Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve.

AIMS: The aim of this study is to evaluate whether post-acute sequelae of COVID-19 cardiovascular syndrome (PASC-CVS) is associated with alterations in coronary circulatory function. MATERIALS AND METHODS: In individuals with PASC-CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N-ammonia and PET/CT in mL/g/min during regadenoson-stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid-distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow-mediated epicardial vasodilation, was calculated. RESULTS: Resting MBF was significantly higher in PASC-CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC-CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC-CVS, not observed in CON (-0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). CONCLUSIONS: Post-acute sequelae of COVID-19 cardiovascular syndrome may be associated with an impairment of flow-mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

Epicardial fat and atrial fibrillation: the perils of atrial failure.

Obesity is a heterogeneous condition, characterized by different phenotypes and for which the classical assessment with body mass index may underestimate the real impact on cardiovascular (CV) disease burden. An epidemiological link between obesity and atrial fibrillation (AF) has been clearly demonstrated and becomes even more tight when ectopic (i.e. epicardial) fat deposition is considered. Due to anatomical and functional features, a tight paracrine cross-talk exists between epicardial adipose tissue (EAT) and myocardium, including the left atrium (LA). Alongside-and even without-mechanical atrial stretch, the dysfunctional EAT may determine a pro-inflammatory environment in the surrounding myocardial tissue. This evidence has provided a new intriguing pathophysiological link with AF, which in turn is no longer considered a single entity but rather the final stage of atrial remodelling. This maladaptive process would indeed include structural, electric, and autonomic derangement that ultimately leads to overt disease. Here, we update how dysfunctional EAT would orchestrate LA remodelling. Maladaptive changes sustained by dysfunctional EAT are driven by a pro-inflammatory and pro-fibrotic secretome that alters the sinoatrial microenvironment. Structural (e.g. fibro-fatty infiltration) and cellular (e.g. mitochondrial uncoupling, sarcoplasmic reticulum fragmentation, and cellular protein quantity/localization) changes then determine an electrophysiological remodelling that also involves the autonomic nervous system. Finally, we summarize how EAT dysfunction may fit with the standard guidelines for AF. Lastly, we focus on the potential benefit of weight loss and different classes of CV drugs on EAT dysfunction, LA remodelling, and ultimately AF onset and recurrence.

Potential Cardiac Amyloid PET/CT Imaging Targets for Differentiating Immunoglobulin Light Chain From Transthyretin Amyloidosis.

PURPOSE OF THE REVIEW: Cardiac involvement in amyloidosis plays a critical role in the clinical manifestation and prognostication. Since advanced treatment options for immunoglobulin light chains (AL) or liver-generated protein transthyretin (TTR) are quite different, a non-invasive and comprehensive imaging approach for the identification and characterization of these forms of cardiac amyloidosis is warranted. RECENT FINDINGS: Various 18Flabeled radiotracers and positron emission tomography (PET) imaging have been appreciated as a as a valid and non-invasive diagnostic approach to identify and quantify disease activity of cardiac amyloidosis. Interestingly, applying 18F-florbetapen and delayed PET imaging may even afford the possibility to not only detect cardiac amyloidosis but also to reliably differentiate between AL and TTR, respectively. This review summarizes contributions of cardiac PET imaging for the non-invasive identification and potential differentiation between AL and TTR amyloidosis that likely holds promise to gear medical treatment in the individual patient for an improved outcome.

Cardiovascular PET/MR imaging: Quo Vadis?

With the recent advent of PET/MRI scanners, the combination of molecular imaging with a variety of known and novel PET radiotracers, the high spatial resolution of MRI, and its potential for multi-parametric imaging are anticipated to increase the diagnostic accuracy in cardiovascular disease detection, while providing novel mechanistic insights into the initiation and progression of the disease state. For the time being, cardiac PET/MRI emerges as potential clinical tool in the identification and characterization of infiltrative cardiac diseases, such as sarcoidosis, acute or chronic myocarditis, and cardiac tumors, respectively. The application of PET/MRI in conjunction with various radiotracer probes in the identification of the vulnerable atherosclerotic plaque also holds much promise but needs further translation and validation in clinical investigations. The combination of molecular imaging and creation of multi-parametric imaging maps with PET/MRI, however, are likely to set new horizons to develop predictive parameters for myocardial recovery and treatment response in ischemic and non-ischemic cardiomyopathy patients. Molecular imaging and multi-parametric imaging in cardiovascular disease with PET/MRI at current stage are at its infancy but bear a bright future.

Myocardial blood flow: Putting it into clinical perspective.

In recent years, positron emission tomography/computed tomography (PET/CT)-determined myocardial perfusion in conjunction with myocardial blood flow (MBF) quantification in mL·g(-1)·min(-1) has emerged from mere research application to initial clinical use in the detection and characterization of the coronary artery disease (CAD) process. The concurrent evaluation of MBF during vasomotor stress and at rest with the resulting myocardial flow reserve (MFR = MBF during stress/MBF at rest) expands the scope of conventional myocardial perfusion imaging not only to the detection of the most advanced and culprit CAD, as evidenced by the stress-related regional myocardial perfusion defect, but also to the less severe or intermediate stenosis in patients with multivessel CAD. Due to the non-specific nature of the hyperemic MBF and MFR, the interpretation of hyperemic flow increases with PET/CT necessitates an appropriate placement in the context with microvascular function, wall motion analysis, and eventually underlying coronary morphology in CAD patients. This review aims to provide a comprehensive overview of various diagnostic scenarios of PET/CT-determined myocardial perfusion and flow quantification in the detection and characterization of clinically manifest CAD.

Septic Cardiomyopathy: From Pathophysiology to the Clinical Setting.

The onset of cardiomyopathy is a common feature in sepsis, with relevant effects on its pathophysiology and clinical care. Septic cardiomyopathy is characterized by reduced left ventricular (LV) contractility eventually associated with LV dilatation with or without right ventricle failure. Unfortunately, such a wide range of ultrasonographic findings does not reflect a deep comprehension of sepsis-induced cardiomyopathy, but rather a lack of consensus about its definition. Several echocardiographic parameters intrinsically depend on loading conditions (both preload and afterload) so that it may be challenging to discriminate which is primitive and which is induced by hemodynamic perturbances. Here, we explore the state of the art in sepsis-related cardiomyopathy. We focus on the shortcomings in its definition and point out how cardiac performance dynamically changes in response to different hemodynamic clusters. A special attention is also given to update the knowledge about molecular mechanisms leading to myocardial dysfunction and that recall those of myocardial hibernation. Ultimately, the aim of this review is to highlight the unsolved issue in the field of sepsis-induced cardiomyopathy as their implementation would lead to improve risk stratification and clinical care.

Classification of Cardiomyopathies from MR Cine Images Using Convolutional Neural Network with Transfer Learning.

The automatic classification of various types of cardiomyopathies is desirable but has never been performed using a convolutional neural network (CNN). The purpose of this study was to evaluate currently available CNN models to classify cine magnetic resonance (cine-MR) images of cardiomyopathies. METHOD: Diastolic and systolic frames of 1200 cine-MR sequences of three categories of subjects (395 normal, 411 hypertrophic cardiomyopathy, and 394 dilated cardiomyopathy) were selected, preprocessed, and labeled. Pretrained, fine-tuned deep learning models (VGG) were used for image classification (sixfold cross-validation and double split testing with hold-out data). The heat activation map algorithm (Grad-CAM) was applied to reveal salient pixel areas leading to the classification. RESULTS: The diastolic-systolic dual-input concatenated VGG model cross-validation accuracy was 0.982 ± 0.009. Summed confusion matrices showed that, for the 1200 inputs, the VGG model led to 22 errors. The classification of a 227-input validation group, carried out by an experienced radiologist and cardiologist, led to a similar number of discrepancies. The image preparation process led to 5% accuracy improvement as compared to nonprepared images. Grad-CAM heat activation maps showed that most misclassifications occurred when extracardiac location caught the attention of the network. CONCLUSIONS: CNN networks are very well suited and are 98% accurate for the classification of cardiomyopathies, regardless of the imaging plane, when both diastolic and systolic frames are incorporated. Misclassification is in the same range as inter-observer discrepancies in experienced human readers.

Deep Learning Supplants Visual Analysis by Experienced Operators for the Diagnosis of Cardiac Amyloidosis by Cine-CMR.

BACKGROUND: Diagnosing cardiac amyloidosis (CA) from cine-CMR (cardiac magnetic resonance) alone is not reliable. In this study, we tested if a convolutional neural network (CNN) could outperform the visual diagnosis of experienced operators. METHOD: 119 patients with cardiac amyloidosis and 122 patients with left ventricular hypertrophy (LVH) of other origins were retrospectively selected. Diastolic and systolic cine-CMR images were preprocessed and labeled. A dual-input visual geometry group (VGG ) model was used for binary image classification. All images belonging to the same patient were distributed in the same set. Accuracy and area under the curve (AUC) were calculated per frame and per patient from a 40% held-out test set. Results were compared to a visual analysis assessed by three experienced operators. RESULTS: frame-based comparisons between humans and a CNN provided an accuracy of 0.605 vs. 0.746 (p < 0.0008) and an AUC of 0.630 vs. 0.824 (p < 0.0001). Patient-based comparisons provided an accuracy of 0.660 vs. 0.825 (p < 0.008) and an AUC of 0.727 vs. 0.895 (p < 0.002). CONCLUSION: based on cine-CMR images alone, a CNN is able to discriminate cardiac amyloidosis from LVH of other origins better than experienced human operators (15 to 20 points more in absolute value for accuracy and AUC), demonstrating a unique capability to identify what the eyes cannot see through classical radiological analysis.

Positron Emission Tomography-Determined Hyperemic Flow, Myocardial Flow Reserve, and Flow Gradient-Quo Vadis?

Positron emission tomography/computed tomography (PET/CT) applied with positron-emitting flow tracers such as 13N-ammonia and 82Rubidium enables the quantification of both myocardial perfusion and myocardial blood flow (MBF) in milliliters per gram per minute for coronary artery disease (CAD) detection and characterization. The detection of a regional myocardial perfusion defect during vasomotor stress commonly identifies the culprit lesion or most severe epicardial narrowing, whereas adding regional hyperemic MBFs, myocardial flow reserve (MFR), and/or longitudinal flow decrease may also signify less severe but flow-limiting stenosis in multivessel CAD. The addition of regional hyperemic flow parameters, therefore, may afford a comprehensive identification and characterization of flow-limiting effects of multivessel CAD. The non-specific origin of decreases in hyperemic MBFs and MFR, however, prompts an evaluation and interpretation of regional flow in the appropriate context with the presence of obstructive CAD. Conversely, initial results of the assessment of a longitudinal hyperemic flow gradient suggest this novel flow parameter to be specifically related to increases in CAD caused epicardial resistance. The concurrent assessment of myocardial perfusion and several hyperemic flow parameters with PET/CT may indeed open novel avenues of precision medicine to guide coronary revascularization procedures that may potentially lead to a further improvement in cardiovascular outcomes in CAD patients.

Cardiac PET/Computed Tomography Applications and Cardiovascular Outcome.

Cardiac PET/computed tomography (CT) in conjunction with different blood flow tracers is increasingly applied for the assessment of myocardial perfusion and myocardial flow reserve (MFR) in the detection of coronary artery disease (CAD). The ability of PET/CT to noninvasively determine regional myocardial blood flow at rest and during vasomotor stress allows the calculation of the MFR, which carries important prognostic information in patients with subclinical forms of cardiomyopathy. The measured MFR optimizes the identification and characterization of the extent and severity of CAD burden, and contributes to the flow-limiting effect of single lesions in multivessel CAD.