Plasma Tenascin-C: a prognostic biomarker in heart failure with preserved ejection fraction.

INTRODUCTION: Tenascin-C is a marker of interstitial fibrosis. We assessed whether plasma Tenascin-C differed between heart failure with preserved ejection fraction (HFpEF) and asymptomatic controls and related to clinical outcomes. MATERIALS AND METHODS: Prospective, observational study of 172 age- and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, males 50%) who underwent phenotyping with 20 plasma biomarkers, echocardiography, cardiac MRI and 6-minute-walk-testing. The primary endpoint was the composite of all-cause death/HF hospitalisation. RESULTS: Tenascin-C was higher in HFpEF compared to controls (13.7 [10.8-17.3] vs (11.1 [8.9-12.9] ng/ml, p < 0.0001). Tenascin-C correlated positively with markers of clinical severity (NYHA, E/E', BNP) and plasma biomarkers reflecting interstitial fibrosis (ST-2, Galectin-3, GDF-15, TIMP-1, TIMP-4, MMP-2, MMP-3, MMP-7, MMP-8), cardiomyocyte stress (BNP, NTpro-ANP), inflammation (MPO, hs-CRP, TNFR-1, IL6) and renal dysfunction (urea, cystatin-C, NGAL); p < 0.05 for all. During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations). In multivariable Cox regression analysis, Tenascin-C (adjusted hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.305-2.360; p < 0.0001) and indexed extracellular volume (HR 1.465, CI 1.019-2.106; p = 0.039) were independently associated with adverse outcomes. CONCLUSIONS: In HFpEF, plasma Tenascin-C is higher compared to age- and sex-matched controls and a strong predictor of adverse outcomes. Trial registration: ClinicalTrials.gov: NCT03050593.

Characterizing heart failure with preserved and reduced ejection fraction: An imaging and plasma biomarker approach.

INTRODUCTION: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. We aimed to characterize HFpEF compared to heart failure with reduced ejection fraction (HFrEF) and asymptomatic hypertensive or non-hypertensive controls. MATERIALS AND METHODS: Prospective, observational study of 234 subjects (HFpEF n = 140; HFrEF n = 46, controls n = 48, age 73±8, males 49%) who underwent echocardiography, cardiovascular magnetic resonance imaging (CMR), plasma biomarker analysis (panel of 22) and 6-minute walk testing (6MWT). The primary end-point was the composite of all-cause mortality and/or HF hospitalization. RESULTS: Compared to controls both HF groups had lower exercise capacity, lower left ventricular (LV) EF, higher LV filling pressures (E/E', B-type natriuretic peptide [BNP], left atrial [LA] volumes), more right ventricular (RV) systolic dysfunction, more focal and diffuse fibrosis and higher levels of all plasma markers. LV remodeling (mass/volume) was different between HFpEF (concentric, 0.68±0.16) and HFrEF (eccentric, 0.47±0.15); p<0.0001. Compared to controls, HFpEF was characterized by (mild) reductions in LVEF, more myocardial fibrosis, LA remodeling/dysfunction and RV dysfunction. HFrEF patients had lower LVEF, increased LV volumes, greater burden of focal and diffuse fibrosis, more RV remodeling, lower LAEF and higher LA volumes compared to HFpEF. Inflammatory/fibrotic/renal dysfunction plasma markers were similarly elevated in both HF groups but markers of cardiomyocyte stretch/damage (BNP, pro-BNP, N-terminal pro-atrial natriuretic peptide and troponin-I) were higher in HFrEF compared to HFpEF; p<0.0001. Focal fibrosis was associated with galectin3, GDF-15, MMP-3, MMP-7, MMP-8, BNP, pro-BNP and NTproANP; p<0.05. Diffuse fibrosis was associated with GDF-15, Tenascin-C, MMP-2, MMP-3, MMP-7, BNP, proBNP and NTproANP; p<0.05. Composite event rates (median 1446 days follow-up) did not differ between HFpEF and HFrEF (Log-Rank p = 0.784). CONCLUSIONS: HFpEF is a distinct pathophysiological entity compared to age- and sex-matched HFrEF and controls. HFpEF and HFrEF are associated with similar adverse outcomes. Inflammation is common in both HF phenotypes but cardiomyocyte stretch/stress is greater in HFrEF.

Left atrial ejection fraction and outcomes in heart failure with preserved ejection fraction.

The aim of this study was to determine whether left atrial ejection fraction (LAEF) quantified with cardiovascular magnetic resonance (CMR) was different between heart failure with preserved ejection fraction (HFpEF) and controls, and its relation to prognosis. As part of our single-centre, prospective, observational study, 188 subjects (HFpEF n = 140, controls n = 48) underwent phenotyping with contrast-enhanced CMR, transthoracic echocardiography, blood sampling and six-minute walk testing. LAEF was calculated using the biplane method. Atrial fibrillation (AF) was present in 43 (31%) of HFpEF subjects. Overall, LAEF (%) was lower in HFpEF patients inclusive of AF (32 ± 16) or those in sinus rhythm alone (41 ± 12) compared to controls (51 ± 11), p < 0.0001. LAEF correlated inversely with maximal and minimal left atrial volumes indexed (r = - 0.602, r = - 0.762), and plasma N-terminal pro-atrial natriuretic peptide (r = - 0.367); p < 0.0001. During median follow-up (1429 days), there were 67 composite events of all-cause death or hospitalization for heart failure (22 deaths, 45 HF hospitalizations) in HFpEF. Lower LAEF (below median) was associated with an increased risk of composite endpoints (Log-Rank: all p = 0.028; sinus p = 0.036). In multivariable Cox regression analysis, LAEF (adjusted hazard ratio [HR] 0.767, 95% confidence interval [CI] 0.591-0.996; p = 0.047) and indexed extracellular volume (HR 1.422, CI 1.015-1.992; p = 0.041) were the only parameters that remained significant when added to a base prognostic model comprising age, prior HF hospitalization, diastolic blood pressure, lung disease, NYHA, six-minute-walk-test-distance, haemoglobin, creatinine and B-type natriuretic peptide. CMR-derived LAEF is lower in HFpEF compared to healthy controls and is a strong prognostic biomarker.

Differential left ventricular and left atrial remodelling in heart failure with preserved ejection fraction patients with and without diabetes.

BACKGROUND: Attempts to characterize cardiac structure in heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes (T2D) have yielded inconsistent findings. We aimed to determine whether patients with HFpEF and T2D have a distinct pattern of cardiac remodelling compared with those without diabetes and whether remodelling was related to circulating markers of inflammation and fibrosis and clinical outcomes. METHODS: We recruited 140 patients with HFpEF (75 with T2D and 65 without). Participants underwent comprehensive cardiovascular phenotyping, including echocardiography, cardiac magnetic resonance imaging and plasma biomarker profiling. RESULTS: Patients with T2D were younger (age 70 ± 9 versus 75 ± 9y, p = 0.002), with evidence of more left ventricular (LV) concentric remodelling (LV mass/volume ratio 0.72 ± 0.15 versus 0.62 ± 0.16, p = 0.024) and smaller indexed left atrial (LA) volumes (maximal LA volume index 48 ± 20 versus 59 ± 29 ml/m2, p = 0.004) than those without diabetes. Plasma biomarkers of inflammation and extracellular matrix remodelling were elevated in those with T2D. Overall, there were 45 hospitalizations for HF and 22 deaths over a median follow-up period of 47 months [interquartile range (IQR) 38-54]. There was no difference in the primary composite endpoint of hospitalization for HF and mortality between groups. On multivariable Cox regression analysis, age, prior HF hospitalization, history of pulmonary disease and LV mass/volume were independent predictors of the primary endpoint. CONCLUSIONS: Patients with HFpEF and T2D have increased concentric LV remodelling, smaller LA volumes and evidence of increased systemic inflammation compared with those without diabetes. This suggests the underlying pathophysiology for the development of HFpEF is different in patients with and without T2D. CLINICALTRIALSGOV IDENTIFIER: NCT03050593.

Relationship Between Focal and Diffuse Fibrosis Assessed by CMR and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

OBJECTIVES: This study sought to assess the presence and extent of focal and diffuse fibrosis in heart failure in patients with preserved ejection fraction (HFpEF) compared to asymptomatic control subjects, and the relationship of fibrosis to clinical outcome. BACKGROUND: Myocardial fibrosis has been implicated in the pathophysiology of HFpEF. METHODS: In this prospective, observational study, 140 subjects of similar age and sex (HFpEF: n = 96; control subjects: n = 44; 73 ± 8 years of age; 49% males) underwent cardiac magnetic resonance imaging. Late gadolinium-enhanced (LGE) imaging and T1 mapping to calculate myocardial extracellular volume indexed to body surface area (iECV) were used to assess fibrosis. RESULTS: Patients with HFpEF had more concentric remodeling and worse diastolic function. Focal fibrosis was more frequent in HFpEF subjects (overall: n = 49; infarction: n = 17; nonischemic cases: n = 36; mixed patterns: n = 4) than in control subjects (overall: n = 3). Diffuse fibrosis was also greater in HFpEF subjects than control subjects (iECV: 13.7 ± 4.4 ml/m2 versus 10.9 ± 2.8 ml/m2; p < 0.0001). During median follow-up (1,429 days), there were 42 composite events (14 deaths; 28 heart failure hospitalizations) in cases of HFpEF. Myocardial infarction revealed on LGE imaging was a predictor of outcomes on univariate analysis only. With multivariate analysis, iECV (hazard ratio [HR]: 1.689; 95% confidence interval [CI]: 1.141 to 2.501; p = 0.009) was an independent predictor of outcome along with mitral peak velocity of early filling (E)-to-early diastolic mitral annular velocity (E') (E/E') ratio (HR: 1.716; 95% CI: 1.191 to 2.472; p = 0.004) and prior HF hospitalization (HR: 2.537; 95% CI: 1.090 to 5.902; p = 0.031). iECV was also significantly associated with ventricular/left atrial remodeling and renal dysfunction: right ventricular end-diastolic volume indexed (r = 0.456; p < 0.0001), left ventricular mass/volume (r = 0.348; p = 0.001), maximal left atrial volume indexed (r = 0. 269; p = 0.009), and creatinine (r = 0.271; p = 0.009). CONCLUSIONS: Both focal and diffuse myocardial fibrosis are more prevalent in HFpEF subjects than in control subjects of similar age and sex. iECV significantly correlates with indices of ventricular/left atrial remodeling and renal dysfunction and is an independent predictor of adverse outcome in HFpEF. (Developing Imaging And plasMa biOmarkers iN Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593).

Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in heart failure with preserved ejection fraction - implications for clinical trials.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a poorly characterized condition. We aimed to phenotype patients with HFpEF using multiparametric stress cardiovascular magnetic resonance imaging (CMR) and to assess the relationship to clinical outcomes. METHODS: One hundred and fifty four patients (51% male, mean age 72 ± 10 years) with a diagnosis of HFpEF underwent transthoracic echocardiography and CMR during a single study visit. The CMR protocol comprised cine, stress/rest perfusion and late gadolinium enhancement imaging on a 3T scanner. Follow-up outcome data (death and heart failure hospitalization) were captured after a minimum of 6 months. RESULTS: CMR detected previously undiagnosed pathology in 42 patients (27%), who had similar baseline characteristics to those without a new diagnosis. These diagnoses consisted of: coronary artery disease (n = 20, including 14 with 'silent' infarction), microvascular dysfunction (n = 11), probable or definite hypertrophic cardiomyopathy (n = 10) and constrictive pericarditis (n = 5). Four patients had dual pathology. During follow-up (median 623 days), patients with a new CMR diagnosis were at higher risk of adverse outcome for the composite endpoint (log rank test: p = 0.047). In multivariate Cox proportional hazards analysis, a new CMR diagnosis was the strongest independent predictor of adverse outcome (hazard ratio: 1.92; 95% CI: 1.07 to 3.45; p = 0.03). CONCLUSIONS: CMR diagnosed new significant pathology in 27% of patients with HFpEF. These patients were at increased risk of death and heart failure hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03050593 . Retrospectively registered; Date of registration: February 06, 2017.

Calculated plasma volume status and prognosis in chronic heart failure.

AIMS: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. METHODS AND RESULTS: First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2) = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. CONCLUSIONS: Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.

Serum albumin changes and multivariate dynamic risk modelling in chronic heart failure.

BACKGROUND: We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling. METHODS AND RESULTS: The survival implication of ∆albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores-a score ≥ 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2. CONCLUSION: Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year.

Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure.

BACKGROUND: An elevated red cell distribution width (RDW) and iron deficiency (ID) at baseline predict enhanced mortality in chronic heart failure (CHF), but little is known about the prognostic implications of their temporal trends. We sought to determine the survival implications of temporal changes in RDW and evolving ID in patients with CHF. METHODS: The relation between red cell indices on first consultation and over time with mortality in 274 stable patients with systolic CHF was analysed. The combination of a rising RDW with a falling mean cell volume (MCV) over time defined evolving ID. RESULTS: Over a median 12 month period, 51% and 23% of patients had a rise in RDW and evolving ID, respectively. After a median follow-up of 27 months, 60 (22%) patients died. A rising RDW predicted enhanced all-cause mortality (unadjusted HR for 1% per week rise 9.27, 95% CI 3.58 to 24.00, P<0.0001) independently and incrementally to baseline RDW, with an absolute increase >0.02% per week optimally predictive. Evolving ID also related to higher rates of mortality (HR 2.78, 95% CI 1.64 to 4.73, P<0.001) and was prognostically worse than a rising RDW alone (P<0.005). Patients with evolving ID who maintained their Hb levels over time had a 2-fold greater risk of death than those whose Hb levels declined without evolving ID. CONCLUSIONS: An expanding RDW and evolving iron deficiency over time predict an amplified risk of death in CHF and should be utilised for risk stratification and/or therapeutically targeted to potentially improve outcomes.

High field cardiac magnetic resonance imaging--current and future perspectives.

Potential advantages of high field cardiac magnetic resonance imaging include superior signal-to-noise ratio, image contrast and spectral separation. These might be used to improve spatial and/or temporal resolution and imaging speed. However, high field imaging presents new challenges to the operator, including increased magnetic field heterogeneity, susceptibility, artefacts and higher specific absorption rate. Recently, studies have reported on the clinical utility of cardiac magnetic resonance imaging at 3 Tesla in the assessment of myocardial function, perfusion and viability, and coronary arteries. The results of these clinical studies are reviewed, as well as emerging applications in myocardial tagging and cardiac spectroscopy.

Tolerance and safety of adenosine stress perfusion cardiovascular magnetic resonance imaging in patients with severe coronary artery disease.

We sought to assess the tolerance and safety of adenosine-stress cardiovascular magnetic resonance (CMR) perfusion imaging in patients with coronary artery disease (CAD). We retrospectively examined all adenosine CMR perfusion scans performed in our centre in patients with known or suspected (CAD) and normal volunteers at either 1.5 or 3 T. All subjects were initially screened for contraindications to adenosine. The dose of adenosine infused was 140 microg/kg/min. Significant CAD was defined angiographically as the presence of at least one stenosis of >50% diameter. Data were collected from 351 consecutive subjects (mean age 62 +/- 11 years, range 25-85 years-245 men). Of the 351 subjects, 305 had a coronary angiogram, the remaining 46 subjects were normal volunteers studied for research protocols. In total, 233 subjects (76%) were found to have significant CAD of whom 128 had multi-vessel disease. There were no deaths, myocardial infarctions, or episodes of bronchospasm during the CMR study. Transient 2nd (Mobitz II) or 3rd-degree atrioventricular (AV) block occurred in 27 patients (8%). There were no sustained episodes of advanced AV block. Transient chest pain was the most common side effect (199 subjects-57%). The use of intravenous adenosine in CMR perfusion imaging is safe and well-tolerated, even in patients with severe CAD. Where a careful screening policy for contraindications to adenosine is followed, serious adverse events in the CMR scanner are relatively rare and symptoms resolve following termination of the infusion, without the need for aminophylline.

Percutaneous treatment of chronic total coronary occlusions improves regional hyperemic myocardial blood flow and contractility: insights from quantitative cardiovascular magnetic resonance imaging.

OBJECTIVES: We sought to investigate temporal changes in contractility and hyperemic and resting myocardial blood flow (MBF) in dependent and remote myocardium after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) by using cardiovascular magnetic resonance (CMR) imaging. BACKGROUND: Data about the physiological consequences of revascularization of CTOs are limited. The use of CMR allows investigation of the regional effects of revascularization on MBF and left ventricular contractility. METHODS: We prospectively recruited 3 patient groups: 17 patients scheduled for CTO PCI, 17 scheduled for PCI of a stenosed but nonoccluded coronary artery (non-CTO), and 6 patients with CTO who were not scheduled for revascularization. All patients undergoing PCI underwent CMR imaging <24 h before PCI, with repeat CMR imaging 24 h and 6 months after PCI. Each CMR scan consisted of cine, perfusion, and delayed enhancement imaging. Regional hyperemic and resting MBF, wall thickening, and transmural extent of infarction were calculated. RESULTS: In both intervention groups, hyperemic MBF in treated segments increased 24 h after PCI compared with baseline: CTO group, 2.1 +/- 0.2 ml/min/g versus 1.4 +/- 0.2 ml/min/g (p < 0.01); non-CTO group, 2.5 +/- 0.2 ml/min/g versus 1.6 +/- 0.2 ml/min/g (p < 0.01). This improvement persisted 6 months after PCI (p < 0.01 for both groups). Contractility in treated segments was improved at 24 h and 6 months after CTO PCI but only at 6 months after non-CTO PCI. In both intervention groups, treated segments no longer had reduced MBF or contractility compared with remote segments. In patients with untreated CTO segments, MBF and wall thickening did not improve at follow-up. CONCLUSIONS: Successful CTO PCI increases hyperemic MBF as early as 24 h after the procedure, with a greater and earlier improvement in regional contractility than after non-CTO PCI, despite a greater likelihood of irreversible injury in CTO segments.

Effect of distal embolization on myocardial perfusion reserve after percutaneous coronary intervention: a quantitative magnetic resonance perfusion study.

BACKGROUND: Studies have shown that a subset of patients demonstrate persistent impairment in microcirculatory function after percutaneous coronary intervention (PCI). Distal embolization of plaque contents has been postulated as the main mechanism for this. We sought to investigate this further by evaluating PCI-induced changes in myocardial perfusion reserve index (MPRI) over time in segments with "distal-type" procedure-related myonecrosis using high-resolution quantitative cardiovascular magnetic resonance imaging. METHODS AND RESULTS: Forty patients undergoing PCI were studied with pre-PCI and 24-hour post-PCI delayed-enhancement magnetic resonance imaging and first-pass perfusion magnetic resonance imaging at rest and stress. Twenty patients underwent a third magnetic resonance imaging scan at 6 months. For perfusion imaging, 3 short-axis images were acquired during every heartbeat with a T1-weighted turboFLASH sequence. MPRI was calculated as the ratio of hyperemic to resting myocardial blood flow and subdivided according to the presence and location of new delayed hyperenhancement. Twenty-one patients demonstrated new distal hyperenhancement after PCI. Mean MPRI in revascularized myocardial segments not demonstrating new HE was significantly increased after the procedure (2.06 [95% CI, 1.99 to 2.13] before PCI and 2.52 [95% CI, 2.42 to 2.62] after PCI; P<0.001). In contrast, MPRI in segments with distal hyperenhancement was reduced after PCI (2.16 [95% CI, 1.95 to 2.37] before PCI; 2.00 [95% CI, 1.82 to 2.19] after PCI; mixed-model z=-4.82; P<0.001). Changes in mean MPRI 24 hours after PCI in segments upstream to new injury were not significantly different compared with perfusion changes in remote myocardium (z=-0.68; P=0.50). At 6 months after the procedure, mean MPRI in segments with new injury improved significantly compared with MPRI measured in these segments at 24 hours after PCI. CONCLUSIONS: MPRI is reduced in myocardial segments that demonstrate new distal irreversible injury at 24 hours after PCI. These reductions are confined to the segments with injury and do not affect the entire supply territory of the culprit vessel.

Cardiovascular magnetic resonance perfusion imaging at 3-tesla for the detection of coronary artery disease: a comparison with 1.5-tesla.

OBJECTIVES: This study was designed to establish the diagnostic accuracy of cardiovascular magnetic resonance (CMR) perfusion imaging at 3-Tesla (T) in suspected coronary artery disease (CAD). BACKGROUND: Myocardial perfusion imaging is considered one of the most compelling applications for CMR at 3-T. The 3-T systems provide increased signal-to-noise ratio and contrast enhancement (compared with 1.5-T), which can potentially improve spatial resolution and image quality. METHODS: Sixty-one patients (age 64 +/- 8 years) referred for elective diagnostic coronary angiography (CA) for investigation of exertional chest pain were studied (before angiogram) with first-pass perfusion CMR at both 1.5- and 3-T and at stress (140 microg/kg/min intravenous adenosine, Adenoscan, Sanofi-Synthelabo, Guildford, United Kingdom) and rest. Four short-axis images were acquired during every heartbeat using a saturation recovery fast-gradient echo sequence and 0.04 mmol/kg Gd-DTPA bolus injection. Quantitative CA served as the reference standard. Perfusion deficits were interpreted visually by 2 blinded observers. We defined CAD angiographically as the presence of > or =1 stenosis of > or =50% diameter in any of the main epicardial coronary arteries or their branches with a diameter of > or =2 mm. RESULTS: The prevalence of CAD was 66%. All perfusion images were found to be visually interpretable for diagnosis. We found that 3-T CMR perfusion imaging provided a higher diagnostic accuracy (90% vs. 82%), sensitivity (98% vs. 90%), specificity (76% vs. 67%), positive predictive value (89% vs. 84%), and negative predictive value (94% vs. 78%) for detection of significant coronary stenoses compared with 1.5-T. The diagnostic performance of 3-T perfusion imaging was significantly greater than that of 1.5-T in identifying both single-vessel disease (area under receiver-operator characteristic [ROC] curve: 0.89 +/- 0.05 vs. 0.70 +/- 0.08; p < 0.05) and multivessel disease (area under ROC curve: 0.95 +/- 0.03 vs. 0.82 +/- 0.06; p < 0.05). There was no difference between field strengths for the overall detection of coronary disease (area under ROC curve: 0.87 +/- 0.05 vs. 0.78 +/- 0.06; p = 0.23). CONCLUSIONS: Our study showed that 3-T CMR perfusion imaging is superior to 1.5-T for prediction of significant single- and multi-vessel coronary disease, and 3-T may become the preferred CMR field strength for myocardial perfusion assessment in clinical practice.

Irreversible myocardial injury: assessment with cardiovascular delayed-enhancement MR imaging and comparison of 1.5 and 3.0 T--initial experience.

PURPOSE: To prospectively compare visualization and quantification of irreversible myocardial injury in patients with chronic myocardial infarction at 1.5- and 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: The institutional research ethics committee approved the study. Participants gave written informed consent. Sixteen male patients (mean age, 66 years +/- 13 [standard deviation]) with myocardial infarction were imaged with the same sequence by the same operator at 1.5 and 3.0 T. After cine imaging, a bolus of gadodiamide was administered. Short-axis images of entire left ventricle (LV) were acquired with a breath-hold T1-weighted segmented inversion-recovery turbo fast low-angle shot (FLASH) sequence. Agreement for myocardial hyperenhancement (HE) mass between field strengths was assessed with Bland-Altman method; agreement for detection and transmural extent of HE was assessed with kappa statistics. Intra- and interobserver reproducibility of mass and transmural extent of HE were assessed at 1.5 and 3.0 T. RESULTS: Bland-Altman analysis revealed no systematic bias (mean difference, 0.2 g; 95% confidence interval: -0.7 g, 1.2 g) and acceptable limits of agreement (-3.3 to 3.8 g) between field strengths for HE mass. HE mass measurements were strongly correlated (R(2) = 0.99); there was no significant difference in measurements at 1.5 and 3.0 T (28.1 g +/- 15.7 [22.6% +/- 10.9 of LV mass] vs 27.8 g +/- 15.7 [22.3% +/- 10.7 of LV mass], respectively; P = .599). For all segments, there was a high degree of agreement for HE detection (kappa = 0.90) and transmural grade (kappa = 0.79) between field strengths. Intra- and interobserver variability were low between both field strengths. Initial inversion time selected to null the signal of normal myocardium at 3.0 T was 57 msec +/- 20 longer than at 1.5 T (P < .01). CONCLUSION: By using the same turbo FLASH MR pulse sequence, there was strong agreement in mass and transmural extent of myocardial HE between 1.5 and 3.0 T.

Cardiac changes in systemic amyloidosis: visualisation by magnetic resonance imaging.

Cardiac involvement is a significant cause of morbidity and mortality in patients with amyloidosis. A 73-year old Caucasian woman was admitted to a hospital with increasing dyspnoea. Examination revealed a large left-sided pleural effusion, gross peripheral oedema and a pan-systolic murmur. The electrocardiogram showed low voltage QRS complexes with lateral T wave inversion. Recent angiography had demonstrated normal coronaries. Echocardiography revealed left ventricular hypertrophy and an ejection fraction of 43%. There was a restrictive filling pattern with elevated left-sided filling pressures, left atrial enlargement and mild mitral regurgitation. The right heart was normal with normal filling pressures. The patient was referred for cardiovascular magnetic resonance imaging for investigation of restrictive cardiomyopathy. This case provides a striking demonstration of the characteristic features of cardiac amyloidosis by cardiovascular magnetic resonance imaging - impaired biventricular systolic function, thickened atrioventricular valves, bi-atrial enlargement, increased atrial septal thickness and left ventricular mass, pleural and pericardial effusions, and the most impressive finding of widespread subendocardial hyperenhancement of both ventricles, as well as the inter-atrial and inter-ventricular septa, representing infiltration with amyloid protein. Cardiac involvement with systemic amyloidosis was suspected and confirmed on biopsy. Cardiovascular magnetic resonance imaging should be considered early in the diagnostic work-up of suspected cardiac amyloidosis.

Determination of cardiac volumes and mass with FLASH and SSFP cine sequences at 1.5 vs. 3 Tesla: a validation study.

PURPOSE: To compare cardiac cine MR imaging using steady state free precession (SSFP) and fast low angle shot (FLASH) techniques at 1.5 and 3 T, and to establish their variabilities and reproducibilities for cardiac volume and mass determination in volunteers. To assess the feasibility of SSFP imaging in patients at 3 T and to determine comparability to volume data acquired at 1.5 T. MATERIALS AND METHODS: Ten healthy volunteers underwent cardiac magnetic resonance imaging using SSFP and segmented gradient-echo FLASH, using both a 1.5 and a 3 T MR system on the same day. Ten patients with impaired left ventricular (LV) function were also studied at both field strengths with SSFP. RESULTS: For both SSFP and FLASH, field strength had no effect on the quantification of LV and right ventricular (RV) volumes, mass, or function (P > or = 0.05 for field strength for all parameters). At both 1.5 and 3 T, SSFP yielded smaller LV mass (e.g., at 3 T 109 +/- 30 g vs. 142 +/- 37 g; P = 0.011) and larger LV volume (e.g., at 3 T end-diastolic volume 149 +/- 37 mL vs. 133 +/- 31 mL at 5 T; P = 0.041) measurements than FLASH. In patients with reduced LV function, all volume and mass measurements were again similar for SSFP sequences at 1.5 vs. 3 T. In volunteers and patients, measurement variabilities for LV parameters were small for both field strength and sequences, ranging between 3.7% and 10.7% for mass. CONCLUSION: Compared to 1.5 T, cardiac cine MR imaging at 3 T, using either FLASH or SSFP sequences, is feasible and highly reproducible. Field strength does not have an influence on quantification of cardiac volume or mass, but the systematic overestimation of LV mass and underestimation of LV volume by FLASH compared to SSFP is present at both 1.5 and 3 T. Normal values for cardiac volumes and mass established at 1.5 T can be applied to scans obtained at 3 T.

Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic resonance study of quantitative perfusion assessment.

BACKGROUND: Although impairment in perfusion reserve is well recognized in hibernating myocardium, there is substantial controversy as to whether resting myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first-pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute quantification of MBF. We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium. METHODS AND RESULTS: Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure, early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial segments in mL . min(-1) . g(-1) by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool. Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained. All coronary lesions were 80% to 95% stenosis in severity. Over all segments, mean MBF normalized by rate-pressure product ("corrected MBF") was 1.2+/-0.3 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments without significant coronary stenosis and 0.7+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments with coronary stenosis before PCI (mixed model controlling for slice and segment z=-23.9, P<0.001). Early after the procedure, the MBF was 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in revascularized segments and 1.3+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in nondiseased segments (z=-6.1, P<0.001). Late after PCI, the systolic wall thickening and end-diastolic wall thickness both increased significantly more (both P<0.001) in the myocardial segments subtended by severe coronary stenosis (8+/-17% to 40+/-19% and 6.5+/-1.1 to 9.3+/-2 mm, respectively) than in the myocardial segments supplied by nondiseased vessels. Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) before PCI and 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) after PCI (z=2.0, P=0.04). CONCLUSIONS: CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments.