Long-term prognostic impact of fasting plasma glucose and myocardial flow reserve beyond other risk factors and heart disease phenotypes.

Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging prognostic determinants in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction might be a comprehensive risk predictor in these patients. The purpose of this study was to assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, predict long-term prognosis beyond other risk factors and presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF. We retrospectively collected long-term follow-up data in 103 patients (mean age 61 ± 10 years, 74 males) with stable chest pain or dyspnoea who underwent cardiac PET/computerized tomography and coronary angiography. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%), or none (22%). At multivariable logistic regression analysis, MBF reserve lower than the median value (OR 1.8, 95% CI 1.5-2.2) was significantly associated with male gender (OR 3.45, 95% CI 1.21-9.83) and hFPG (OR 3.87, 95% CI 1.17-12.84) among all risk factors. In a median follow-up of 10.9 years (interquartile range 7.8-13.9), 39 patients (37.8%) died (13.6% cardiac death). At multivariable Cox analyses including all risk factors and disease phenotypes, age (HR 1.07, 95% CI 1.02-1.12), hFPG (HR 2.18, 95% CI 1.02-4.63), and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) were independent predictors of death (global χ 2 37.41, P = 0.0004). These results suggest a strong long-term prognostic role of hFPG and depressed MBF reserve in a high-risk population of patients with a high prevalence of obstructive CAD or HF.

Value of Ischemia and Coronary Anatomy in Prognosis and Guiding Revascularization Among Patients With Stable Ischemic Heart Disease.

BACKGROUND: The value of physiological ischemia versus anatomic severity of disease for prognosis and management of patients with stable coronary artery disease (CAD) is widely debated. METHODS: A total of 1764 patients who had rest-stress cadmium-zinc-telluride single-photon emission computed tomography myocardial perfusion imaging and angiography (invasive or computed tomography) were prospectively enrolled and followed for cardiac death/nonfatal myocardial infarction. The CAD prognostic index (CADPI) was used to quantify the extent and severity of angiographic disease. Prognostic value was assessed using Cox models, adjusted for pretest risk, known CAD, stressor, left ventricular ejection fraction, %ischemia and infarct, CADPI, and early (90-day) revascularization. Incremental prognostic value was evaluated using net reclassification index. RESULTS: The mean age was 69.7±9.5 years, 24.4% were women, and 29.3% had known CAD. Significant ischemia (>10%) was present in 28.4%. Nonobstructive, single, and multivessel disease was present in 256 (14.5%), 772 (43.8%), and 736 (41.7%), respectively. Early revascularization occurred in 579 (32.8%). Cardiac death/myocardial infarction occurred in 148 (8.4%) over a 4.6-year median follow-up. Both %ischemia and CADPI provided independent and incremental prognostic value over pretest clinical risk (P<0.001). In a model containing both ischemia and anatomy, ischemia was prognostic (hazard ratio per 5% ↑, 1.35 [95% CI, 1.11-1.63]; P=0.002) but CADPI was not (hazard ratio per 10-unit ↑, 1.09 [95% CI, 0.99-1.20]; P=0.07). Early revascularization modified the risk associated with %ischemia (interaction P=0.003) but not with CADPI (interaction P=0.6). %Ischemia and single-photon emission computed tomography variables added incremental prognostic value over clinical risk and CADPI (net reclassification index, 20.3% [95% CI, 9%-32%]; P<0.05); however, CADPI was not incrementally prognostic beyond pretest risk, %ischemia, and single-photon emission computed tomography variables (net reclassification index, 3.1% [95% CI, -5% to 15%]; P=0.21). CONCLUSIONS: Ischemic burden provides independent and incremental prognostic value beyond CAD anatomy and identifies patients who benefit from early revascularization. The anatomic extent of disease has independent prognostic value over clinical risk factors but offers limited incremental benefit for prognosis and guiding revascularization beyond physiological severity (ischemia).

Myocardial ischemia in patients with mild-to-moderate aortic stenosis: Interaction with cardiac remodeling and adverse events.

BACKGROUND: The association between aortic valve stenosis (AVS) and myocardial perfusion abnormalities has been incompletely characterized. We sought to assess the predictors of myocardial ischemia in patients with mild-to-moderate AVS, and its relationship with long-term prognosis. METHODS: Eighty-nine patients with mild-to-moderate AVS (peak velocity between 2.6 and 4.0 m/second and aortic valve area > .6 cm2/m2), preserved left ventricular (LV) function, and either normal coronary arteries (28 patients) or non-obstructive coronary artery disease (<50% stenosis; 61 patients) were individuated. Myocardial perfusion imaging was performed using a cadmium-zinc-telluride camera, and the summed difference score (SDS) was computed. The presence of either LV hypertrophy (LVH) (LV mass index [LVMI] > 115 g/m2 [males] or 95 g/m2 [females]) or concentric LV remodeling (relative wall thickness: >.42) was determined at two-dimensional echocardiography. RESULTS: Forty (45%) and 49 (55%) patients had mild and moderate AVS, respectively. Fifty (56%), 17 (19%), and 22 (25%) patients had normal LV geometry, concentric LV remodeling, and LVH, respectively. An interaction between LV remodeling and inducible ischemia was revealed with progressively higher values of SDS in patients with normal LV geometry (3 ± 3), concentric remodeling (4 ± 2), and LVH (7 ± 2) (P < .001). Accordingly, a moderate correlation existed between LVMI and SDS values (R: .67; P < .001). After a median follow-up of 84 ± 47 months, 27 adverse events were recorded, including 19 AV replacements and 8 deaths. On multivariable analysis, the presence of LVH (hazard ratio [HR]: 6.46; 95% confidence interval [CI]: 2.09-20.00; P = .001) and a higher SDS (HR: 1.41; 95% CI: 1.15-1.75; P = .001) were the two independent predictors of AE. CONCLUSIONS: In patients with mild-to-moderate AVS, myocardial ischemia correlates with the severity of adverse LV remodeling. Patients with LVH and ischemia are at increased risk of AE.

[18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

The Role of Scintigraphy with Bone Radiotracers in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.

Wild-type transthyretin cardiac amyloidosis is not rare in elderly subjects: the CATCH screening study.

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population. METHODS AND RESULTS: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1000 accepted. The following red flags were searched: interventricular septal thickness ≥ 12 mm, any echocardiographic, electrocardiographic or clinical hallmark of CA, or high-sensitivity troponin T ≥ 14 ng/L. Individuals with at least one red flag (n = 346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnoea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (Grade 3), left ventricular (LV) wall thickening, Grade 2 and 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 1000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a Grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP < 300 ng/L. The prevalence of ATTR-CA in subjects ≥ 65 years was calculated as 0.46% (i.e. 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). CONCLUSION: Wild-type transthyretin cardiac amyloidosis is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease.

Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a heart condition mostly found in older adults. Wild-type transthyretin cardiac amyloidosis is considered a rare disease, although no systematic screening has been performed yet. The study aimed to understand how common this disease is among the general population aged 65­90 years in Pisa, Italy. To do this, general practitioners offered screening for ATTRwt-CA to their patients within this age group. The initial step of the screening involved checking for certain warning signs (red flags), like abnormal thickness in a part of the heart called the interventricular septum, unusual heart function observed through various tests, or elevated levels of a specific heart protein. Out of 1000 individuals who began the screening process, 346 showed at least one of these red flags and were further examined using bone scintigraphy (a type of imaging test) and tests for a specific protein related to this condition. Of these, 216 agreed to proceed with these additional tests. The results showed that four of these patients actually had ATTRwt-CA. Their conditions varied in severity, with some showing more intense signs of the disease on the heart scans, thicker heart walls, and higher levels of heart stress proteins. All four patients experienced mild difficulty in breathing during physical activity. Based on these findings, the study concluded that about 0.46% of elderly individuals in the general population might have ATTRwt-CA, indicating that the disease is somewhat more common in this age group than previously thought.

Bayesian Convolutional Neural Networks in Medical Imaging Classification: A Promising Solution for Deep Learning Limits in Data Scarcity Scenarios.

Deep neural networks (DNNs) have already impacted the field of medicine in data analysis, classification, and image processing. Unfortunately, their performance is drastically reduced when datasets are scarce in nature (e.g., rare diseases or early-research data). In such scenarios, DNNs display poor capacity for generalization and often lead to highly biased estimates and silent failures. Moreover, deterministic systems cannot provide epistemic uncertainty, a key component to asserting the model's reliability. In this work, we developed a probabilistic system for classification as a framework for addressing the aforementioned criticalities. Specifically, we implemented a Bayesian convolutional neural network (BCNN) for the classification of cardiac amyloidosis (CA) subtypes. We prepared four different CNNs: base-deterministic, dropout-deterministic, dropout-Bayesian, and Bayesian. We then trained them on a dataset of 1107 PET images from 47 CA and control patients (data scarcity scenario). The Bayesian model achieved performances (78.28 (1.99) % test accuracy) comparable to the base-deterministic, dropout-deterministic, and dropout-Bayesian ones, while showing strongly increased "Out of Distribution" input detection (validation-test accuracy mismatch reduction). Additionally, both the dropout-Bayesian and the Bayesian models enriched the classification through confidence estimates, while reducing the criticalities of the dropout-deterministic and base-deterministic approaches. This in turn increased the model's reliability, also providing much needed insights into the network's estimates. The obtained results suggest that a Bayesian CNN can be a promising solution for addressing the challenges posed by data scarcity in medical imaging classification tasks.

Sex-specific associations of myocardial perfusion imaging with outcomes in patients with suspected chronic coronary syndrome.

BACKGROUND: Myocardial perfusion scintigraphy (MPS) is an established diagnostic technique for inducible ischemia in patients with suspected chronic coronary syndrome (CCS). Some MPS findings, most notably an ischemia extent>10% of the left ventricle (LV), hold prognostic significance and support maximization of anti-ischemic treatment. We aimed to assess sex-specific associations of MPS findings with cardiovascular (CV) events in a population at high risk of CCS. METHODS: In a prospective cohort study, 1,229 consecutive patients (age 70 ± 9.5 years, 73.5% males) without known CCS were referred to stress-rest MPS. All patients were followed for a median of 4.6 years for CV events. RESULTS: Men and women had comparable risk profiles and incidence rates of CV events (6.6% vs. 4.6% respectively, P = 0.186). A summed stress score (SSS) > 7 was associated with the primary endpoint, including CV death and/or nonfatal myocardial infarction (MI) (adjusted hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.79-5.46; P = 0.001), all-cause mortality (HR, 3.01; 95% CI, 1.31-6.93; P = 0.01), and incidence of late revascularization (HR, 1.84; 95% CI, 1.22-2.78; P = 0.004) in men but not women. A summed difference score (SDS) > 6 was related to a higher rate of the primary endpoint only in men (adjusted HR, 1.97; 95% CI, 1.18-3.30; P = 0.009). CONCLUSIONS: Among patients undergoing a diagnostic workup for suspected CCS, stress perfusion and reversible ischemia abnormalities may independently predict worse survival and more CV events in men. However, the obtained results indicated the need for sex-specific cutoffs to refine risk stratification and assist in clinical decisions on anti-ischemic therapy beyond coronary artery anatomy.

Prognostic impact of patients' management based on anatomic/functional phenotype: a study in patients with chronic coronary syndromes.

BACKGROUND: In stable coronary artery disease (CAD), the prognostic interaction between clinical variables and treatment appropriateness based on anatomic/functional phenotype needs to be evaluated. METHODS: 1585 consecutive patients underwent myocardial perfusion scintigraphy and coronary angiography within 90 days. Obstructive CAD (> 70% stenosis) with downstream moderate-to-severe ischemia (> 10%) was considered significant. Coronary revascularization was considered appropriate if all hemodynamically significant lesions were revascularized, while medical therapy only was deemed appropriate in the absence of hemodynamically significant CAD. RESULTS: Obstructive CAD and moderate-to-severe ischemia were documented in 1184 (75%) and 466 (29%) patients, respectively. Over mean follow-up of 4.7 ± 2.5 years, the primary endpoint (cardiac death and non-fatal myocardial infarction) occurred in 132 (8.2%) patients. Of patients with obstructive CAD, 797 (67%) were managed appropriately. Patients' management was inappropriate in 389 patients, because either non-hemodynamically significant lesions were revascularized (50%, including 2 patients with non-obstructive lesions being inappropriately revascularized) or ischemia-causing CAD was left untreated (50%). At multivariate analysis, an inappropriate management (P < .001) was correlated with the primary endpoint, together with previous myocardial infarction (P = .009), lower ejection fraction (P < .001) and higher glucose levels (P < .001). CONCLUSIONS: In stable CAD patients, management based on anatomic/functional phenotyping was correlated with a prognostic advantage at long-term follow-up. Correlation between treatment categories and patients' prognosis. A significantly higher event-rate was observed in patients where hemodynamically significant coronary lesions were left untreated-either because MT was not-adherently chosen or in the case of incomplete revascularization-than in those that were revascularized completely (17.6% vs 5.1%; P < .001). Conversely, the revascularization of non-hemodynamically significant CAD correlated with a higher event-rate than that of similar patients managed medically (13.8% vs 8.3%, P = .04). The event-rate of patients in whom coronary revascularization was performed in the presence of hemodynamically significant CAD ('appropriate revascularization') was similar to those with "No CAD/non-obstructive CAD" (5.1% vs 3.5%; P = NS).

Impact of appropriateness in clinical practice: data from a single-centre nuclear cardiology laboratory.

Aims: To verify the level of appropriateness of referral to our nuclear cardiology laboratory for stress myocardial perfusion imaging (MPI) and explore the correlation between test appropriateness patterns and ischaemia. Methods and results: In 1870 consecutive patients (mean age 73 ± 12 years; 33% female) undergoing MPI, the level of imaging test appropriateness was evaluated according to the 2023 Appropriate Use Criteria (AUC) and the current European Society of Cardiology (ESC) guidelines for the management of chronic coronary syndromes. The evidence of moderate-to-severe ischaemia (i.e. summed difference score >7) was recorded. According to the AUC criteria, the MPI of 1638 (88%), 130 (7%), and 102 (5%) patients could be classified as 'appropriate', 'inappropriate', and 'uncertain', respectively. Similarly, in 1685 (90%) patients, the referral to MPI was adherent to ESC guidelines, while in 185 (10%), it was not. The majority of appropriate MPI tests showed the presence of moderate-to-severe ischaemia (55%), while only a limited number (10%; P < 0.05) of MPI tests with uncertain clinical appropriateness or clearly inappropriate indications did not. In patients managed adherently to ESC guidelines, invasive coronary angiography more frequently showed obstructive coronary artery disease (CAD) (93 vs. 47%, P < 0.001) and led to coronary revascularization (65 vs. 23%, P < 0.001) compared with patients managed non-adherently. Conclusion: In a single-centre, single-national, single-modality population, the current rate of appropriate MPI tests is high. Appropriate referrals are associated with a higher probability of moderate-to-severe ischaemia and better downstream resource utilization than inappropriate ones.

Tissue Characterization in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) has long been considered a rare disease, but recent advancements in diagnostic tools have led to a reconsideration of the epidemiology of CA. Amyloid light-chain (AL) and transthyretin (ATTR) amyloidoses are the most common forms of cardiac amyloidosis. Due to the distinct treatments and the different prognoses, amyloid typing is crucial. Although a non-biopsy diagnosis can be obtained in ATTR amyloidosis when certain diagnostic criteria are fulfilled, tissue characterization still represents the gold standard for the diagnosis and typing of CA, particularly in AL amyloidosis. The present review focuses on the status of tissue characterization in cardiac amyloidosis, from histochemistry to immunohistochemistry and mass spectrometry, as well as on its future directions.

The role of cardiovascular magnetic resonance in the evaluation of acute myocarditis and inflammatory cardiomyopathies in clinical practice - a comprehensive review.

Inflammatory cardiomyopathy (I-CMP) is defined as myocarditis in association with cardiac dysfunction and/or ventricular remodelling. It is characterized by inflammatory cell infiltration into the myocardium and has heterogeneous infectious and non-infectious aetiologies. A complex interplay of genetic, autoimmune, and environmental factors contributes to the substantial risk of deteriorating cardiac function, acute heart failure, and arrhythmia as well as chronic dilated cardiomyopathy and its sequelae. Multi-parametric cardiovascular magnetic resonance (CMR) imaging is sensitive to many tissue changes that occur during myocardial inflammation, regardless of its aetiology. In this review, we summarize the various aetiologies of I-CMP and illustrate how CMR contributes to non-invasive diagnosis.

Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis.

Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods and Results We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68-81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%-30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%-23%; range, 5%-60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. Conclusions Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.

Have Volume-based Parameters of Positron Emission Tomography/Computed Tomography Prognostic Relevance for Patients With Potentially Platinum-responsive Recurrent Ovarian Cancer? A Single Center Italian Study.

BACKGROUND/AIM: To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer. PATIENTS AND METHODS: This retrospective investigation analyzed 67 patients at first relapse. RESULTS: At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival. CONCLUSION: Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.

Deep-learning-based cardiac amyloidosis classification from early acquired pet images.

The objective of the present work was to evaluate the potential of deep learning tools for characterizing the presence of cardiac amyloidosis from early acquired PET images, i.e. 15 min after [18F]-Florbetaben tracer injection. 47 subjects were included in the study: 13 patients with transthyretin-related amyloidosis cardiac amyloidosis (ATTR-CA), 15 patients with immunoglobulin light-chain amyloidosis (AL-CA), and 19 control-patients (CTRL). [18F]-Florbetaben PET/CT images were acquired in list mode and data was sorted into a sinogram, covering a time interval of 5 min starting 15 min after the injection. The resulting sinogram was reconstructed using OSEM iterative algorithm. A deep convolutional neural network (CAclassNet) was designed and implemented, consisting of five 2D convolutional layers, three fully connected layers and a final classifier returning AL, ATTR and CTRL scores. A total of 1107 2D images (375 from AL-subtype patients, 312 from ATTR-subtype, and 420 from Controls) have been considered in the study and used to train, validate and test the proposed network. CAclassNet cross-validation resulted with train error mean ± sd of 2.001% ± 0.96%, validation error of 4.5% ± 2.26%, and net accuracy of 95.49% ± 2.26%. Network test error resulted in a mean ± sd values of 10.73% ± 0.76%. Sensitivity, specificity, and accuracy evaluated on the test dataset were respectively for AL-CA sub-type: 1, 0.912, 0.936; for ATTR-CA: 0.935, 0.897, 0.972; for control subjects: 0.809, 0.971, 0.909. In conclusion, the proposed CAclassNet model seems very promising as an aid for the clinician in the diagnosis of CA from cardiac [18F]-Florbetaben PET images acquired a few minutes after the injection.

The Role of 18FDG PET/CT in the Assessment of Endocarditis, Myocarditis and Pericarditis.

Endocarditis, myocarditis and pericarditis are a heterogeneous group of phenotypic syndromes where the culprit area of inflammation is the heart. Inflammation may be determined by an infective agent, toxins, drugs or an activated immune system. Clinical manifestations can be subtle and diagnosis remains a challenge for cardiologists, requiring high level of suspicion and advanced multimodal cardiac imaging to avoid life-threatening consequences. The purpose of this review is to report the recent advances of PET/CT imaging with 18FDG in helping the management of patients affected by inflammatory heart disease. Two independent reviewers searched in PubMed articles published before or in June 2019 and final decisions on the inclusion of references were done in consensus with a third reviewer. At the end of the selection process 23/206 articles on "cardiac inflammation"; 26/235 articles on "endocarditis", "prosthetic heart valve", "pacemaker", "implantable cardiac device"; 7/103 articles on "myocarditis"; 13/330 articles on sarcoidosis" and 2/19 articles on "pericarditis" were included. Compared with the conventional methods, molecular imaging has the advantage to non-invasively and directly trace the inflammatory process, and to identify earlier the presence and the extent of intra-cardiac and extra-cardiac involvement, to enable quantification of disease activity, guide therapeutic interventions, and monitor treatment success.