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

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 reverse ventricular remodeling and possibly to changes in cardiac collagen synthesis and degradation. We investigated the relationship of biomarkers of myocardial collagen metabolism and volumetric response to CRT. METHODS: We prospectively studied 46 heart failure patients (mean age 61±9 years, 87% male) who underwent CRT implantation. Plasma concentrations of amino-terminal propeptide 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 baseline 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.

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.

[Approach to the Treatment of Atrial Fibrillation in Patients with Cardiovascular Risk Profile: Multicentric International Study].

INTRODUCTION: Atrial fibrillation (AF), the most common arrhythmia that requires treatment, does not come out of the focus of researchers. Monitoring its prevalence and effects of therapy is a good guideline approach to the growing population of patients in which this arrhythmia occurs. OBJECTIVE: The aim of the study was to evaluate the efficacy of treatment of AF and cardiovascular profiles in the observed population. METHODS: In this observational, cross-sectional, multicenter, international study, 584 patients in 30 centers in Serbia and Slovenia, older than 18 years and with AF or in sinus rhythm with a history of AF, were included. The assessment of the efficacy of treatment of AF was performed by analyzing the frequency of adequate therapeutic effect of medication in rhythm or frequency control in patients with AF. RESULTS: The results confirmed that the highest incidence of AF duration is more than seven days, and is accompanied by symptoms. Inadequate frequency regulation was registered at 8.9% of patients. Hypertension was registered in two-thirds of all patients, while other cardiovascular risk factors were registered in about one-third of patients. An echocardiographic finding in the group of patients with AF confirms generally adequate left ventricular function with a slightly enlarged left atrium (4.6±0.8 cm). Increasing age and time from the first episode of AF decreases the probability of maintaining sinus rhythm, while symptomatic AF had a positive impact on the presence of sinus rhythm. Propafenone, sotalol and amiodarone showed a statistically significant connection with a positive therapeutic response, while 3-blockers had a negative impact on the probability of establishing and maintaining sinus rhythm. CONCLUSION: Characteristics of therapeutic approaches, risks, comorbidity of patient populations in Slovenia and Serbia correspond to the fullest extent with the recommendations for good clinical practice, which further stresses the need for extensive measures in these regions.

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.

[Long-term follow-up after catheter-ablation of atrioventricular junction and pacemaker implantation in patients with uncontrolled atrial fibrillation and heart failure].

INTRODUCTION: Atrioventricular (AV) junction ablation coupled with pacemaker implantation is an effective therapeutic option for rate control in atrial fibrillation (AF) and heart failure (HF). However, there is controversy regarding the long-term outcome of the procedure, since right ventricular stimulation can lead to left ventricular remodelling and HF. OBJECTIVE: The aim of the study was to determine a 5-year outcome of the procedure on survival, HF control and myocardial function in patients with HF and uncontrolled AF. METHODS: All patients with AF and HF who underwent AV-junction ablation with pacemaker implantation in our institution were followed after the procedure. HF diagnosis was established if > or = 2 of the following criteria were present: 1) ejection fraction (EF) < or = 45%; 2) previous episode of congestive HF (CHF); 3) NYHA-class > or = 2; and 4) use of drug-therapy for HF. RESULTS: Study included 32 patients (25 males; 53.4 +/- 9.6 years). The mean heart rate was 121 +/- 25 bpm before and 75 +/- 10 bpm after ablation (p=0.001). Over the follow-up of 5.0 +/- 4.0 years nine patients (28.1%) died (five died suddenly, three of terminal CHF and one of stroke). After the procedure, CHF occurrence was reduced (p=0.001), as well as the annual number of hospitalizations (p=0.001) and the number of drugs for CHF (p=0.028). In addition, NYHA-class and EF were improved, from 3.3 +/- 0.7 to 1.6 +/- 0.8 (p<0.001) and from 39 +/- 11% to 51 +/- 10% (p<0.001), respectively. CONCLUSION: In HF patients with uncontrolled AF, 5-year mortality after AV-junction ablation and pacemaker implantation was 28%. In the majority of these patients good rate of AF and HF control were achieved, as well as the improvement of functional status and myocardial contractility.

[Pacemaker optimization guided by echocardiography in cardiac resynchronization therapy]. / Ehokardiografski bodjena optimizacija rada pejsmejkera kod resinhronizacione terapije slabosti srca.

INTRODUCTION: Cardiac resynchronization therapy (CRT) or biventricular pacing is a contemporary treatment in the management of advanced heart failure. Echocardiography plays an evolving and important role in patient selection for CRT, follow-up of acute and chronic CRT effects and optimization of device settings after biventricular pacemaker implantation. In this paper we illustrate usefulness of echocardiography for successful AV and VV timing optimization in patients with CRT. A review of up-to-date literature concerning rationale for AV and VV delay optimization, echocardiographic protocols and current recommendations for AV and VV optimization after CRT are also presented. OUTLINE OF CASES: The first case is of successful AV delay optimization guided by echocardiography in a patient with dilated cardiomyopathy treated with CRT is presented. Pulsed blood flow Doppler was used to detect mitral inflow while programming different duration of AV delay. The AV delay with optimal transmittal flow was established. The optimal mitral flow was the one with clearly defined E and A waves and maximal velocity time integral (VTI) of the mitral flow. Improvement in clinical status and reverse left ventricle remodelling with improvement of ejection fraction was registered in our patient after a month. The second case presents a patient with heart failure caused by dilated cardiomyopathy; six months after CRT implantation the patient was still NYHA class III and with a significantly depressed left ventricular ejection fraction. Optimization of VV interval guided by echocardiography was undertaken measuring VTI of the left ventricular outflow tract (LVOT) during programming of different VV intervals. The optimal VV interval was determined using a maximal LVOT VTI. A month after VV optimization our patient showed improvement in LV ejection fraction. CONCLUSION: Optimal management of patients treated with CRT integrate both clinical and echocardiographic follow-up with, if needed, echocardiographically guided optimization of AV and VV delays, which offers the possibility of additional clinical improvement in such patients.

[Implantable "loop recorder"--a new diagnostic tool for syncope of unknown cause].

INTRODUCTION: The implantable loop recorder (ILR) is a new diagnostic tool in cardiology for establishing the causes of unexplained syncope in patients where standard conventional tests, invasive tests included, have failed. The device is a diagnostic "pacemaker," surgically implanted underneath the skin of the chest, with leads attached to the case of the device, not requiring endovenous lead implantation. Heart rhythm is monitored continuously on the basis of an endless loop, up to a maximum period of 14 months. Recording is carried out either by applying an outside activator whenever symptoms occur, or automatically, according to a pre-set algorithm for bradycardia, tachycardia, and/or asystolic detection. OBJECTIVE: The aim of this study was to present this new diagnostic method as well as our first experiences with its implementation. METHOD: We followed 5 patients (3 male, 2 female, mean age: 46.4 +/- 19) who had ILRs ("Reveal Plus," Medtronic Inc., USA) implanted at our centre, over a period of 14 months (7.6 +/- 5.5), concentrating on their clinical course, symptom occurrence, and electronically monitored heart rhythm at the time of ILR auto activation and/or recordings triggered by outside activation whenever a patient's symptoms were discernible. RESULTS: In three patients, the ILR revealed syncope aetiology by documenting heart rhythm at the time of its occurrence. In one patient, involving a lethal outcome, the ILR was not explanted, so that the rhythm at the time of the fatal syncope, although assumed, remained undocumented. In one, most recently implanted patient, follow-up is still in progress. CONCLUSION: The implantable loop recorder represents an important innovation and a step forward in establishing the causes of recurrent syncope, which cannot be determined by standard invasive and non-invasive testing.