Marco Guglielmo

Rationale and design of the PERFECTION (comparison between stress cardiac computed tomography PERfusion versus Fractional flow rEserve measured by Computed Tomography angiography In the evaluation of suspected cOroNary artery disease) prospective study

BACKGROUND Non-invasive stress tests are commonly used as gatekeepers to invasive coronary angiography (ICA) in patients with suspected coronary artery disease (CAD). New computed tomography angiography (CTA) techniques such as fractional flow reserve calculated by CTA (FFRCT) and stress myocardial computed tomography perfusion (CTP) have emerged as potential strategies to combine anatomical and functional evaluation of CAD in one technique. The aim of this study is to compare per-vessel diagnostic accuracy of FFRCT versus stress myocardial CTP for the detection of functionally significant coronary artery disease (CAD), using invasive FFR as the reference standard. METHODS Subjects with suspected CAD due to chest pain who have no contra-indications to FFRCT or stress myocardial CTP and who are referred for non-emergent, clinically indicated invasive coronary angiography (ICA), will be enrolled. A total of 300 subjects will be enrolled within 24 months. RESULTS The primary study endpoint will be the comparison of per-vessel diagnostic accuracy of CTA versus FFRCT versus stress myocardial CTP for the diagnosis of hemodynamically significant stenosis as defined by invasive FFR ≤0.80. CONCLUSIONS In the PERFECTION study, the comparison between FFRCT and stress myocardial CTP will provide understanding about which technology is more accurate for the diagnosis of functionally significant CAD.

Reliability and feasibility of longitudinal AFI global and segmental strain compared with 2D left ventricular volumes and ejection fraction: intra- and inter-operator, test–retest, and inter-cycle reproducibility

AIMS Echocardiographic evaluation of 2D longitudinal peak systolic strain (LPSS) can detect initial impairment of left ventricular (LV) function in heart disease. Global LPSS (GLPSS) variability has been assessed in small groups and segmental LPSS has not been determined. We compared variability of GLPSS and segmental LPSS with that of 2D LV volumes and ejection fraction (EF) in patients with and without heart diseases. METHODS AND RESULTS 2D speckle tracking analysis was performed on LV apical views using automated function imaging (AFI) software (GE Healthcare). Intra-operator, inter-cycle, and test-retest variability (bias and CR, coefficient of reproducibility; MPE, mean percent error; CV, coefficient of variation) was assessed for GLPSS, 18 segments of LPSS, and LV volumes and EF in 40 patients (720 segments), and inter-operator variability in 250 patients (4500 segments). Feasibility of segmental tracking was 93.1%. Variability of GLPSS increased from a minimum intra-operator CV = -2.6% to a maximum test-retest CV = -5.4% and was lower than that assessed for volumes and EF. Segmental intra-operator LPSS CV ranged from -5.6 to -14.7%, and test-retest from -8 to -22%, and was at worst similar to variability of end-systolic volume. In the 8.3% of segments with the highest variability, this was related to suboptimal imaging, minor changes in scan angulation, and insufficient ROI width. CONCLUSION Overall, reproducibility of GLPSS is excellent and superior to that of 2D EF, whereas segmental LPSS reproducibility is good and similar to that of LV volumes. Both are suitable for diagnosis and follow-up of LV global and regional systolic function.

Prognostic Benefit of Cardiac Magnetic Resonance Over Transthoracic Echocardiography for the Assessment of Ischemic and Nonischemic Dilated Cardiomyopathy Patients Referred for the Evaluation of Primary Prevention Implantable Cardioverter-Defibrillator Therapy.

Background—The aim of this study was to determine the prognostic benefit of cardiac magnetic resonance (CMR) over transthoracic echocardiography (TTE) in ischemic cardiomyopathy and nonischemic dilated cardiomyopathy patients evaluated for primary prevention implantable cardioverter–defibrillator therapy. Methods and Results—We enrolled 409 consecutive ischemic and dilated cardiomyopathy patients (mean age: 64±12 years; 331 men). All patients underwent TTE and CMR, and left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricle ejection fraction (LVEF) were evaluated. In addition, late gadolinium enhancement was also assessed. All patients were followed up for major adverse cardiac events (MACE) defined as a composite end point of long runs of nonsustained ventricular tachycardia, sustained ventricular tachycardia, aborted sudden cardiac death, or sudden cardiac death. The median follow-up was 545 days. CMR showed higher left ventricle end-diastolic volume (mean difference: 43±22.5 mL), higher left ventricle end-systolic volume (mean difference: 34±20.5 mL), and lower LVEF (mean difference: −4.9±10%) as compared to TTE (P<0.01). MACE occurred in 103 (25%) patients. Patients experiencing MACE showed higher left ventricle end-diastolic volume, higher left ventricle end-systolic volume, and lower LVEF with both imaging modalities and higher late gadolinium enhancement per-patient prevalence as compared to patients without MACE. At multivariable analysis, CMR-LVEF ⩽35% (hazard ratio=2.18 [1.3–3.8]) and the presence of late gadolinium enhancement (hazard ratio=2.2 [1.4–3.6]) were independently associated with MACE (P<0.01). A model based on CMR-LVEF ⩽35% or CMR-LVEF ⩽35% plus late gadolinium enhancement detection showed a higher performance in the prediction of MACE as compared to TTE-LVEF resulting in net reclassification improvement of 0.468 (95% confidence interval, 0.283–0.654; P<0.001) and 0.413 (95% confidence interval, 0.23–0.63; P<0.001), respectively. Conclusions—CMR provides additional prognostic stratification as compared to TTE, which may have direct impact on the indication of implantable cardioverter–defibrillator implantation.

Additional value of inflammatory biomarkers and carotid artery disease in prediction of significant coronary artery disease as assessed by coronary computed tomography angiography.

Aims To evaluate the relationship between an incremental model including cardiovascular risk factors, carotid disease, and inflammatory biomarkers to predict the presence of obstructive coronary artery disease (CAD). Methods and results A total of 134 consecutive and asymptomatic intermediate-risk patients (mean age 61 ± 9 years, 52% men) were enrolled. Each subject underwent circulating levels assessment of interleukin (IL)-2r, IL-6, IL-8, IL-10, high-sensitivity C-reactive protein (hs-CRP) and carotid and coronary artery evaluation using carotid ultrasound and coronary computed tomography angiography (CCTA), respectively. Carotid disease was diagnosed in 71 (53%) patients. Obstructive and multi-vessel CAD were found in 50 (37%) and 18 (14%) patients, respectively. Patients in whom CCTA showed multi-vessel CAD had a higher rate of carotid disease (89 vs. 46%, P = 0.001) and increased values of all interleukins when compared with patients without multi-vessel obstructive CAD. The univariate and multivariate analysis showed that male gender, diabetes, carotid disease, and IL-6 were independently associated with obstructive CAD. At receiver operating characteristic curve analysis, the multivariate model (including male gender, carotid disease, IL-6 > 5.9 pg/mL, and diabetes) showed the highest area under the curve for prediction of obstructive CAD, multi-vessel CAD, and high-risk plaque defined as mixed and/or remodelled plaque when compared with all other models (P < 0.001). Conclusion Among asymptomatic intermediate-risk patients, the presence of increased IL6 levels in addition to traditional risk factors (male gender with diabetes) and carotid artery disease predicts higher rates of obstructive CAD and it could be of help to identify which subset of asymptomatic patients could be referred to CCTA for screening.

The presence of remodeled and mixed atherosclerotic plaques at coronary ct angiography predicts major cardiac adverse events — The CAFÉ-PIE Study

BACKGROUND It is still unclear how to exploit information made available by coronary computed tomography angiography (CCTA) on coronary artery disease (CAD) features in order to better predicting major adverse cardiac events (MACEs). Aim of this study was to validate the prognostic role of a comprehensive and simplified CT-derived score in patients evaluated for suspected CAD. METHODS A prospective registry included 477 consecutive symptomatic patients without known CAD who underwent clinically-indicated CCTA. All patients were followed-up for MACE occurrence for a period of 49±15-month. RESULTS The mean CT Score was 10.5±10.8, with a MACE rate of 11.3%. There was a stepwise relationship between MACE rate during follow-up and CT Score values. MACEs were 1.9% in patients with CT Score<10 (reference group), 16.6% in those with CT Score 10-20 (OR 9.9, 95% C.I. 3.5-27.8 vs. reference group, p<0.001), 24.5% in those with CT Score 21-30 (OR 16.6, 95% C.I. 6.1-45.0 vs. reference group, p<0.001), and 47.4% in those with CT Score>30 (OR 46.1, 95% C.I. 13.0-162.9 vs. reference group, p<0.001) (p for trend <0.001). At ROC curve analysis, CT Score was the best predictor of MACE (AUC: 0.81, CI 95%: 0.78-0.84) as compared to Diamond and Forrester score (p<0.001), segment stenosis score (p<0.05) and segment involved score (p<.0.01). CONCLUSIONS The use of an integrated score obtained with CCTA and based on the presence of remodeled and mixed atherosclerotic coronary plaques may improve MACE prediction in symptomatic patients at intermediate risk outweighing that provided by standard clinical and CCTA scores.

G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy.

Background Takotsubo cardiomyopathy (TTC) is an increasingly reported clinical syndrome that mimics acute myocardial infarction without obstructive coronary artery disease and is characterized by transient systolic dysfunction of the apical and/or mid-segments of the left ventricle. The syndrome mainly occurs in postmenopausal women with high adrenergic state conditions. Nowadays, the pathophysiology of TTC is not yet known and the possibility of a genetic predisposition is controversial. Aims The purpose of this study was to assess the genetic susceptibility to TTC through analysis of the L41Q polymorphism of the G-protein-coupled receptor kinase 5 (GRK5). Methods and results In a cohort of 20 patients enrolled in two tertiary Italian centers with diagnosis of TTC, accordingly to the commonly accepted Mayo Clinic criteria and in 22 healthy individuals (control) we have evaluated the polymorphism in GRK5 gene. The TTC patients had a mean age of 65 ± 9 years and 19 of 20 were women. The presence of one or two L41 alleles of GRK5 was significantly more frequent in TTC group than in the control group (40 vs. 8%, P = 0.0372). Conclusion In our study, we have found a significant difference in the frequency of GRK5 polymorphism between TTC patients and controls, supporting a genetic predisposition to this cardiac syndrome.

Prevalence of Calcification of the Mitral Valve Annulus in Patients Undergoing Surgical Repair of Mitral Valve Prolapse

Factors correlating to mitral annulus calcification (MAC) include risk factors predisposing to atherosclerosis. In patients with mitral valve (MV) prolapse (MVP), other anatomic or mechanical factors have been supposed to facilitate MAC. The aims of this study were, in patients with MVP undergoing MV repair, (1) to describe the prevalence and characteristics of MAC, (2) to correlate MAC with clinical risk factors, coronary involvement, and aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in fibroelastic deficiency (FED) versus Barlows disease (BD) and correlate MAC to surgical outcomes (repair vs replacement). In 410 consecutive patients with MVP suitable for surgical MV repair, detailed clinical and echocardiographic data were collected to characterize MAC in BD and FED. MAC was found in 99 patients (24%). Age, female gender, coronary artery disease, and cardiovascular risk factors were correlated with MAC. MAC was equally distributed in FED and BD groups despite patients with FED being older with more cardiovascular risk factors. The most common localization of MAC was annular involvement adjacent to P2 (75%), P1 (31%), and P3 (35%). The presence of MAC affected surgical outcomes in both groups (8% patients with MAC underwent replacement after a first attempt of repair vs 3% without MAC). MAC is a common finding in patients undergoing MV repair, and several clinical characteristics correlate with MAC either in FED or BD. In conclusion, despite very high percentage of repairability, MAC influences surgical outcomes and very detailed echo evaluation is advocated.

Non-responders to cardiac resynchronization therapy: Insights from multimodality imaging and electrocardiography. A brief review

BACKGROUND Cardiac resynchronization therapy (CRT) is a successful strategy for heart failure (HF) patients. The pre-requisite for the response is the evidence of electrical dyssynchrony on the surface electrocardiogram usually as left bundle branch block (LBBB). Non-response to CRT is a significant problem in clinical practice. Patient selection, inadequate delivery and sub-optimal left ventricle lead position may be important causes. OBJECTIVES In an effort to improve CRT response multimodality imaging (especially echocardiography, computed tomography and cardiac magnetic resonance) could play a decisive role and extensive literature has been published on the matter. However, we are so far from routinary use in clinical practice. Electrocardiography (with respect to left ventricle capture and QRS narrowing) may represent a simple and low cost approach for early prediction of potential non-responder, with immediate practical implications. CONCLUSION This brief review covers the current recommendations for CRT in HF patients with particular attention to the potential benefits of multimodality imaging and electrocardiography in improving response rate.

Evaluation of coronary plaque characteristics with coronary computed tomography angiography in patients with non-obstructive coronary artery disease: a long-term follow-up study

Aims Recent studies suggested that even non-obstructive coronary artery disease (CAD) increases major cardiovascular adverse events (MACE) rate. Aim of this study was to evaluate whether coronary computed tomography angiography (CCTA) may detect specific plaque characteristics that may affect prognosis in patients with non-obstructive CAD. Methods We enrolled 245 patients who underwent CCTA between April 2004 and April 2007 for suspected CAD and were found to have non-obstructive CAD. Positive remodelling index (PRI), low-attenuation plaque (LAP), plaque burden (PB), spotty calcification (SC), and napkin-ring sign (NRS) have been evaluated for each coronary plaque detected. Acute coronary syndrome, all-cause/cardiac death, and very late elective revascularization (vl-ER) were the endpoints of the study. Results A total of 28 events were recorded (2 STEMI, 4 NSTEMI, 6 UA, 2 cardiac deaths, 4 non-cardiac death, and 10 vl-ERs) at long-term follow-up (98 ± 20 months). When adjusted for significant clinical variables PRI > 1.4 (HR 3.31 CI 95% 1.11-9.91, P = 0.0392), LAP (HR 8.45 CI 95% 2.22-32.21, P = 0.0019), PB > 0.7 (HR 5.25 CI 95% 1.45-19.03, P = 0.0120), and NRS (HR 12.52 CI 95% 1.51-103.90, P = 0.0198) were still significantly associated with higher rate of hard cardiac events at follow-up. The Kaplan-Meyer curves confirmed lower cumulative hard cardiac events-free survival in patients presenting at least one coronary plaque with two or more high-risk characteristics when compared with patients with no lesion with more than one high-risk plaque characteristics (log-rank P < 0.0001). Conclusions High-risk plaque characteristics at CCTA (PRI > 1.4, PB > 0.7, LAP, and NRS) seem to be promising for risk stratification of patients with non-obstructive CAD.

Atrial Fibrillation: Diagnostic Accuracy of Coronary CT Angiography Performed with a Whole-Heart 230-µm Spatial Resolution CT Scanner

Purpose To assess image quality, interpretability, diagnostic accuracy, and radiation exposure of a computed tomography (CT) scanner with 16-cm coverage and 230-µm spatial resolution at coronary artery evaluation in patients with atrial fibrillation (AF) by using invasive coronary angiography (ICA) as the reference method and to compare the results with those obtained in patients with sinus rhythm (SR). Materials and Methods Written informed consent and institutional ethics committee approval were obtained. Between March 2015 and February 2016, 166 consecutive patients were prospectively enrolled (83 with AF, 83 with SR). They underwent ICA and coronary CT angiography performed with a whole-heart CT scanner. Image quality, coronary segment interpretability, effective dose (ED), and diagnostic accuracy were assessed at CT angiography and were compared with those attained with ICA. Diagnostic performance of the groups was compared with the pairwise McNemar test. Results Mean heart rate during scanning was 83 beats per minute ± 21 (standard deviation) in the AF group and 63 beats per minute ± 14 in the SR group (P < .01). Coronary interpretability was 98.5% in the AF group and 98.4% in the SR group (P = .96). In a segment-based analysis, sensitivity and specificity in the detection of coronary stenosis of more than 50% compared with detection of ICA were 96.4% and 98.7%, respectively, in the chronic AF group (P = .98) and 95.6% and 98.1%, respectively, in the SR group (P = .32). In a patient-based analysis, sensitivity and specificity were 95.2% and 97.6%, respectively, in the chronic AF group (P = .95) and 97.8% and 94.7%, respectively, in the SR group (P = .93). Conclusion Whole-heart CT enables evaluation of coronary arteries with high image quality, low radiation exposure, and high diagnostic accuracy in patients with chronic AF, with a diagnostic performance similar to that in patients with SR.