Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction.

Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .

Cardiovascular magnetic resonance evaluation of symptomatic severe aortic stenosis: association of circumferential myocardial strain and mortality.

BACKGROUND: It is unknown whether circumferential strain is associated with prognosis after treatment of aortic stenosis (AS). We aimed to characterise strain in severe AS, using myocardial tagging cardiovascular magnetic resonance (CMR), prior to and following Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR), and determine whether abnormalities in strain were associated with outcome. METHODS: CMR was performed pre- and 6 m post-intervention in 98 patients (52 TAVI, 46 SAVR; 77 ± 8 years) with severe AS. TAVI patients were older (80.9 ± 6.4 vs. 73.0 ± 7.0 years, p < 0.01) with a higher STS score (2.06 ± 0.6 vs. 6.03 ± 3.4, p < 0.001). Tagged cine images were acquired at the basal, mid and apical LV levels with a complementary spatial modulation of magnetization (CSPAMM) pulse sequence. Circumferential strain, strain rate and rotation were calculated using inTag© software. RESULTS: No significant change in basal or mid LV circumferential strain, or of diastolic strain rate, was seen following either intervention. However, a significant and comparable decline in LV torsion and twist was observed (SAVR: torsion 14.08 ± 8.40 vs. 7.81 ± 4.51, p < 0.001, twist 16.17 ± 7.01 vs.12.45 ± 4.78, p < 0.01; TAVI: torsion 14.43 ± 4.66 vs. 11.20 ± 4.62, p < 0.001, twist 16.08 ± 5.36 vs. 12.36 ± 5.21, p < 0.001) which likely reflects an improvement towards normal physiology following relief of AS. Over a maximum 6.0y follow up, there were 23 (16%) deaths following valve intervention. On multivariable Cox analysis, baseline mid LV circumferential strain was significantly associated with all-cause mortality (hazard ratio, 1.03; 1.01-1.05; p = 0.009) independent of age, LV ejection fraction and STS mortality risk score. ROC analysis indicated a mid LV circumferential strain > -18.7% was associated with significantly reduced survival. CONCLUSION: TAVI and SAVR procedures are associated with comparable declines in rotational LV mechanics at 6 m, with largely unchanged strain and strain rates. Pre-operative peak mid LV circumferential strain is associated with post-operative mortality.

Comparison of global myocardial strain assessed by cardiovascular magnetic resonance tagging and feature tracking to infarct size at predicting remodelling following STEMI.

BACKGROUND: To determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) remodelling independent of infarct size (IS). METHODS: Sixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1-3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling - a composite score based on development of either end-diastolic volume index [EDVI] ≥20% or end-systolic volume index [ESVI] ≥15% at follow-up compared to baseline. RESULTS: The magnitude of GCS was higher when measured using FT (-21.1 ± 6.3%) than with tagging (-12.1 ± 4.3; p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64-to 0.71) and IS (ρ -0.62 to-0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling - Odds Ratio 1.05 (95% CI 1.01-1.10, p = 0.03), area under the ROC curve 0.70 (95% CI 0.52-0.87, p = 0.04). CONCLUSION: Baseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI.

Assessment of aortic stiffness by cardiovascular magnetic resonance following the treatment of severe aortic stenosis by TAVI and surgical AVR.

BACKGROUND: Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV). METHODS AND RESULTS: A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m. CONCLUSIONS: Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved.

Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile: A pooled analysis.

BACKGROUND: The diagnosis of type 2 diabetes (T2D) in younger adults, an increasingly common public health issue, is associated with a higher risk of cardiovascular complications and mortality, which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age. AIM: To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D. METHODS: A pooled dataset was used, comprised of data from five previous studies of adults with T2D, including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years. Anthropometric and blood biomarker measurements included body weight, body mass index (BMI), waist circumference, body fat percentage, glycaemic control (HbA1c), lipid profile and blood pressure. Univariable and multivariable linear regression models, adjusted for diabetes duration, sex, ethnicity and smoking status, were used to investigate the association between age at diagnosis and each cardiovascular risk factor. RESULTS: A higher proportion of participants diagnosed with T2D under the age of 40 were female, current smokers and treated with glucose-lowering medications, compared to participants diagnosed later in life. Participants diagnosed with T2D under the age of 40 also had higher body weight, BMI, waist circumference and body fat percentage, in addition to a more adverse lipid profile, compared to participants diagnosed at an older age. Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight [95% confidence interval (CI): 0.52-0.82 kg], 0.18 kg/m2 higher BMI (95%CI: 0.10-0.25) and 0.32 cm higher waist circumference (95%CI: 0.14-0.49), after adjustment for duration of diabetes and other confounders. Younger age at diagnosis was also significantly associated with higher HbA1c, total cholesterol, low-density lipoprotein cholesterol and triglycerides. CONCLUSION: The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile, compared to those diagnosed later in life.

Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date.

The prevalence of type 2 diabetes (T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms, with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.

Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.

OBJECTIVE: To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). DESIGN: A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. SETTING: University hospitals of Leeds and Leicester, UK. PATIENTS: 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. MAIN OUTCOME MEASURES: Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. RESULTS: All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. CONCLUSIONS: There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.

Semi-quantitative assessment of right ventricular function in comparison to a 3D volumetric approach: a cardiovascular magnetic resonance study.

Right ventricular (RV) volume measurements with cardiovascular magnetic resonance (CMR) is considered the gold standard, but acquisition and analysis remain time-consuming. The aim of our study was therefore to investigate the accuracy and performance of a semi-quantitative assessment of RV function in CMR, compared to the standard quantitative approach. Seventy-five subjects with pulmonary hypertension (15), anterior myocardial infarction (15), inferior myocardial infarction (15), Brugada syndrome (15) and normal subjects (15) underwent cine CMR. RV end-systolic and end-diastolic volumes were determined to calculate RV ejection fraction (EF). Four-chamber cine images were used to measure tricuspid annular plane systolic excursion (TAPSE). RV fractional shortening (RVFS) was calculated by dividing TAPSE by the RV end-diastolic length. RV EF correlated significantly with TAPSE (r = 0.62, p < 0.01) and RVFS (r = 0.67, p < 0.01). Sensitivity to predict RV dysfunction was comparable between TAPSE and RVFS, with higher specificity for RVFS, but comparable areas under the ROC curve. Intra- and inter-observer variability of RV EF was better than TAPSE (3%/4% versus 7%/15%, respectively). For routine screening in clinical practice, TAPSE and RVFS seem reliable and easy methods to identify patients with RV dysfunction. The 3D volumetric approach is preferred to assess RV function for research purposes or to evaluate treatment response.

Extent of myocardial infarction and reverse remodeling assessed by cardiac magnetic resonance in patients with and without right bundle branch block following alcohol septal ablation for obstructive hypertrophic cardiomyopathy.

Percutaneous alcohol septal ablation (ASA) is an established technique for the relief of refractory symptoms in patients with obstructive hypertrophic cardiomyopathy. Most subjects develop right bundle branch block (RBBB) after ASA, but it is not known whether these patients have similar infarct characteristics, which may influence left ventricular (LV) pressure gradient reduction and reverse remodeling, compared with those without RBBB. Twenty-seven consecutive patients (15 men, 12 women; mean age 62 +/- 16 years) were studied with electrocardiography and cardiac magnetic resonance imaging at baseline and 1 and 6 months (n = 25) after ASA. Infarct size and location were determined at 1 month by delayed contrast-enhanced cardiac magnetic resonance imaging. The 17 subjects who developed RBBB tended to have larger infarcts (creatine kinase-MB 251 +/- 92 vs 148 +/- 97 IU, p = 0.03; cardiac magnetic resonance imaging mass 22.5 +/- 9.3 vs 16.6 +/- 8.3 g, p = 0.1) and were more likely to have sustained anterior and inferior septal transmural infarctions (9 of 17 vs 1 of 10, p = 0.03) than those without RBBB. Those who developed RBBB had greater LV mass reductions at 6 months (46 +/- 26 vs 29 +/- 13 g, p = 0.04) despite similar reductions in LV pressure gradients (64 +/- 31 vs 56 +/- 32 mm Hg). In conclusion, patients who develop RBBB after ASA tend to have more extensive transmural septal infarctions and greater reverse remodeling than those without RBBB.

Myocardial strain and symptom severity in severe aortic stenosis: insights from cardiovascular magnetic resonance.

BACKGROUND: Symptomatic severe aortic stenosis (AS) is a class I indication for replacement in patients when left ventricular ejection fraction (LVEF) is preserved. However, symptom reporting is often equivocal and decision making can be challenging. We aimed to quantify myocardial deformation using cardiovascular magnetic resonance (CMR) in patients classified by symptom severity. METHODS: Forty-two patients with severe AS referred to heart valve clinic were studied using tagged CMR imaging. All had preserved LVEF. Patients were grouped by symptoms as either "none/mild" (n=21, NYHA class I, II) or "significant" (n=21, NYHA class III, IV, angina, syncope) but were comparable for age (72.8±5.4 vs. 71.0±6.8 years old, P=0.345), surgical risk (EuroSCORE II: 1.90±1.7 vs. 1.31±0.4, P=0.302) and haemodynamics (peak aortic gradient: 55.1±20.8 vs. 50.4±15.6, P=0.450). Thirteen controls matched in age and LVEF were also studied. LV circumferential strain was calculated using inTag© software and longitudinal strain using feature tracking analysis. RESULTS: Compared to healthy controls, patients with severe AS had significantly worse longitudinal and circumferential strain, regardless of symptom status. Patients with "significant" symptoms had significantly worse peak longitudinal systolic strain rates (-83.352±24.802%/s vs. -106.301±43.276%/s, P=0.048) than those with "no/mild" symptoms, with comparable peak longitudinal strain (PLS), peak circumferential strain and systolic and diastolic strain rates. CONCLUSIONS: Patients with severe AS who have no or only mild symptoms exhibit comparable reduction in circumferential and longitudinal fibre function to those with significant symptoms, in whom AVR is clearly indicated. Given these findings of equivalent subclinical dysfunction, reportedly borderline symptoms should be handled cautiously to avoid potentially adverse delays in intervention.

Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. METHODS AND RESULTS: We performed a 1-year, double-blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0-16), patients were randomly assigned to initial monotherapy (losartan 50-100 mg or hydrochlorothiazide 12.5-25 mg crossing over at 8 weeks), or initial combination (losartan 50-100 mg plus hydrochlorothiazide 12.5-25 mg). In phase 2 (weeks 17-32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33-52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7-6.0 mm Hg) less over 32 weeks (P<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: -0.4 to 2.8 mm Hg], P=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events. CONCLUSIONS: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617.

Right ventricular function following surgical aortic valve replacement and transcatheter aortic valve implantation: A cardiovascular MR study.

OBJECTIVE: The response of the RV following treatment of aortic stenosis is poorly defined, reflecting the challenge of accurate RV assessment. Cardiovascular magnetic resonance (CMR) is the established reference for imaging of RV volumes, mass and function. We sought to define the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon RV function in patients treated for severe aortic stenosis using CMR. METHODS: A 1.5T CMR scan was performed preoperatively and 6months postoperatively in 112 (56 TAVI, 56 SAVR; 76±8years) high-risk severe symptomatic aortic stenosis patients across two UK cardiothoracic centres. RESULTS: TAVI patients were older (80.4±6.7 vs. 72.8±7.2years, p<0.05) with a higher STS score (2.13±0.73 vs. 5.54±3.41%, p<0.001). At 6months, SAVR was associated with a significant increase in RV end systolic volume (33±10 vs. 37±10ml/m2, p=0.008), and decrease in RV ejection fraction (58±8 vs. 53±8%, p=0.005) and tricuspid annular plane systolic excursion (22±5 vs. 14±3mm, p<0.001). Only 4 (7%) SAVR patients had new RV late gadolinium hyper-enhancement with no new cases seen in the TAVI patients at 6months. Longer surgical cross-clamp time was the only predictor of increased RV end systolic volume at 6months. Post-TAVI, there was no observed change in RV volumes or function. Over a maximum 6.3year follow-up, 18(32%) of TAVI patients and 1(1.7%) of SAVR patients had died (p=0.001). On multivariable Cox analysis, the RV mass at 6m post-TAVI was independently associated with all-cause mortality (HR 1.359, 95% CI 1.108-1.666, p=0.003). CONCLUSIONS: SAVR results in a deterioration in RV systolic volumes and function associated with longer cross-clamp times and is not fully explained by suboptimal RV protection during cardiopulmonary bypass. TAVI had no adverse impact upon RV volumes or function.

Global myocardial strain assessment by different imaging modalities to predict outcomes after ST-elevation myocardial infarction: A systematic review.

AIM: To conduct a systematic review relating myocardial strain assessed by different imaging modalities for prognostication following ST-elevation myocardial infarction (STEMI). METHODS: An online literature search was performed in PubMed and OVID(®) electronic databases to identify any studies that assessed global myocardial strain parameters using speckle-tracking echocardiography (STE) and/or cardiac magnetic resonance imaging (CMR) techniques [either myocardial tagging or feature tracking (FT) software] in an acute STEMI cohort (days 0-14 post-event) to predict prognosis [either development of major adverse cardiac events (MACE)] or adverse left ventricular (LV) remodelling at follow-up (≥ 6 mo for MACE, ≥ 3 mo for remodelling). Search was restricted to studies within the last 20 years. All studies that matched the pre-defined search criteria were reviewed and their results interpreted. Due to considerable heterogeneity between studies, meta-analysis was not performed. RESULTS: A total of seven studies (n = 7) were identified that matched the search criteria. All studies used STE to evaluate strain parameters - five (n = 5) assessed global longitudinal strain (GLS) (n = 5), one assessed GLS rate (GLS-R) (n = 1) and one assessed both (n = 1). Three studies showed that GLS independently predicted the development of adverse LV remodelling by multivariate analysis - odds ratio between 1.19 (CI: 1.04-1.37, P < 0.05) and 10 (CI: 6.7-14, P < 0.001) depending on the study. Four studies showed that GLS predicted the development of MACE - hazard ratio (HR) between 1.1 (CI: 1-1.1, P = 0.006) and 2.34 (1.10-4.97, P < 0.05). One paper found that GLS-R could significantly predict MACE - HR 18 (10-35, P < 0.001) - whilst another showed it did not. GLS < -10.85% had sensitivity/specificity of 89.7%/91% respectively for predicting the development of remodelling whilst GLS < -13% could predict the development of MACE with sensitivity/specificity of 100%/89% respectively. No suitable studies were identified that assessed global strain by CMR tagging or FT techniques. CONCLUSION: GLS measured acutely post-STEMI by STE is a predictor of poor prognosis. Further research is needed to show that this is true for CMR-based techniques.

Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design.

AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. METHODS AND RESULTS: CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. CONCLUSIONS: The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.

Functional outcome after revascularization in patients with chronic ischemic heart disease: a quantitative late gadolinium enhancement CMR study evaluating transmural scar extent, wall thickness and periprocedural necrosis.

In patients with chronic ischemic myocardial dysfunction, late gadolinium enhancement CMR (LGE-CMR) accurately depicts the regional extent of fibrosis and predicts functional recovery after revascularization. We hypothesized that the predictive accuracy of LGE-CMR could be optimized by not only taking into account the transmural extent of hyperenhancement but also the amount of residual, non-enhanced viable myocardium, and procedure related necrosis. We studied 45 patients with chronic ischemic left ventricular dysfunction, who underwent cine and LGE-CMR 1 month before and 3 months after surgical or percutaneous revascularization. Segmental and global function, scar, presence of a significant residual viable rim (defined as >or=4.5 mm), and procedure related necrosis were fully quantified using standardized methods and objective thresholds. Sixty percent of segments without hyperenhancement showed functional improvement at follow-up. No improvement was observed in segments with >75% segmental extent of hyperenhancement (SEH), while segments with 1-25%, 26-50%, and 51-75% SEH were 4, 8, and 20 times less likely to improve (multilevel analysis, p<0.001). Thickness of the viable rim largely paralleled total wall thickness; therefore, the presence of a significant viable rim did not provide additional diagnostic value beyond SEH. Procedure related necrosis was found in 12 (27%) patients. The presence of procedure related necrosis was the only (negative) predictor of changes in left ventricular volumes and ejection fraction. In conclusion, we found that functional outcome after revascularization was influenced by both transmural extent of hyperenhancement and procedure related necrosis. However, the presence of a significant residual, viable rim was of no additional diagnostic value.