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.

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.

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.

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.

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.

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.