Functional substrate analysis in patients with persistent atrial fibrillation.

OBJECTIVES: The aim of this study was to describe the correlation between atrial electrogram duration map (AEDUM), spatiotemporal electrogram dispersion (STED) and low voltage areas (LVA) in patients with persistent atrial fibrillation (PsAF). BACKGROUND: The degree of left atrial (LA) tissue remodelling and augmented anisotropic conduction is one of the major issues related to PsAF ablation outcome. METHODS: This study enrolled consecutive patients with PsAF undergoing pulmonary vein isolation. In all patients, voltage, AEDUM and STED maps were created, and the correlation was reported between these three mapping methods. RESULTS: A total of 40 patients with PsAF were enrolled. The mean age was 62.2 ± 7.4 years, and males were 72.5% (n = 29). The overall bipolar voltage of the LA was 3.06 ± 1.87 mV. All patients had at least one AEDUM area (overall AEDUM area: 21.8 ± 8.2 cm2); the mean longest electrogram (EGMs) duration was 90 ± 19 ms. STED areas with < 120 ms was 46.3 ± 20.2 cm2 which covered 45 ± 22% of the LA surface. AEDUM and STED areas were most frequently reported on the roof, the anterior wall and the septum. The extension of the AEDUM areas was significantly smaller than STED areas with CL < 120 ms (21.8 ± 8.2 vs 46.3 ± 20.2; p-value < 0.0001). In 24 patients (60%), AEDUM areas was entirely included in the STED areas with CL < 120 ms. In the three (7.5%) patients with LVA, no correspondence with STED and AEDUM was noted. CONCLUSION: AEDUM and STED maps allow to identify areas of conductive dysfunction as a possible atrial substrate even if a normal voltage is detected.

Ablation of persistent atrial fibrillation based on atrial electrogram duration map: methodology and clinical outcomes from the AEDUM pilot study.

BACKGROUND: Catheter ablation of persistent atrial fibrillation (PsAF) represents a challenge for the electrophysiologist and there are still divergences regarding the best ablative approach to adopt. Create a new map of the duration of atrial bipolar electrograms (Atrial Electrogram DUration Map, AEDUM) to recognize a functional substrate during sinus rhythm and guide a patient-tailored ablative strategy for PsAF. METHODS: Forty PsAF subjects were assigned in a 1:1 ratio to either for PVI alone (Group B1) or PVI+AEDUM areas ablation (Group B2). A cohort of 15 patients without AF history undergoing left-sided accessory pathway ablation was used as a control group (Group A). In all patients, voltage and AEDUM maps were created during sinus rhythm. The minimum follow-up was 12 months, with rhythm monitoring via 48-h ECG Holter or by implantable cardiac device. RESULTS: Electrogram (EGM) duration was higher in Group B than in Group A (49±16.2ms vs 34.2±3.8ms; p-value<0.001). In Group B the mean cumulative AEDUM area was 21.8±8.2cm2; no difference between the two subgroups was observed (22.3±9.1cm2 vs 21.2±7.2cm2; p-value=0.45). The overall bipolar voltage recorded inside the AEDUM areas was lower than in the remaining atrial areas [median: 1.30mV (IQR: 0.71-2.38mV) vs 1.54mV (IQR: 0.79-2.97mV); p-value: <0.001)]. Low voltage areas (<0.5mV) were recorded in three (7.5%) patients in Group B. During the follow-up [median 511 days (376-845days)] patients who underwent PVI-only experienced more AF recurrence than those receiving a tailored approach (65% vs 35%; p-value= 0.04). CONCLUSIONS: All PsAF patients exhibited AEDUM areas. An ablation approach targeting these areas resulted in a more effective strategy compared with PVI only.

Modified sympathicotomy in patients with refractory ventricular tachycardia and structural heart disease: a single-center experience.

BACKGROUND: Modified cardiac sympathetic denervation (CSD) with stellate ganglion (SG) sparing is a novel technique for cardiac neuromodulation in patients with refractory ventricular tachycardia (VT). OBJECTIVES: Our aim is to describe the mid- to long-term clinical outcome of the modified CSD with SG sparing in a series of patients with structural heart disease (SHD) and refractory VT. METHODS: All consecutive patients with SHD and refractory VT undergoing modified CSD were enrolled. Baseline clinical characteristics and periprocedural data were collected for all patients. The primary outcome was any recurrence of sustained VT. RESULTS: We enrolled 15 patients (age: 69.2 ± 7.9 years; male 100%) undergoing modified CSD. Left ventricular ejection fraction was 37 ± 11% and all patients had an implantable cardiac defibrillator (ICD); the underlying cardiomyopathy was non-ischemic in 73.3% of them. At least one previous ablation had been attempted in 66.6% of cases. The 73.3% of patients underwent bilateral CSD and the mean effective surgical time was 10.8 ± 2.4 min per side; no major periprocedural complication occurred. After a median follow-up time of 15 months (IQR: 8.5-24.5 months), the primary outcome occurred in 47.6% of cases. All patients experienced a reduction of ICD shocks after CSD (3.1 ICD shocks/patient before vs. 0.3 ICD shocks/patient after CSD; p-value: 0.001). Bilateral CSD and a VT cycle length < 340 ms were associated with better outcomes. CONCLUSIONS: A modified CSD approach with stellate ganglion sparing appears to be safe, fast, and effective in the treatment of patients with SHD and refractory VTs.

Impact of COVID-19 Pandemic on Cardiac Electronic Device Management and Role of Remote Monitoring.

During the coronavirus disease 2019 (COVID-19) worldwide pandemic, patients with cardiac implantable electronic device (CIED) refused scheduled follow-up visits because of the risk of infection. In this scenario, different telemedicine strategies have been implemented to ensure continuity of care to CIED patients. Patients can be monitored through dedicated applications, telephone calls, or virtual visits providing easy access to valuable information, such as arrhythmic events, acute decompensation manifestations, and device-related issues, without the need for in-person visits. This review provides a comprehensive description of the many possible applications of telemedicine for CIED patients during the COVID-19 period.

The connubium among diabetes, chronic kidney disease and atrial fibrillation.

The burden of cardiovascular comorbid conditions was significantly higher in patients with atrial fibrillation (AF); most of them are affected by hypertension, chronic kidney disease (CKD) and/or diabetes mellitus (DM). DM represents a well-known risk factor for the development and maintenance of AF; the coexistence of DM and AF is also associated with an increased risk of mortality and stroke. Moreover, DM is currently the main cause of renal impairment and the leading cause of dialysis in the world. The hyperglycemia is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease. Long-term thromboembolic preventive therapy in AF patients with DM and CKD may be more challenging because both DM and CKD have been independently associated with an increased thromboembolic and bleeding risk, which results from the prothrombotic and proinflammatory status. Vitamin K antagonists (VKAs) are characterized by numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. On the other hand, Direct Oral Anticoagulants (DOACs) are currently contraindicated in dialysis patients even if mounting evidence suggests that they may have a nephroprotective role in AF patients with DM and CKD. Consequently, the choice of anticoagulant therapy in this setting of patient seems to be very challenging. The aim of this review is to investigate the role of DOACs in diabetic patients and its nephroprotective role by reviewing the current literature.

Outcome of a Modified Sympathicotomy for Cardiac Neuromodulation of Untreatable Ventricular Tachycardia.

OBJECTIVES: This study aimed to describe the preliminary results of a modified sympathicotomy for cardiac sympathetic denervation (CSD), which may reduce the predictive risk and intraoperative surgical time of the procedure. BACKGROUND: CSD, in patients with refractory ventricular tachycardia (VT), is comprehensively recognized as an important treatment option for patients with structural heart disease as well as congenital inherited arrhythmia syndrome. METHODS: We consecutively enrolled 5 patients with refractory VT. Baseline demographic, medical, and surgical data as well as arrhythmia outcomes and procedural complications were evaluated. RESULTS: A total of 5 patients (mean age: 67.4 years) were enrolled for the treatment of refractory VT with a modified CSD technique. In 3 of 5 patients, an overall reduction in VT burden (ranging from 75% to 100%) and VT number was observed after the CSD despite an in-hospital early recurrence. CONCLUSIONS: A modified CSD (sympathicotomy T2-T5) with stellate ganglion sparing and the use of unipolar radiofrequency is feasible, effective, and safe in the setting of untreatable VT.

Interatrial conduction times in paroxysmal atrial fibrillation patients with normal atrial volume and their correlation with areas of local prolonged bipolar electrograms.

BACKGROUND: Recent evidence has shown that the presence of abnormal substrate can be demonstrated also among patients with "lone" AF. OBJECTIVES: Interatrial conduction slowing is likely to characterize patients with paroxysmal atrial fibrillation (AF) and it could be correlated to the left atrium area of prolonged local bipolar endocardial electrograms. METHODS: P-wave duration (PWD), amplified PWD and endocavitary interatrial conduction time (IACT), were analyzed in 60 patients; 30 undergoing de novo ablation for paroxysmal AF with normal atrial volumes and without any other cardiac disease and 30 of similar age undergoing electrophysiological study for atrioventricular nodal reentrant tachycardia or atrioventricular re- entrant tachycardia. In patients with AF, voltage maps and local bipolar electrograms (LBE) duration map were evaluated. RESULTS: Although PWD was <120 ms in 28 patients with AF and in 29 controls, patients with AF exhibited longer PWD, amplified-PWD and IACT. Although low-voltage areas (<0.5 mV) were not found in the study population, 28 of them demonstrated areas with LBE longer than 60 ms. These LBE were found mainly in the roof of the left atrium and their extension was correlated to IACT (R = 0.51, p = 0.004). IACT >135.5 ms identified the subjects who experienced AF with 90% sensitivity and 97% specificity. CONCLUSION: A subclinical interatrial conduction disturbance is demonstrable in subjects with paroxysmal AF and normal left atrial volume. IACT has a good correlation to the areas of abnormal LBE in the left atrium. IACT >135 ms identified subjects who have experienced AF.

Association between ventricular pacing and persistent atrial fibrillation in patients indicated to elective pacemaker replacement: Results of the Prefer for Elective Replacement MVP (PreFER MVP) randomized study.

BACKGROUND: Pacing in the right ventricle can cause a variety of detrimental effects, including atrial tachyarrhythmias (atrial tachycardia [AT]/atrial fibrillation [AF]). OBJECTIVE: The purpose of this study was to evaluate the incidence and predictors of persistent AT/AF in patients with long-term exposure to ventricular pacing. METHODS: In a multicenter international trial, 605 patients (age 75 ± 11 years, 240 women) referred for replacement of an implanted pacemaker or implantable cardioverter-defibrillator (ICD), with a history of high-percentage (>40%) ventricular pacing, were randomly allocated to standard dual-chamber pacing or managed ventricular pacing (MVP), a pacing modality that minimizes ventricular pacing. The main end-point of this secondary analysis of the PreFER MVP randomized study was persistent AT/AF, defined as ≥7 consecutive days with AT/AF or AT/AF interrupted by atrial cardioversion or AT/AF present during 2 consecutive follow-up visits. RESULTS: Persistent AT/AF was observed in 71 patients (11.7%) after 2 years of follow-up. At multivariable Cox regression analysis, prior AT/AF (hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.20-6.22, P = .017) and ventricular pacing percentage, estimated in the first 3 months, ≥10% (HR 3.24, 95% 95% CI 1.13-9.31, P = .029) were independent predictors for persistent AT/AF. MVP was associated with persistent AT/AF risk (HR 3.41, 95% 95% CI 1.10-10.6, P = .024) in the subgroup of patients with baseline long PR interval (PR >230 ms) but not in the whole population. CONCLUSION: In pacemaker and ICD replacement patients, a high percentage of ventricular pacing is associated with higher risk of persistent AT/AF. Use of algorithms that minimize right ventricular pacing may benefit patients with normal spontaneous AV conduction but should be evaluated with caution in patients with long PR interval.

Intra-QT spectral coherence as a possible noninvasive marker of sustained ventricular tachycardia.

Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the q wave to the T wave peak (QTp) and the one from T wave peak to the T wave end (Te) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the QTp-Te spectral coherence. The latter was significantly lower in patients with sustained VT than in those without (0.508 ± 0.150 versus 0.607 ± 0.150, P < 0.05). Although the responsible mechanism remains conjectural, the QTp-Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias.

Managed ventricular pacing compared with conventional dual-chamber pacing for elective replacement in chronically paced patients: results of the Prefer for Elective Replacement Managed Ventricular Pacing randomized study.

BACKGROUND: Several studies have shown that unnecessary right ventricular pacing has detrimental effects. OBJECTIVE: To evaluate whether minimization of ventricular pacing as compared with standard dual-chamber pacing (DDD) improves clinical outcomes in patients referred for pacemaker or implantable cardioverter-defibrillator (ICD) replacement. METHODS: In an international single-blind, multicenter, randomized controlled trial, we compared DDD with managed ventricular pacing (MVP), a pacing mode developed to minimize ventricular pacing by promoting intrinsic atrioventricular conduction. We included patients referred for device replacement with >40% ventricular pacing, no cardiac resynchronization therapy upgrade indication, no permanent atrial fibrillation (AF), and no permanent complete atrioventricular block. Follow-up was for 2 years. The primary end point was cardiovascular hospitalization. The intention-to-treat analysis was performed by using Kaplan-Meier method and the log-rank test. RESULTS: We randomized 605 patients (556 referred for pacemaker and 49 referred for ICD replacement; mean age 75 ± 11 years; 365 [60%] men, at 7.7 ± 3.3 years from first device implantation) to MVP (n = 299) or DDD (n = 306). We found no significant differences in the primary end point cardiovascular hospitalization (MVP: 16.3% vs DDD: 14.5%; P = .72) and the secondary end point persistent AF (MVP: 15.4% vs DDD: 11.2%; P = .08), permanent AF (MVP: 4.1% vs DDD: 3.1%; P = .44), and composite of death and cardiovascular hospitalization (MVP: 23.9% vs DDD: 20.2%; P = .48). MVP reduced right ventricular pacing (median 5% vs 86%; Wilcoxon, P < .0001) as compared with DDD. CONCLUSIONS: In patients referred for pacemaker and ICD replacement with clinically well-tolerated long-term exposure to >40% ventricular pacing in the ventricle, a strategy to minimize ventricular pacing is not superior to standard DDD in reducing incidence of cardiovascular hospitalizations.

Influence of aging and chronic heart failure on temporal dispersion of myocardial repolarization.

BACKGROUND AND PURPOSE: QT and T(peak)-T(end) (Te) intervals are associated with sudden cardiac death in patients with chronic heart failure (CHF). We studied age-dependent influence on short-term temporal dispersion of these two variables in patients with postischemic CHF. METHOD: We grouped 75 CHF and 53 healthy control subjects into three age subsets: ≤ 50 years, >50 years and ≤ 65 years, and >65 years. We then calculated the following indices: QT and Te variability index (QTVI and TeVI), the ratio between the short-term variability (STV) of QT or Te, and the STV of resting rate (RR) (QT/RR STV and Te/RR STV). RESULTS: In all different age subgroups, patients with CHF showed a higher level of QTVI than age-matched control subjects (≤ 50 years: P < 0.0001; >50 years and ≤ 65 years: P < 0.05; >65 years: P < 0.05). Patients with CHF < 50 years old also had all repolarization variability indices higher than normal age-matched controls (TeVI, P < 0.05; QT/RR STV, P < 0.05; Te/RR STV, P < 0.05), whereas we did not find any difference between the two older classes of subjects. Both QTVI (r²: 0.178, P < 0.05) and TeVI (r²: 0.433, P < 0.001) were positively related to age in normal subjects, even if the first correlation was weaker than the second one. CONCLUSION: Our data showed that QTVI could be used in all ages to evaluate repolarization temporal liability, whereas the other indices are deeply influenced by age. Probably, the age-dependent increase in QTVI was more influenced by a reduction of RR variability reported in older normal subjects.

Indexes of temporal myocardial repolarization dispersion and sudden cardiac death in heart failure: any difference?

BACKGROUND: The QT variability index, calculated between Q- and the T-wave end (QTend VI), is an index of temporal myocardial repolarization lability associated with sudden cardiac death (SCD) in chronic heart failure (CHF). Little is known about temporal variability in the other two temporal myocardial repolarization descriptors obtained from Q-Tpeak and Tpeak -Tend intervals. We therefore investigated differences between these indexes in patients with CHF who died suddenly and in those who survived with a left ventricular ejection fraction (LVEF) ≤35% or >35%. METHODS AND RESULTS: We selected 127 ECG and systolic blood pressure (SPB) recordings from outpatients with CHF all of whom had been followed up for 30 months. We calculated RR and SPB variability by power spectral analysis and QTend VI, QTpeak VI, Tpeak Tend VI. We then subdivided data patients into three groups SCD, LVEF ≤ 35%, and LVEF > 35%. The LVEF was higher in the SCD than in the LVEF ≤ 35% group, whereas no difference was found between the SCD and LVEF > 35% groups. QTend VI, QTpeak VI, and Tpeak Tend VI were higher in the SCD and LVEF ≤ 35% groups than in the LVEF > 35% group. Multivariate analysis detected a negative relationship between all repolarization variability indexes, low frequency obtained from RR intervals and LVEF. CONCLUSIONS: Our data show that variability in the first (QTpeak VI) and second halves of the QT interval (Tpeak -Tend VI) significantly contributes to the QTend VI in patients with CHF. Further studies should investigate whether these indexes might help stratify the risk of SCD in patients with a moderately depressed LVEF.

Effect of Acute Mental Stress on Heart Rate and QT Variability in Postmyocardial Infarction Patients.

Emotionally charged events are associated with an increased risk of sudden cardiac death (SCD). In this study we assessed RR and QT variability index (QTVI) at baseline during anger recall test (AR). We calculated QTVI from a 5-min ECG recording and from a 10-beats segment around the presumed maximum sympathetic activation in thirty post-myocardial infarction patients under ß-blocker therapy and 10 controls underwent. In all groups, the low-frequency component of RR and SBP increased during AR. In all recordings, the QTVI calculated on a 5-min ECG recording and the QTVI(10 beats) were higher in patients than in controls (P < 0.05). The QTVI during AR remained unchanged from baseline within each group. Conversely, during AR, the QTVI(10 beats) in controls diminished significantly (P < 0.05) from baseline whereas in patients remained unchanged. The inability to buffer an acute stress-induced increase in sympathetic activity could explain why events charged with acute stress are associated with an increased risk of ventricular arrhythmias in this setting of patients and support the role of cognitive behavior stress management strategies.

Epicardial ganglionated plexus stimulation decreases postoperative inflammatory response in humans.

BACKGROUND: Surgical cardiac revascularization produces a high degree of systemic inflammation and the secretion of several cytokines. Intensive postoperative inflammation may increase the incidence of postoperative atrial fibrillation and favor organ dysfunctions. No data documenting the anti-inflammatory properties of epicardial vagal ganglionated plexus stimulation are available. OBJECTIVE: To verify the feasibility and safety of postoperative inferior vena cava-inferior atrial ganglionated plexus (IVC-IAGP) burst stimulation and the effectiveness of this approach in reducing serum levels of inflammatory cytokines. METHODS: In 27 patients who were candidates for off-pump surgical revascularization, the IVC-IAGP was located during surgery, a temporary wire was inserted, and a negative atrioventricular node dromotropic effect was obtained in 20 patients on applying high-frequency burst stimulation. In 5 patients atrial fibrillation or phrenic nerve stimulation was induced, and the remaining 15 patients served as the experimental group. Twenty additional patients underwent off-pump surgical revascularization without IVC-IAGP stimulation and served as the control group. On arrival in the intensive care unit, the experimental group underwent IVC-IAGP stimulation for 6 hours. Blood samples were collected at different times. RESULTS: The serum levels of cytokines were not statistically different at baseline and on arrival in the intensive care unit between the groups, while they proved statistically different after 6 hours of stimulation: interleukin-6 (EG: 121 ± 71 pg/mL vs CG: 280 ± 194 pg/mL; P = .004), tumor necrosis factor-α (EG: 2.68 ± 1.81 pg/mL vs CG: 5.87 ± 3.48 pg/mL; P = .003), vascular endothelial growth factor (EG: 93 ± 43 pg/mL vs CG: 177 ± 86 pg/mL; P = .002), and epidermal growth factor (EG: 79 ± 48 pg/mL vs CG: 138 ± 76 pg/mL; P = .012). CONCLUSIONS: Prolonged burst IVC-IAGP stimulation after surgical revascularization appears to be feasible and safe and significantly reduces inflammatory cytokines in the postoperative period.

Endocardial vagal atrioventricular node stimulation in humans: reproducibility on 18-month follow-up.

AIMS: Control of atrioventricular (AV) node conduction by means of high-frequency stimulation (HFS) of efferent AV node vagal stimulation (AVNS) fibres enables the ventricular rate (VR) to be modulated during atrial fibrillation (AF). The aims of this study were to verify, on 18-month follow-up, the reproducibility of the dromotropic effect obtained on implantation and the long-term reliability of the system in patients who received an implantable cardioverter-defibrillator (ICD) with a standard atrial lead positioned at a location suitable for AVNS. METHODS AND RESULTS: We enrolled 12 patients with paroxysmal or persistent AF who were candidates for ICD. The right atrium was mapped to locate the pacing site, and a transvenous screw-in lead was implanted in that region. The voltages required for VR modulation (25% VR reduction) and complete AV block at different pulse durations (from 0.1 to 0.5 ms) were recorded. Eleven out of 12 patients underwent 18-month follow-up examination. Atrial pacing parameters were adequate and did not differ from the baseline values (all P > 0.05): pacing threshold 0.9 ± 0.5 V (0.5 ms pulse duration) and impedance 556 ± 121 Ω, with P-wave amplitude of 1.6 ± 0.7 mV. High-frequency stimulation induced VR modulation in nine patients and complete AV block in eight patients at pulse durations ≥0.3 ms. No differences were observed in the voltages for VR modulation and complete AV block between implantation and 18-month examination (all P > 0.100). CONCLUSION: Ventricular rate control during AF was obtained under HFS 18 months after implantation in patients with the atrial lead positioned at a location suitable for AVNS. The pacing outputs needed to achieve the dromotropic effect were comparable to those measured on implantation.

Autonomic function during closed loop stimulation and fixed rate pacing: heart rate variability analysis from 24-hour Holter recordings.

AIM: Aim of this retrospective study was to analyze the effect of closed-loop stimulation (CLS) and DDD pacing mode on autonomic balance, and to evaluate heart rate variability (HRV) during CLS stimulation. METHODS AND MATERIALS: Autonomic balance was estimated by a 24-hour HRV analysis of paced and spontaneous beats in patients implanted with a dual-chamber pacemaker (Inos(2+) CLS-Biotronik GmbH, Berlin, Germany) and randomly assigned to CLS or DDD pacing mode. Patients underwent two 24-hour electrocardiogram Holter recordings at the end of each 3-month pacing mode period. Each Holter recording was automatically scanned to extract sequences of consecutive beats of the same type [atrial paced (Ap)-sequence and atrial spontaneous (As)-sequence], lasting at least 130 beats. RESULTS: Eight hundred and ten sequences were extracted from 15 patients, and the following spectral parameters were evaluated during both CLS and DDD mode: the total power (variance), the absolute and percentage (relative to the total power) powers of the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) components, as well as the LF/HF power ratio. DISCUSSION: The two main findings of this study were: in all the patients, CLS seems to mimic short-term physiological HRV, although the variability (total power) was lower than that relative to the spontaneous beats; the HRV of the spontaneous beats had an higher LF/HF when the pacemaker was programmed as DDD respect to CLS, consistent with a shift toward sympathetic predominance.

Early impairment of myocardial function in young patients with beta-thalassemia major.

BACKGROUND AND OBJECTIVE: One of the chief causes of death in patients with beta-thalassemia major (TM) remains heart failure due to iron overload. We investigated possible differences in myocardial function between a population of young asymptomatic patients with TM and healthy controls all of whom underwent an echocardiographic study, including tissue Doppler (TDI) and strain imaging (SI) analysis and cardiac magnetic resonance imaging (MRI). METHODS: 30 young asymptomatic patients with TM (16 taking deferoxamine and 14 taking deferiprone) and 30 healthy subjects underwent a cardiac MRI with T2* technique and an echocardiographic evaluation including systolic myocardial velocities (Sm), early (Em) and late (Am) diastolic velocities and systolic strain (S) at the level of basal segments of the lateral left ventricle (LV), interventricular septum (Septal) and lateral right ventricle (RV) wall. The differences in T2* values and echocardiographic parameters were also compared in patients with TM subgrouped according to iron chelation therapy. RESULTS: The following TDI and SI measures were lower in patients than in controls: LV-Sm (P < 0.05), S-LV (P < 0.001), Septal-Sm (P < 0.05), Septal-Em (P < 0.001), S-Septal (P < 0.001), RV-Sm (P < 0.001), RV-Em (P < 0.001), RV-Em/Am (P < 0.05) and S-RV (P < 0.05). Myocardial function was better in the patients receiving deferiprone than those receiving deferoxamine. T2* values were higher in controls than in patients with TM and in those treated with deferiprone than those treated with deferoxamine. MRI data well correlated with SI parameters. CONCLUSIONS: Study underlines that, even in a population of young, asymptomatic and well-chelated patients with TM, there is an impairment of myocardial function and that this condition could be easily detected by more advanced ultrasound techniques such as TDI and SI. The better indices of myocardial function in patients treated with deferiprone clearly needs confirmation from larger prospective studies.

QT variability strongly predicts sudden cardiac death in asymptomatic subjects with mild or moderate left ventricular systolic dysfunction: a prospective study.

AIMS: The most widely accepted marker for stratifying the risk of sudden cardiac death (SCD) in post myocardial infarction patients is a depressed left ventricular function. Left ventricular ejection fractions (EF) of 35% or less increase the risk of sudden death but values between 35 and 40% raise concern. The underlying pathophysiological mechanism is sustained ventricular tachycardia or fibrillation, both associated with increased cardiac repolarization variability. We assessed whether the indices of QT variability from a short-term electrocardiographic (ECG) recording predict sudden death. METHODS AND RESULTS: A total of 396 subjects with chronic heart failure (CHF) due to post-ischaemic cardiomyopathy, with an EF between 35 and 40% and in NYHA class I, underwent a 5 min ECG recording to calculate the following variables: QT variance (QT(v)), QT normalized for the square of the mean QT (QTVN), and QT variability index (QTVI). Corrected QT (QT(c)) was calculated from a 12-lead ECG recording. All participants were followed for 5 years. A multivariable survival model indicated that a QTVI greater than or equal to the 80th percentile indicated a high risk of SCD [hazards ratio (HR) 4.6, 95% confidence interval (CI) 1.5-13.4, P = 0.006] and, though to a lesser extent, a high risk of total mortality (HR 2.4, 95% CI 1.2-4.9, P = 0.017). The model including QTVI as a continuous variable confirmed a similar high risk for SCD (HR 2.9, 95% CI 1.3-6.5, P = 0.01) and for total mortality (HR 2.6, 95% CI 1.3-5.2, P = 0.008). CONCLUSION: Although asymptomatic patients with CHF who have a slightly depressed EF are at low risk of sudden death, the category is extraordinarily numerous. The QTVI could be helpful in stratifying the risk of sudden death in this otherwise undertreated population.

Influence of cardiac-resynchronization therapy on heart rate and blood pressure variability: 1-year follow-up.

BACKGROUND: Several studies have shown that cardiac-resynchronization therapy (CRT) improves haemodynamic function, cardiac symptoms, and heart rate variability (HRV) and reduces the risk of mortality and sudden death in subjects with chronic heart failure (CHF). In subjects with CHF, power spectral values for the low-frequency (LF) component of RR variability < or =13 ms2, are associated with an increased risk of sudden death. AIMS AND METHODS: To assess whether spectral indexes obtained by power spectral analysis of HRV and systolic blood pressure (SBP) variability could predict malignant ventricular arrhythmias in patients with severe CHF treated with an implantable cardioverter-defibrillator (ICD) alone or with ICD+CRT. In addition, changes in non-invasive spectral indices using short-term power spectral analysis of HRV and SBP variability during controlled breathing in 15 patients with CHF treated with an ICD alone and 16 patients receiving ICD+CRT, were assessed pre-treatment and at 1 year. RESULTS: Arrhythmias necessitating an appropriate ICD shock were more frequent in subjects who had low LF power. CRT improved all spectral components, including LF power. CONCLUSIONS: Low LF power values predict an increased risk of malignant ventricular arrhythmias; after 1 year of CRT most non-spectral and spectral data, including LF power, improved. Whether these improvements lead to better long-term survival in patients with CHF remains unclear.

Effect of pacemaker rate-adaptation on 24 h beat-to-beat heart rate and blood pressure profiles.

AIMS: The aims of the study were to evaluate the 24-h beat-to-beat heart rate (RR) and blood pressure changes during closed loop stimulation (DDD-CLS) pacing and conventional fixed rate DDD pacing with respect to spontaneous activity. METHODS: We simultaneously and continuously measured beat-to-beat heart rate and blood pressure for 24 h in patients implanted with Inos2+ (Biotronik GmbH, Berlin, Germany). A randomised cross-over comparison of DDD-CLS and DDD pacing was performed by short- and long-term analyses. RESULTS: Seventeen patients (10 males, aged 46-85 years) were enroled in the study: 11 completed the protocol. The percentage of atrial stimulation was 72.87% during DDD-CLS and 38.36% in DDD (P=0.003). All patients were 100% stimulated in the ventricle. On average, the percentage increase of paced RR intervals with respect to spontaneous beats was only 7.4% in DDD-CLS but 20.1% in DDD (P=0.0001). A significant correlation between spontaneous and paced RR profiles was obtained only during DDD-CLS (r(DDD-CLS)=0.77, r(DDD)=0.23, P=0.01). Short-term analysis revealed a 3.79% reduction of the escape interval in DDD-CLS and 8.19% in DDD, and the relative fall in diastolic blood pressure was 1.14% in DDD-CLS and 3.81% in DDD. CONCLUSION: DDD-CLS provided physiological heart rate fluctuations throughout the 24-h test. The blood pressure profiles of paced and spontaneous beats were comparable. The onset of paced rhythm in DDD-CLS resulted in a less pronounced decrease in heart rate and fall in diastolic pressure than in DDD.