A treatment algorithm for ischemic cardiomyopathy.

Treatment of ischemic cardiomyopathy has been the focus of increased attention by cardiologists due to recent evidence of an important outcome study comparing percutaneous coronary intervention (PCI) plus optimal medical treatment vs optimal medical treatment alone, concluding for the futility of myocardial revascularization by PCI. A relatively older trial of coronary artery bypass grafting (CABG) in the same condition, on the other hand, had concluded for some prognostic improvement at a long-term follow-up. This short manuscript addresses how to triage such patients, frequently encountered in medical practice and considering clinical presentation, imaging results, and surgical risk, to provide practical guidance to treatment.

Myocardial Revascularization in Patients With Ischemic Cardiomyopathy: For Whom and How.

Background Myocardial revascularization has been advocated to improve myocardial function and prognosis in ischemic cardiomyopathy (ICM). We discuss the evidence for revascularization in patients with ICM and the role of ischemia and viability detection in guiding treatment. Methods and Results We searched for randomized controlled trials evaluating the prognostic impact of revascularization in ICM and the value of viability imaging for patient management. Out of 1397 publications, 4 randomized controlled trials were included, enrolling 2480 patients. Three trials (HEART [Heart Failure Revascularisation Trial], STICH [Surgical Treatment for Ischemic Heart Failure], and REVIVED [REVascularization for Ischemic VEntricular Dysfunction]-BCIS2) randomized patients to revascularization or optimal medical therapy. HEART was stopped prematurely without showing any significant difference between treatment strategies. STICH showed a 16% lower mortality with bypass surgery compared with optimal medical therapy at a median follow-up of 9.8 years. However, neither the presence/extent of left ventricle viability nor ischemia interacted with treatment outcomes. REVIVED-BCIS2 showed no difference in the primary end point between percutaneous revascularization or optimal medical therapy. PARR-2 (Positron Emission Tomography and Recovery Following Revascularization) randomized patients to imaging-guided revascularization versus standard care, with neutral results overall. Information regarding the consistency of patient management with viability testing results was available in ≈65% of patients (n=1623). No difference in survival was revealed according to adherence or no adherence to viability imaging. Conclusions In ICM, the largest randomized controlled trial, STICH, suggests that surgical revascularization improves patients' prognosis at long-term follow-up, whereas evidence supports no benefit of percutaneous coronary intervention. Data from randomized controlled trials do not support myocardial ischemia or viability testing for treatment guidance. We propose an algorithm for the workup of patients with ICM considering clinical presentation, imaging results, and surgical risk.

Antithrombotic Therapy for Peripheral Revascularisation.

Lower extremity artery disease (LEAD) represents a major public health burden, affecting hundreds of millions of people worldwide. Although risk-factor modification, exercise training and medical treatment are the mainstays of the management of LEAD, endovascular or surgical revascularisation is recommended when there is the risk of limb amputation and when drug-resistant claudication severely affects patient lifestyle. Over recent years, the number of peripheral vascular interventions (PVI) has soared worldwide, driven by the improvements in endovascular techniques and devices. This growth was accompanied by a large number of clinical trials aimed at assessing the safety and efficacy of the various revascularisation modalities, while very little evidence was collected regarding the best antithrombotic treatment in patients undergoing peripheral revascularisation. In particular, considering the extensive length of diseased vessels usually treated in PVI, an optimised approach to both platelet function and coagulation cascade is of paramount importance. However, the role of antiplatelet and anticoagulant drugs following lower extremity revascularisation is largely extrapolated from the coronary field. Current guidelines recommend long-term single antiplatelet treatment for the majority of both endovascular and surgical revascularisation procedures, preceded by an initial short-term dual antiplatelet treatment in case of PVI. We present an overview of the indications and techniques of both endovascular and surgical peripheral revascularisation, followed by an in-depth analysis of the available evidence regarding type and duration of antiplatelet and anticoagulant treatment following revascularisation.

Evaluation of left ventricular mass on cadmium-zinc-telluride imaging: Validation against cardiac magnetic resonance.

BACKGROUND: Single-photon emission computed tomography has shown relevant limitations in the quantification of left ventricular (LV) mass. We sought to compare the estimates of LV mass on Cadmium-Zinc-Telluride (CZT) myocardial perfusion imaging (MPI) as compared to cardiac magnetic resonance (CMR). METHODS AND RESULTS: Twenty-five patients underwent MPI on a CZT camera and CMR on a 1.5 T scanner within 12 ± 3 weeks. LV mass was quantified on CZT images using two softwares: 4D-MSPECT (4DM) and Emory Cardiac Toolbox (ECTb). LV mass by CMR was quantified using MASS software (Medis, Leiden, The Netherlands). LV mass values obtained with 4DM and ECTb were highly reproducible [intraclass correlation coefficients .98 (95% CI .97-.99), and .98 (95% CI 0.97-.99), respectively]. The mean LVM mass values were 151 ± 44 g on CMR, 151 ± 43 g with 4DM (P = NS vs CMR), and 157 ± 42 g with ECTb (P < .001 vs CMR; P = .007 vs 4DM) CZT images. There was an excellent correlation between LV mass values between CMR and both 4DM (R2 = .95; P < .001) and ECTb (R2 = .98; P < .001) with narrow limits of agreement (- 13.6% to + 13.4% for 4DM, and - 5.6% to + 14.1% for ECTb). CONCLUSIONS: The evaluation of LV mass is feasible on CZT images, showing excellent agreement with CMR.

Relationships between cardiac innervation/perfusion imbalance and ventricular arrhythmias: impact on invasive electrophysiological parameters and ablation procedures.

PURPOSE: To assess the relationship between regional myocardial perfusion and sympathetic innervation parameters at myocardial scintigraphy and intra-cavitary electrophysiological data in patients with ventricular arrhythmias (VA) submitted to invasive electrophysiological study and ablation procedure. METHODS: Sixteen subjects underwent invasive electrophysiological study with electroanatomical mapping (EAM) followed by trans-catheter ablations of VA. Before ablation all patients were studied with a combined evaluation of regional myocardial perfusion and sympathetic innervation by means of tomographic 99mTc-tetrofosmin and 123I- metaiodobenzylguanidine cadmium-zinc-telluride (CZT) scintigraphies, respectively. Off-line spatial co-registration of CZT perfusion and innervation data with the three-dimensional EAM reconstruction was performed in every patient. RESULTS: CZT revealed the presence of myocardial scar in 55 (20 %) segments. Of the viable myocardial segments, 131 (60 %) presented a preserved adrenergic innervation, while 86 (40 %) showed a significantly depressed innervation (i.e. innervation/perfusion mismatch). On EAM, the invasively measured intra-cavitary voltage was significantly lower in scarred segments than in viable ones (1.7 ± 1.5 mV vs. 4.0 ± 2.2 mV, P < 0.001). Interestingly, among the viable segments, those showing an innervation/perfusion mismatch presented a significantly lower intra-cavitary voltage than those with preserved innervation (1.9 ± 2.5 mV vs. 4.7 ± 2.3 mV, P < 0.001). Intra-cardiac ablation was performed in 63 (23 %) segments. On multivariate analysis, after correction for scar burden, the segments showing an innervation/perfusion mismatch remained the most frequent ablation targets (OR 5.6, 95 % CI 1.5-20.8; P = 0.009). CONCLUSIONS: In patients with VA, intra-cavitary electrical abnormalities frequently originate at the level of viable myocardial segments with depressed sympathetic innervation that frequently represents the ultimate ablation target.

Appropriate use criteria in clinical routine practice: implications in a nuclear cardiology lab.

The efforts for a broad application of the appropriate use criteria to reduce inappropriate nuclear stress testing have frequently been unsuccessful and the reported rates of inappropriateness have varied widely between studies. We sought to analyze the criteria of clinical appropriateness of a cohort of consecutive patients referred to our nuclear cardiology laboratory to perform stress myocardial perfusion imaging (MPI) and to assess the relationships between test appropriateness and the evaluation of ischaemia. A cohort of 251 consecutive patients, admitted to our Institute from January to March 2015, who underwent stress/rest MPI on a dedicated cardiac camera equipped with cadmium-zinc-telluride detectors, was selected. The level of clinical appropriateness of each MPI test was categorized in each patient according to the AUC criteria. According to the accepted criteria, the majority of the MPI stress-tests could be classified as clinically appropriate (218 of 251, 87 % of the tests), while only 16 (6 %) and 17 (7 %) resulted of uncertain appropriateness or clearly inappropriate, respectively. Of the 251 appropriate tests, 22 (10 %), 65 (30 %), and 131 (60 %) showed the presence of a mild (SDS < 4), moderate (4 ≥ SDS < 7), and severe (SDS ≥ 7) ischemic burden, respectively, while none of the inappropriate test showed moderate-to-severe ischaemia (P < 0.001 for comparisons). The rate of inappropriate MPI tests is considerably low in a high-volume laboratory. Appropriate and inappropriate studies identify patients at high and low probability of significant ischemia, respectively, providing insights on the effects of the level of appropriateness on stress-test results.

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.

MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction.

PURPOSE: The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac (18)F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. METHODS: We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. RESULTS: Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. CONCLUSION: Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques.

Relationships between myocardial perfusion abnormalities and poststress left ventricular functional impairment on cadmium-zinc-telluride imaging.

PURPOSE: To evaluate the interplay between myocardial ischaemic burden and poststress left ventricular (LV) systolic and diastolic abnormalities in patients with suspected or known coronary artery disease (CAD). METHODS: A total of 471 patients underwent myocardial perfusion imaging by cadmium-zinc-telluride scintigraphy and coronary angiography. A fast imaging protocol was used with stress imaging performed 10 - 15 min after tracer injection. The summed difference score (SDS) and the percent stress-to-rest ratios for LV ejection fraction and peak filling rate (PFR), measures of stress-induced systolic and diastolic impairment, were computed from scintigraphic images. A SDS of >3 was considered abnormal and >7 a marker of moderate-to-severe ischaemia. RESULTS: Of the 471 patients, 321 (68%) showed significant CAD in one (27%), two (23%) or three (18%) vessels. The extent of CAD associated with gradual alterations in SDS (P < 0.001). Interestingly, while impairment in the percent stress-to-rest PFR ratio paralleled the increase in the extent of CAD (P < 0.001 for trend), the occurrence of significant stress-induced systolic dysfunction was limited to patients with multivessel disease (P < 0.001 vs. patients without CAD, and P = 0.002 vs. patients with single-vessel disease). Similarly, while a strict correlation between percent stress-to-rest PFR ratio and myocardial ischaemic burden was evident (P < 0.001), significant stress-induced LV systolic impairment was limited to patients with moderate-to-severe ischaemia (P < 0.001 vs. patients with no or mild ischaemia). CONCLUSION: Stress-induced LV diastolic impairment is associated with a less extensive ischaemic burden and CAD extent than poststress systolic dysfunction, which is limited to patients with multivessel CAD.

Diastolic dysfunction assessed by ultra-fast cadmium-zinc-telluride cardiac imaging: impact on the evaluation of ischaemia.

AIM: The aim of this study was to evaluate the possible impact of stress-induced left ventricular (LV) diastolic dysfunction at cadmium-zinc-telluride (CZT) imaging, on the detection of significant coronary artery disease (CAD). METHODS AND RESULTS: Four hundred and twenty-five consecutive patients underwent myocardial perfusion imaging at rest and after stress with a low-dose CZT protocol and the evaluation of coronary anatomy by invasive or computed coronary angiography. The summed difference score (SDS) was calculated in every patient. Left ventricular ejection fraction and peak filling rate (PFR) at baseline and after stress were derived from gated CZT images and the '% stress-to-rest' PFR difference, as an indicator of stress-induced diastolic dysfunction, determined. In the study population, the mean SDS was 5 ± 4, while mean stress PFR and rest PFR were 2.5 ± 0.8 end-diastolic volumes (EDV)/s and 2.5 ± 0.7 EDV/s, respectively. There was a strict correlation between the presence and extent of CAD and both myocardial SDS and '% stress-to-rest' PFR (P < 0.001 for both). Interestingly, while myocardial SDS and '% stress-to-rest' PFR were significantly correlated (P < 0.001), they resulted independent predictors of the presence of significant CAD (P < 0.001 and P < 0.032, respectively). Of note, at receiving operating characteristic analysis, a '% stress-to-rest' PFR ≤3 showed 71% sensitivity in unmasking the presence of significant coronary luminal narrowings. CONCLUSION: The present study shows that the assessment of stress-induced diastolic dysfunction with an ultrafast scintigraphic protocol can improve the accuracy in detection of significant ischaemic heart disease.

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.

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.

Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients.

PURPOSE: In patients with chest pain, stress-induced myocardial perfusion abnormalities are often the result of depressed myocardial blood flow (MBF) reserve. We investigated the relative contribution of cardiovascular risk factors and coronary atherosclerosis to MBF abnormalities in anginal patients. METHODS: We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain who underwent quantitative evaluation of MBF by PET at rest and after dipyridamole infusion, and quantitative coronary angiography (invasive or by 64-slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45 %) were excluded. Coronary atherosclerosis of ≥50 % was defined as obstructive. RESULTS: At rest median MBF was 0.60 ml min-1 g-1, and after dipyridamole infusion median MBF was 1.22 ml min-1 g-1. MBF reserve was <2 in 77 of 167 patients (46 %). Coronary atherosclerosis was present in 67 patients (40 %), 26 with obstructive disease. In a univariate analysis several variables were associated with reduced MBF at rest, including male gender, coronary atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia, including male gender, insulin resistance (IR), smoking habit, LV ejection fraction and end-diastolic diameter. In a multivariate analysis, after adjustment for LV function and for pharmacological treatments, male gender was the only independent predictor of reduced MBF at rest (P < 0.001), while male gender (P = 0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve. Coronary atherosclerosis, male gender and IR showed additive effects on hyperaemic MBF. CONCLUSION: In patients with chest pain and normal LV systolic function, IR, male gender and coronary atherosclerosis are independent and additive determinants of impaired hyperaemic MBF.

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.