Imaging in Infective Endocarditis-Current Opinions and Trends in Cardiac Computed Tomography.

Infective endocarditis is a rare disease with an increasing incidence and an unaltered high mortality rate, despite medical development. Imaging plays an integrative part in the diagnosis of infective endocarditis, with echocardiography as the initial diagnostic test. Research data in the utility of cardiac computed tomography (CCT) in the diagnostic algorithm of IE are rising, which indicates its importance in detection of IE-related lesion along with the exclusion of coronary artery disease. The latest 2023 European Society of Cardiology Guidelines in the management of IE classified CCT as class of recommendation I and level of evidence B in detection of both valvular and paravalvular lesions in native and prosthetic valve endocarditis. This review article provides a comprehensive and contemporary review of the role of CCT in the diagnosis of IE, the optimization of acquisition protocols, the morphology characteristics of IE-related lesions, the published data of the diagnostic performance of CCT in comparison to echocardiography as the state-of-art method, as well as the limitations and future possibilities.

The Role of Echocardiography and Cardiac Computed Tomography in Diagnosis of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a rare disease with a high mortality rate and rising incidence, requiring timely and precise diagnosis in order to choose appropriate therapy. Imaging of morphologic lesions is an integrative part of diagnosis. Artifacts and the patient's habitus make echocardiography difficult to visualize advanced-form IE. Cardiac computed tomography (CCT) constantly shows an additive diagnostic value due to high resolution of cardiac anatomy. Conjecturally, joint application of both diagnostic tests improves overall sensitivity and specificity in diagnosing IE. METHODS: Patients with definite IE underwent transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and CCT. We analyzed valvular and paravalvular IE lesions in all three imaging methods and compared them to surgical or autopsy findings. We calculated sensitivity, specificity, diagnostic accuracy, and positive and negative predictive value of both imaging tests individually and jointly used. RESULTS: We examined 78 patients, male to female ratio 2:1, mean age 52.29 ± 16.62. We analyzed 85 valves, 70 native valves, 13 prosthetic valves, and 2 corrected valves due to Ozaki procedure, along with a central shunt and 4 pacemaker leads. As a single test, the sensitivity and specificity of CCT, TTE, and TEE for valvular lesions were 91.6/20%, 65.5/57.9%, and 60/84%, and paravalvular lesions were 100/0%, 46/10.5%, and 14.7/100%. When combined together, sensitivity and specificity for valvular lesions rose to 96.6/0% and paravalvular lesions to 100/0%. We also analyzed the diagnostic performance for each test in single and mutual application, per specific IE lesion. CONCLUSION: In the individual application, CCT in comparison to TTE and TEE shows better diagnostic performance in detection of valvular and paravalvular lesions. In joint application, there is a statistically significant difference in performance compared to their single use, especially in prosthetic valves and invasive forms of IE native valves.

Information-Theoretic Analysis of Cardio-Respiratory Interactions in Heart Failure Patients: Effects of Arrhythmias and Cardiac Resynchronization Therapy.

The properties of cardio-respiratory coupling (CRC) are affected by various pathological conditions related to the cardiovascular and/or respiratory systems. In heart failure, one of the most common cardiac pathological conditions, the degree of CRC changes primarily depend on the type of heart-rhythm alterations. In this work, we investigated CRC in heart-failure patients, applying measures from information theory, i.e., Granger Causality (GC), Transfer Entropy (TE) and Cross Entropy (CE), to quantify the directed coupling and causality between cardiac (RR interval) and respiratory (Resp) time series. Patients were divided into three groups depending on their heart rhythm (sinus rhythm and presence of low/high number of ventricular extrasystoles) and were studied also after cardiac resynchronization therapy (CRT), distinguishing responders and non-responders to the therapy. The information-theoretic analysis of bidirectional cardio-respiratory interactions in HF patients revealed the strong effect of nonlinear components in the RR (high number of ventricular extrasystoles) and in the Resp time series (respiratory sinus arrhythmia) as well as in their causal interactions. We showed that GC as a linear model measure is not sensitive to both nonlinear components and only model free measures as TE and CE may quantify them. CRT responders mainly exhibit unchanged asymmetry in the TE values, with statistically significant dominance of the information flow from Resp to RR over the opposite flow from RR to Resp, before and after CRT. In non-responders this asymmetry was statistically significant only after CRT. Our results indicate that the success of CRT is related to corresponding information transfer between the cardiac and respiratory signal quantified at baseline measurements, which could contribute to a better selection of patients for this type of therapy.

Effects of Cardiac Resynchronization Therapy on Cardio-Respiratory Coupling.

In this study, the effect of cardiac resynchronization therapy (CRT) on the relationship between the cardiovascular and respiratory systems in heart failure subjects was examined for the first time. We hypothesized that alterations in cardio-respiratory interactions, after CRT implantation, quantified by signal complexity, could be a marker of a favorable CRT response. Sample entropy and scaling exponents were calculated from synchronously recorded cardiac and respiratory signals 20 min in duration, collected in 47 heart failure patients at rest, before and 9 months after CRT implantation. Further, cross-sample entropy between these signals was calculated. After CRT, all patients had lower heart rate and CRT responders had reduced breathing frequency. Results revealed that higher cardiac rhythm complexity in CRT non-responders was associated with weak correlations of cardiac rhythm at baseline measurement over long scales and over short scales at follow-up recording. Unlike CRT responders, in non-responders, a significant difference in respiratory rhythm complexity between measurements could be consequence of divergent changes in correlation properties of the respiratory signal over short and long scales. Asynchrony between cardiac and respiratory rhythm increased significantly in CRT non-responders during follow-up. Quantification of complexity and synchrony between cardiac and respiratory signals shows significant associations between CRT success and stability of cardio-respiratory coupling.

Diagnostic value of implantable loop recorders in patients with unexplained syncope or palpitations.

BACKGROUND: The implantable loop recorder (ILR) is a small cardiac rhythm-monitoring device. Our aim was to determine ILR diagnostic value in patients with unexplained syncope, presyncope, or palpitations suggesting cardiac arrhythmias. METHODS: This has been a retrospective, observational, single-center study. We included 181 patients in whom ILR was implanted at the Clinical Center of Serbia between January 2006 and July 2019. An event was marked as diagnostic if it led to a diagnosis and ILR was considered diagnostic if it verified or excluded an arrhythmia as the cause of syncope or palpitations. RESULTS: The mean age was 51.8 ± 17.8 years and 94 (51.9%) were male. The mean follow-up period was 20.2 ± 15.8 months. ILR was diagnostic in 98 patients (54.1%). There was no significant difference in diagnostic value of ILR in regard to the baseline patients' characteristics. The mean time to occurrence of the diagnostic event was 11.1 ± 9.6 months. The time to occurrence of a diagnostic event did not differ significantly between patients who underwent basic as compared to extended diagnostics before ILR implantation. CONCLUSIONS: ILR was able to achieve an etiological diagnosis in 54.1% of patients with unexplained syncope, presyncope, or palpitations suggesting cardiac arrhythmias. In a subgroup of patients with recurrent palpitations, ILR was significantly less diagnostic than in patients with syncope or presyncope. ILR should be implanted beforehand in syncope evaluation process.

Multiscale Entropy Analysis: Application to Cardio-Respiratory Coupling.

It is known that in pathological conditions, physiological systems develop changes in the multiscale properties of physiological signals. However, in real life, little is known about how changes in the function of one of the two coupled physiological systems induce changes in function of the other one, especially on their multiscale behavior. Hence, in this work we aimed to examine the complexity of cardio-respiratory coupled systems control using multiscale entropy (MSE) analysis of cardiac intervals MSE (RR), respiratory time series MSE (Resp), and synchrony of these rhythms by cross multiscale entropy (CMSE) analysis, in the heart failure (HF) patients and healthy subjects. We analyzed 20 min of synchronously recorded RR intervals and respiratory signal during relaxation in the supine position in 42 heart failure patients and 14 control healthy subjects. Heart failure group was divided into three subgroups, according to the RR interval time series characteristics (atrial fibrillation (HFAF), sinus rhythm (HFSin), and sinus rhythm with ventricular extrasystoles (HFVES)). Compared with healthy control subjects, alterations in respiratory signal properties were observed in patients from the HFSin and HFVES groups. Further, mean MSE curves of RR intervals and respiratory signal were not statistically different only in the HFSin group (p = 0.43). The level of synchrony between these time series was significantly higher in HFSin and HFVES patients than in control subjects and HFAF patients (p < 0.01). In conclusion, depending on the specific pathologies, primary alterations in the regularity of cardiac rhythm resulted in changes in the regularity of the respiratory rhythm, as well as in the level of their asynchrony.

Differentiation of Heart Failure Patients by the Ratio of the Scaling Exponents of Cardiac Interbeat Intervals.

Heart failure (HF) is one of the most frequent heart diseases. It is usually characterized with structural and functional cardiac abnormalities followed by dysfunction of autonomic cardiac control. Current methods of heartbeat interval analysis are not capable to differentiate HF patients and some new differentiation of HF patients could be useful in the determination of the direction of their treatment. In this study, we examined potential of the ratio of the short-term and long-term scaling exponents (α 1 and α 2) to separate HF patients with similar level of reduced cardiac autonomic nervous system control and with no significant difference in age, left ventricular ejection fraction (LVEF) and NYHA class. Thirty-five healthy control subjects and 46 HF patients underwent 20 min of continuous supine resting ECG recording. The interbeat interval time series were analyzed using standardized power spectrum analysis, detrended fluctuation analysis method and standard Poincaré plot (PP) analysis with measures of asymmetry of the PP. Compared with healthy control group, in HF patients linear measures of autonomic cardiac control were statistically significantly reduced (p < 0.05), heart rate asymmetry was preserved (C up > C down, p < 0.01), and long-term scaling exponent α 2 was significantly higher. Cluster analysis of the ratio of short- and long-term scaling exponents showed capability of this parameter to separate four clusters of HF patients. Clusters were determined by interplay of presence of short-term and long-term correlations in interbeat intervals. Complementary measure, commonly accepted ratio of the PP descriptors, SD2/SD1, showed tendency toward statistical significance to separate HF patients in obtained clusters. Also, heart rate asymmetry was preserved only in two clusters. Finally, a multiple regression analysis showed that the ratio α 1/α 2 could be used as an integrated measure of cardiac dynamic with complex physiological background which, besides spectral components as measures of autonomic cardiac control, also involves breathing frequency and mechanical cardiac parameter, left ventricular ejection fraction.

Bidirectional Cardio-Respiratory Interactions in Heart Failure.

We investigated cardio-respiratory coupling in patients with heart failure by quantification of bidirectional interactions between cardiac (RR intervals) and respiratory signals with complementary measures of time series analysis. Heart failure patients were divided into three groups of twenty, age and gender matched, subjects: with sinus rhythm (HF-Sin), with sinus rhythm and ventricular extrasystoles (HF-VES), and with permanent atrial fibrillation (HF-AF). We included patients with indication for implantation of implantable cardioverter defibrillator or cardiac resynchronization therapy device. ECG and respiratory signals were simultaneously acquired during 20 min in supine position at spontaneous breathing frequency in 20 healthy control subjects and in patients before device implantation. We used coherence, Granger causality and cross-sample entropy analysis as complementary measures of bidirectional interactions between RR intervals and respiratory rhythm. In heart failure patients with arrhythmias (HF-VES and HF-AF) there is no coherence between signals (p < 0.01), while in HF-Sin it is reduced (p < 0.05), compared with control subjects. In all heart failure groups causality between signals is diminished, but with significantly stronger causality of RR signal in respiratory signal in HF-VES. Cross-sample entropy analysis revealed the strongest synchrony between respiratory and RR signal in HF-VES group. Beside respiratory sinus arrhythmia there is another type of cardio-respiratory interaction based on the synchrony between cardiac and respiratory rhythm. Both of them are altered in heart failure patients. Respiratory sinus arrhythmia is reduced in HF-Sin patients and vanished in heart failure patients with arrhythmias. Contrary, in HF-Sin and HF-VES groups, synchrony increased, probably as consequence of some dominant neural compensatory mechanisms. The coupling of cardiac and respiratory rhythm in heart failure patients varies depending on the presence of atrial/ventricular arrhythmias and it could be revealed by complementary methods of time series analysis.

Uncoupling of cardiac and respiratory rhythm in atrial fibrillation.

Rearranged origin of heart rhythm in patients with atrial fibrillation (AF) influences the regulation of the heart and consequently the respiratory rhythm, and the bidirectional interaction of these rhythms not documented. Hence, we examined coupling of the RR interval and the respiration (Resp) signal by coherence, Granger causality and the cross-sample entropy method of time series analysis in patients with AF and a healthy control group. In healthy subjects, the influence of respiration on cardiac rhythm was found as increased coherence at the breathing frequency (BF) range, significantly stronger interaction and synchrony from Resp to RR than from RR to Resp. On the contrary, in patients with AF, coherence at BF diminished, there were no causal interactions between signals in both directions, which resulted in equally great asynchrony between them. In AF, the absence of full functionality of the sinoatrial node, as an integrator of neural cardiac control, resulted in diminished vagal modulation of heart periods and consequently impaired bidirectional cardio-respiratory interaction.

Generalized Poincaré Plots-A New Method for Evaluation of Regimes in Cardiac Neural Control in Atrial Fibrillation and Healthy Subjects.

Classical Poincaré plot is a standard way to measure nonlinear regulation of cardiovascular control. In our work we propose a generalized form of Poincaré plot where we track correlation between the duration of j preceding and k next RR intervals. The investigation was done in healthy subjects and patients with atrial fibrillation, by varying j,k ≤ 100. In cases where j = k, in healthy subjects the typical pattern was observed by "paths" that were substituting scatterplots and that were initiated and ended by loops of Poincaré plot points. This was not the case for atrial fibrillation patients where Poincaré plot had a simple scattered form. More, a typical matrix of Pearson's correlation coefficients, r(j,k), showed different positions of local maxima, depending on the subject's health condition. In both groups, local maxima were grouped into four clusters which probably determined specific regulatory mechanisms according to correlations between the duration of symmetric and asymmetric observed RR intervals. We quantified matrices' degrees of asymmetry and found that they were significantly different: distributed around zero in healthy, while being negative in atrial fibrillation. Also, Pearson's coefficients were higher in healthy than in atrial fibrillation or in signals with reshuffled intervals. Our hypothesis is that by this novel method we can observe heart rate regimes typical for baseline conditions and "defense reaction" in healthy subjects. These data indicate that neural control mechanisms of heart rate are operating in healthy subjects in contrast with atrial fibrillation, identifying it as the state of risk for stress-dependent pathologies. Regulatory regimes of heart rate can be further quantified and explored by the proposed novel method.

Is pacemaker therapy the right key to patients with vasovagal syncope?

Introduction: Vasovagal syncope is the most common type of reflex syncope. Efficacy of cardiac pacing in this indication has not been the subject of many studies and pacemaker therapy in patients with vasovagal syncope is still controversial. Objective: This study aimed to assess the efficacy and safety of pacing therapy in treatment of patients with vasovagal syncope, to determine contribution of new therapeutic models in increasing its success, and to identify risk factors associated with a higher rate of symptoms after pacemaker implantation. Methods: A retrospective study included 30 patients with pacemaker implanted due to vasovagal syncope in the Pacemaker Center, Clinical Center of Serbia, between November 2003 and June 2014. Head-up tilt test was performed to diagnose vasovagal syncope. Patients with cardioinhibitory and mixed type of disease were enrolled in the study. Results: Mean age was 48.1 ± 11.1 years and 18 (60%) patients were men. Mean follow-up period was 5.9 ± 3.0 years. Primarily, implantable loop recorder was implanted in 10 (33.3%) patients. Twenty (66.7%) patients presented cardioinhibitory and 10 (33.3%) mixed type of vasovagal syncope. After pacemaker implantation, 11 (36.7%) patients had syncope. In multiple logistic regression analysis we showed that syncope is statistically more likely to occur after pacemaker implantation in patients with mixed type of vasovagal syncope (p = 0.018). There were two (6.7%) perioperative surgical complications. Conclusion: Pacemaker therapy is a safe treatment for patients with vasovagal syncope, whose efficacy can be improved by strict selection of patients. We showed that symptoms occur statistically more often in patients with mixed type of disease after pacemaker implantation.