sex , body weight , and peak CK levels . Stepwise linear regression with PAI-1 rise expressed as a continuous variable showed that independent predictors of higher PAI-1 rise were heart failure , thrombus aspiration , and body weight .Stepwise binary logistic regression included 7 variables significant in the univariate analysis . It showed that independent predictors of PAI-1 rise higher than 3.7 U/mL were heart failure , women , patients with heart failure , worse final TIMI flow , lower left ventricular ejection fraction (LVEF) , and lower BMI .Two patients (2.3%) died during hospital treatment, both due to acute complications of myocardial infarction. All discharged patients were available for 5-year follow-up. Eleven additional deaths (12.6%) occurred during follow-up due to the following causes: cardiac causes in 8 patients , shock following surgical treatment for intestinal ileus in 1 patient, and unknown cause in 2 patients. All deaths in patients with PAI-1 activity rise higher than 3.7 U/mL were of cardiovascular origin. Higher death rate was found in patients older than 65 . Multivariate analysis using enter- and forward-stepwise approach included age, sex, heart failure occurrence, no-reflow phenomenon, thrombaspiration use, final TIMI flow (expressed as TIMI flow 3 or <3), and PAI-1 activity rise higher than 3.7 U/mL as covariates. In both approaches, the only independent predictors of death were final TIMI flow and PAI-1 activity rise higher than 3.7 U/mL , and the observed death rate of 50%. These results are in accordance with the study by Collet et al   . FurtherIn conclusion, PAI-1 activity rise in acute STEMI patients treated with primary PCI was associated with high-risk features and poorer long-term survival. This finding could improve the accuracy of long-term prognosis in STEMI patients. Further studies are needed to clarify whether the determined relation is casual or causative. If the latter is true, additional efforts to produce and clinically test PAI-1 antagonists are required.


A fragmented QRS complex (fQRS) is caused by conduction abnormalities of the ventricle secondary to myocardial ischemia and/or scar in patients with myocardial infarction. However, the implications of the fQRS in the development of coronary artery disease with myocardial ischemia in those without a scar remain unknown.We studied electrocardiograms (ECGs) obtained from 150 patients  with myocardial ischemia, which was confirmed by performing both, a nuclear exercise stress test and coronary angiography. We also studied ECGs obtained from 601 patients  who showed a negative nuclear exercise stress test (control group). Patients in whom the nuclear exercise stress test showed a myocardial scar were excluded.P = 0.011). The sensitivity, specificity, positive, and negative predictive values of fQRS in diagnosing myocardial ischemia were 32.0, 77.9, 26.5, and 82.1%, respectively. The fQRS  was an independent predictor of myocardial ischemia after adjusting for age, sex, current smoking habits, ST‐T changes on ECG, as well as histories of hypertension, diabetes, and dyslipidemia. Moreover, the fQRS showed an incremental prognostic value over conventional risk factors  and over a combination of conventional factors and ST‐T changes .An fQRS was more commonly observed in patients with myocardial ischemia  than in the control group  (The fQRS is a moderately sensitive and independent predictor of myocardial ischemia. Early diagnosis and identification of CAD are indispensable, and therefore improved electrocardiographic (ECG) parameters are required for prompt and accurate diagnosis of CAD. A fragmented QRS (fQRS) complex observed in a 12‐lead ECG has been shown to represent inhomogeneous activation of the ventricular myocardium.2t test for continuous variables and the χ2 test for categorical variables. A multivariate logistic regression model was used to identify independent predictors of myocardial ischemia on SPECT. The Cox proportional hazard model was used to evaluate the incremental prognostic values of variables. Incremental variables added to the model at each step were considered significant when the difference in the log‐likelihood values associated with each model corresponded to P < 0.05. All P‐values were two‐sided, and P < 0.05 was considered statistically significant. All statistical analysis was performed using the SPSS software version 20.0 for Windows .Among all patients who underwent exercise myocardial perfusion SPECT for evaluation of suspected CAD at Kyungpook National University Hospital  between January 2006 and December 2016, we studied 751 consecutive patients who showed myocardial ischemia on myocardial perfusion SPECT, which was confirmed using coronary angiography (CAG) (ischemia group) and who showed a negative exercise treadmill test and normal myocardium on SPECT (control group). Exclusion criteria were: patients with inconsistent results or myocardial scars observed on an exercise treadmill test and myocardial SPECT, patients with myocardial ischemia on myocardial SPECT, which was not confirmed by CAG (patients did not undergo CAG or no significant coronary artery stenosis was identified using CAG), patients demonstrating a left ventricular ejection fraction (LVEF) <50% observed on echocardiography, and those with a history of myocardial infarction (MI) and/or percutaneous coronary intervention. Demographic and clinical characteristics including age, sex, body mass index, cardiovascular risk factors, and comorbidities , laboratory tests, LVEF, and ECG findings were recorded. The LVEF was assessed using two‐dimensional echocardiography obtained several days before and after exercise myocardial perfusion SPECT. We obtained 12‐lead ECGs  on the nearest day before and after exercise myocardial perfusion SPECT, and these were analyzed by two independent cardiologists. Disagreements were resolved through consensus. An fQRS was defined as changes in QRS morphology (<120 ms) with diverse RSR′ patterns, that is, additional R (R′) waves, notching, S waves, or > 1 R′ waves in two contiguous leads.3Of the 751 patients  who showed myocardial ischemia using myocardial perfusion SPECT, fQRS, and myocardial ischemia were identified in 181 (24.1%) and 150 (20.0%) patients, respectively. Baseline characteristics of patients are shown in Table P = 0.011).Univariate analysis showed that patients with myocardial ischemia were older and included a greater percentage of men. In addition, this group included a higher percentage of current smokers and those with a history of hypertension, diabetes, and dyslipidemia. There was no difference in body mass index, previous cerebrovascular disease, laboratory findings, and LVEF based on the presence or absence of myocardial ischemia. Among ECG parameters, patients with myocardial ischemia showed a significantly higher percentage of ST‐T changes. However, the pathological Q wave was not statistically significantly different between the groups. Patients with myocardial ischemia identified on SPECT included a higher percentage of current smokers, as well as those with hypertension, diabetes, and hyperlipidemia. The fQRS was more common in the ischemia group  than in the control group  (An fQRS was identified on an ECG in 181 patients 24.1%) (Table 4.1% (TabP = 0.040) was an independent predictor of myocardial ischemia observed on SPECT after adjusting for age, sex, current smoking, ST‐T changes on ECG, and histories of hypertension, diabetes, and hyperlipidemia. In addition to current smoking , hypertension , diabetes , hyperlipidemia  and ST‐T changes on ECG   and over a combination of conventional risk factors and ST‐T changes   Ours is a single‐center, observational study; thus, the potential effects of unmeasured or unknown factors on study outcomes cannot be excluded. (b) We did not perform an anatomical study using modalities such as computed tomography angiography for the detection of coronary artery stenosis in the control group. However, we enrolled patients who showed negative results using myocardial SPECT with an exercise treadmill test as the control group, and we consider this was enough to exclude myocardial ischemia.5The fQRS is a moderately sensitive independent predictor of myocardial ischemia. Therefore, using this simple ECG parameter may help to identify patients with suspected CAD who need further aggressive evaluation and treatment.The authors declare no potential conflict of interests.


Conduction disease and arrhythmias represent a major cause of mortality in myotonic muscular dystrophy type 1 (MMD1). Permanent pacemaker (PPM) implantation is the cornerstone of therapy to reduce cardiovascular mortality in MMD1. Cardiovascular magnetic resonance (CMR) studies demonstrate a high prevalence of myocardial fibrosis in MMD1, however the association between CMR myocardial fibrosis with late gadolinium enhancement (CMR-LGE) and surface conduction abnormality is not well established in MMD1.We investigated whether myocardial fibrosis by CMR-LGE is associated with surface conduction abnormalities meeting criteria for PPM implantation according to current guidelines in a cohort of patients with genetically confirmed MMD1.Patients with genetically confirmed MMD1 were retrospectively evaluated. 12-lead electrocardiography (ECG) performed within 6 months of CMR was necessary for inclusion. The severity and extent of MMD1 was quantified using a validated Muscular Impairment Rating Scale (MIRS). Based on current guidelines for device-based therapy of cardiac rhythm abnormalities, we defined surface conduction abnormality as the presence of ECG alterations meeting criteria for PPM implant (class I or II indications): PR interval > 200 ms (type I atrioventricular (AV) block) and/or mono or bifascicular block (QRS > 120 ms), or evidence of advanced AV block. Balanced steady-state free precession sequences (bSSFP) were used for assessment of left ventricular (LV) volumes and ejection fraction. MOdified Look-Locker Inversion Recovery (MOLLI) acquisition schemes were used to acquire T1 maps. Patients’ charts were reviewed up to 12 months post-CMR for occurrence of PPM implantation.p = 0.015) and higher disease severity on the MIRS scale (p = 0.041). High prevalence of myocardial fibrosis by CMR-LGE was detected in subjects with and without surface conduction abnormality with no significant difference between the two cohorts . By multivariate logistic regression analysis, disease length was the only independent variable associated with surface conduction abnormality ; while CMR-LGE was not associated with conduction abnormality .Fifty-two patients  were included. Overall, 31 (60%) patients had a surface conduction abnormality and 22 (42%) demonstrated midwall myocardial fibrosis by CMR-LGE. After a median of 57 days from CMR exam, 15 patients (29%) underwent PPM implantation. Subjects with vs. without surface conduction abnormality had significantly longer disease length  contains supplementary material, which is available to authorized users. Myotonic muscular dystrophy type 1 (MMD1) is the most common muscular dystrophy in adults and is characterized by progressive muscle degeneration leading to disabling weakness and wasting with myotonia, in combination with multisystem involvement . CTG repConduction abnormalities and cardiac arrhythmias represent a major cause of mortality in MMD1; thus the prevention of sudden cardiac death (SCD) is central to patient management –6. CardiMyocardial fibrosis has been identified in autopsies from patients with MMD1 together with fatty infiltration and myocyte hypertrophy and degeneration , 8. CardWe sought to evaluate the association between the presence and extent of CMR-LGE myocardial fibrosis and surface conduction abnormalities meeting criteria for PPM implantation according to current guidelines in a cohort of patients with genetically confirmed MMD1.We retrospectively evaluated consecutive patients from the Muscular Dystrophy Clinic of The Ohio State University Medical Center, with genetically confirmed diagnosis of MMD1 referred for a clinical CMR between April 2012 and March 2017. Subsequent decision-making regarding PPM implantation was done at the clinical discretion of the referring provider, typically based on ECG findings, and did not incorporate CMR data. Standard 12-lead ECG performed within 6 months of CMR exam was necessary for inclusion. Exclusion criteria included standard contraindications to perform a CMR exam: severe claustrophobia, presence of a pacing device, ferromagnetic foreign body, active implant, known allergy to gadolinium-based contrast, or advanced kidney disease (e.g. glomerular filtration rate < 30 mL/min/1.73 m2). The Ohio State University Institutional Review Board approved this retrospective study and waived informed consent.All patients underwent a comprehensive clinical evaluation and physical examination during their clinical visit. The severity and extent of MMD was quantified using a validated Muscular Impairment Rating Scale (MIRS) related to the clinical distribution and extent of muscle weakness and myotonia . The NewElectrical parameters were assessed from a standard 12-lead surface ECG. Based on current American College of Cardiology Foundation/ American Heart Association/Heart Rhythm Society (ACCF/AHA/HRS) guidelines for device-based therapy of cardiac rhythm abnormalities , we defiAll images were acquired on a single 1.5T CMR scanner with a 12-element phased array chest coil . Balanced steady-state free precession sequences (bSSFP) were used for assessment of LV volumes, ejection fraction (LVEF) and LV mass. LGE imaging was performed using a gradient-echo inversion recovery sequence with magnitude and phase sensitive inversion recovery reconstructions 10 min after 0.2 mmol/kg of gadolinium based contrast agent . LV volup <  0.05. SPSS Statistic 21.0  International Business Machines, Inc., Armonk, New York, USA) was used for all statistical analyses.Data are presented as mean ± standard deviation (SD) or as median and interquartile range (IQR) for continuous variables and as proportions for categorical variables. The mean values of continuous, normally distributed variables were compared with the 2-sample t-test. Comparison of median values or proportions was done with the 2-sample Wilcoxon rank-sum test, and Fisher exact test, respectively. Univariate logistic regression analysis was used to find individual variables associated with surface conduction abnormality. After testing for collinearity, multivariate stepwise-backward logistic regression analysis was used to find independent variables associated with surface conduction abnormality. The association between CMR-LGE, surface conduction abnormality and PPM implant was also assessed with Spearman correlation analysis. An additional analysis was performed to compare clinical and ECG characteristics according to the presence vs. absence of LGE. Statistical significance was set at two tailed Fifty-two patients with genetically confirmed MMD1 , 38% male, 41 ± 14 years, met criteria for inclusion in the study. Overall, thirty-one patients (60%) demonstrated surface conduction abnormality: 20 (38%) with a prolonged PR interval (mean 232 ± 51 ms); 5 (9.6%) with a prolonged PR interval associated with RBBB; 2 (3.8%) patients had a prolonged PR interval associated with LBBB; 2 (3.8%) had LBBB alone, one patient had RBBB alone, and one had Mobitz AV block type I. Baseline demographic, clinical and ECG characteristics according to presence or absence of surface conduction abnormality are presented in Table p = 0.015) and demonstrated higher MIRS scores (p = 0.041) compared to subjects without conduction abnormalities  received a PPM: 7 subjects were implanted due to coexistence of first degree AV and fascicular block, 4 for presence of bifascicular block associated with either a first degree AV block or a prolonged HV interval, 2 for a prolonged HV interval, one for presence of second degree AV block (Mobitz type I), and one for presence of I degree AV block   Table .Table 3Cp = 0.999). Further, LGE mass and LGE% were similar between the two groups. ECV tended to be higher in the conduction abnormality group, albeit values were within the normal range in both groups . Data on native myocardial and post-contrast T1 values according to different MOLLI sequences and presence vs. absence of conduction abnormality are presented in Additional file The median time between the CMR exam and the ECG was 21 days (IQR 7–54). Subjects with conduction abnormality demonstrated similar LVEF, LV volumes, LV mass, and left atrial (LA) volumes compared to those without conduction abnormality Table . ImportaOf 22 LGE-positive subjects, all demonstrated midwall fibrosis; in 17 subjects (77%) the interventricular septum was involved, the inferior and inferolateral segments were involved in four subjects (18%), and the anterior wall was involved in one subject (5%). An analysis of clinical and ECG data according to the presence vs. absence of LGE was also conducted  nor was LGE%  or LGE mass . Similar findings were also true for the association between CMR-LGE and PPM implant .Disease length and Cornell voltage were associated with surface ECG conduction abnormality on univariate analysis. Disease length was the only independent variable associated with conduction abnormality in the multivariate model  followed by inferior and inferolateral regions (18%) – these findings are consistent with prior literature. In the study by Petri et al. there were 12 patients with LGE positivity, 50% exhibited fibrosis in the septum (anteroseptum and hinge points) and 33% in the inferior and inferolateral regions . SimilarOur study suggests that myocardial fibrosis and conduction system abnormality may be two distinct phenomena occurring simultaneously in the myocardium of subjects affected by MMD1 and possibly carrying an interrelated but independent risk for adverse cardiovascular events. Recent studies seem to support this hypothesis, suggesting a possible relation between molecular mechanisms and surface conduction abnormalities , 32. An An additional aspect of our study is data on both replacement and interstitial fibrosis. In this cohort of MMD1 patients, we identified and quantified replacement fibrosis by LGE, and quantified interstitial fibrosis utilizing T1 mapping to obtain ECV values. Although there was a trend towards higher ECV values in patients with surface conduction abnormality, ECV was not statistically significantly different between the two groups. Further studies are needed to elucidate the nature of interstitial fibrosis in MMD1 .Another important result of our study is the demonstration of high prevalence of myocardial fibrosis by CMR-LGE in subjects without surface conduction abnormality (43%). This finding has two relevant implications: i) myocardial fibrosis by CMR-LGE and surface conduction abnormality can occur independently in MMD and ii) additional studies are needed to know if detection of fibrosis afforded by CMR-LGE helps in predicting tachyarrhythmia risk in MMD that may not be captured by conduction abnormalities. The presence of myocardial fibrosis by CMR-LGE plays a key role in multiple cardiomyopathies as an important prognosticator for worse cardiovascular outcomes, particularly ventricular arrhythmias and sudden cardiac death –37. In pFinally, similar to MMD1, MMD type 2 also manifests with cardiac involvement , 40. ConThis is a single center, retrospective study and the results should be confirmed in a large, multicenter, prospective study powered for both bradyarrhythmias as well as tachyarrhythmic SCD events.It could be speculated that lack of correlation between myocardial fibrosis by CMR-LGE with surface conduction abnormality could be related to relatively early course of disease from the point of view of myocardial structural abnormality; however our findings rather support the opposite conclusion for the following reasons: i) there is a high prevalence of myocardial fibrosis which demonstrates that myocardial structural abnormality was frequent in this population ii) LV mass index was in the low normal range, which in line with previous studies, confirms evident muscle wasting typical for MMD1 iii) finally the length of MMD1 (median > 12 years in the whole population) excludes the possibility of an early stage of the disease where myocardial structural abnormality could have been absent or not detectable with CMR. Although we did not see trends towards significance with respect to myocardial fibrosis by CMR-LGE between our two cohorts, and our study is one of the largest CMR based studies in MMD1, our acceptance of the null hypothesis may relate to our sample size.As the intent of our manuscript was to determine the association between myocardial fibrosis by CMR-LGE and surface conduction abnormality, we retrospectively included all consecutive patients with contrasted CMR exams and ECGs performed within 6 months. Our study spanned nearly 5 years during which two different MOLLI sequences were used at our institution, MOLLI 3(3)3(3)5 initially and then MOLLI 5(3)3. This is a limitation of our study.ECV values were calculated from ROIs placed in the interventricular septum from the mid short axis view, hence they are not representative of the whole myocardium. However, according to recent literature and consensus documents, septal segments have proven to be the most reproducible as they are less frequently affected by off-resonance artifacts , 22. AddMyocardial fibrosis by CMR-LGE in patients with MMD1 is highly prevalent but not related to surface conduction abnormality meeting criteria for PPM implantation according to current guidelines.Our findings support the concept that MMD1 is characterized by a complex phenotype where conduction system dysfunction and myocardial fibrosis assessed by CMR-LGE are independent phenomena possibly with additive but independent prognostic significance.High prevalence of myocardial fibrosis by CMR-LGE in the absence of surface conduction abnormalities warrants longer term follow-up to understand how CMR informs risk stratification in this disease.Additional file 1:Table S1. T1 mapping in patients with and without conduction abnormality. Table S2. Patient characteristics according to CMR-LGE findings. Table S3. Electrocardiographic Characteristics According to CMR-LGE findings. Table S4. Full Univariate Logistic Regression Analysis of Variables Associated with Surface Conduction Abnormality. Fig. S1. Representative ECG and CMR findings in the study cohort including T1 mapping. Panels A shows an patient with abnormal ECG with prolonged PR interval and right bundle branch block, his corresponding native T1 map in panel B (utilizing MOLLI 3(3)3(3)5) and post-contrast T1 map in panel C yielding an ECV of 24%. Panel D demonstrates septal and inferolateral midwall fibrosis in the same patient. Panel E demonstrates a patient without conduction abnormality; his pre- and post-contrast T1 maps in panels F and G (utilizing MOLLI 5(3)3) yield an ECV of 23% and panel H demonstrates fibrosis in the inferior RV insertion site.


Ebstein's anomaly remains a relatively ignored disease. Lying in the 'NoMan's land' between congenital and valve surgeons, it largely remainsinadequately studied. We report our short-term results of treating it as a'one and a half ventricle heart' and propose that the true tricuspid annulus(TTA) 'Z' score be used as an objective criterion for estimation of'functional' right ventricle (RV).22 consecutive patients undergoing surgery for Ebstein's anomaly werestudied. Echocardiography was performed to assess the type and severity ofthe disease, tricuspid annular dimension and its 'Z' score. Patients wereoperated by a modification of the cone repair, with addition ofannuloplasty, bidirectional cavopulmonary shunt (BCPS) and right reductionatrioplasty to provide a comprehensive repair. TTA 'Z' score was correlatedlater with postplication indexed residual RV volume.P<0.001). Residual RV volumereduced to 71.96±3.8% of the expected volume and there was asignificant negative correlation (rho −0.83) between TTA 'Z' score andindexed residual RV volume. During the follow-up of 20.54±7.62months, the functional class improved from 2.59±0.7 to1.34±0.52 (P<0.001).There was one (4.5%) early and no late postoperative death. There was asignificant reduction in tricuspid regurgitation grading  isrecommended. The short-term outcomes of our technique are promising. The complex lesion was named Ebstein's anomaly andincluded septal and posterior leaflet adherence to the underlying myocardium withdownward displacement of the functional tricuspid annulus, resulting in dilatationof atrialized portion of right ventricle (RV) and true tricuspid annulus . It is a rare congenital cardiac anomaly, occurring inapproximately 1 per 200,000 live births and accounting for <1% of all cases ofcongenital heart disease,3. The complexity of theanomaly led to several classifications being proposed, especially those proposed byCarpentier et al.and Celermajer et al.. Various surgical techniques have been described for therepair of this complex pathology, depending on the surgeon's understanding ofanatomical and functional alterations that involve the tricuspid valve, rightatrium, RV and conduction system-11. Most ofthe techniques involved repair in the leaflet and annular level with plication ofthe atrialized RV either horizontally or vertically, resulting in a monocuspid orbicuspid valve,8,12. We describe a standardized technique of aphysiologically and anatomically complete trileaflet repair of Ebstein's anomaly. Inview of the inevitable association of RV dysfunction with tricuspid deformity, acomprehensive repair of all subcomponents of the anomaly has been practised at ourinstitute for a possible long-term event-free survival of these patients. Itincludes: 1) Plication of the atrialized right ventricle; 2) Reduction of tricuspidvalve annulus resulting in neoannulus; 3) Trileaflet repair of tricuspid valve; 4)Tricuspid ring annuloplasty; 5) Right atrial reduction ± MAZE; 6)Bidirectional cavopulmonary shunt (BCPS). To prove the need for BCPS shunt, wemeasured the residual volume of RV after plication and correlated it with theexpected indexed RV volume.In 1866, Wilhelm Ebstein described a complex congenital cardiac anomaly during theautopsy of a 19-year-old cyanotic manBetween January 2012 to July 2016, 22 consecutive patients underwent surgery forEbstein's anomaly at the Department of Cardiothoracic Surgery, U.N. Mehta Instituteof Cardiology & Research Centre, Ahmedabad.Preoperative data including age, sex, previous cardiac surgery, cyanosis,palpitations, dyspnea on exertion, pedal edema, hepatomegaly, presence of otherassociated cardiac anomalies, arrhythmias, renal dysfunction, congestive cardiacfailure, need for ventilatory support, etc., were collected. Preoperativeechocardiography using Vivid i  was performed to evaluate theseverity and type of disease, degree of tricuspid regurgitation (TR), truetricuspid annular dimension with 'Z' score, tricuspid annular plane systolicexcursion (TAPSE), and left ventricular ejection fraction (LVEF). The TTA wasmeasured in four chamber view as the maximal lateral diastolic distance at thelevel of an echocardiographically identifiable annulus. If a patient had ahistory of palpitations and/or the electrocardiogram showed arrhythmias, thenelectrophysiological studies were performed.Operation is performed via median sternotomy and cardiopulmonary bypass (CPB) isinstituted with aortic, high superior vena cava and inferior vena cavacannulation. Intraoperative transoesophageal echocardiography is routinely used.Before initiating CPB, direct intraoperative pulmonary artery pressure ismeasured to confirm the feasibility of Glenn shunt (mean pulmonary arterypressure <15 mmHg). Moderate systemic hypothermia (32ºC) and antegradecold blood cardioplegia are established. A standard oblique right atriotomy isperformed with an incision from the right atrial appendage (RAA) towards theinferior vena cava, which is parallel to the right atrioventricular groove. Theleft heart is vented via patent foramen ovale or atrial septal defect. Thetricuspid valve anatomy is examined using valve hooks and the atrialized RV isevaluated. Complete detachment and delamination of anterior tricuspid leaflet(ATL) and posterior tricuspid leaflet (PTL) are performed preserving someattachments to papillary muscles. The septal tricuspid leaflet (STL) is alsodetached and delaminated to reach the true annulus by 'somersaulting' of STL. Duringdelamination, as many chords as possible are retained after fenestration to becut at a later stage if they prevent rotation of the leaflets around theannulus. Fenestrations present in ATL and PTL are closed using 6-0 polypropylenesuture. After delamination, atrialized RV is plicated in vertical fashion justcloser to the true annulus. A 75 ml, 26 Fr (Bard) Foley catheter is passedacross the tricuspid valve and the balloon is slowly inflated to measure theright ventricular volume. Once measured, the balloon is deflated and thecatheter is retrieved. The true annulus is circumferentially plicated using two5-0 polypropylene sutures to create a 'neoannulus', thus reducing the area oftricuspid annulus to be covered by leaflet tissue . The detPostoperative hospital mortality, intensive care unit (ICU) length of stay,postoperative hospital stay, reoperation for bleeding, renal failure, and anypostoperative arrhythmias were observed. Postoperatively and at dischargeechocardiographic TR was assessed by two independent operators and graded from 1to 4. The highest grade was recorded as the TR degree. Follow-up was done at 1,3 and 6 months postoperatively and 6 months later. At follow-up, New York HeartAssociation (NYHA) class of all patients was recorded. Echocardiographicevaluation was again performed by two independent operators for TR degree, TAPSEand BCPS patency.P<0.05 was considered for statistical significance.The statistical calculations were performed using SPSS software v 20.0 . Continuous and categorical data were expressed as mean ± SD andas proportions, respectively. The echocardiographic TTA 'Z' score preoperativelycalculated was correlated with the intraoperative residual RV volume . The correlation between variables wascalculated using Spearman's correlation coefficient. The cutoff value of2 around 90% (ranging from 50% to 94%). One (4.5%) of the patientson presentation had supraventricular tachycardia, which was evaluated byelectrophysiological studies, but no aberrant pathway was found. The remainingpatients at the time of presentation were in sinus rhythm. Four (18.2%) patients hadassociated ventricular septal defect, 18 patients had atrial septal defect/PFO andone (4.5%) patient had associated left superior vena cava draining into the coronarysinus. Echocardiographically, 4 (18.2%) patients were Carpentier type B, 17 (77.3%)patients were type C and one (4.5%) was type D. Mean TTA was 49.86±7.4 mm(ranging from 36 mm to 66 mm) with a mean 'Z' score of 3.72±0.57 (rangingfrom 2.32 to 5.28). Of the 22 operated patients, there were 13 (59.1%) with TTA 'Z'score of +2 to +4 and 9 (40.9%) with 'Z' score of ≥ 4. Ten (45.5%) patientshad TR grade 3 and 12 (54.5%) had TR grade 4 . Ofthe 22 patients, there were 8 (36.4%) females and 14 (63.6%) males. Cyanosis waspresent in 4 (18.2%) of the patients, however, almost all were desaturated withSPO grade 4 .The mean functional NYHA class at presentation was 2.59±0.7. Two (9.09%)patients presented NYHA class IV with bilateral pedal edema and hepatomegaly andechocardiography showing TR grade 4. Of these two, one patient had previouslyundergone repair of the tricuspid valve with BCPS at another centre. He wasre-repaired successfully by our technique. The other child, a 1.5-year-old male, hadright heart failure, on high inotropic and ventilatory support preoperatively. Thispatient was Carpentier type D, presented tricuspid incompetence grade 4, with 'Z'score of TTA being +5.28. The patient could not be weaned off CPB after completionof the procedure and is the only mortality of our series..It shows that after plication of RV inferior aneurysmal wall, right ventricularvolume is reduced to 71.96+3.8% of the expected volume. When correlated with thepreoperative TTA 'Z' score, there was a significant negative correlation between TTA'Z' score and the postplication indexed residual right ventricular volume, with acorrelation coefficient of −0.83. It means that, as TTA 'Z' score increases, theindexed postplication residual RV volume reduces significantly  patient developedcomplete heart block, for which a permanent epicardial pacemaker implantation wasperformed later. Postoperative facial swelling and upper limb edema was noticed inonly one (4.5%) case in the postoperative period, which was resolved on the5tive day .P<0.001). MeanTAPSE at follow-up was 16 mm compared to the preoperative mean TAPSE of 13.9 mm(P<0.0001) (The follow-up was 100% complete with a mean follow-up period of 20.54±7.62months (ranging from 10 to 36 months). There has been no late death to date. One(4.54%) patient needed reoperation for worsening NYHA class and increasing grade oftricuspid incompetence with dilatation of tricuspid annulus. This was a 1.5-year-oldchild who was operated according to our technique, except for non-placement of atricuspid annuloplasty ring . Finally, the child underwent the Starnes procedure followed byextracardiac Fontan procedure. At the last follow-up, all patients were in NYHAclass I or II. The functional class (NYHA) and TR grade had improved significantly .2. In Ebstein's anomaly, the displacement of the septaland posterior leaflets (> 8 mm/m2) ranges from very minimal to severe.This displacement effectively divides the ventricle into two regions, a partproximal to it that is functionally integrated with the right atrium and a partdistal to it that is the effectively functional right ventricle.In normal hearts, the septal and posterior leaflets are displaced downward inrelation to the anterior mitral valve leaflet, but displacement is less than 8mm/m,14-16.Celermajer et al.found in their study that the actuarial survival rate was 67% at 1 year and 59% at10 years. In childhood, adolescence and adult life, there was a continuous attritionrelated to hemodynamic deterioration and sudden and unexpected death. Even those whohad an incidentally detected murmur had a small, but continuous, hazard for latedeath.Hence, patients with Ebstein's anomaly require early surgery. The worst subset ofpatients presents earlier (i.e. infancy) and may more oftenCarpentier classification type D, compared to older children. Of all neonates withthe diagnosis of Ebstein's anomaly, 20% to 40% did not survive 1 month, and <50%survive to 5 years,17.Several studies have described natural history of Ebstein's anomalyand Celemajer et al. described the disease based on anatomical severity.However, although Carpentier classification describes anatomy well, it is not reallyprognostic, while the extended Glasgow Outcome Scale is prognostic, but verydifficult to calculate. In Ebstein's anomaly, there is a disproportionate dilatationof atrialized RV with marked dilatation of the true tricuspid valve annulus (rightatrioventricular junction). The more severe the displacement of the septaltricuspid valve leaflet, more is the atrialized right ventricle, which furtherdilates and leads to dilatation of the true tricuspid valve annulus (i.e. higher Carpentier type). Thus, we propose the measurementof this TTA by echocardiography as a surrogate marker for the severity of Ebstein'sanomaly and suggest that its measurement be used as a guide to decide to add a BCPS.The TTA 'Z' score can be taken as a management tool for the patient with Ebstein'sanomaly. TTA 'Z' scores ≥4 indicate an excessively dilated tricuspid annulus. It is unlikely that this RV will be able to meeta complete cardiac output for long and will continue to dilate unless preload isreduced with a BCPS in addition to the tricuspid valve repair. For TTA 'Z' score of+2 to +4, we recommend the addition of BCPS, especially for patients with Carpentiertype C and D for a long-term volume reduction and a potential RV reverseremodelling. Tricuspid valve with a TTA 'Z' score ≤2represents the 'forme fruste' of Ebstein's anomaly and does not need a BCPS iftricuspid valve repair is being done. The addition of BCPS is further supported byour observations: 1) after plication, the residual volume of RV is approximately 70%of the indexed RV volume expected; 2) The plication of the atrialized RV will leadto splinting effect on the inferior RV wall, which will not contribute to the RVejection; 3) A dilated cardiomyopathic residual RV will not be functioningnormally.Carpentier et al. annulus . The truWe recommend adding BCPS to tricuspid valve repair when:TTA 'Z' score of ≥4 with any Carpentier type;TTA 'Z' score is between +2 and +4 with Carpentier types C and D.described cyanosis as the preoperative criterion to decide to add BCPS, otherwise,this decision was made intraoperatively after coming off bypass. However, we feltthat an addition of BCPS should be an elective rather than a salvage decision. Themoment the BCPS is salvaging the heart and repairing it, it means that the repairwas reactive rather than proactive. In addition, it means that the heart alreadydilated too much to reverse remodel very well, even with preload reduction. Reverseremodelling of the heart is possible with a prophylactic BCPS when myocardial musclefibres were not stretched beyond their maximum sarcomere length because at thatstage myocardial fibres are no longer contractile and act like any other connectivetissue fiber.Malhotra et al.. This is another reason why we started BCPS whenresidual RV volume is less than 80% than expected.In our series, bidirectional Glenn was performed in 20 (90.9%) patients. Theremaining two patients were Carpentier type B, with TTA 'Z' score of 2.2 and 2.1,requiring very minimal plication of the atrialized RV. Their postplication RV volumewas 81% and 84% of the expected indexed RV volume. Therefore, BCPS was notperformed. We observed that patients with type B generally have less displacement,leading to less atrialized RV and required less plication. Thus, BCPS should not beroutinely performed in patients with type B class with a Z score of +2. We alsoobserved that, after plication of the atrialized RV, indexed residual RV volume inour series was much lower than the expected indexed RV volume described in theliterature-21. In ourseries, the residual RV after plication of ARV was 70% of the expected indexed RVvolume, which precludes a biventricular repair. Lange et al. have not added a BCPS totheir repair, probably because of a different subset of patients in their series, astheir postoperative RV end diastolic volume was close to normal. However, they leftan interatrial communication of 5-6 mm in their patients, which would act as atrigger to decompress a failing RV. BCPS proposes to prevent precisely that,i.e., development of RV failure. Chauvaud etal. had36% BCPS in their series, since their patient spectrum was much like ours.In recent years, many authors have published successful management of Ebstein'sanomaly using biventricular approaches-25. A bidirectionalcavopulmonary anastomosis will decrease the volume load on the already compromisedright ventricular geometry in Ebstein's anomaly. Additionally, bidirectionalcavopulmonary anastomosis will reduce transtricuspid valve flow and a moreaggressive tricuspid annuloplasty may be performed, if required, in order to reduceTR to a minimum. Some series have, in fact, demonstrated that reduction of rightventricular preload alone may be sufficient to reduce TR to the point where notricuspid valve intervention is required and maximum native valve structure can bepreserved,18,25.Reduction in the functional RV load will have a significant effect on tricuspidvalvular functionthpostoperative day. Some authors also reported abnormal AV fistulas due toBCPS intheir series, but we have not observed this complication.One of the major concerns in performing a bidirectional cavopulmonary anastomosis isthe effect of elevated pressure and pulsatility in the superior vena cava. However,in our study, facial swelling and upper limb edema was noticed in only one (4.54%)case in the postoperative period, which was also resolved on the 5. In advanced cases, thisdilated RV may cause bulging of ventricular septum leftward and cause compression ofthe left ventricular chamber. Hence, plication of the atrialized RV during surgerywill provide several advantages: 1) Reduction of non-functional portion of the rightventricle; 2) Better blood flow dynamics in right ventricle; 3) Reduction of leftventricular compression, thereby improving left ventricular function; 4) Elevatingthe papillary muscles, which facilitates the closure of the anterior leaflet againstthe septum in systole.Another concern of Ebstein's anomaly is the presence of a dilated atrialized rightventricle, which is a result of right ventricular cardiomyopathy,28. The Ebstein'smalformation is one of the most suitable lesions to which this concept may beapplied, especially because the pulmonary artery pressure in Ebstein's anomaly isnever high. However, poor LVEF, mean PA pressure >20 mmHg, PVR of > 4 Woodunits, LVEDP >12 mmHg preclude one and a half ventricle repair, as alreadymentioned by other authors,25.The one and a half ventricle repair for hypoplastic right heart is increasinglygaining a prominent role in the management of complex congenital heartdiseases,29. More than one accessorypathway is found in 6% to 36% of cases. Most of these accessory pathways aresituated around the malformed tricuspid valve-32.Antegrade and retrograde conduction through these fast conducting atrioventricularaccessory pathways result in arrhythmias such as paroxysmal tachyarrhythmias, wideQRS tachycardia, ventricular tachycardia or flutter, atrial fibrillation or atrialflutter,34. In our study, only one(4.5%) patient had supraventricular tachycardia. Although preoperativeelectrophysiologic studies did not reveal any accessory pathways in this patient, inthe postoperative period, the patient recovered in sinus rhythm and did not have anyepisodes of SVT during follow-up. None of our patients demonstrated arrhythmias inthe postoperative period. We presume that the plication of the true dilatedtricuspid annulus and the dilated atrialized right ventricle, along withcircumferential reattachment of disconnected ATL and PTL to the neoannulus, mayinterrupt some of these accessory pathways, which may help reduce the incidence ofpostoperative arrhythmias. In addition, RAA amputation and right atrial reductionwould prevent arrhythmias originating from RAA due to right atrial dilatation.In Ebstein's anomaly, as the STL is displaced downwards, there is a discontinuity ofcentral fibrous body and septal atrioventricular ring, which results in directmuscular connections between atria and ventricles. These may result inpre-excitation, most commonly for atrioventricular block and rarelyfor sinus node dysfunction. In our study, one (4.5%) patient needed a permanentpostoperative pacemaker for complete heart block. The concern in performing BCPS isthe lost access through superior vena cava for transvenous endocardial leadplacement.In patients with Ebstein's anomaly, permanent postoperative pacing may be required in3.7% of the cases,35 have produced goodresults with biventricular repair, our strategy has to stand the test of time.Magnetic resonance imaging evaluation of these patients during follow-up over alonger period could be more informative.Our study limitation is the small number of patients, the lack of a control groupand the short follow-up period. In addition, the long-term complications ofbidirectional Glenn have to be keep in mind. Our use of the Foley catheter tomeasure RV volume may incur an error of approximately 10% in measurement. Asother authorsEbstein's anomaly is a right ventricular cardiomyopathy and truly a one and a halfventricle heart. A higher TTA 'Z' score correlates with a higher Carpentier classand lower functional RV volume. These patients always do better with completetrileaflet tricuspid repair and offloading of RV with BCPS. TTA 'Z' score ≥4,irrespective of the Carpentier type, should always require a BCPS, while Carpentiertypes C and D with TTA 'Z' score between +2 to +4 should also be considered for aBCPS . Compreh


Left bundle branch block (LBBB) is associated with abnormal left ventricular (LV) contraction, and is frequently associated with co-morbid cardiovascular disease, but the effect of an isolated (i.e. in the absence of cardiovascular dissease) LBBB on biventricular volumes and ejection fraction (EF) is not well characterized. The objective of this study was to compare LV and right ventricular (RV) volumes and EF in adults with an isolated LBBB to matched healthy controls and to population-derived normative values, using cardiovascular magnetic resonance (CMR) imaging.We reviewed our clinical echocardiography database and the Framingham Heart Study Offspring cohort CMR database to identify adults with an isolated LBBB. Age-, sex-, hypertension-status, and body-surface area (BSA)-matched controls were identified from the Offspring cohort. All study subjects were scanned using the same CMR hardware and imaging sequence. Isolated-LBBB cases were compared with matched controls using Wilcoxon paired signed-rank test, and to normative reference values via Z-score.n = 18, 10F) ranged in age from 37 to 82 years. An isolated LBBB was associated with larger LV end-diastolic and end-systolic volumes (both p < 0.01) and lower LVEF  with similar myocardial contraction fraction. LVEF in isolated LBBB was nearly two standard deviations (Z = − 1.95) below mean sex and age-matched group values. LV stroke volume, cardiac output, and mass, and all RV parameters were similar (p = NS) between the groups.Isolated-LBBB subjects (Adults with an isolated LBBB have greater LV volumes and markedly reduced LVEF, despite the absence of overt cardiovascular disease. These data may be useful toward the clinical interpretation of imaging studies performed on patients with an isolated LBBB. The prevalence of left bundle-branch block (LBBB) in the general population has been estimated to range from 0.2 to 1.1% . LBBB isPrior two-dimensional (2D) (non-volumetric) transthoracic echocardiographic studies have shown a reduction in LV ejection fraction (LVEF) , 12 as wWe identified potential cases from two databases: the clinical echocardiography laboratory database at Beth Israel Deaconess Medical Center (BIDMC), and the Framingham Heart Study’s database of Offspring cohort members who underwent CMR during 2002–2006. The BIDMC database was queried to identify all patients referred for a resting transthoracic echocardiogram for assessment of a LBBB from January 2010 through December 2014. Among these patients, echocardiographic reports and other electronic medical record sources were reviewed. Any patient with an echocardiographic abnormality other than presence of abnormal septal motion typical of LBBB or greater than mild valvular disease, was excluded. Additionally, patients with any cardiac symptoms , known cardiovascular disease , age > 85 years, diabetes, peripheral vascular disease, prior cerebrovascular events, or history of potential cardiotoxic chemotherapy exposure were excluded. This process identified 10 adults, who were invited to participate in the present study. Written informed consent was provided by each participant and the study was approved by the BIDMC Committee on Clinical Investigations; the study is in compliance with the Declaration of Helsinki. Verbal confirmation of the absence of CVD, diabetes, and use of chemotherapy were obtained from each subject. Each subject underwent an electrocardiogram (ECG) immediately prior to the CMR to confirm the presence of a LBBB on that day. We further identified 8 adults with isolated LBBB from among the 1794 members of the Framingham Offspring cohort who previously underwent CMR at BIDMC as part of a separate research study . That stn = 18) were selected from among the Framingham Offspring cohort members who previously underwent CMR and were free of clinical CVD and LBBB. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or use of antihypertensive medication.Age-, sex-, hypertension-status and body-surface area (BSA)-matched controls , with a commercial 5-element cardiac array receiver coil. Following localizing scans, 2D end-expiratory breath-hold, ECG-gated, balanced steady-state free precession sequence cine images were obtained in the LV short-axis orientation encompassing both ventricles from base to apex . One slice was acquired with each 10–15 s breath- hold. The same hardware and imaging sequence was used to scan all study participants, including both controls and cases, regardless of whether cases were identified from the BIDMC or Framingham databases.1×A2 /L, where A1 and A2 were areas measured in 2 chamber and 4 chamber views, respectively, and L was the longest atrial length, and RA volume (RAV) = 0.85 × A2/L, where A was area measured in the 4 chamber view.LV endocardial borders were manually traced at end-diastole and end-systole. LV epicardial borders were also traced at end-diastole. For consistency in analysis, LV trabeculations and papillary muscles were considered LV cavitary volume. Stroke volume (SV) was the difference between LV end-diastolic and end-systolic volumes. LVEF and RVEF were computed as SV divided by end-diastolic volume (EDV) in each ventricle. LV mass was calculated by multiplying the end-diastolic myocardial volume by myocardial density (1.05 g/ml) and indexed to BSA. Myocardial contraction fraction (MCF), a volumetric measure of myocardial shortening, was calculated as the ratio of LV SV to LV myocardial volume. Standard 2 chamber and 4 chamber cine images were obtained to determine left atrial (LA) and right atrial (RA) volumes by biplane method (LA volume (LAV) = 0.85×Ap < 0.05 was considered significant. To compare ventricular parameters among isolated-LBBB patients with population-derived reference values, BSA-indexed (i) LV mass and biventricular volumes were converted to Z-scores  based on published sex and 10-year-age-group specific normal values. LV reference values were derived from 852 healthy adults free of any history of hypertension or CVD [Results from normally-distributed continuous data are expressed as mean ± standard deviation (SD). Non-indexed LV and RV parameters were compared between the isolated-LBBB group and matched controls using the Wilcoxon paired signed rank test; a n or CVD  and RV vn or CVD . SpecifiBaseline characteristics are shown in Table p < 0.02), but LV stroke volume and cardiac output were similar (both p = NS). The isolated LBBB group also had a lower LVEF , end-systolic volume (ESV), and end-systolic volume index (ESVi) were greater in the LBBB group than among controls , as was raw LVEF, r = − 0.56, p = 0.017. Both cardiac index and normalized cardiac index were inversely correlated with QRS duration; this was borderline significant for normalized cardiac index  but not cardiac index . LV volumes were not significantly correlated with QRS duration, nor were any RV parameters.Among the patients with isolated LBBB, QRS duration ranged from 126 to 158 ms (mean 142 ± 11 ms). Normalized LVEF (z-score) was inversely correlated with QRS duration with In this CMR study of healthy adults with an isolated LBBB, we found increased LV volumes and lower LVEF than age, sex, hypertension and BSA-matched individuals without LBBB. Compared to population means, LVEF among patients with isolated LBBB was nearly two standard deviations below that of healthy adults; this difference was principally attributable to increased LVESVi, which was over 2 SD greater than the population average. However, LV stroke volume, cardiac output and mass were similar to matched healthy controls and to population averages. Similarly, RV volumes and RVEF did not differ from matched controls or from population averages.p < 0.001). As a result of abnormal septal contribution, global LVEF was reduced in LBBB patients (54 ± 7% vs 62 ± 15%). LV and RV volumes were not reported in their study. Similarly, in another study assessing intraventricular asynchrony by transthoracic echocardiography, Melek and colleagues also found a depressed biplane LVEF in isolated LBBB (54 ± 7% vs 61 ± 6%) [Prior investigators have used non-invasive cardiac imaging to examine LV volumes and LVEF in isolated LBBB. Radionuclide ventriculography was performed by Grines et al. in a study of 18 subjects with isolated LBBB to determine whether the abnormal septal motion in LBBB patients contributed to abnormalities in LV performance . They fo61 ± 6%) . However2 vs 75 ± 11 ml/m2) and LVESV index (47 ± 15 ml/m2 vs 28 ± 6 ml/m2) [2 vs 53 ± 12 g/m2, p = 0.04). In contrast to this and the 2D echocardiographic study of Vernooy et al. [Data suggest that volumetric methods are superior to biplane methods for assessment of LV volumes . van Dij6 ml/m2) . They aly et al. , we founFew data are available on RV volume and EF in isolated LBBB. Van Dijk et al. used 2D Doppler transthoracic echocardiography to assess RV dimensions and function in 15 patients with “asymptomatic” LBBB . RV dimeThe mechanism of the observed depressed LVEF in patients with an isolated LBBB is likely secondary to the altered septal electrical activation  leading MCF is an independent measure of assessing myocardial shortening shown by King et al. to be useful for assessing differences in myocardial performance in patients with similar degree of hypertrophy . In our Our data are overall consistent with prior assessments of isolated LBBB, but augments the literature in several ways. We compared biventricular volumes and global systolic function among persons with isolated LBBB to age/gender matched controls as well as to population-based normative reference values. Use of the Z-score allowed us to quantify deviation from normal in terms of easily interpreted standard deviations. Additionally, we present biventricular results in the same subjects, using image data acquired in the same scanning session. Finally, we used volumetric CMR, which is widely considered the gold standard for determination of ventricular volumes and EF.Our study has several limitations. Similar to prior studies on this topic, the isolated LBBB cohort is relatively small, despite screening four consecutive years of patients from the BIDMC clinical echocardiography database and a subset of the Framingham Offspring cohort. While this is likely a result of the relative rarity of isolated LBBB, our methods allowed us to exclude CVD with high confidence based on review of hospital electronic medical records and extensive Framingham data. CMR contrast was not used and thus no late gadolinium enhancement images were available to assess for occult coronary artery disease or focal fibrosis, but no subject had cine CMR evidence for regional dysfunction other than the septum. Furthermore, our control population had not undergone LGE evaluation and therefore comparison between the two groups would not have been possible. We did not study differences between ECG patterns of LBBB often seen in CAD or myopathic patients, as our subjects were free of these disorders. Finally, data regarding the duration of LBBB and its impact on long-term outcomes are unknown.Using the reference standard of volumetric CMR, adults with an isolated LBBB have greater LV volumes, lower global LVEF, and similar LV mass as compared with age, sex, hypertension-status, and BSA-matched individuals. RV size and function as well as atrial anatomy are similar. These data are important to consider in the clinical interpretation of LV and RV volumes and EF, LV mass, and atrial anatomy in isolated LBBB patients referred for CMR.


Effective mask ventilation is an essential skill for any practitioner engaged in airway management. Recent methods to objectively describe mask ventilation using waveform capnography help practitioners to monitor and communicate the effectiveness of mask ventilation. Gentle mask ventilation is now considered acceptable during rapid sequence induction/intubation after loss of consciousness, hence reducing the incidence of hypoxia prior to tracheal intubation. Mask ventilation can be enhanced with muscle relaxation, a double C-E grip, and jaw thrust. This is particularly relevant for patients with reduced apnoea time. An awareness of the complications associated with mask ventilation may help reduce the morbidity associated with this technique. Effective ventilation technique and optimum device selection are important aspects for resuscitation of the newborn. Teaching correct establishment and maintenance of mask ventilation is essential for safe patient care. This review will examine some of the latest developments concerning mask ventilation for adult and paediatric patients. The latest method to address this problem has also applied waveform capnography as an objective measure of adequate alveolar ventilation2. A four-point scale has been designed which grades the quality of mask ventilation according to the pattern and magnitude of the capnography.Given the significance of mask ventilation (MV), it is important to be able to measure and objectively describe the outcome of this procedure. Previous attempts to do this have been largely subjective, complicated, and rarely applied. In a Japanese Society of Anaesthesiologists airway management guideline, it was proposed that three distinct capnogram waveforms could be used to grade ventilation during MV2) wave and plateau. Grade B has no plateau and a smaller wave with ETCO2 at least 10 mmHg. Grade C has no plateau and ETCO2 <10 mmHg, and grade D has no ETCO2. Objective capnograph findings are supplemented with a check box which includes Guedel airway, one- or two-handed technique, and nasopharyngeal airway. These details help to explain how the difficult MV was managed. Waveform capnography can therefore be used as a monitor of effective mask ventilation and also a method to communicate relative difficulty in a similar way to the Cormack-Lehane scale used to record laryngoscopy. Another helpful objective measure of MV is spirometry. Both inspiration and expiration can be measured with flow volume loops. This facility is available on many anaesthetic machines.Grade A includes a large end-tidal carbon dioxide  was described to avoid aspiration of gastric contents and other debris during emergency airway management5. The incidence of hypoxia during RSII can be as high as 35.9% (SpO2 <95%)6. Hypoxia during this phase is particularly prevalent in those individuals with reduced apnoea tolerance including infants, obese patients, and pregnant women. Oxygen desaturation in overweight patients during RSII was also seen earlier in patients receiving succinylcholine versus rocuronium. This observation was explained by increased metabolism secondary to succinylcholine fasciculations5.It is now known that some patients can become hypoxic during the apnoea phase between pre-oxygenation and tracheal intubation7. This is consistent with a 1987 study of MV during apnoea that demonstrated no gas in the stomach with gentle MV, only half of patients suffering gastric gas with maximal inflation, and no gas in the stomach with cricoid pressure onThe authors’ opinion from the 2015 Difficult Airway Society practice guideline for the management of unexpected difficult tracheal intubation in adults was that gentle MV prior to tracheal intubation is recommended to prolong apnoea time without hypoxiaImmediately after the intravenous injection of anaesthetic drugs, MV becomes necessary to support ventilation and avoid potential airway obstruction. It is common practice for an anaesthetist to apply a face mask to the patient’s face with one hand while squeezing an anaesthetic circuit ventilation bag with the other hand. Similarly, a self-inflating bag is often operated with only one hand applied to the face mask.et al. found that expiratory flow limitation (EFL) and obesity independently explained reduced MV efficiency9. It was also found that resorting to two-handed MV effectively restored inefficient MV. Sato also found that tidal volume during one-handed MV increased by more than 70% during the first minute. This has been attributed to deepening of anaesthesia and the onset of neuromuscular blockade, but other physiological mechanisms could also help to explain this observation. Interaction between lung volume and pharyngeal collapse and increased chest wall rigidity secondary to opiate administration could contribute to difficult MV during anaesthesia, particularly in patients with SDB and obesity. Clinically, obesity, lingual tonsils, and patients with a history of SDB are important to detect preoperatively in an effort to decrease difficult MV11. Obesity was identified as one of the risk factors for difficult and impossible MV13. Correct positioning may improve conditions for effective mask ventilation by adopting anti-Trendelenburg or Fowler positions to reduce abdominal pressure on the diaphragm.In a study comparing MV in normal patients and patients with multiple risk factors for sleep disordered breathing (SDB), Sato14.MV generally improves after the onset of muscle relaxation. Patients with distal airway obstruction, including tracheomalacia and mediastinal masses, are rare exceptions and should not be paralysed. In these cases, paralysis can lead to extrinsic large airway compression, elimination of diaphragmatic movement, and decreased expiratory flow. The practice of testing the quality of MV prior to the administration of neuromuscular blockers is no longer supported15. Airway manoeuvres include jaw thrust, head tilt, and chin lift. Of these, jaw thrust is the most effective to open the obstructed airway in an anaesthetised child16.Maintaining a patent airway during an inhalation induction of anaesthesia can be particularly challenging in infants with micrognathia. Optimum MV techniques may be required in these patients. This technique includes two people: one ventilates the bag using 100% oxygen and a respiratory rate consistent with the resting respiratory rate of the child. A double C-E grip with fingers on the jaw and mask helps to create a jaw thrust and minimises leaks around the mask. Ventilation can then proceed with an assistant squeezing the bag or the use of a pressure-controlled ventilator7. Yet, despite the importance of MV, there are reports of complications arising from MV and known incidences of difficult and impossible MV for adults and children during anaesthesia.Mask ventilation is regarded as the cornerstone of airway management and the position of safety when other airway techniques fail. In the Difficult Airway Society 2015 guidelines for the management of unanticipated difficult intubation in adults, step 3 applies to MV, when tracheal intubation and supraglottic airway insertion have been attempted and failedet al. found a difficult MV incidence of 1.4% (1:71)12. Difficulty was defined as grade 3 on a four-point scale of MV difficulty defined by Hanet al.17. A subsequent study by Kheterpalet al. of 53,041 patients found an incidence of 0.15% (1:666) impossible MV13. Unexpected difficult MV in a group of 484 children was 6.6%18.In a prospective study of 22,660 MV attempts, Kheterpal19. The presence of a beard may create large gas leaks around the face mask. This problem can be pre-empted by shaving the beard or applying an occlusive dressing with a hole cut in it for the mouth. A case of difficult facial morphology, secondary to a frontonasal encephalocele in a term infant, created difficult conditions for MV. This was overcome with a novel solution by using an inverted adult size five face mask over the infant’s face20.Various complications have been reported with MV. Difficulty achieving a seal with the face mask can be attributed to edentulous facies. Replacing the dentures or packing the sides of the face around the facemask are simple solutionsAspiration is a common complication of MV which can be obviated, if possible, by observing fasting guidelines or using a gastric tube to drain the stomach before airway management. Application of cricoid pressure may also help reduce gastric distension during MV, but caution is required because cricoid pressure may also make MV difficult.21.Inability to oxygenate and ventilate during MV can improve with head up positioning, administering a neuromuscular blocker, and the use of oropharyngeal and nasopharyngeal airways, jaw thrust, and two-handed mask ventilation2, leading to vasoconstriction. Small tidal volumes (6–7 ml/kg) and a short inflation duration of 1 second are recommended and help to avoid rapid or forceful breaths22.Poor MV technique can have adverse physiological consequences, particularly during emergency airway management. For example, hyperventilation decreases PaCO23. Each of these components can potentially fail. For example, a case of a faulty non-rebreathing patient valve led to excessive positive end expiratory pressure (PEEP) and inspiration without expiration, causing excessive intrathoracic pressure. The implications of this included decreased lung compliance, high inspiratory pressure, high airway resistance, and a pneumomediastinum. As a consequence of these changes, decreased venous return can lead to decreased cardiac output and a false-negative capnograph can also occur, resulting in a false diagnosis of oesophageal intubation23.Mechanical failure of a non-rebreathing self-inflating bag can cause patient morbidity. There are multiple components to a self-inflating bag including a cuffed mask, non-rebreathing patient valve, self-inflating ventilation bag, air-intake valve, oxygen nipple for oxygen tubing, oxygen reservoir bag, and a reservoir system pressure release valve25. Options to administer PPV include a flow-inflating or self-inflating resuscitation bag or a T-piece resuscitator device. There is little comparative evidence available to evaluate the merits of these devices. Two randomised controlled trials in newborn infants compared the T-piece resuscitator and a self-inflating bag. One examined short- and intermediate-term morbidity and mortality outcomes and found no difference between the two devices26. The other study found that both a mask leak and airway obstruction were common during MV with PPV using a T-piece and a self-inflating bag. These problems can be recognised and corrected by using a respiratory function monitor (RFM) which displays gas flow, tidal volume, and pressure waves27.Up to 10% of newborn infants receive some form of respiratory support at birth. Current American and European resuscitation guidelines recommend the administration of positive pressure ventilation (PPV) to treat apnoea in preterm and term infants28.A study using lung models compared the Ambu self-inflating bag and the Neopuff T-piece resuscitator. Five experienced clinicians ventilated preterm, term, and infant lung models. Compliance, delivery pressure, and inflation rates were measured. The Ambu SIB accurately delivered targeted pressures to all three models, but it was not possible to deliver targeted pressures to the infant model with the Neopuff infant resuscitator29.A clinical study of MV in preterm infants used an RFM to compare spontaneous breaths and PPV using a round silicone face mask and a T-piece device. Tidal volume, peak inspiratory pressure, peak end expiratory pressure, and mask leak were measured. It was found that large leaks occurred around the face mask and high tidal volumes occurred during PPV in contrast to smaller volumes found during spontaneous breathing with CPAP30.A recent prospective cohort study involving 1,962 premature neonates compared PPV at birth with a T-piece resuscitator or self-inflating MV without PEEP. Outcome measures included survival to hospital discharge without bronchopulmonary dysplasia, severe peri-intraventricular haemorrhage, and periventricular leukomalacia. The study showed that the T-piece resuscitator resulted in patients being more likely to survive to hospital discharge while avoiding major morbidities31.MV is an important clinical skill which requires training and practice with good technique. An optimum MV technique has been devised based on a literature review and the development of a conceptual framework. This approach addresses MV in terms of inadequate mask seal, increased airway resistance, and decreased respiratory compliance. Techniques can be taught to address difficulties in each of these categories32. Trainee participants in a paediatric context demonstrated improved tidal volumes and inspiratory pressures when practicing two-person compared to one-person MV33. Training accurate respiratory rates during paediatric MV can be improved with the use of a metronome34.Learning curves are more rapid and less variable for MV than for tracheal intubation. In one study, novice interns achieved a 20% failure rate or better after a median of 25 proceduresThis review of MV emphasises current approaches to this important clinical skill. MV is a core skill in airway management and is the default technique when all others fail. Successful MV requires good technique and regular practice.