Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction.

AIMS: In diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by If-inhibition in this HFPEF-model. METHODS AND RESULTS: Control mice, diabetic mice (db/db), and db/db mice treated for 4 weeks with the If-inhibitor ivabradine (db/db-Iva) were compared. Aortic distensibility was measured by magnetic resonance imaging. Left ventricular (LV) pressure-volume analysis was performed in isolated working hearts, with biochemical and histological characterization of the cardiac and aortic phenotype. In db/db aortic stiffness and fibrosis were significantly enhanced compared with controls and were prevented by HR reduction in db/db-Iva. Left ventricular end-systolic elastance (Ees) was increased in db/db compared with controls (6.0 ± 1.3 vs. 3.4 ± 1.2 mmHg/µL, P < 0.01), whereas other contractility markers were reduced. Heart rate reduction in db/db-Iva lowered Ees (4.0 ± 1.1 mmHg/µL, P < 0.01), and improved the other contractility parameters. In db/db active relaxation was prolonged and end-diastolic capacitance was lower compared with controls (28 ± 3 vs. 48 ± 8 µL, P < 0.01). These parameters were ameliorated by HR reduction. Neither myocardial fibrosis nor hypertrophy were detected in db/db, whereas titin N2B expression was increased and phosphorylation of phospholamban was reduced both being prevented by HR reduction in db/db-Iva. CONCLUSION: In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans.

Multicenter clinical experience with an atrial lead designed to minimize far-field R-wave sensing.

AIMS: To evaluate a novel atrial lead designed to reduce far-field sensing. METHODS AND RESULTS: Sixty-three patients with standard pacing indications were randomized to receive an OptiSense 1699T (St Jude Medical, USA) or conventional pacing lead in the right atrium. Post-implant follow-up was conducted for all patients at 90 days and for a subset at 360 days. Standard electrical parameters were measured. Thresholds of sensing were determined for far-field ventricular signals. The number of inappropriate mode switches was determined from the stored intracardiac electrogram (IEGM). At 90 days, an IEGM Holter recorded 24 h of IEGM. With atrial sensitivity programmed at 0.3 mV, no far-field sensing occurred in the OptiSense group, but it did occur in 20% and 30% of the control group at 90 and 360 days, respectively. Inappropriate mode switching was observed in 4% of the OptiSense group in contrast to 23% of the control group. The IEGM Holter found no far-field sensing in the OptiSense group, but did find 83 023 far-field events from 22% of control patients. The standard electrical parameters of the OptiSense leads were acceptable. CONCLUSION: The OptiSense lead reduced ventricular far-field sensing in the atrium while maintaining satisfactory pacing and sensing performance, resulting in less inappropriate mode switch.

Responders to cardiac resynchronization therapy with narrow or intermediate QRS complexes identified by simple echocardiographic indices of dyssynchrony: the DESIRE study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended for patients with NYHA class III-IV refractory heart failure (HF), ejection fraction <35% and a QRS >120 ms. We attempted to identify responders to CRT from echocardiographic (echo) indices of mechanical dyssynchrony in patients with QRS<150 ms. METHODS AND RESULTS: The study enrolled 51 men and 9 women (mean age: 64.5 years) in NYHA class III (n=54) or IV (n=6) presenting with a mean ejection fraction: 25.7%, LV end-diastolic diameter: 69.1 mm, and QRS=121+/-19 ms. All patients were implanted with a CRT system and followed for 1 year. Implantation was preceded and followed by clinical, functional and Doppler (D)-echo evaluation. The primary combined endpoint included 1) death from any cause, 2) HF-related hospitalisations, and 3) NYHA class at 6 months. Before implant, 27 patients had > or =1 echo criterion of mechanical dyssynchrony (DES+ group) and 33 had no evidence of dyssynchrony (DES- group). At 12 months, 8 patients (4 per group) had died, 7 from HF. As regards the primary endpoint at 6 months, 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated. Clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES- (42%) patients (P<0.04). Baseline QRS duration did not predict response to CRT. CONCLUSIONS: In this population of HF patients with QRS<150 ms, the presence of mechanical dyssynchrony at baseline D-echo examination, but not the QRS width, predicted 6-month clinical response to CRT.

Morphology-enhanced atrial event classification improves sensing in pacemakers.

BACKGROUND: In atrial-based pacing, appropriate therapy and reliable diagnostics depend on detection and discrimination of atrial signals. Accurate classification of atrial events is mainly confounded by oversensing of ventricular far-field R-wave signals (FFRW), but attempts to reject FFRWs by manipulating atrial sensitivity and/or postventricular atrial blanking period (PVAB) may result in undersensing (especially of atrial fibrillation, AF) or in 2:1 atrial flutter detection. The objective of this study is therefore to evaluate if such methods can be improved by morphology-enhanced atrial event classification (MORPH). METHODS: Twenty-four-hour ambulatory atrial electrograms were recorded from continuous telemetry of digital pacemakers. Half of the recording was used for collecting two individual morphology parameters that discriminated P-waves from FFRWs in every patient (learning phase). The other half was used to test the MORPH algorithm against traditional methods (classification phase). RESULTS: In 44/48 patients, data were suitable for analysis. Average P and FFRW amplitudes were 1.96 mV versus 0.61 mV (P < 0.001). The interval between ventricular events and FFRW oversensing (VA interval) averaged at 14 ms during sensing and at 118 ms during pacing in the ventricle. Compared to nominal ("Factory") settings, the MORPH algorithm improved the sensitivity for P-wave recognition from 97.2% to 99.2%, the specificity from 91.9% to 99.96%, and the accuracy from 95.3% to 99.4% (P < 0.01 for all). CONCLUSIONS: By improving atrial signal discrimination, morphology analysis of atrial electrograms allows for high atrial sensitivity settings, and potentially improves the reliability of atrial arrhythmia diagnostics in heart rhythm devices.

Biventricular versus conventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg Biventricular Pacing Evaluation (HOBIPACE).

OBJECTIVES: The Homburg Biventricular Pacing Evaluation (HOBIPACE) is the first randomized controlled study that compares the biventricular (BV) pacing approach with conventional right ventricular (RV) pacing in patients with left ventricular (LV) dysfunction and a standard indication for antibradycardia pacing in the ventricle. BACKGROUND: In patients with LV dysfunction and atrioventricular block, conventional RV pacing may yield a detrimental effect on LV function. METHODS: Thirty patients with standard indication for permanent ventricular pacing and LV dysfunction defined by an LV end-diastolic diameter > or =60 mm and an ejection fraction < or =40% were included. Using a prospective, randomized crossover design, three months of RV pacing were compared with three months of BV pacing with regard to LV function, N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration, exercise capacity, and quality of life. RESULTS: When compared with RV pacing, BV stimulation reduced LV end-diastolic (-9.0%, p = 0.022) and end-systolic volumes (-16.9%, p < 0.001), NT-proBNP level (-31.0%, p < 0.002), and the Minnesota Living with Heart Failure score (-18.9%, p = 0.01). Left ventricular ejection fraction (+22.1%), peak oxygen consumption (+12.0%), oxygen uptake at the ventilatory threshold (+12.5%), and peak circulatory power (+21.0%) were higher (p < 0.0002) with BV pacing. The benefit of BV over RV pacing was similar for patients with (n = 9) and without (n = 21) atrial fibrillation. Right ventricular function was not affected by BV pacing. CONCLUSIONS: In patients with LV dysfunction who need permanent ventricular pacing support, BV stimulation is superior to conventional RV pacing with regard to LV function, quality of life, and maximal as well as submaximal exercise capacity.

Acute performance evaluation of a new ventricular automatic capture algorithm.

AIMS: This study evaluated the acute clinical performance of a new ventricular automatic capture algorithm developed to work with all lead types and pacing vectors. METHODS AND RESULTS: During regular pacemaker implant or replacement, AutoThreshold and manual threshold tests were performed in ventricular unipolar (UP) and bipolar (BP, if applicable) pacing using a customized external prototype INSIGNIA pacemaker. The success rate and accuracy of two different modes (commanded and ambulatory) of the automatic capture algorithm were used to evaluate the performance. Loss-of-capture events (two consecutive non-captured beats without backup pacing) were used to assess safety. Data of 53 patients (33 DDD/20 VVI) from four medical centres were analysed. Tested leads included 43 BP and 10 UP from nine manufacturers, and seven had electrodes with low polarization. The rate of successful commanded and ambulatory AutoThreshold tests was 96 and 94%, respectively, with an average absolute threshold difference compared with manual threshold of < 0.1 V at 0.4 ms (commanded 0.07 +/- 0.07 V and ambulatory 0.08 +/- 0.07 V). There was no significant difference in performance between UP/BP pacing, polarization, and lead type. No loss-of-capture event was observed. CONCLUSION: When successful, the ventricular automatic capture algorithm accurately determined pacing thresholds in either a UP or BP pacing configuration among all leads tested.

Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular pacing.

AIMS: To examine the performance of AAIsafeR2, a new pacing mode to minimize the cumulative proportion of ventricular pacing in patients who do not need regular ventricular support. METHODS AND RESULTS: The safety of AAIsafeR2 was examined in 123 recipients (73 +/- 12 years old, 51% men) of dual chamber pacemakers implanted for sinus node dysfunction, paroxysmal AV block or the bradycardia-tachycardia syndrome. Data were collected from pacemaker diagnostics, and the first 43 patients underwent 24-h Holter recordings before being discharged from the hospital with AAIsafeR2 activated. No adverse event related to AAIsafeR2 was observed. All ventricular pauses detected on Holter tapes triggered immediate back-up ventricular pacing. Appropriate switches to DDD occurred in 97 of 123 patients. In 69 of 123 devices (56%) switches to DDD were non-sustained, and the average % ventricular pacing in this group was 0.2+/-0.5%. CONCLUSION: AAIsafeR2 mode seems to be safe and reliable in patients with infrequent slowing or pauses in ventricular activity, while maintaining ventricular pacing below 1%.

A new endocardial "over-the-wire" or stylet-driven left ventricular lead: first clinical experience.

Transvenous left ventricular (LV) leads are primarily inserted "over-the-wire" (OTW). However, a stylet-driven (SD) approach may be a helpful alternative. A new polyurethane-coated, unipolar LV lead can be placed either by a stylet or a guide wire, which can be inserted into the lead body from both ends. The multicenter OVID study evaluates the clinical performance of this new steroid- and nonsteroid eluting lead. The primary endpoint is the LV lead implant success rate after identification of the coronary sinus (CS). Secondary endpoints include complication rate, short- and long-term lead characteristics, overall procedure and LV lead placement duration, total fluoroscopy time, and lead handling characteristics ratings. To date, 96 patients with heart failure (68 +/- 9 years old, 76% men) are enrolled. The CS was identified in 95 patients and, in 85 (88.5%), the LV lead was successfully implanted. The final lead positioning was lateral in 41%, posterolateral in 35%, anterolateral in 18%, and great cardiac vein in 6% of patients. In 70%, the 85 successful implantations, both stylet-driven and guide-wire techniques were used, a stylet only was used in 22%, and a guide wire only in 8%. Mean overall duration of 85 successful procedures was 112 +/- 40 minutes, total fluoroscopy time 28 +/- 15 minutes, and the duration of LV lead placement was 35 +/- 29 minutes. During a 3-month follow-up, the loss of LV capture occurred in three and phrenic nerve stimulation in six patients. The mean long-term pacing threshold is 0.8 V/0.5 ms and pacing impedance is 550 Omega. The OVID data suggest that these new leads are safe and effective. The choice of both OTW and SD techniques during lead implantation offers greater procedural flexibility.

A new dual-chamber pacing mode to minimize ventricular pacing.

Despite the low long-term incidence of high-degree atrioventricular (AV) block and the known negative effects of ventricular pacing, programming of the AAI mode in patients with sinus node dysfunction (SND) remains exceptional. A new pacing mode was, therefore, designed to combine the advantages of AAI with the safety of DDD pacing. AAIsafeR behaves like the AAI mode in absence of AV block. First- and second-degree AV blocks are tolerated up to a predetermined, programmable limit, and conversion to DDD takes place in case of high-degree AV block. From DDD, the device may switch back to AAI, provided AV conduction has returned. The safety of AAIsafeR was examined in 43 recipients (70 +/- 12-year old, 24 men) of dual chamber pacemakers implanted for SND or paroxysmal AV block. All patients underwent 24-hour ambulatory electrocardiographic recordings before hospital discharge and at 1 month of follow-up with the AAIsafeR mode activated. No AAIsafeR-related adverse event was observed. At 1 month, the device was functioning in AAIsafeR in 28 patients (65%), and the mean rate of ventricular pacing was 0.2%+/- 0.4%. Appropriate switches to DDD occurred in 15 patients (35%) for frequent, unexpected AV block. AAIsafeR mode was safe and preserved ventricular function during paroxysmal AV block, while maintaining a very low rate of ventricular pacing. The performance of this new pacing mode in the prevention of atrial fibrillation will be examined in a large, controlled study.

Digital technology in cardiac pacing: methods for morphology analysis of sensed endocavitary signals.

UNLABELLED: Proper functioning of a pacemaker depends exclusively on the detection of intrinsic cardiac signals. Conventional devices merely establish the presence of an endocavitary potential, but do not evaluate it qualitatively. The recent incorporation of digital signal processing of sensed events in pacemaker permits diagnostic characterization heretofore impossible. METHODS: Digital processing was used in 268 cardiac cycles recorded from 5 patients during elective dual chamber pacemaker replacement, The signals were classified in real time by an external pacemaker equipped with hardware and software capabilities for this purpose. RESULTS: The parameters used for morphological analysis were the minimum value of the slope signal and the minimum value of the filtered signal. The discrimination of a true atrial signal from a far-field R wave was correct in every patient (p < 0.0001). CONCLUSION: Digital devices may monitor and classify every event continually, and dramatically increase device reliability and the amount of information that can be processed and stored.

Selective site pacing: the right ventricular approach.

Animal data and recent findings in humans have questioned the appropriateness of pacing the heart from the right ventricular apex. Numerous, mostly small sized, studies have evaluated alternative sites within the right ventricle. There is now sufficient evidence that right ventricular apical pacing in patients with left ventricular dysfunction with or without heart failure is detrimental. Pacing from the right side of the heart as an attempt at nonpharmacological therapy for heart failure, turns out to be obsolete. In antibradycardia pacing with the need for continuous ventricular support, the interest in preserving left ventricular function drives the ongoing search for the most favorable pacing site within the right ventricle. Results, so far, are conflicting which may be attributed to the inhomogeneity of patient groups, the small cohorts studied, the differing protocols used, and the lack of accepted definitions of right ventricular lead positions. Larger studies are needed to evaluate intraoperative criteria for optimal lead placement and the potential benefit of nonapical right ventricular pacing.

Impact of fusion avoidance on performance of the automatic threshold tracking feature in dual chamber pacemakers: a multicenter prospective randomized study.

The Autocapture algorithm enables automatic capture verification on a beat-by-beat basis by recognizing the evoked response signal following each pacemaker stimulus. The algorithm intends to increase patient safety while decreasing energy consumption. However, the occurrence of fusion beats, particularly during dual chamber pacing, may limit the energy saving effect of Autocapture. The aim of this multicenter, prospective, randomized study was to evaluate the impact of the Fusion Avoidance (FA) algorithm on the incidence of fusion beats. Thirty-eight patients (mean age 69 +/- 13 years) with intrinsic AV conduction who were implanted with an Affinity DR were studied. After programming a PV/AV delay of 120/190 ms, patients were randomized to FA On or Off. Each group was further randomized with respect to activation of the AutoIntrinsic Conduction Search (AICS) algorithm. The total number of beats, ventricular paced beats, fusion beats, backup pulses, and threshold searches were analyzed from 24-hour Holter recordings. The number of total beats was comparable in both FA groups. The number of total ventricular paced beats, fusion beats, backup pulses, and threshold searches were significantly reduced in the FA On group (% reduction: 68% P < 0.001, 75% P < 0.01, 95% P < 0.01, and 94% P < 0.05, respectively). The number of ventricular paced beats with full capture was significantly reduced when AICS was activated (P < 0.05). In conclusion, the FA algorithm substantially reduces the amount of ventricular paced beats, fusion beats, unnecessary backup pulses and threshold searches, and therefore, provides added benefits in energy saving obtained by Autocapture.