Goran Milasinovic

Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure

AIMS In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. METHODS AND RESULTS This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. CONCLUSIONS This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.

A Multicenter Study of Shock Pathways for Subcutaneous Implantable Defibrillators

A purely subcutaneous implantable cardioverter defibrillator (ICD) requires higher energy but may be an effective alternative to transvenous ICDs to deliver lifesaving therapies.

Prognostic role of coronary flow reserve for left ventricular functional improvement after cardiac resynchronization therapy in patients with dilated cardiomyopathy

AIMS The aim of the study was to assess the value of coronary flow reserve (CFR) for predicting improvement of left ventricular function after cardiac resynchronization therapy (CRT). METHODS AND RESULTS Study population included 40 patients (mean age 58 ± 9 years) with heart failure (ejection fraction 25, 7 ± 5, 4%) and QRS duration of 158 ± 22 ms, planned for CRT. Before and after CRT implantation, CFR was measured non-invasively during hyperaemia induced with adenosine. Responders were defined by decrease in end-systolic volume ≥15%. Follow-up echocardiography and CFR measurements were obtained after 6 months. At baseline there was no significant difference in left ventricular ejection fraction (LVEF), QRS duration, 6 min walk test distance and coronary flow velocity at rest between responder (n = 26) vs. non-responder group (n = 14, P = ns). Before CRT implantation, responders compared with non-responders, showed a greater increase in coronary flow velocity during hyperaemia, and consequently higher CFR: 2.41 ± 0.60 vs. 1.61 ± 0.45 (P = 0.001). There was significant correlation between CFR before CRT implantation and LVEF after 6 months (r = 0.545, P = 0.001). End-diastolic, end-systolic left ventricular diameter, and CFR before CRT were predictors of LV functional improvement. By multivariate analysis, only CFR before CRT was independent predictor of left ventricular recovery in the follow-up period (P = 0.001). CONCLUSION Our results demonstrate that preserved CFR in patients with dilated cardiomyopathy is predictive of left ventricular improvement after CRT implantation.

Prediction of a good response to cardiac resynchronization therapy in patients with severe dilated cardyomyopathy: could conventional echocardiography be the answer after all?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m2 (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)

Summary statement: EHRA summit 2010 with the participation of Central-Eastern European countries: 'ICD for Life' Initiative--fighting against sudden cardiac death in emerging economies.

The conference of the ‘Implantable Cardioverter Defibrillator for Life’ Initiative—Fighting against Sudden Cardiac Death in Emerging Economies was jointly organized by the European Heart Rhythm Association and the Hungarian Society of Cardiology. The aim of the summit was to demonstrate the benefit and efficacy of the prevention of sudden cardiac death (SCD). Sudden cardiac death is responsible for a significant number of deaths at an annual level and it is the leading cause of death in industrial countries. Many arrhythmias could be treated by means of device therapy and this would also reduce the death rates. The target of the summit was to build bridges between medical, political, and industrial sectors to procure greater political and economic care and support for the primary and secondary prevention of sudden cardiac death, heart failure, and arrhythmias. The number of implantable cardioverter-defibrillator (ICD) implantations has increased enormously in the recent years based on the proven efficacy of implantable devices in the treatment of heart failure and heart rhythm disturbances. However, many patients with high risk of SCD still do not undergo ICD implantation. The reason is partly economic, and partly due to the lack of public awareness and the lack of qualified specialists. The conference emphasized that both the theoretical background of device therapy—professional recommendations, choice of implantable devices, programming, and problem solving—and the practical education of implantation methods are important to increase the implantation rates. The paradoxity of the effort to reduce SCD in economies in transition is that there is a high prevalence of high-risk patients on one side and actual implant rates both for primary and secondary prevention are disproportially low. The summit attempted to reflect regional disparities, their political, economic, financial, and, last but not least, educational background through a series of lectures held by the representatives of countries …

The Relationship of Myocardial Collagen Metabolism and Reverse Remodeling after Cardiac Resynchronization Therapy

Summary Background: In the majority of patients with a wide QRS complex and heart failure resistant to optimal medical therapy, cardiac resynchronization therapy (CRT) leads to rever se ventricular remodeling and possibly to changes in cardiac collagen synthesis and degradation. We investigated the relationship of biomarkers of myocardial collagen meta bolism and volumetric response to CRT. Methods: We prospectively studied 46 heart failure patients (mean age 61±9 years, 87% male) who underwent CRT im plantation. Plasma concentrations of amino-terminal pro peptide type I (PINP), a marker of collagen synthesis, and carboxy-terminal collagen telopeptide (CITP), a marker of collagen degradation, were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume at 6-month follow-up. Results: Baseline PINP levels showed a negative correlation with both left ventricular end-diastolic volume (r=−0.51; p=0.032), and end-systolic diameter (r=−0.47; p=0.049). After 6 months of device implantation, 28 patients (61%) responded to CRT. No significant differences in the base-line levels of PINP and CITP between responders and nonresponders were observed (p>0.05 for both). During follow-up, responders demonstrated a significant increase in serum PINP level from 31.37±18.40 to 39.2±19.19 μg/L (p=0.049), whereas in non-responders serum PINP levels did not significantly change (from 28.12±21.55 to 34.47±18.64 μg/L; p=0.125). There were no significant changes in CITP levels in both responders and non-responders (p>0.05). Conclusions: Left ventricular reverse remodeling induced by CRT is associated with an increased collagen synthesis in the first 6 months of CRT implantation.

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.

Transvenous lead placement and its pre-sternal tunneling to the contralateral side as a solution for pacemaker system upgrade in case of the subclavian vein thrombosis

Nikola RADOVANOVIĆ Pacemaker Center Clinical Center of Serbia Dr Koste Todorovića 8 11000 Belgrade, Serbia nikolar86@gmail.com SUMMARY Introduction Chronic right ventricular pacing can deteriorate cardiac function. Consequently, pacemaker system upgrades are more frequently indicated. These interventions can be hindered by venous thrombosis. In literature, it is rarely described that this problem is resolved by implanting a new lead for left ventricle (LV) stimulation on the opposite side of the previously implanted pacemaker and then subcutaneously transferring it to the old pocket. Case outline A 75-year-old male patient was hospitalized due to a planned pacemaker upgrade in December 2015. A dual-chamber pacemaker had been implanted due to sinus node dysfunction in 2011. During the previous 18 months he had been complaining about symptoms of heart failure. An upgrade to the cardiac resynchronization therapy (CRT) with a new CRT-P device was indicated due to the LV dilatation with the ejection fraction decrease, clinical deterioration, and the presence of high percentage of ventricular pacing. In October 2015, the mentioned intervention was unsuccessful due to total left subclavian vein thrombosis on the side of the previously implanted pacemaker. Anticoagulation therapy was ordinated and the reevaluation was postponed. During this hospitalization, venography confirmed total left subclavian vein thrombosis despite the anticoagulation therapy. It was decided to implant a new LV lead on the right side and then subcutaneously shift it by pre-sternal tunneling to the previous left prepectoral pocket. The intervention was uneventful. The first controls have shown stable pacemaker parameters. Conclusion This case report confirms that contralateral lead placement and subcutaneous pre-sternal tunnelling of the lead is feasible and safe in patients with an implanted pacemaker, an indication for system upgrade and ipsilateral vein obstruction.

Gauging the response to cardiac resynchronization therapy: The important interplay between predictor variables and definition of a favorable outcome

Selection of patients who are viable candidates for cardiac resynchronization therapy (CRT), prediction of the response to CRT as well as an optimal definition of a favorable response, all require further exploration. The purpose of this study was to evaluate the interplay between the prediction of the response to CRT and the definition of a favorable outcome.

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.