Giancarlo Todiere

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

Background—The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results—A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ⩽0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88–0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69–0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65–0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). Conclusions—In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979199.

Progression of Myocardial Fibrosis Assessed With Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy

OBJECTIVES This study sought to assess the rate of progression of fibrosis by 2 consecutive cardiac magnetic resonance (CMR) examinations and its relation with clinical variables. BACKGROUND In hypertrophic cardiomyopathy (HCM) myocardial fibrosis, detected by late gadolinium enhancement (LGE), is associated to a progressive ventricular dysfunction and worse prognosis. METHODS A total of 55 HCM patients (37 males; mean age 43 ± 18 years) underwent 2 CMR examinations (CMR-1 and CMR-2) separated by an interval of 719 ± 410 days. Extent of LGE was measured, and the rate of progression of LGE (LGE-rate) was calculated as the ratio between the increment of LGE (in grams) and the time (months) between the CMR examinations. RESULTS At CMR-1, LGE was detected in 45 subjects, with an extent of 13.3 ± 15.2 g. At CMR-2, 53 (96.4%) patients had LGE, with an extent of 24.6 ± 27.5 g. In 44 patients, LGE extent increased significantly (≥1 g). Patients with apical HCM had higher increments of LGE (p = 0.004) and LGE-rate (p < 0.001) than those with other patterns of hypertrophy. The extent of LGE at CMR-1 and the apical pattern of hypertrophy were independent predictors of the increment of LGE. Patients with worsened New York Heart Association functional class presented higher increase of LGE (p = 0.031) and LGE-rate (p < 0.05) than those with preserved functional status. CONCLUSIONS Myocardial fibrosis in HCM is a progressive and fast phenomenon. LGE increment, related to a worse clinical status, is more extensive in apical hypertrophy than in other patterns.

Right Ventricular Ischemic Injury in Patients With Acute ST-Segment Elevation Myocardial Infarction. Characterization With Cardiovascular Magnetic Resonance

Background— Experimental data show that the right ventricle (RV) is more resistant to ischemia than the left ventricle. To date, limited data are available in humans because of the difficulty of discriminating reversible from irreversible ischemic damage. We sought to characterize RV ischemic injury in patients with reperfused myocardial infarction using cardiovascular magnetic resonance. Methods and Results— In 3 tertiary centers, 242 consecutive patients with reperfused acute ST-segment elevation myocardial infarction were studied with cardiovascular magnetic resonance at 1 week and 4 months after myocardial infarction. T2-weighted and postcontrast cardiovascular magnetic resonance scans were used to depict myocardial edema and late gadolinium enhancement, respectively. Early after infarction, RV edema was common (51% of patients), often associated with late gadolinium enhancement (31% of patients). Remarkably, RV edema and late gadolinium enhancement were found in 33% and 12% of anterior left ventricular infarcts, respectively. Baseline regional and global RV functions were inversely related to the presence and extent of RV edema and RV late gadolinium enhancement. At follow-up, a significant decrease in frequency (25/242 patients; 10%) and extent of RV late gadolinium enhancement was observed (P<0.001). With the use of multivariable analysis, the presence of RV edema was an independent predictor of RV global function improvement during follow-up (&bgr;-coefficient=0.221, P=0.003). Conclusions— Early postinfarction RV ischemic injury is common and is characterized by the presence of myocardial edema, late gadolinium enhancement, and functional abnormalities. RV injury is not limited to inferior infarcts but is commonly found in anterior infarcts as well. Cardiovascular magnetic resonance findings suggest reversibility of acute RV dysfunction with limited permanent myocardial damage at 4-month follow-up.

Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study

Background— In idiopathic dilated cardiomyopathy, there are scarce data on the influence of late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance on left ventricular (LV) remodeling. Methods and Results— Fifty-eight consecutive patients with idiopathic dilated cardiomyopathy underwent baseline clinical, biohumoral, and instrumental workup. Medical therapy was optimized after study enrollment. Cardiovascular magnetic resonance was used to assess ventricular volumes, function, and LGE extent at baseline and 24-month follow-up. LV reverse remodeling (RR) was defined as an increase in LV ejection fraction ≥10 U, combined with a decrease in LV end-diastolic volume ≥10% at follow-up. &Dgr;LGE extent was the difference in LGE extent between follow-up and baseline. LV-RR was observed in 22 patients (38%). Multivariate regression analysis showed that the absence of LGE at baseline cardiovascular magnetic resonance was a strong predictor of LV-RR (odds ratio, 10.857 [95% confidence interval, 1.844–63.911]; P=0.008) after correction for age, heart rate, New York Heart Association class, LV volumes, and LV and right ventricular ejection fractions. All patients with baseline LGE (n=26; 45%) demonstrated LGE at follow-up, and no patient without baseline LGE developed LGE at follow-up. In LGE-positive patients, there was an increase in LGE extent over time (P=0.034), which was inversely related to LV ejection fraction variation (Spearman &rgr;, −0.440; P=0.041). Five patients showed an increase in LGE extent >75th percentile of &Dgr;LGE extent, and among these none experienced LV-RR and 4 had a decrease in LV ejection fraction ≥10 U at follow-up. Conclusions— In patients with idiopathic dilated cardiomyopathy, the absence of LGE at baseline is a strong independent predictor of LV-RR at 2-year follow-up, irrespective of the initial clinical status and the severity of ventricular dilatation and dysfunction. The increase in LGE extent during follow-up was associated with progressive LV dysfunction.

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population

AIMS Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.

Prognostic significance of myocardial extracellular volume fraction in nonischaemic dilated cardiomyopathy

Aims In nonischaemic dilated cardiomyopathy (NICM), replacement myocardial fibrosis as detected by late gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR) is associated with poor prognosis. We investigated the as-yet unexplored prognostic significance of interstitial fibrosis in NICM, using T1-mapping CMR. Methods Eighty-nine NICM patients (63 men, age 59 ± 14 years) with left ventricular systolic dysfunction (ejection fraction 41 ± 13%) underwent comprehensive clinical and CMR evaluation, with extracellular volume fraction (ECV) estimation from pre and postcontrast T1 mapping. Fifteen healthy individuals (11 men, mean age 52 ± 11 years) were used as controls. The end-point was a composite of cardiovascular death, hospitalization for heart failure and appropriate defibrillator intervention. Results Myocardial ECV was higher in NICM patients (0.31 ± 0.05) than controls (0.25 ± 0.04, P < 0.01). In NICM patients, myocardial ECV correlated with left ventricular ejection fraction (R2 = 0.13), LGE extent (R2 = 0.17), Doppler E/E′ (R2 = 0.17) and ventricular tachycardias (R2 = 0.21) at 24-h ECG monitoring (P < 0.05 for all). During a median follow-up of 24 months (interquartile range 12–42 months), 12 events occurred and higher myocardium ECV was independently associated with the occurrence of the composite end-point (P < 0.01). Conclusion In NICM patients, myocardial ECV was increased compared with normal individuals, likely reflecting extracellular matrix remodelling and collagen deposition, and resulted an independent prognostic predictor beyond all other conventional clinical, electrocardiographic and echocardiographic parameters.

Right ventricular remodelling in systemic hypertension: a cardiac MRI study

Background Consistent evidence shows an impact of systemic haemodynamic overload on the right ventricle, but its functional and structural consequences have received scarce attention for several reasons including the difficult application of conventional imaging techniques due to the complex shape and orientation of that cardiac chamber. Aims To evaluate whether mild to moderate, uncomplicated hypertension associates with abnormal right ventricular structure and function and how those changes relate to homologous changes in the left ventricle. Data were acquired by steady-state free-precession cardiac MRI, the state of the art tool for the morphological and functional evaluation of the right ventricle. Materials and methods Twenty-five (12 women) uncomplicated, untreated, essential hypertensive patients were compared with 24 (13 women) sedentary normotensive controls of comparable age. Wall thickness, indexed ventricular mass, end-diastolic volumes, early peak filling rate, a correlate of diastolic relaxation, and ejection fraction were measured at both ventricles. Remodelling index, the ratio of ventricular mass to end-diastolic volume, was used as an index of concentricity. Results Right ventricular mass index, ventricular wall thickness and remodelling index were greater in hypertensive subjects and associated with reduced peak filling rate, a pattern consistent with concentric right ventricular remodelling. In the hypertensive group, positive, highly significant biventricular correlations existed between indexed mass, early peak filling rate and ejection fraction. Conclusions Systemic hypertension associates with concentric right ventricular remodelling and impaired diastolic function, confirming that the unstressed ventricle is not immune to the effects of systemic hypertension. Structural and functional right ventricular adaptation to systemic hypertension tends to parallel the homologous modifications induced by systemic haemodynamic overload on the left ventricle.

Reference values of cardiac volumes, dimensions, and new functional parameters by MR: A multicenter, multivendor study.

To define reference values of cardiac volumes, dimensions, and new morpho‐functional parameters normalized for age, gender, and body surface area by cine‐bSSFP (balanced steady‐state free‐precession) magnetic resonance (MR).

Measurement of myocardial amyloid deposition in systemic amyloidosis: insights from cardiovascular magnetic resonance imaging

Cardiac involvement in systemic amyloidosis is caused by the extracellular deposition of misfolded proteins, mainly immunoglobulin light chains (AL) or transthyretin (ATTR), and may be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to measure myocardial extracellular volume (ECV) in amyloid patients with a novel T1 mapping CMR technique and to determine the correlation between ECV and disease severity.

Age-dependent changes in elastic properties of thoracic aorta evaluated by magnetic resonance in normal subjects

OBJECTIVES Aortic stiffness is an independent cardiovascular risk factor. Cardiac magnetic resonance (CMR) allows evaluation of aortic elastic properties by different indexes such as distensibility, the maximum rate of systolic distension (MRSD) and pulse wave velocity (PWV). We sought to define age-dependent changes of indexes of elastic properties of the thoracic aorta in healthy subjects. METHODS We enrolled 85 healthy subjects (53 males) free of overt cardiovascular disease subdivided into 6 classes of age (from 15 to >60 years). Distensibility, MRSD and PWV were measured by the analysis of CMR images acquired using a 1.5 T clinical scanner. RESULTS MRSD and distensibility decreased progressively through the classes of age (P < 0.001) after an initial plateau between 20 and 30 years in males and 15 and 20 years in females. Pulse wave velocity increased progressively with the age (P < 0.001). Distensibility was related to body mass index (P = 0.002), surface area (P < 0.005), weight (P = 0.005) and to left ventricular parameters such as mass index (P < 0.001) and end-diastolic volume index (P = 0.002). MRSD was related to end-diastolic volume index (P < 0.001) but not to body parameters. PWV was not related to body and ventricular parameters. CONCLUSIONS This study confirmed that physiological ageing is associated with a progressive impairment of the elastic properties of the aortic wall. Results of this study may be useful for the early identification of subjects with impaired aortic wall properties providing referral values of elasticity indexes assessed by CMR in different classes of age.