Cardiac hybrid imaging

Computed tomography coronary angiography (CTCA) and myocardial perfusion imaging techniques (single photon emission computed tomography, SPECT, or positron emission tomography, PET) are established non-invasive modalities for the diagnosis of coronary artery disease (CAD). Cardiac hybrid imaging consists of the combination (or ‘fusion') of both modalities and allows obtaining complementary morphological (coronary anatomy, stenoses) and functional (myocardial perfusion) information in a single setting. However, hybrid cardiac imaging has also generated controversy with regard to which patients should undergo such integrated examinations for clinical effectiveness and minimization of costs and radiation dose. The feasibility and clinical value of hybrid imaging has been documented in small cohort studies and selected series of patients. Hybrid imaging appears to offer superior diagnostic and prognostic information compared with stand-alone or side-by-side interpretation of data sets. Particularly in patients with multivessel disease, the hybrid approach allows identification of flow-limiting coronary lesions and thereby provides useful information for the planning of revascularization procedures. Furthermore, integration of the detailed anatomical information from CTCA with the high molecular sensitivity of SPECT and PET may be useful to evaluate targeted molecular and cellular abnormalities in the future. While currently still restricted to specialized cardiac centres, the ongoing efforts to reduce radiation exposure and the increasing clinical interest will further pave the way for an increasing use of cardiac hybrid imaging in clinical practic

Cardiac computed tomography: indications, applications, limitations, and training requirements: Report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT of the European Society of Cardiology and the European Council of Nuclear Cardiology

As a consequence of improved technology, there is growing clinical interest in the use of multi-detector row computed tomography (MDCT) for non-invasive coronary angiography. Indeed, the accuracy of MDCT to detect or exclude coronary artery stenoses has been high in many published studies. This report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT (WG 5) of the European Society of Cardiology and the European Council of Nuclear Cardiology summarizes the present state of cardiac CT technology, as well as the currently available data concerning its accuracy and applicability in certain clinical situations. Besides coronary CT angiography, the use of CT for the assessment of cardiac morphology and function, evaluation of perfusion and viability, and analysis of heart valves is discussed. In addition, recommendations for clinical applications of cardiac CT imaging are given and limitations of the technique are describe

Detrimental proarrhythmogenic interaction of Ca2+/calmodulin-dependent protein kinase II and NaV1.8 in heart failure

An interplay between Ca2+/calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na+ current (INaL) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform NaV1.8 for CaMKIIδc-dependent proarrhythmia. In a CRISPR-Cas9-generated human iPSC-cardiomyocyte homozygous knock-out of NaV1.8, we demonstrate that NaV1.8 contributes to INaL formation. In addition, we reveal a direct interaction between NaV1.8 and CaMKIIδc in cardiomyocytes isolated from patients with heart failure (HF). Using specific blockers of NaV1.8 and CaMKIIδc, we show that NaV1.8-driven INaL is CaMKIIδc-dependent and that NaV1.8-inhibtion reduces diastolic SR-Ca2+ leak in human failing cardiomyocytes. Moreover, increased mortality of CaMKIIδc-overexpressing HF mice is reduced when a NaV1.8 knock-out is introduced. Cellular and in vivo experiments reveal reduced ventricular arrhythmias without changes in HF progression. Our work therefore identifies a proarrhythmic CaMKIIδc downstream target which may constitute a prognostic and antiarrhythmic strategy

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine

Metabolomic Profiling in Patients with Different Hemodynamic Subtypes of Severe Aortic Valve Stenosis

Severe aortic stenosis (AS) is a common pathological condition in an ageing population imposing significant morbidity and mortality. Based on distinct hemodynamic features, i.e., ejection fraction (EF), transvalvular gradient and stroke volume, four different AS subtypes can be distinguished: (i) normal EF and high gradient, (ii) reduced EF and high gradient, (iii) reduced EF and low gradient, and (iv) normal EF and low gradient. These subtypes differ with respect to pathophysiological mechanisms, cardiac remodeling, and prognosis. However, little is known about metabolic changes in these different hemodynamic conditions of AS. Thus, we carried out metabolomic analyses in serum samples of 40 AS patients (n = 10 per subtype) and 10 healthy blood donors (controls) using ultrahigh-performance liquid chromatography–tandem mass spectroscopy. A total of 1293 biochemicals could be identified. Principal component analysis revealed different metabolic profiles in all of the subgroups of AS (All-AS) vs. controls. Out of the determined biochemicals, 48% (n = 620) were altered in All-AS vs. controls (p < 0.05). In this regard, levels of various acylcarnitines (e.g., myristoylcarnitine, fold-change 1.85, p < 0.05), ketone bodies (e.g., 3-hydroxybutyrate, fold-change 11.14, p < 0.05) as well as sugar metabolites (e.g., glucose, fold-change 1.22, p < 0.05) were predominantly increased, whereas amino acids (e.g., leucine, fold-change 0.8, p < 0.05) were mainly reduced in All-AS. Interestingly, these changes appeared to be consistent amongst all AS subtypes. Distinct differences between AS subtypes were found for metabolites belonging to hemoglobin metabolism, diacylglycerols, and dihydrosphingomyelins. These findings indicate that relevant changes in substrate utilization appear to be consistent for different hemodynamic subtypes of AS and may therefore reflect common mechanisms during AS-induced heart failure. Additionally, distinct metabolites could be identified to significantly differ between certain AS subtypes. Future studies need to define their pathophysiological implications

Atrial Fibrillation and Heart Failure

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and has a strong association with heart failure (HF). It often remains unclear if HF is the cause or consequence of AF due to the complexity of the processes that are involved in both the perpetuation of AF and the development of HF. To date, two therapeutic strategies are accepted as the standard of care in AF patients with heart failure. Rhythm control aims to permanently restore sinus rhythm, whereas a rate-control strategy aims to slow ventricular rate without the termination of AF. In the last 5 years a tremendous number of important studies have been published investigating the optimal therapeutic strategy in HF patients. This review highlights the important studies with respect to the involvement of AF in promoting left-ventricular dysfunction and discusses the optimal strategy in HF patients suffering from AF

Contact force sensing manual catheter versus remote magnetic navigation ablation of atrial fibrillation: a single-center comparison

Abstract Background Data comparing remote magnetic catheter navigation (RMN) with manual catheter navigation in combination with contact force sensing (MCN-CF) ablation of atrial fibrillation (AF) is lacking. The primary aim of the present retrospective comparative study was to compare the outcome of RMN versus (vs.) MCN-CF ablation of AF with regards to AF recurrence. Secondary aim was to analyze periprocedural risk, ablation characteristics and repeat procedures. Methods We retrospectively analyzed 452 patients undergoing a total of 605 ablations of AF: 180 patients were ablated using RMN, 272 using MCN-CF. Results Except body mass index there was no significant difference between groups at baseline. After a mean 1.6 ± 1.6 years of follow-up and 1.3 ± 0.4 procedures, 81% of the patients in the MCN-CF group remained free of AF recurrence compared to 53% in the RMN group ( P  < 0.001). After analysis of 153 repeat ablations (83 MCN-RF vs. 70 RMN; P  = 0.18), there was a significantly higher reconnection rate of pulmonary veins after RMN ablation ( P  < 0.001). In multivariable Cox-regression analysis, RMN ablation ( P  < 0.001) and left atrial diameter ( P  = 0.013) was an independent risk factor for AF recurrence. Procedure time, radiofrequency application time and total fluoroscopy time and fluoroscopy dose were higher in the RMN group without difference in total number of ablation points. Complication rates did not differ significantly between groups ( P  = 0.722). Conclusions In our retrospective comparative study, the AF recurrence rate and pulmonary vein reconnection rate is significantly lower with more favorable procedural characteristics and similar complication rate utilizing MCN-CF compared to RMN

Next-generation atrial fibrillation ablation: clinical performance of pulsed-field ablation and very high-power short-duration radiofrequency

Abstract Introduction Pulsed-field energy (PFA) and very high-power short-duration radiofrequency (vHPSD-RF) are two novel ablation methods for pulmonary vein isolation (PVI). Both PFA and vHPSD-RF show promise for improving efficacy, safety, and reducing procedure durations. However, direct comparisons between these two techniques are scarce. Methods and results Retrospective analysis of 82 patients with symptomatic AF. Of these, 52 patients received PFA and 30 received vHPSD-RF (90 W, 4 s) as index procedure. At the 6-month follow-up, AF recurrence occurred in 4 patients following PFA and 5 patients following vHPSD-RF ( p -value = 0.138). Significant improvements in the EHRA and NYHA stages were evident in both PFA ( p  < 0.001 and p  = 0.047, respectively) and vHPSD-RF groups ( p  = 0.007 and p  = 0.012, respectively). The total procedure duration and the left atrial dwell time were significantly shorter in the PFA group (64 ± 19 min vs. 99 ± 32 min, p  < 0.001 and 41 ± 12 min vs. 62 ± 29 min, p  < 0.001, respectively). The fluoroscopy time and dose area product were significantly higher in PFA (14 ± 6 vs. 9 ± 5 min, p  < 0.001 and 14 ± 9 vs. 11 ± 9 Gy cm 2 , p  = 0.046, respectively). One patient in the vHPSD-RF group suffered a stroke, not directly linked to the procedure (0 vs. 1 major complication, p  = 0.366). Conclusion Based on this retrospective single-center study, PFA and vHPSD-RF were associated with similar effectiveness and safety profiles. PFA was linked to shorter procedure times and higher radiation exposure compared to vHPSD-RF. Graphical Abstrac