Severe mental illness: cardiovascular risk assessment and management.

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.

Peripheral artery disease in patients with schizophrenia as compared to controls.

BACKGROUND: Patients with schizophrenia have an increased prevalence of risk factors for peripheral artery disease (PAD) and is expected to have an increased prevalence of PAD. PAD can be detected utilizing toe-brachial index (TBI) which screens for vascular pathology proximal to the toes. METHODS: Using a cross-sectional design, we defined the subpopulations: (1) Patients diagnosed with schizophrenia less than 2 years before inclusion (SCZ < 2), (2) Psychiatric healthy controls matched to subpopulation 1 on sex, age, and smoking status, and (3) Patients diagnosed with schizophrenia 10 or more years before inclusion (SCZ ≥ 10). TBI was calculated by dividing toe pressures by systolic brachial blood pressure, and PAD was defined by TBI < 0.70. Logistic regression analysis with PAD as outcome and sex, age, smoking status, BMI, skin temperature, diagnosis of schizophrenia, and comorbidities as explanatory variables was conducted. RESULTS: PAD was present in 26.2% of patients diagnosed with SCZ < 2 (17 of 65) and in 18.5% of psychiatric healthy controls (12 of 65) with no statistically significant difference in prevalence rates (p = 0.29). PAD was present in 22.0% of patients diagnosed with SCZ ≥ 10 (31 of 141). In logistic regression, patients diagnosed with SCZ < 2 had an increased odds of PAD with psychiatric healthy controls as reference (Odds ratio = 2.80, 95% confidence interval 1.09-7.23, p = 0.03). The analysis was adjusted for age, sex, smoking status, BMI and comorbidities such as hypertension, diabetes and heart disease. CONCLUSIONS: This study did not find statistically significant increased prevalence rates of PAD in patients with schizophrenia even though patients with SCZ were compared to psychiatric healthy controls using TBI. Utilizing logistic regression PAD was associated with schizophrenia diagnosis within the last 2 years, age and skin temperature. As PAD is initially asymptomatic, screening could be relevant in patients with schizophrenia if other risk factors are prevalent. Further large-scale multicenter studies are warranted to investigate schizophrenia as a potential risk factor for PAD. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02885792.

Time trends of coronary procedures, guideline-based drugs and all-cause mortality following acute coronary syndrome in patients with bipolar disorder.

AIM: This study analyzed time trends in the use of coronary procedures, guideline-based drugs, and 1-year all-cause and presumed cardiovascular mortality (CV) following acute coronary syndrome (ACS) in patients with and without bipolar disorder (BD). METHOD: Using Danish registries 497 patients with ACS and BD in the period 1996-2016 were matched 1:2 on age, sex and year of ACS to patients without preexisting psychiatric disease. RESULTS: Patients with BD and ACS received fewer coronary angiography (CAG) compared to psychiatric healthy controls (PHC). However, the difference between the populations decreased over time. For percutaneous coronary intervention (PCI) and coronary artery bypass (CABG) no differences in trend over time were found. In general patients with BD redeemed fewer prescriptions of guideline-based tertiary prophylactic drugs compared to PHCs. The difference remains constant over time for all drugs except for acetylsalicylic acid, lipid-lowering drugs and beta blockers, where the difference decreased. The 1-year all-cause mortality gap and the presumed CV mortality gap remained unchanged. CONCLUSION: Despite improvements in treatment disparities regarding CAG, acetylsalicylic acid, lipid-lowering drugs and beta-blockers, the treatment gap remained unchanged concerning PCI and CABG. Likewise, patients with BD experienced a lower rate of the remaining redeemed prescriptions. The overall crude mortality risk ratio for patients with BD experiencing ACS remained unchanged over the study period compared to PHC.

Impact of diabetes on 1-year clinical outcome in patients undergoing revascularization with the BioFreedom stents or the Orsiro stents from the SORT OUT IX trial.

This sub-study of the SORT OUT IX trial sought to compare clinical outcomes between patients with diabetes randomized to implantation of either the polymer-free biolimus A9-coated BioFreedom stent (BF-BES) or the ultra-thin strut, biodegradable polymer sirolimus-eluting Orsiro stent (O-SES). Patients with diabetes have an increased risk of target lesion failure (TLF) after percutaneous coronary intervention (PCI). The impact of different stent types in patients with diabetes is still discussed. A total of 607 of the 3151 patients (19.3%) enrolled in the SORT OUT IX study had diabetes. Randomization was stratified by patients with/without diabetes; 304 received BF-BES and 303 O-SES. The primary endpoint was TLF, which was a composite of cardiac death, myocardial infarction (not related to other than the index lesion) and target lesion revascularization (TLR) within 1 year. After 1 year, patients with diabetes had higher TLF (7.2% vs. 3.7%, incidence rate ratio [IRR]: 1.65; 95% confidence interval [CI]: 1.08-2.50), than patients without diabetes. TLF did not differ significantly between BF-BES and O-SES in patients with diabetes (8.2% vs. 6.3%, IRR: 1.17; 95% CI: 0.63-2.20). In patients with diabetes, cardiac death occurred in 2.3% of BF-BES and in 3.6% of O-SES (IRR: 0.58; 95% CI: 0.23-1.45) and TLR occurred in 5.3% and 2.3% of BF-BES and O-SES, respectively (IRR: 2.12; 95% CI: 0.81-5.56). Definite stent thrombosis rates of 1.3% were found in both stent types. Patients with diabetes had higher 1-year TLF rate after PCI compared to patients without diabetes, whereas TLF did not differ significantly between the two stent types BF-BES and O-SES in patients with diabetes.

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

BACKGROUND: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. RESULTS: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001). CONCLUSIONS: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.

In vivo calibration of the T2* cardiovascular magnetic resonance method at 1.5 T for estimation of cardiac iron in a minipig model of transfusional iron overload.

BACKGROUND: Non-invasive estimation of the cardiac iron concentration (CIC) by T2* cardiovascular magnetic resonance (CMR) has been validated repeatedly and is in widespread clinical use. However, calibration data are limited, and mostly from post-mortem studies. In the present study, we performed an in vivo calibration in a dextran-iron loaded minipig model. METHODS: R2* (= 1/T2*) was assessed in vivo by 1.5 T CMR in the cardiac septum. Chemical CIC was assessed by inductively coupled plasma-optical emission spectroscopy in endomyocardial catheter biopsies (EMBs) from cardiac septum taken during follow up of 11 minipigs on dextran-iron loading, and also in full-wall biopsies from cardiac septum, taken post-mortem in another 16  minipigs, after completed iron loading. RESULTS: A strong correlation could be demonstrated between chemical CIC in 55 EMBs and parallel cardiac T2* (Spearman rank correlation coefficient 0.72, P < 0.001). Regression analysis led to [CIC] = (R2* - 17.16)/41.12 for the calibration equation with CIC in mg/g dry weight and R2* in Hz. An even stronger correlation was found, when chemical CIC was measured by full-wall biopsies from cardiac septum, taken immediately after euthanasia, in connection with the last CMR session after finished iron loading (Spearman rank correlation coefficient 0.95 (P < 0.001). Regression analysis led to the calibration equation [CIC] = (R2* - 17.2)/31.8. CONCLUSIONS: Calibration of cardiac T2* by EMBs is possible in the minipig model but is less accurate than by full-wall biopsies. Likely explanations are sampling error, variable content of non-iron containing tissue and smaller biopsies, when using catheter biopsies. The results further validate the CMR T2* technique for estimation of cardiac iron in conditions with iron overload and add to the limited calibration data published earlier.

Coronary artery calcium in patients with schizophrenia.

BACKGROUND: Coronary heart disease (CHD) is a major cause of increased mortality rates in patients with schizophrenia. Moreover, coronary artery calcium (CAC) score is associated with CHD. We hypothesized that patients with schizophrenia have more CAC than the general population and aimed to investigate the CAC score in patients with schizophrenia compared to norms based on the general population. Additionally, this study investigated if age, sex, diabetes, dyslipidemia and smoking were associated with the CAC score. METHODS: In a cross-sectional study, 163 patients with schizophrenia underwent cardiac computed tomography, and the CAC score was measured and compared to norms by classifying the CAC scores in relation to the age- and gender matched norm 50th, 75th and 90th percentiles. Logistic and linear regression were carried out to investigate explanatory variables for the presence and extent of CAC, respectively. RESULTS: A total of 127 (77.9%) patients had a CAC score below or equal to the matched 50th, 20 (12.3%) above the 75th and nine (5.5%) above the 90th percentile. Male sex (P < 0.05), age (P < 0.001) and smoking (P < 0.05) were associated with the presence of CAC while age (P < 0.001) and diabetes (P < 0.01) were associated with the extent of CAC. CONCLUSIONS: The amount of CAC in patients with schizophrenia follows norm percentiles, and variables associated with the CAC score are similar in patients with schizophrenia and the general population. These findings indicate that the CAC score may not be sufficient to detect the risk of CHD in patients with schizophrenia. Future studies should explore other measures of subclinical CHD, including measures of peripheral atherosclerosis or cardiac autonomic neuropathy to improve early detection and intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02885792 , September 1, 2016.

Cardiovascular autonomic neuropathy in patients with schizophrenia.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is an independent predictor of cardiovascular disease (CVD) in patients with diabetes as well as in patients with pre-diabetes and metabolic syndrome. Patients with schizophrenia have an increased rate of metabolic syndrome, pre-diabetes and diabetes as compared to the general population. Despite of this, occurrence CAN has not been investigated in patient with schizophrenia. Therefore, the aims of this study were (1) to evaluate the feasibility testing for CAN with a new clinical tool and (2) report the prevalence of early and manifest CAN in patients with schizophrenia. METHODS AND RESULTS: Patients with diagnosed schizophrenia and with a disease duration ≥10 years were matched 1:1 on age and gender at screening with psychiatric healthy controls. CAN was defined as ≥ two abnormal standard cardiovascular autonomic reflex tests (lying-to-standing, deep breathing, and Valsalva maneuver) using the VagusTM device. A total of 46 patients with schizophrenia were included and matched to psychiatric healthy controls. Manifest CAN were more frequently presented in patients with schizophrenia (39% vs. 6% for controls, p<.0001). Sensitivity analysis of 41 subjects with schizophrenia without diabetes matched to 41 psychiatric healthy controls, showed similar results (37% vs. 5% for controls, p<.0001). CONCLUSION: CAN is highly prevalent in patients with schizophrenia. Testing for CAN is feasible and might be a new clinically tool for detecting early stages of CVD in patients with schizophrenia.

Consequences of parenteral iron-dextran loading investigated in minipigs. A new model of transfusional iron overload.

Patients with blood transfusion-dependent anemias develop transfusional iron overload (TIO), which may cause cardiosiderosis. In patients with an ineffective erythropoiesis, such as thalassemia major, common transfusion regimes aim at suppression of erythropoiesis and of enteral iron loading. Recent data suggest that maintaining residual, ineffective erythropoiesis may protect from cardiosiderosis. We investigated the common consequences of TIO, including cardiosiderosis, in a minipig model of iron overload with normal erythropoiesis. TIO was mimicked by long-term, weekly iron-dextran injections. Iron-dextran loading for around one year induced very high liver iron concentrations, but extrahepatic iron loading, and iron-induced toxicities were mild and did not include fibrosis. Iron deposits were primarily in reticuloendothelial cells, and parenchymal cardiac iron loading was mild. Compared to non-thalassemic patients with TIO, comparable cardiosiderosis in minipigs required about 4-fold greater body iron loads. It is suggested that this resistance against extrahepatic iron loading and toxicity in minipigs may at least in part be explained by a protective effect of the normal erythropoiesis, and additionally by a larger total iron storage capacity of RES than in patients with TIO. Parenteral iron-dextran loading of minipigs is a promising and feasible large-animal model of iron overload, that may mimic TIO in non-thalassemic patients.

Time Trends in the Use of Coronary Procedures, Guideline-Based Therapy, and All-Cause Mortality following the Acute Coronary Syndrome in Patients with Schizophrenia.

AIM: Schizophrenia is associated with high cardiovascular mortality predominantly as a result of acute coronary syndrome (ACS). The aim of this study is to analyze time trends of coronary procedures, guideline-based therapy, and all-cause mortality in patients diagnosed with schizophrenia. METHODS AND RESULTS: This Danish nationwide register-based study analyzed 734 patients with a baseline diagnosis of schizophrenia and an incident diagnosis of ACS in the period between January 1, 1996, and December 31, 2015. The 734 patients with schizophrenia were matched to 2,202 psychiatric healthy controls (PHC). No change over time was seen in the relative difference between the population with schizophrenia and the PHC in the use of coronary angiography, percutaneous coronary intervention, and coronary bypass grafting, nor in 1-year mortality or guideline-based therapy following ACS. Patients with schizophrenia had higher prevalence rates of diabetes, chronic obstructive pulmonary disease, and stroke, and a lower prevalence of hypertension (p < 0.05). CONCLUSION: The gap in the use of coronary procedures, guideline-based therapy, and all-cause mortality following ACS in patients with schizophrenia compared to those without has remained constant over the past 2 decades.

Comparison of the polymer-free biolimus-coated BioFreedom stent with the thin-strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population treated with percutaneous coronary intervention: Rationale and design of the randomized SORT OUT IX trial.

BACKGROUND: In patients with increased bleeding risk during dual antiplatelet therapy, the biolimus A9-coated BioFreedom, a stainless steel drug-coated stent devoid of polymer, has shown superiority compared to a bare-metal stent. The aim of this study was to investigate whether the polymer-free biolimus A9-coated BioFreedom is noninferior to a modern thin-strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The multicenter SORT OUT IX trial (NCT02623140) randomly assigned all-comers patients to treatment with the BioFreedom drug-coated stent or the biodegradable polymer Orsiro stent in 4 Danish University Hospitals. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection based on Danish registries will be used and continue through 5 years. Assuming an event rate of 4.2% in each stent group, 1,563 patients in each treatment arm will provide 90% power to detect noninferiority of the drug-coated BioFreedom stent with a noninferiority margin of 2.1%. RESULTS: A total of 3,150 patients have been randomized and enrolled in the study. CONCLUSIONS: The SORT OUT IX trial will determine whether the drug-coated BioFreedom stent is noninferior to a modern biodegradable polymer Orsiro stent.

BEtablocker Treatment After acute Myocardial Infarction in revascularized patients without reduced left ventricular ejection fraction (BETAMI): Rationale and design of a prospective, randomized, open, blinded end point study.

BACKGROUND: Current guidelines on the use of ß-blockers in post-acute myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF) are based on studies before the implementation of modern reperfusion and secondary prevention therapies. It remains unknown whether ß-blockers will reduce mortality and recurrent MI in contemporary revascularized post-MI patients without reduced LVEF. DESIGN: BETAMI is a prospective, randomized, open, blinded end point multicenter study in 10,000 MI patients designed to test the superiority of oral ß-blocker therapy compared to no ß-blocker therapy. Patients with LVEF ≥40% following treatment with percutaneous coronary intervention or thrombolysis and/or no clinical signs of heart failure are eligible to participate. The primary end point is a composite of all-cause mortality or recurrent MI obtained from national registries over a mean follow-up period of 3 years. Safety end points include rates of nonfatal MI, all-cause mortality, ventricular arrhythmias, and hospitalizations for heart failure obtained from hospital medical records 30 days after randomization, and from national registries after 6 and 18 months. Key secondary end points include recurrent MI, heart failure, cardiovascular and all-cause mortality, and clinical outcomes linked to ß-blocker therapy including drug adherence, adverse effects, cardiovascular risk factors, psychosocial factors, and health economy. Statistical analyses will be conducted according to the intention-to-treat principle. A prespecified per-protocol analysis (patients truly on ß-blockers or not) will also be conducted. CONCLUSIONS: The results from the BETAMI trial may have the potential of changing current clinical practice for treatment with ß-blockers following MI in patients without reduced LVEF. EudraCT number 2018-000590-75.

Impact of diabetes on clinical outcomes after revascularization with sirolimus-eluting and biolimus-eluting stents with biodegradable polymer from the SORT OUT VII trial.

OBJECTIVES: In this substudy of the SORT OUT VII trial, the clinical outcomes among patient with diabetes mellitus treated with Orsiro sirolimus-eluting stent (O-SES; Biotronik, Bülach, Switzerland) or Nobori biolimus-eluting stent (N-BES; Terumo, Tokyo, Japan) were compared. BACKGROUND: Diabetes is associated with increased risk of target lesion failure (TLF) after percutaneous coronary intervention. METHODS: In total, 2525 patients were randomized to stent implantation with O-SES (n = 1261, diabetes: n = 236) or N-BES (n = 1264, diabetes: n = 235). The primary endpoint, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 2 years. RESULTS: At 2 year, TLF did not differ between O-SES vs N-BES in diabetic (9.3% vs 9.4%; RR 0.98, 95% CI 0.54-1.78) patients. The individual components of the primary endpoint did not differ among stent type. In diabetics, cardiac death occurred in 3% of O-SES-treated and in 3.8% of N-BES-treated patients (RR 0.77, 95% CI 0.29-2.08), MI occurred in 3.0% of O-SES-treated and in 3.8% of N-BES-treated patients (RR 0.76, 95% CI 0.28-2.06) and TLR occurred in 5,5% of O-SES-treated and in 6.0% of N-BES-treated patients (RR 0.91, 95% CI 0.43-1.95). CONCLUSION: TLF did not differ between O-SES- and N-BES-treated diabetic patients.

Coronary stent implantation and adverse cardiac events after surgery.

BACKGROUND: In the risk assessment of patients considered for non-cardiac surgery and with recent coronary stent implantation, coronary drug-eluting stent implantation procedure characteristics may be taken into account. We aimed to evaluate associations between coronary drug-eluting stent implantation procedure characteristics and the risk of myocardial infarction and all-cause death within 30 days after non-cardiac surgery. DESIGN: Patients with coronary drug-eluting stents were identified using the Western Denmark Heart Registry. Surgical procedures performed after stent implantation were detected using the Danish National Patient Registry. We used registry-based detection of myocardial infarction and all-cause death. RESULTS: Of 22 590 patients treated with drug-eluting stents between 2005 and 2012, 4046 underwent non-cardiac surgery within 1 and 12 months after stent implantation. We found no significant association between the risk of myocardial infarction or all-cause death within 30 days after surgery and number of arteries treated (1 [reference] vs more), number of lesions treated (1 [reference] vs more), segments treated (left main and proximal left anterior descending artery vs other [reference]), total stent length (<20 mm [reference] vs ≥20 mm), number of stents (1 [reference] vs >1) and largest balloon diameter (≥3 mm [reference] vs <3 mm). All-cause death, but not myocardial infarction, risk was lower among patients treated with first-generation vs second-generation stents (odds ratio 0.58). CONCLUSIONS: We identified no significant associations between stent implantation procedure characteristics and risk of myocardial infarction or all-cause death among patients undergoing non-cardiac surgery. All-cause death was lower with first- vs second-generation drug-eluting stents.

The significance of ST-elevation in aVL in anterolateral myocardial infarction: An assessment by cardiac magnetic resonance imaging.

BACKGROUND: Anterolateral myocardial infarction (MI) is traditionally defined on the electrocardiogram by ST-elevation (STE) in I, aVL, and the precordial leads. Traditional literature holds STE in lead aVL to be associated with occlusion proximal to the first diagonal branch of the left anterior descending coronary artery. However, concomitant ischemia of the inferior myocardium may theoretically lead to attenuation of STE in aVL. We compared segmental distribution of myocardial area at risk (MaR) in patients with and without STE in aVL. METHODS: We identified patients in the MITOCARE study presenting with a first acute MI and new STE in two contiguous anterior leads from V1 to V6 , with or without aVL STE. Patients underwent cardiac magnetic resonance imaging 3-5 days after acute infarction for quantitative assessment of MaR. RESULTS: A total of 32 patients met inclusion criteria; 13 patients with and 19 without STE in lead aVL. MaR > 20% at the basal anterior segment was seen in 54% of patients with aVL STE, and 11% of those without (p = 0.011). MaR > 20% at the apical inferior segment was seen in 62% and 95% of patients with and without aVL STE, respectively (p = 0.029). The total MaR was not different between groups (44% ± 10% and 39% ± 8.3% respectively, p = 0.15). CONCLUSION: Patients with anterior STEMI and concomitant STE in aVL have less MaR in the apical inferior segment and more MaR in the basal anterior segment.

Correlation of anteroseptal ST elevation with myocardial infarction territories through cardiovascular magnetic resonance imaging.

BACKGROUND: Anteroseptal ST elevation myocardial infarction (STEMI) is traditionally defined on the electrocardiogram (ECG) by ST elevation (STE) in leads V1-V3, with or without involvement of lead V4. It is commonly taught that such infarcts affect the basal anteroseptal myocardial segment. While there are suggestions in the literature that Q waves limited to V1-V4 represent predominantly apical infarction, none have evaluated anteroseptal ST elevation territories. We compared the distribution of the myocardium at risk (MaR) in STEMI patients presenting with STE limited to V1-V4 and those with more extensive STE (V1-V6). METHODS: We identified patients in the MITOCARE study presenting with a first acute STEMI and new STE in at least two contiguous anterior leads from V1 to V6. Patients underwent cardiac magnetic resonance (CMR) imaging three to five days after acute infarction. RESULTS: Thirty-two patients met inclusion criteria. In patients with STE in V1-V4 (n = 20), myocardium at risk (MaR) > 50% was seen in 0%, 85%, 75%, 100%, and 90% in the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. The group with STE in V1-V6 (n = 12), MaR > 50% was seen in 8%, 83%, 83%, 92%, and 83% of the same segments. CONCLUSIONS: Patients with acute STEMI and STE in leads V1-V4, exhibit MaR in predominantly apical territories and rarely in the basal anteroseptum. We found no evidence to support existence of isolated basal anteroseptal or septal STEMI. "Anteroapical" infarction is a more precise description than "anteroseptal" infarction for acute STEMI patients exhibiting STE in V1-V4.

Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: Terminal "QRS distortion" on the electrocardiogram (ECG) (based on Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia, associated with adverse cardiovascular outcome in ST-segment elevation myocardial infarction (STEMI). In addition, ECG indices of the acuteness of ischemia (based on Anderson-Wilkins Acuteness Score) indicate myocardial salvage potential. We assessed whether severe ischemia with or without acute ischemia is predictive of infarct size (IS), myocardial salvage index (MSI) and left ventricular ejection fraction (LVEF) in anterior versus inferior infarct locations. METHODS: In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2-6days after primary percutaneous coronary intervention (pPCI). LVEF was measured by echocardiography 30days after pPCI. RESULTS: ECG analysis of 85 patients with available CMR resulted in 20 (23%) cases with severe and non-acute ischemia, 43 (51%) with non-severe and non-acute ischemia, 17 (20%) with non-severe and acute ischemia, and 5 (6%) patients with severe and acute ischemia. In patients with anterior STEMI (n=35), ECG measures of severity and acuteness of ischemia identified significant and stepwise differences in myocardial damage and function. Patients with severe and non-acute ischemia had the largest IS, smallest MSI and lowest LVEF. In contrast, no difference was observed in patients with inferior STEMI (n=50). CONCLUSIONS: The applicability of ECG indices of severity and acuteness of myocardial ischemia to estimate myocardial damage and salvage potential in STEMI patients treated with pPCI, is confined to anterior myocardial infarction.

Appropriateness of anteroseptal myocardial infarction nomenclature evaluated by late gadolinium enhancement cardiovascular magnetic resonance imaging.

BACKGROUND: In traditional literature, it appears that "anteroseptal" MIs with Q waves in V1-V3 involve basal anteroseptal segments although studies have questioned this belief. METHODS: We studied patients with first acute anterior Q-wave (>30ms) MI. All underwent late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI). RESULTS: Those with Q waves in V1-V2 (n=7) evidenced LGE >50% in 0%, 43%, 43%, 57%, and 29% of the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. Patients with Q waves in V1-V3 (n=14), evidenced involvement was 14%, 43%, 43%, 50%, and 7% of the same respective segments. In those with extensive anterior Q waves (n=7), involvement was 0%, 71%, 57%, 86%, and 86%. CONCLUSIONS: Q-wave MI in V1-V2/V3 primarily involves mid- and apical anterior and anteroseptal segments rather than basal segments. Data do not support existence of isolated basal anteroseptal or septal infarction. "Anteroapical infarction" is a more appropriate term than "anteroseptal infarction."

Administration of the Mitochondrial Permeability Transition Pore Inhibitor, TRO40303, prior to Primary Percutaneous Coronary Intervention, Does Not Affect the Levels of Pro-Inflammatory Cytokines or Acute-Phase Proteins.

OBJECTIVES: In the MITOCARE study, reperfusion injury was not prevented after administration of the mitochondrial permeability transition pore (mPTP) opening inhibitor, TRO40303, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The effects of TRO40303 on pro-inflammatory cytokines and acute-phase proteins were assessed. METHODS: STEMI patients (n = 163, mean age 62 years) with chest pain within 6 h before admission for pPCI were randomized to intravenous bolus of TRO40303 (n = 83) or placebo (n = 80) prior to reperfusion. We tested whether the groups differed in levels of IL-1ß, IL-6, IL-10, TNF, and high-sensitive C-reactive protein at various time points (0, 12, and 72 h) after PCI. Further, potential differences between groups in the change of biomarker levels between 0 and 72 h, 0 and 12 h, and 12 and 72 h were tested. RESULTS: There were no statistically significant differences between the two groups, neither in levels of pro-inflammatory cytokines nor in levels of acute-phase proteins, and there were no statistically significant differences in the change of biomarker levels between the groups considering the time intervals from 0 to 72 h, from 0 to 12 h, and from 12 to 72 h. CONCLUSION: The administration of the mPTP, TRO40303, prior to reperfusion does not alter the pharmacokinetics of pro-inflammatory cytokines or acute-phase proteins during the first 72 h after PCI.

Time-resolved tracking of the atrioventricular plane displacement in Cardiovascular Magnetic Resonance (CMR) images.

BACKGROUND: Atrioventricular plane displacement (AVPD) is an indicator for systolic and diastolic function and accounts for 60% of the left ventricular, and 80% of the right ventricular stroke volume. AVPD is commonly measured clinically in echocardiography as mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE), but has not been applied widely in cardiovascular magnetic resonance (CMR). To date, there is no robust automatic algorithm available that allows the AVPD to be measured clinically in CMR with input in a single timeframe. This study aimed to develop, validate and provide a method that automatically tracks the left and right ventricular AVPD in CMR images, which can be used in the clinical setting or in applied cardiovascular research in multi-center studies. METHODS: The proposed algorithm is based on template tracking by normalized cross-correlation combined with a priori information by principal component analysis. The AVPD in each timeframe is calculated for the left and right ventricle separately using CMR long-axis cine images of the 2, 3, and 4-chamber views. The algorithm was developed using a training set (n = 40), and validated in a test set (n = 113) of healthy subjects, athletes, and patients after ST-elevation myocardial infarction from 10 centers. Validation was done using manual measurements in end diastole and end systole as reference standard. Additionally, AVPD, peak emptying velocity, peak filling velocity, and atrial contraction was validated in 20 subjects, where time-resolved manual measurements were used as reference standard. Inter-observer variability was analyzed in 20 subjects. RESULTS: In end systole, the difference between the algorithm and the reference standard in the left ventricle was (mean ± SD) -0.6 ± 1.9 mm (R = 0.79), and -0.8 ± 2.1 mm (R = 0.88) in the right ventricle. Inter-observer variability in end systole was -0.6 ± 0.7 mm (R = 0.95), and -0.5 ± 1.4 mm (R = 0.95) for the left and right ventricle, respectively. Validation of peak emptying velocity, peak filling velocity, and atrial contraction yielded lower accuracy than the displacement measures. CONCLUSIONS: The proposed algorithm show good agreement and low bias with the reference standard, and with an agreement in parity with inter-observer variability. Thus, it can be used as an automatic method of tracking and measuring AVPD in CMR.