Riccardo Liga

Structural Abnormalities of the Coronary Arterial Wall—in Addition to Luminal Narrowing—Affect Myocardial Blood Flow Reserve

Multislice CT provides information on coronary luminal narrowing and on the structural abnormalities of the coronary arterial wall using densitometric analysis. We sought to investigate the effects of coronary luminal narrowing, structural abnormalities of the coronary arterial wall, and cardiovascular risk factors on regional and global myocardial blood flow (MBF) reserve. Methods: We studied 68 patients (mean age ± SD, 61 ± 10 y; 41 men, 27 women) with an intermediate probability of coronary artery disease. We measured the severity of coronary stenoses and the fibroadipose, fibromuscular, and calcium components of the coronary arterial wall by 64-row multislice CT coronary angiography. We also measured regional and global MBF reserve by PET using 13N-ammonia as a flow tracer at rest and after dipyridamole. Results: One or more significant coronary stenoses (≥50% luminal narrowing) was present in 32 patients (47%), and nonsignificant stenoses were present in 15 patients (22%). Regional MBF reserve was significantly different in the territories perfused by normal coronary arteries, nonsignificant coronary stenoses, and significant coronary stenoses (P < 0.001). Calcium content was higher in the coronary arteries with significant or nonsignificant stenoses (0.95% ± 1.08% and 0.73% ± 0.93%, respectively) than in those without stenoses (0.11% ± 0.38%, P < 0.001). Significant coronary stenosis (P = 0.047) and calcium content (P = 0.017) were the only independent determinants of impaired regional MBF reserve using multivariate analysis. At multiple logistic regression analysis, the Framingham risk score, an index of global cardiovascular risk burden, was the only significant determinant of global MBF reserve (P = 0.028). Conclusion: Coronary stenoses and coronary calcium content independently affect regional MBF reserve. Framingham risk score is the only significant determinant of global MBF reserve.

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.

Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium–zinc–telluride camera: first clinical experience

AIMS To investigate the relationships between regional adrenergic innervation heterogeneity, myocardial perfusion, and contractile function obtained by means of a low-dose imaging protocol with a cadmium-zinc-telluride (CZT) dedicated camera. METHODS Twenty-eight patients with or without ischaemic heart disease underwent (123)I-metaiodobenzylguanidine (MIBG) planar scintigraphic and CZT early and delayed evaluations followed by (99m)Tc-tetrofosmin rest gated CZT with a single-day protocol. The heart-to-mediastinum ratio and the washout rate were computed from planar (123)I-MIBG images. The summed (123)I-MIBG defect scores (SS-MIBG) were semi-quantitatively assessed from CZT images. The summed rest score (SRS), summed motion score (SMS), and summed thickening score (STS) were quantitated from (99m)Tc-tetrofosmin images. RESULTS Sixteen patients showed a depressed left ventricular systolic function [ejection fraction (EF)<50%]. They presented higher SRS (P = 0.007), SMS (P < 0.001), STS (P < 0.001), and early SS-MIBG (P = 0.007) values than those with normal contractile function. Interestingly, higher early SS-MIBG values, index of regional sympathetic innervation heterogeneity, clustered with more elevated SRS (P = 0.023), and more impaired measures of regional and global left ventricle systolic function, i.e. SMS (P = 0.046), STS (P = 0.014), and EF (P = 0.027). At multivariate analysis, a higher SRS (P = 0.039) remained the only independent predictor of more elevated early SS-MIBG values. In the 20 of 28 ischaemic patients, the correlations between early SS-MIBG and SMS (P = 0.017) and also STS (P = 0.036) were further confirmed. The effective dose of the investigation was 4.2 ± 0.72 mSv. CONCLUSIONS An altered early SS-MIBG, assessed with a low-dose imaging protocol and a CZT cardiac camera, identifies patients with more impaired myocardial perfusion and contractile function.

Nicotine addiction and coronary artery disease: impact of cessation interventions.

Cigarette smoking is the leading preventable cause of death worldwide, and a considerable proportion of smoking-related fatalities are attributable to coronary artery disease (CAD). The detrimental effects of smoking span all stages in the development of CAD ranging from the early functional alterations in the endothelium and the microcirculation to the late clinicopathological manifestations of atherosclerotic plaques. Smoking results in the generation of free radicals and increased oxidative stress which plays a central role in the pathogenetic mechanisms leading to atherosclerotic disease. It causes reduced nitric oxide bioavailability and lipid peroxidation which are crucial initial steps of plaque formation. Furthermore, smoking enhances leukocyte and platelet activation and promotes local and systemic inflammation, which contribute to plaque progression and maturation. Finally, alterations in fibrinolytic and prothrombotic factors create a pro-thrombogenic environment which harbours the risk of plaque rupture and thrombosis. In smokers, the cessation of smoking is the most important intervention for cardiovascular risk reduction. Total mortality can be reduced by 36% which is comparable to established modern secondary preventive therapies. Nonetheless, non-aided cessation attempts are notoriously poor with a success rate of less than 10%. Patient counselling and pharmacological therapies are important aides for smoking cessation and can improve success rates by two to threefold. However, there is still need for improved strategies of smoking cessation to reduce the high socioeconomic impact of smoking.

Evaluation of left ventricular diastolic function with a dedicated cadmium-zinc-telluride cardiac camera: comparison with Doppler echocardiography

AIMS To evaluate the relationships between measures of left ventricular (LV) filling dynamics at cadmium-zinc-telluride (CZT) imaging and indexes of LV diastolic function at transthoracic echocardiography. METHODS AND RESULTS Two hundred and forty-seven patients underwent myocardial perfusion imaging at rest and after stress with a low-dose CZT protocol and a baseline transthoracic echocardiography study. All patients were submitted to invasive or computed coronary angiography. The peak filling rate (PFR) and the time to PFR (TPFR) were derived from gated CZT images as measures of LV filling dynamics. LV diastolic function was also evaluated at echocardiography and the presence of significantly increased LV filling pressures determined. Increased LV filling pressures at transthoracic echocardiography were evident in 103 (42%) patients. Interestingly, independently from the presence of coronary artery disease, there was a strict correlation between the presence and severity of LV diastolic dysfunction at echocardiography and CZT-derived measures of filling dynamics, i.e., PFR (P = 0.001) and TPFR (P = 0.001). At receiving operating characteristic analysis, a composite index of reduced PFR (≤2.11 end-diastolic volume s(-1)) and increased TPFR (>234 ms) showed a sensitivity of 84% and a specificity of 67% in unmasking the presence of elevated LV filling pressures at echocardiography. CONCLUSIONS CZT-derived measures of LV filling dynamics correlate with echocardiographic parameters of diastolic function and may identify the presence of increased LV filling pressures.

T−786→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy

BackgroundInsulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T−786→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T−786→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy.MethodA group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T−786→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index > 2.5) were determined in all patients.ResultsGenotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p < 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p < 0.04).ConclusionsT−786→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease.

Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.

Objective— Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. Approach and Results— Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25–75 percentiles) value of plasma hs-cTnT was 6.17 (4.2–9.1) ng/L and of NT-proBNP was 61.66 (31.2–132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). Conclusions— In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.

Real-time respiratory triggered SPECT myocardial perfusion imaging using CZT technology: impact of respiratory phase matching between SPECT and low-dose CT for attenuation correction

Aims To assess the impact of respiratory phase matching between single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) and low-dose computed tomography (CT) for attenuation correction (AC). Methods and results Forty patients underwent 1-day 99mTc-tetrofosmin pharmacological stress/rest SPECT-MPI using a cadmium–zinc–telluride gamma camera. Low-dose CT for AC was performed at deep-inspiration breath-hold. SPECT-MPI was acquired once with free-breathing (FB) and repeated at deep-inspiration breath-hold (BH) to match the respiratory phase of AC. From these acquisitions we reconstructed four data sets: free-breathing SPECT-MPI without AC (non-corrected; FB-NC), breath-hold SPECT-MPI without AC (non-corrected; BH-NC), free-breathing SPECT-MPI with AC (FB-AC), and breath-hold SPECT-MPI with AC (BH-AC), the latter representing respiratory-phase-matched AC SPECT-MPI. We compared semi-quantitative segmental tracer uptake, visual diagnosis, inter-observer agreement, and image quality. Compared with FB-NC, deep-inspiration BH-NC increases inferior and lateral uptake, but decreases septal uptake. Addition of AC to FB increases inferior and septal uptake, but decreases anterolateral uptake. Combining breath-hold MPI with breath-hold CT AC (BH-AC) increases inferior, inferolateral, and septal uptake, but reduces apical uptake, without affecting anterolateral uptake, with significant differences to all other protocols. Frequency of normal scans increases across protocols: 10% with FB-NC, 21% with BH-NC, 38% with FB-AC, and 51% with BH-AC. Image quality and inter-observer agreement were highest for BH-AC among all protocols. Conclusion Compared with non-corrected breath-hold SPECT-MPI and with free-breathing AC SPECT-MPI, respiratory-phase-matched AC SPECT-MPI significantly affects segmental semi-quantitative uptake, increases the frequency of normal scans, yields the best inter-observer agreement, and significantly improves image quality. These findings suggest a potential role of respiratory triggered SPECT-MPI in clinical routine.

Neuro-cardiac imaging has a proven value in patient management: Con

The sympathetic nervous system (SNS) is important in cardiac pathophysiology. By increasing heart rate and arterial blood pressure, the SNS plays a central role to adapt cardiac performance to conditions of increased external needs. Accordingly, a sympathetic surge instantaneously ameliorates left ventricular (LV) contractility and relaxation, abruptly increasing cardiac working capacities. However, while an elevated sympathetic tone may be beneficial in the short term, a chronic elevation of SNS activity, as in the case of congestive heart failure (CHF), has been clearly associated with a significantly higher rate of adverse events. Accordingly, an accurate evaluation of cardiac SNS activity has become a sine qua non in modern clinical cardiology. However, most of the techniques for the assessment of cardiac sympathetic tone (i.e., baroreflex sensitivity) offer an indirect estimation of its level of activation. Nuclear cardiac imaging has been considered the reference standard for the evaluation of cardiac innervation, allowing the evaluation of SNS activity in (semi)-quantitative terms. Therefore, in the last decades, both positron emission tomography (PET) and conventional nuclear imaging techniques [either planar scintigraphy or single-photon emission computed tomography (SPECT)] have been demonstrated to allow the characterization of cardiac sympathetic innervation. On one hand, PET imaging, with its higher image resolution, radiotracers’ versatility, and intrinsically quantitative nature, is widely considered the quality standard of cardiac SNS evaluation. On the other hand, conventional nuclear imaging, with its robustness, availability, and relatively limited operational costs, still represents the most frequently performed imaging test for cardiac innervation imaging. More specifically, despite the theoretical advantages of more refined techniques (i.e., PET and SPECT), planar scintigraphy with I-metaiodobenzylguanidine (I-MIBG) remains the workhorse of innervation imaging. Consequently, after almost 30 years from their introduction in the research arena, the two measures of cardiac sympathetic tone derived at planar scintigraphy, namely the heart-to-mediastinum (H/M) ratio and the washout rate of I-MIBG, still represent the most validated measures of LV innervation that are available, with the H/M ratio as reference standard. So, a depressed H/M ratio of I-MIBG has been shown to associate with a significantly worse prognosis, independently of LV ejection fraction. Moreover, in those years, a plethora of small-numbered studies have demonstrated the association between abnormal H/M values and various measures of LV structural and functional impairment, almost translating it as a universal marker of cardiac risk. Nevertheless, despite these apparently promising results, cardiac innervation imaging has a minimal, if any, clinical role in western countries, with currently no indications in major clinical guidelines, except for Japan. In order to understand this, some of the most evident limitations of cardiac I-MIBG imaging should be carefully considered.

Quantification of epicardial and intrathoracic fat volume does not provide an added prognostic value as an adjunct to coronary artery calcium score and myocardial perfusion single-photon emission computed tomography

AIMS To compare the predictive value of epicardial and intrathoracic fat volume (EFV, IFV), coronary artery calcium (CAC) score, and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for major adverse cardiac events (MACE). METHODS AND RESULTS Follow-up was obtained in 275 patients with known or suspected coronary artery disease (CAD), who underwent SPECT-MPI including non-contrast cardiac computed tomography (CT) for attenuation correction to evaluate ischaemic heart disease and in whom EFV, IFV, and CAC score were calculated from non-contrast CT. Associations between fat volume, traditional cardiovascular risk factors, CAC score, and SPECT-MPI results were assessed and MACE predictors identified by Cox proportional hazard regression and global χ(2) statistics. After a median follow-up of 2.9 years, MACE were recorded in 38 patients. In univariate Cox regression analysis, EFV and IFV were predictors of MACE (P = 0.013 and P = 0.004, respectively). In multivariate analysis, EFV and IFV provided incremental predictive value beyond traditional cardiovascular risk factors (P < 0.05 and P < 0.01). However, after adjustment for CAC score and SPECT-MPI results, EFV and IFV fell short of statistical significance as independent outcome predictors. CONCLUSION Quantification of EFV and IFV is associated with MACE and may improve risk stratification beyond traditional cardiovascular risk factors. However, once CAC score and/or SPECT-MPI results are known, EFV and IFV do not provide any added clinically relevant prognostic value. Further studies may identify the subpopulation with the largest relative merit of EFV and IFV as an adjunct to SPECT-MPI and CAC score.