Programmed deep septal stimulation: A novel maneuver for the diagnosis of left bundle branch capture during permanent pacing.

INTRODUCTION: Permanent deep septal stimulation with capture of the left bundle branch (LBB) enables maintenance/restoration of the physiological activation of the left ventricle. However, it is almost always accompanied by the simultaneous engagement of the local septal myocardium, resulting in a fused (nonselective) QRS complex, therefore, confirmation of LBB capture remains difficult. METHODS: We hypothesized that programmed extrastimulus technique can differentiate nonselective LBB capture from myocardial-only capture as the effective refractory period (ERP) of the myocardium is different from the ERP of the LBB. Consecutive patients undergoing pacemaker implantation underwent programmed stimulation delivered from the lead implanted in a deep septal position. Responses to programmed stimulation were categorized on the basis of sudden change in the QRS morphology of the extrastimuli, observed when ERP of LBB or myocardium was encroached upon, as: "myocardial," "selective LBB," or nondiagnostic (unequivocal change of QRS morphology). RESULTS: Programmed deep septal stimulation was performed 269 times in 143 patients; in every patient with the use of a basic drive train of 600 milliseconds and in 126 patients also during intrinsic rhythm. The average septal-myocardial refractory period was shorter than the LBB refractory period: 263.0 ± 34.4 vs 318.0 ± 37.4 milliseconds. Responses diagnostic for LBB capture ("myocardial" or "selective LBB") were observed in 114 (79.7%) of patients. CONCLUSIONS: A novel maneuver for the confirmation of LBB capture during deep septal stimulation was developed and found to enable definitive diagnosis by visualization of both components of the paced QRS complex: selective paced LBB QRS and myocardial-only paced QRS.

His bundle has a shorter chronaxie than does the adjacent ventricular myocardium: Implications for pacemaker programming.

BACKGROUND: Strength-duration curves for permanent His bundle (HB) pacing are potentially important for pacemaker programming. OBJECTIVES: We aimed to calculate strength-duration curves and chronaxies of the HB and of the adjacent right ventricular (RV) working myocardium and to analyze zones of selective HB capture and battery current drain when pacing at different pulse durations (PDs). METHODS: Consecutive patients with permanent HB pacing were studied. The RV and HB capture thresholds were assessed at several PDs. Battery current drain and zones of selective HB capture at PDs of 0.1, 0.2, 0.4, and 1.0 ms were determined. RESULTS: In the whole group (N = 127), the HB chronaxie was shorter than the RV chronaxie. This difference was driven by patients with selective HB pacing (HB chronaxie 0.47 ms vs RV chronaxie 0.79 ms). The strength-duration curve for the HB had a lower rheobase and its steep portion started at shorter PDs, thus creating wider distance-zone of programmable selective HB pacing-between the HB and RV strength-duration curves at shorter PDs. The battery current drain was lower with pacing at PDs of 0.1-0.4 ms vs 1.0 ms. Chronaxie-adjusted PDs offered the lowest current drain. CONCLUSION: For the first time, the strength-duration curves for permanent selective and nonselective HB pacing were determined. Selective HB capture and battery longevity can be promoted by shorter PDs (0.2 ms). Longer PDs (1.0 ms) offer greater safety margin for RV capture and may be preferable if simultaneous RV capture during HB pacing is desired.

Programmed His Bundle Pacing: A Novel Maneuver for the Diagnosis of His Bundle Capture.

BACKGROUND: During permanent nonselective His bundle (ns-HB) pacing, it is crucial to confirm HB capture/exclude that only right ventricle (RV) myocardial septal pacing is present. Because the effective refractory period (ERP) of the working myocardium is different than the ERP of the HB, we hypothesized that it should be possible to differentiate ns-HB capture from RV myocardial capture using programmed extrastimulus technique. METHODS: In consecutive patients during HB pacemaker implantation, programmed HB pacing was delivered from the screwed-in HB pacing lead. Premature beats were introduced at 10-ms steps during intrinsic rhythm and also after a drive train of 600 ms. The longest coupling interval that resulted in an abrupt change of QRS morphology was considered equal to ERP of HB or RV myocardium. RESULTS: Programmed HB pacing was performed from 50 different sites in 32 patients. In 34 of 36 cases of ns-HB pacing, the RV myocardial ERP was shorter than HB ERP (271.8±38 versus 353.0±30 ms; P<0.0001). Programmed HB pacing using a drive train resulted in a typical abrupt change of paced QRS morphology: from ns-HB to RV myocardial QRS (34 of 36 cases) or to selective HB QRS (2 of 36 cases). Programmed HB pacing delivered during native conduction resulted in obtaining selective HB QRS in 20 of 34 and RV myocardial QRS in 14 of 34 of the ns-HB cases. In RV myocardial-only pacing cases (false ns-HB pacing, n=14), such responses were not observed-the QRS morphology remained stable. Therefore, the programmed HB pacing correctly diagnosed all ns-HB cases and all RV myocardial pacing cases. CONCLUSIONS: A novel maneuver for the diagnosis of HB capture, based on the differences in ERP between HB and myocardium, was formulated, assessed, and found as diagnostically valuable. This method is unique in enabling to visualize selective HB QRS in patients with otherwise obligatory ns-HB pacing (RV myocardial capture threshold

Cardiac resynchronization therapy-induced acute shortening of QRS duration predicts long-term mortality only in patients with left bundle branch block.

AIMS: QRS narrowing with initiation of biventricular pacing might be an acute electrocardiographic indicator of correction of left bundle branch block (LBBB)-induced depolarization delay and asynchrony. However, its impact on prognosis remains controversial, especially in non-LBBB patients. Our goal was to evaluate the impact of QRS narrowing on long-term mortality and morbidity in a large cohort of patients undergoing cardiac resynchronization therapy (CRT) with different pre-implantation QRS types: LBBB, non-LBBB, and permanent right ventricular pacing. METHODS AND RESULTS: This study included consecutive patients who underwent CRT device implantation. Study endpoints: death from any cause or urgent heart transplantation and death from any cause/urgent heart transplantation or hospital admission for heart failure. All pre- and post-implantation electrocardiograms were analysed using digital callipers, high-amplitude augmentation, 100 mm/s paper speed, and global QRS duration measurement method. A total of 552 CRT patients entered the survival analysis. During the 9 years observation period, 232 (42.0%) and 292 (52.9%) patients met primary and secondary endpoints, respectively. QRS narrowing predicted survival in the Kaplan-Meier analysis only in patients with LBBB. Multivariate Cox regression model showed that QRS narrowing was the major determinant of both study endpoints, with hazard ratios of 0.46 and 0.43, respectively. There was a strong relationship between mortality risk and shortening/widening of the QRS, albeit only in the LBBB group. Patients with non-LBBB morphologies had unfavourable prognosis similar to that in LBBB patients without QRS narrowing. CONCLUSION: Acute QRS narrowing in patients with LBBB might be a desirable endpoint of CRT device implantation.

Intermittent preexcitation indicates "a low-risk" accessory pathway: Time for a paradigm shift?

We report three patients with intermittent loss of the preexcitation pattern in the ECG that had undergone an electrophysiological study. Despite apparently poorly conducting accessory pathway (AP), in each case a fast anterograde conduction, either during spontaneous atrial fibrillation or during incremental atrial pacing (on isoproterenol) was documented; shortest preexcited RR intervals of 200-240 ms were observed. We review the literature and conclude that intermittent preexcitation observed on resting 12-lead ECG lacks sufficient specificity for the diagnosis of an AP with long refractory period and cannot be considered a substitute for electrophysiological study in patients with this electrocardiographical phenomenon.

Magnesium supplementation in patients with hypertension.

Introduction: European Society of Hypertension (ESH/ESC) and Polish Society of Hypertension (PTNT) guidelines do not recommend magnesium supplementation as an adjunctive therapy of patients with arterial hypertension. Nevertheless, Polish Institute of Food and Nutrition suggests increased supplementation of magnesium ions among hypertensive patients in everyday diet. Aim: The aim of the study was to assess a frequency of using magnesium supplements by hypertensive patients including demographic and clinical characteristics of the study group. Metodology: From October 2015 to January 2016 data of 309 hypertensive patients from Outpatient Clinic were collected and analyzed. We assessed: demographic and medical therapy data, results of office blood pressure and heart rate measurements. Results: We collected data of 309 patients aged between 19 and 84 (mean age 54.9±15.2 years) who were diagnosed with hypertension (HA). Mean time from diagnosis of HA was 12.8±9.9 years. The study group was represented in majority by subjects with secondary school level (40.8%) and university education (31.7%), retried (38.5%) or white-collars (26.9%). The proportion of patients using magnesium supplementation was 47.9% in the study group. Women more common than men were using magnesium supplements (68.2%, p=0.0001). Subjects preferred organic forms of magnesium supplements (85.1%) rather than inorganic (11.5%) or chelats (3.4%). There was no significant differences in SBP (142 vs 140 mmHg; p=0.93), DBP (80 vs 82 mmHg; p=0.42) and HR (71.5 vs 70.0 per min.; p=0.21) in group with and without magnesium supplementation. Pharmacological treatment and the proportion of patients that reach BP target (BP< 140/90 mmHg) were comparable in subgroup's analysis. Conclusions: Nearly half of hypertensive patients, especially women, use magnesium supplements regularly. Organic forms are preferable. Supplemental doses of magnesium ions did not associate with SBP, DBP and HR values and reaching BP target in hypertensive patients.

Blood pressure changes in patients with chronic heart failure undergoing slow breathing training.

BACKGROUND: Slow breathing training (SBT) has been proposed as a new non-pharmacological treatment able to induce favorable effects in patients with chronic heart failure (CHF). However, no information is available regarding its effects on orthostatic blood pressure (BP) changes in these patients, an issue of practical relevance given the reported BP-lowering effect of SBT. The aim of this study is to evaluate the influence of SBT on BP and whether SBT induces orthostatic hypotension (OH) or changes in quality of life (QoL) in CHF patients. METHODS: The analysis was performed as part of an ongoing crossover open trial aimed at assessing the clinical effectiveness of SBT in treated patients with CHF. The patients underwent 10-12 weeks of SBT with the RESPeRATE device and 10-12 week follow-up under usual care. Patients were randomly divided into two groups: group I began with SBT, followed by usual care; group II began with usual care, followed by SBT. Patients undergoing SBT were asked to perform each day two separate 15 min sessions of device-guided SBT at a breathing frequency of 6 breaths/min. In all patients, before the enrollment and after each study phase, clinical data collection and BP measurements in sitting, supine and standing position were performed. OH was defined as a decrease of ≥ 20 mmHg in systolic blood pressure (SBP) or ≥ 10 mmHg in diastolic blood pressure (DBP) within 3 min of standing. QoL was assessed three times at the beginning, and after each phase of the study by the Minnesota Living with Heart Failure (MLHF) questionnaire. RESULTS: Forty patients (two equal groups) completed the study, with the following baseline characteristics: 32 males/eight females, age 63.3 ± 13.4 years, 25 with ischemic CHF, 37 in New York Heart Association class II and three in class III, left ventricular ejection fraction 30.8 ± 6.7%, mean BP 138.7 ± 16.5/83.1 ± 11.5 mmHg, 23 with arterial hypertension and four with a history of stroke. There were no significant differences between the groups in clinical characteristics, SBP and DBP at rest, while seated and before and after standing up. OH prevalence was low and did not change during the study (10% vs 10%). No significant difference in average SBP and DBP changes secondary to body position were found when comparing the two study phases. Decrease in MLHF score was observed in group I during SBT (p = 0.002), but not in group II. CONCLUSIONS: Our data indicate that SBT is safe, does not affect the prevalence of OH in CHF patients and shows a non-significant tendency to improve QoL. These results should be confirmed in a larger sample of patients to support the safety of SBT and its possible benefits as a novel component of cardiorespiratory rehabilitation programs in CHF.

Vitamin D and vitamin D receptor activators in treatment of hypertension and cardiovascular disease.

Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation, and control of other hormonal systems. Many cells that play an important role in the cardiovascular system express the Vitamin D receptor (VDR) and respond to 1,25-(OH)2D (the active product of vitamin D conversion by hydroxylase) with cell-specific function and gene regulation. These cells include cardiomyocytes, vascular endothelial cells, vascular smooth muscle cells, phagocytes, and cells of the nephron, which produce renin. VDR activators (calcitriol and paricalcitol) are available for the treatment of vitamin D deficiency, which can result from inadequate cutaneous production and/or low dietary intake. Vitamin-D deficient patients present a higher risk of cardiovascular disease than the general population. Recent clinical observations have shown that VDR activator therapy provides survival benefit and also has a positive impact on cardiovascular function. Compelling results have arisen from previous studies of mice with disrupted genes of the vitamin D signaling pathways. In mice lacking VDR or CYP27B1 (1α-hydroxylase - an enzyme, which converts vitamin D to its active form), in addition to the expected phenotype (hypocalcaemia, secondary hyperparathyroidism and osteomalacia), development of hypertension and cardiac hypertrophy were also observed. Moreover, these mice presented with overexpression of renin and atrial natriuretic peptide. VDR may play a role in regulating smooth-muscle-cell (SMC) proliferation, thrombosis, fibrinolysis and vessel relaxation. The influence of VDR activators on the modulation of renin expression and vascular function may reduce mortality, organ damage, and cardiovascular morbidity in VDR-activator-treated patients with hypertension. Since clinical use of calcitriol is largely limited, because of the side effect of hypercalcemia, calcitriol analogues have been synthesized to obtain compounds with better therapeutic profiles. The main purpose of this article is to review the role of vitamin D and vitamin D receptor activators in cardiovascular diseases, especially hypertension and its treatment. Due to the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D supplementation therapy may be warranted in this population.

Sodium and potassium and the pathogenesis of hypertension.

The evidence relating blood pressure to salt intake in humans originates from population studies and randomized clinical trials of interventions on dietary salt intake. Estimates from meta-analyses of trials in normotensive subjects generally are similar to estimates derived from prospective population studies (+1.7-mm Hg increase in systolic blood pressure per 100 mmol increment in 24-hour urinary sodium). This estimate, however, does not translate into an increased risk of incident hypertension in subjects consuming a high-salt diet. The meta-analyses of intervention trials have consistently shown that potassium supplementation is associated with lowering of blood pressure. However, prospective studies relating health outcomes to 24-hour urinary sodium and/or potassium excretion produced inconsistent results. Taken together, available evidence does not support the current recommendations of a generalized and indiscriminate reduction of salt intake at the population level, although the blood-pressure lowering effect of dietary sodium restriction might be of value in hypertensive patients. Potassium supplementation in hypertensive patients or healthy persons is not recommended by the current guidelines, but importance of adhering to healthy diet rich in vegetables and fruits is emphasized.

Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure.

AIMS: Periodic breathing with central sleep apnoea (CSA) is common in heart failure patients and is associated with poor quality of life and increased risk of morbidity and mortality. We conducted a prospective, non-randomized, acute study to determine the feasibility of using unilateral transvenous phrenic nerve stimulation for the treatment of CSA in heart failure patients. METHODS AND RESULTS: Thirty-one patients from six centres underwent attempted transvenous lead placement. Of these, 16 qualified to undergo two successive nights of polysomnography-one night with and one night without phrenic nerve stimulation. Comparisons were made between the two nights using the following indices: apnoea-hypopnoea index (AHI), central apnoea index (CAI), obstructive apnoea index (OAI), hypopnoea index, arousal index, and 4% oxygen desaturation index (ODI4%). Patients underwent phrenic nerve stimulation from either the right brachiocephalic vein (n = 8) or the left brachiocephalic or pericardiophrenic vein (n = 8). Therapy period was (mean ± SD) 251 ± 71 min. Stimulation resulted in significant improvement in the AHI [median (inter-quartile range); 45 (39-59) vs. 23 (12-27) events/h, P = 0.002], CAI [27 (11-38) vs. 1 (0-5) events/h, P≤ 0.001], arousal index [32 (20-42) vs. 12 (9-27) events/h, P = 0.001], and ODI4% [31 (22-36) vs. 14 (7-20) events/h, P = 0.002]. No significant changes occurred in the OAI or hypopnoea index. Two adverse events occurred (lead thrombus and episode of ventricular tachycardia), though neither was directly related to phrenic nerve stimulation therapy. CONCLUSION: Unilateral transvenous phrenic nerve stimulation significantly reduces episodes of CSA and restores a more natural breathing pattern in patients with heart failure. This approach may represent a novel therapy for CSA and warrants further study.