Reply to Sanfilippo et al. Caution Is Warranted When Assessing Diastolic Function Using Transesophageal Echocardiography. Comment on "Kyle et al. Consensus Defined Diastolic Dysfunction and Cardiac Postoperative Morbidity Score: A Prospective Observational Study. J. Clin. Med. 2021, 10, 5198".

We thank Sanfilippo and colleagues for their insightful comments about the assessment of diastolic function with transesophageal echocardiography (TEE) [...].

Negative interaction between nitrates and remote ischemic preconditioning in patients undergoing cardiac surgery: the ERIC-GTN and ERICCA studies.

Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2-5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413-0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.

Consensus Defined Diastolic Dysfunction and Cardiac Postoperative Morbidity Score: A Prospective Observational Study.

Diastolic dysfunction is associated with major adverse outcomes following cardiac surgery. We hypothesized that multisystem endpoints of morbidity would be higher in patients with diastolic dysfunction. A total of 142 patients undergoing cardiac surgical procedures with cardiopulmonary bypass were included in the study. Intraoperative assessments of diastolic function according to the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines using transesophageal echocardiography were performed. Cardiac Postoperative Morbidity Score (CPOMS) on days 3, 5, 8, and 15; length of stay in ICU and hospital; duration of intubation; incidence of new atrial fibrillation; 30-day major adverse cardiac and cerebrovascular events were recorded. Diastolic function was determinable in 96.7% of the dataset pre and poststernotomy assessment (n = 240). Diastolic dysfunction was present in 70.9% (n = 88) of measurements before sternotomy and 75% (n = 93) after sternal closure. Diastolic dysfunction at either stage was associated with greater CPOMS on D5 (p = 0.009) and D8 (p = 0.009), with CPOMS scores 1.24 (p = 0.01) higher than in patients with normal function. Diastolic dysfunction was also associated with longer durations of intubation (p = 0.001), ICU length of stay (p = 0.019), and new postoperative atrial fibrillation (p = 0.016, OR (95% CI) = 4.50 (1.22-25.17)). We were able to apply the updated ASE/EACVI guidelines and grade diastolic dysfunction in the majority of patients. Any grade of diastolic dysfunction was associated with greater all-cause morbidity, compared with patients with normal diastolic function.

Diagnostic performance of T1 and T2 mapping to detect intramyocardial hemorrhage in reperfused ST-segment elevation myocardial infarction (STEMI) patients.

PURPOSE: To investigate the performance of T1 and T2 mapping to detect intramyocardial hemorrhage (IMH) in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). MATERIALS AND METHODS: Fifty STEMI patients were prospectively recruited between August 2013 and July 2014 following informed consent. Forty-eight patients completed a 1.5T cardiac magnetic resonance imaging (MRI) with native T1 , T2 , and T2* maps at 4 ± 2 days. Receiver operating characteristic (ROC) analyses were performed to assess the performance of T1 and T2 to detect IMH. RESULTS: The mean age was 59 ± 13 years old and 88% (24/48) were male. In all, 39 patients had interpretable T2* maps and 26/39 (67%) of the patients had IMH ( T2* <20 msec on T2* maps). Both T1 and T2 values of the hypointense core within the area-at-risk (AAR) performed equally well to detect IMH (T1 maps AUC 0.86 [95% confidence interval [CI] 0.72-0.99] versus T2 maps AUC 0.86 [95% CI 0.74-0.99]; P = 0.94). Using the binary assessment of presence or absence of a hypointense core on the maps, the diagnostic performance of T1 and T2 remained equally good (T1 AUC 0.87 [95% CI 0.73-1.00] versus T2 AUC 0.85 [95% CI 0.71-0.99]; P = 0.90) with good sensitivity and specificity (T1 : 88% and 85% and T2 : 85% and 85%, respectively). CONCLUSION: The presence of a hypointense core on the T1 and T2 maps can detect IMH equally well and with good sensitivity and specificity in reperfused STEMI patients and could be used as an alternative when T2* images are not acquired or are not interpretable. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:877-886.

Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling.

BACKGROUND: The presence of intramyocardial hemorrhage (IMH) in ST-segment-elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. METHODS AND RESULTS: Forty-eight ST-segment-elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54-64] ms versus 53 [51-56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson's rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). CONCLUSIONS: The majority of ST-segment-elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with persistently elevated T2 values in the surrounding infarct tissue and adverse LV remodeling. IMH and residual myocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment-elevation myocardial infarction patients.

Automated Extracellular Volume Fraction Mapping Provides Insights Into the Pathophysiology of Left Ventricular Remodeling Post-Reperfused ST-Elevation Myocardial Infarction.

BACKGROUND: Whether the remote myocardium of reperfused ST-segment elevation myocardial infarction (STEMI) patients plays a part in adverse left ventricular (LV) remodeling remains unclear. We aimed to use automated extracellular volume fraction (ECV) mapping to investigate whether changes in the ECV of the remote (ECVR emote) and infarcted myocardium (ECVI nfarct) impacted LV remodeling. METHODS AND RESULTS: Forty-eight of 50 prospectively recruited reperfused STEMI patients completed a cardiovascular magnetic resonance at 4±2 days and 40 had a follow-up scan at 5±2 months. Twenty healthy volunteers served as controls. Mean segmental values for native T1, T2, and ECV were obtained. Adverse LV remodeling was defined as ≥20% increase in LV end-diastolic volume. ECVR emote was higher on the acute scan when compared to control (27.9±2.1% vs 26.4±2.1%; P=0.01). Eight patients developed adverse LV remodeling and had higher ECVR emote acutely (29.5±1.4% vs 27.4±2.0%; P=0.01) and remained higher at follow-up (28.6±1.5% vs 26.6±2.1%; P=0.02) compared to those without. Patients with a higher ECVR emote and a lower myocardial salvage index (MSI) acutely were significantly associated with adverse LV remodeling, independent of T1Remote, T1Core and microvascular obstruction, whereas a higher ECVI nfarct was significantly associated with worse wall motion recovery. CONCLUSIONS: ECVR emote was increased acutely in reperfused STEMI patients. Those with adverse LV remodeling had higher ECVR emote acutely, and this remained higher at follow-up than those without adverse LV remodeling. A higher ECVR emote and a lower MSI acutely were significantly associated with adverse LV remodeling whereas segments with higher ECVI nfarct were less likely to recover wall motion.

Effect of Remote Ischaemic Conditioning in Oncology Patients Undergoing Chemotherapy: Rationale and Design of the ERIC-ONC Study--A Single-Center, Blinded, Randomized Controlled Trial.

Cancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long-term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia-reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia-reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC-ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC-ONC trial is a single-center, blinded, randomized, sham-controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline-based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5-minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high-sensitivity troponin-T over 6 cycles of chemotherapy and 12 months follow-up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N-terminal pro-brain natriuretic peptide levels at 3 months follow-up, and changes in mitochondrial DNA, micro-RNA, and proteomics after chemotherapy. The ERIC-ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low-cost cardioprotectant in cancer patients undergoing anthracycline-based chemotherapy.

Early targeted brain COOLing in the cardiac CATHeterisation laboratory following cardiac arrest (COOLCATH).

INTRODUCTION: Trials demonstrate significant clinical benefit in patients receiving therapeutic hypothermia (TH) after cardiac arrest. However, incidence of mortality and morbidity remains high in this patient group. Rapid targeted brain hypothermia induction, together with prompt correction of the underlying cause may improve outcomes in these patients. This study investigates the efficacy of Rhinochill, an intranasal cooling device over Blanketrol, a surface cooling device in inducing TH in cardiac arrest patients within the cardiac catheter laboratory. METHODS: 70 patients were randomized to TH induction with either Rhinochill or Blanketrol. Primary outcome measures were time to reach tympanic ≤34 °C from randomisation as a surrogate for brain temperature and oesophageal ≤34 °C from randomisation as a measurement of core body temperature. Secondary outcomes included first hour temperature drop, length of stay in intensive care unit, hospital stay, neurological recovery and all-cause mortality at hospital discharge. RESULTS: There was no difference in time to reach ≤34 °C between Rhinochill and Blanketrol (Tympanic ≤34 °C, 75 vs. 107 mins; p=0.101; Oesophageal ≤34 °C, 85 vs. 115 mins; p=0.151). Tympanic temperature dropped significantly with Rhinochill in the first hour (1.75 vs. 0.94 °C; p<0.001). No difference was detected in any other secondary outcome measures. Catheter laboratory-based TH induction resulted in a survival to hospital discharge of 67.1%. CONCLUSION: In this study, Rhinochill was not found to be more efficient than Blanketrol for TH induction, although there was a non-significant trend in favour of Rhinochill that potentially warrants further investigation with a larger trial.

The Effect of Remote Ischemic Conditioning and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients: Rationale and Design of the ERIC-GTN Study.

Remote ischemic conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce perioperative myocardial injury in patients undergoing coronary artery bypass grafting and/or valve surgery. The role of intravenous glyceryl trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial ( http://www.clinicaltrials.gov: NCT01864252). The ERIC-GTN trial is a single-site, double-blind, randomized, placebo-controlled study. Consenting adult patients (age > 18 years) undergoing elective coronary artery bypass grafting ± valve surgery with blood cardioplegia will be eligible for inclusion. Two hundred sixty patients will be randomized to 1 of 4 treatment groups following anesthetic induction: (1) RIC alone, a RIC protocol comprising three 5-minute cycles of simultaneous upper-arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone, a simulated sham RIC protocol followed by an IV GTN infusion; (3) RIC + GTN, a RIC protocol followed by an IV GTN infusion; and (4) neither RIC nor GTN, a sham RIC protocol followed by IV placebo infusion. The primary endpoint will be perioperative myocardial injury as quantified by the 72-hour area-under-the-curve serum high-sensitivity troponin T. The ERIC-GTN trial will determine whether intraoperative GTN therapy is cardioprotective during cardiac surgery and whether it affects RIC cardioprotection.

Lack of language skills and knowledge of local culture in international medical graduates: Implications for the NHS.

International Medical Graduates (IMGs) form a coherent part of the National Health Service (NHS). Nearly 25% of the doctors working in the NHS are IMGs who obtained their primary medical degree from outside the EU. Moving to a different country that holds a different set of values and belief systems can be very challenging for IMGs, which in turn could have a significant effect on the service provided to NHS patients. This article will address the issue of effective communication skills within the IMG population and will explore the underlying issues behind this problem.