Davide Saporito

Phrenic stimulation: a challenge for cardiac resynchronization therapy.

Background—Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices. Methods and Results—In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites (P<0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V. Conclusions—PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference.Background— Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices. Methods and Results— In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites ( P <0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V. Conclusions— PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference. Received December 14, 2008; accepted June 10, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response.

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or = 150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration < or = 150 pg/ml might be a clinically useful predictor of medium-term response to CRT.

Telecardiology and Remote Monitoring of Implanted Electrical Devices: The Potential for Fresh Clinical Care Perspectives

Telecardiology may help confront the growing burden of monitoring the reliability of implantable defibrillators/pacemakers. Herein, we suggest that the evolving capabilities of implanted devices to monitor patients’ status (heart rhythm, fluid overload, right ventricular pressure, oximetry, etc.) may imply a shift from strictly device-centered follow-up to perspectives centered on the patient (and patient-device interactions). Such approaches could provide improvements in health care delivery and clinical outcomes, especially in the field of heart failure. Major professional, policy, and ethical issues will have to be overcome to enable real-world implementation. This challenge may be relevant for the evolution of our health care systems.

Interventricular Delay Interval Optimization in Cardiac Resynchronization Therapy Guided by Echocardiography Versus Guided by Electrocardiographic QRS Interval Width

Present devices for cardiac resynchronization therapy offer the possibility of tailoring the hemodynamic effect of biventricular pacing by optimization of the interventricular delay (VV) beyond atrioventricular (AV)-interval optimization. It was not yet defined whether a QRS width-based strategy may be a helpful tool for echocardiography for device programming. The aim of the study was to investigate the relation between VV-interval optimization guided by echocardiography and guided by QRS interval width. One hundred six patients with a cardiac resynchronization therapy device for > or =3 months were enrolled. All patients underwent echocardiographic AV and VV delay optimization. The AV interval was optimized according to the E wave-A wave (EA) interval and left ventricular filling time. At the optimal AV delay, VV optimization was performed by measuring the aortic velocity time integral at 5 different settings: simultaneous right and left ventricle output, left ventricle pre-excitation (left ventricle + 40 and 80 ms, respectively), and right ventricle pre-excitation (right ventricle + 40 and 80 ms, respectively). A 12-lead electrocardiogram was recorded and QRS duration was measured in the lead with the greatest QRS width. The electrocardiographic (ECG)-optimized VV interval was defined according to the narrowest achievable QRS interval among 5 VV intervals. The echocardiographic-optimized VV interval was left ventricle + 40 ms in 28 patients, left ventricle + 80 ms in 15 patients, simultaneous in 46 patients, right ventricle + 40 ms in 14 patients, and right ventricle + 80 ms in 3 patients. Significant concordance (kappa = 0.69, p <0.001) was found between the echocardiographic- and ECG-optimized VV interval. In conclusion, significant concordance appeared to exist during biventricular pacing between VV programming based on the shortest QRS interval at 12-lead ECG pacing and echocardiographic-guided VV-interval optimization. A combined ECG- and echocardiographic approach could be a less time-consuming solution in performing this operation.

Cardiac resynchronization therapy : Effects on left and right ventricular ejection fraction during exercise

In patients with heart failure and wide QRS complex, cardiac resynchronization therapy (CRT) is associated with improvement of symptoms and cardiac function. This study examined the effects of a 3‐month period of CRT on left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and on LV volumes, both at rest and during exercise. A CRT system was implanted in 15 patients with severe heart failure and wide QRS. Before implant and 3 months later, all patients underwent assessment of cardiac performance with equilibrium Tc99 radionuclide angiography with imaging in the best septal left anterior oblique view. Exercise was performed on a bicycle ergometer. At 3 months, a significant improvement in New York Heart Association functional class was observed, and radionuclide angiography showed a significant decrease in LV volumes and a significant increase in LVEF at rest, as well as a significant increase in LVEF during exercise. The remodeling processes associated with CRT did not appear to include RV function, since RVEF did not improve, and changes in RVEF did not correlate with changes in LVEF, neither at rest nor during exercise.

Left ventricular versus biventricular pacing: a randomized comparative study evaluating mid-term electromechanical and clinical effects.

Background: Although left ventricular (LV) pacing has been proposed as an alternative to biventricular (BIV) pacing for heart failure (HF) patients, few comparative data are available on the electromechanical effects of these pacing modalities at mid‐term follow‐up. Aim: To investigate the clinical and echocardiographic effects of LV versus BIV pacing in a mid‐term randomized study. Methods: After implantation of a device with LV/BIV pacing capabilities, 22 patients with chronic HF and left bundle branch block were randomized to LV or BIV pacing. Patients were assessed both preimplantation and after 3 months by clinical examination, ECG and echocardiography with pulsed tissue Doppler imaging. Results: At 3 months LV pacing improved clinical parameters, LV ejection fraction (+5%, range 5–8%, P = 0.007) and intraventricular dyssynchrony (−40 ms, range −50 to −15 ms, in septal to lateral delay, P = 0.008) to a similar extent to BIV pacing. A decrease in interventricular mechanical delay (−25 ms, range −40 to −5 ms, P = 0.008) and QRS duration (−28 ms, range −40 to −5 ms, P = 0.008) was observed in BIV, but not in LV patients. Conclusion: In this pilot evaluation, LV pacing appeared to be associated with clinical benefits similar to BIV pacing at mid‐term follow‐up, and this was combined with an improvement in intraventricular dyssynchrony, regardless of variations in interventricular dyssynchrony and QRS duration. Echocardiographic evaluation of intraventricular dyssynchrony seems to be an appropriate method for assessing the chronic response to LV pacing.

Potential of non-antiarrhythmic drugs to provide an innovative upstream approach to the pharmacological prevention of sudden cardiac death.

Sudden cardiac death (SCD) is the most common cause of death and often occurs in low-risk patients. Present prevention strategies, mainly confined to high-risk subjects (proposed implantable cardioverter defibrillators recipients), have a limited effect on SCD burden in the general population. A relatively unexplored strategy for extending SCD prevention could imply targeting the early (upstream) processes of the complex cascade leading to SCD by non-antiarrhythmic drugs (i.e., β-blockers, aldosterone antagonists, angiotensin-converting enzyme inhibitors, angiotensin receptor-blocker agents, statins and omega-3 fatty acids). In this innovative pharmacological perspective, agents with upstream effects may also be used in high-risk patients in association with a strictly downstream intervention, such as the implantable cardioverter defibrillator, in an attempt to obtain an additive/synergetic effect.

Troponin I Rise After Pacemaker Implantation at the Time of Universal Definition of Myocardial Infarction

We assessed incidence, magnitude, and time course of cardiac troponin I (cTnI) increase after pacemaker implantation in patients without acute coronary syndromes (ACSs). Seventy patients (mean age 71 years, interquartile range 44 to 92, 38 men) undergoing elective implantation of a single-/dual-chamber pacemaker with active/passive fixation leads were enrolled, excluding subjects with clinical suspicion of ACS, abnormal basal cTnI level, or presenting conditions predisposing to abnormal cTnI. Cardiac TnI concentrations were determined in basal conditions, at the end of the procedure, and after 8, 12, and 24 hours. Single-/dual-chamber devices were implanted in 31 of 39 patients. Cardiac TnI peak concentration occurred within the 12-hour assay in 69 of 70 patients; 26 of 70 had a cTnI above the normal cut-off range. All patients presented normal cTnI at 24-hour assay. In conclusion, pacemaker implantation is associated with increases of cTnI levels in up to 37% of patients. This can affect the specificity of cTnI assessment for ruling out ACS, especially within 12 hours after the procedure. These data deserve consideration in a contemporary setting, in which troponin has gathered a pivotal role in the diagnosis and therapy of ACS, and in particular clinical presentations in which electrocardiogram loses its diagnostic capabilities (due to paced rhythms) and symptoms may be lacking or confusing.

Automatic verification of ventricular stimulation: fusion management algorithm.

Background: Ventricular stimulation with automatic control and back‐up pulse warrants maximum safety for the patient and increases device longevity. Fusion phenomenon may hinder evoked response (ER) detection and cause unnecessary back‐up stimulation. We evaluated an automatic fusion beat management algorithm and its relationship with atrioventricular (AV) interval programming in a DDD/R pacemaker.

Interventricular Delay Optimization: A Comparison among Three Different Echocardiographic Methods

Aim of the study: To compare three different methods for obtaining interventricular‐(VV) interval optimization. Methods: A total of 30 patients undergoing cardiac resynchronization therapy (CRT) were enrolled. All the patients underwent VV‐interval optimization performed with three different echocardiographic methods at seven different settings: simultaneous right (RV) and left (LV) ventricular pacing, LV stimulation only, LV preexcitation (LV+20,+40,+60 ms, respectively), RV preexcitation (RV+20 and+40 ms, respectively). Optimal VV delay was selected by: (1) measuring the aortic velocity time integral (VTI method); (2) measuring the time to maximum delay between septal and lateral longitudinal motion in the four‐chamber view (velocity method); and (3) measuring the segment with maximal temporal difference of peak circumferential strain in short‐axis view at papillary muscles level, (strain method). Velocity and strain methods measurements were obtained relying on two‐dimensional ultrasound border tracking algorithm thus providing angle‐independent measurements. Results: Immediately after CRT, VTI, maximum peak circumferential strain delay and maximum septal‐to‐lateral delay were significantly improved (P < 0.001). Particularly, VV‐interval optimization determined a further improvement of these indices as compared to the other VV settings (P < 0.001). Furthermore, a substantial concordance was found between the optimal VV interval obtained according to the VTI method and velocity method (k = 0.68), between the optimal VV interval obtained according to the VTI method and strain method (k = 0.63); and between the optimal VV interval obtained according to the velocity method and strain method (k = 0.71). Conclusions: VV‐interval optimization was shown to determine a further benefit beyond CRT. A significant concordance was present between VV programming based on different echocardiographic methods. (Echocardiography 2010;27:38‐43)