Riccardo Massa

Efficacy of Low Interatrial Septum and Right Atrial Appendage Pacing for Prevention of Permanent Atrial Fibrillation in Patients with Sinus Node Disease: Results from the Electrophysiology-Guided Pacing Site Selection (EPASS) Study

Background— The role of pacing sites and atrial electrophysiology on the progression of atrial fibrillation (AF) to the permanent form in patients with sinus node dysfunction (SND) has never been investigated. The aim of the study was to investigate the relationship between atrial electrophysiology and the efficacy of atrial pacing at the low interatrial septum (IAS) or at the right atrial appendage (RAA) to prevent persistent/permanent AF in patients with SND. Methods and Results— The Electrophysiology-Guided Pacing Site Selection (EPASS) Study was a prospective, controlled, randomized study. Atrial refractoriness, basal and incremental conduction times from the RAA to the coronary sinus ostium were measured before implantation, and the difference (&Dgr;CTos) was calculated. Patients with &Dgr;CTos ≥50 ms (study group) and those with &Dgr;CTos <50 ms (control group) were randomly assigned to RAA or IAS with algorithms for continuous atrial stimulation “on.” The primary end point was time to development of permanent or persistent AF within a 2-year follow-up in the study group, IAS versus RAA. Data were analyzed by intention to treat. One hundred two patients (77±7 years, 44 mol/L) were enrolled, 69 (68%) in the study group and 33 (32%) in the control group. Of these, 97 ended the study, respectively, randomly assigned: 29 IAS versus 36 RAA and 18 IAS versus 14 RAA. After a mean follow-up of 15±7 (median, 17) months, 11 (16.6%) patients in the study group met the primary end point: 2 IAS versus 9 RAA (log rank=3.93, P=0.047). Conclusions— In patients with SND and intra-atrial conduction delay, low IAS pacing was superior to RAA pacing in preventing progression to persistent or permanent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239226.

Spinal cord stimulation affects T-wave alternans in patients with ischaemic cardiomyopathy: a pilot study

AIMS An antiarrhythmic effect of spinal cord stimulation (SCS) has been recognized in an animal model. The actual mechanism is still mainly unknown. An adrenergic output reduction has been advocated as the main mechanism, although a modulation effect on the arrhythmic substrate has not yet been investigated. We studied T-wave alternans (TWA) modifications to test the hypothesis that SCS affects the arrhythmic substrate. METHODS AND RESULTS We performed TWA assessment in three high-risk patients who previously had undergone implantation of both implantable cardioverter defibrillator and SCS to treat refractory angina. The test was performed after switching off the SCS and after 2 and 24 h stimulation at the default amplitude. The protocol was executed 2 months apart in order to assess the reproducibility of the results, collecting a total of 18 TWA reports. In all the three patients, we observed a significant reduction of TWA amplitude after 2 h stimulation. All the tests were classified as negative after 24 h stimulation with the nominal parameters. CONCLUSION Spinal cord stimulation results in a decrease in the TWA magnitude, and thus it seems to positively affect the arrhythmic substrate in a time-dependent manner.

Proportion of patients needing an implantable cardioverter defibrillator on the basis of current guidelines: impact on healthcare resources in Italy and the USA. Data from the ALPHA study registry

AIMS Implantable cardioverter defibrillators (ICD) improve survival in selected patients with left ventricular dysfunction or heart failure (HF). The objective is to estimate the number of ICD candidates and to assess the potential impact on public health expenditure in Italy and the USA. METHODS AND RESULTS Data from 3513 consecutive patients (ALPHA study registry) were screened. A model based on international guidelines inclusion criteria and epidemiological data was used to estimate the number of eligible patients. A comparison with current ICD implant rate was done to estimate the necessary incremental rate to treat eligible patients within 5 years. Up to 54% of HF patients are estimated to be eligible for ICD implantation. An implantation policy based on guidelines would significantly increase the ICD number to 2671 implants per million inhabitants in Italy and to 4261 in the USA. An annual increment of prophylactic ICD implants of 20% in the USA and 68% in Italy would be necessary to treat all indicated patients in a 5-year timeframe. CONCLUSION Implantable cardioverter defibrillator implantation policy based on current evidence may have significant impact on public health expenditure. Effective risk stratification may be useful in order to maximize benefit of ICD therapy and its cost-effectiveness in primary prevention.

Risk stratification of ischaemic patients with implantable cardioverter defibrillators by C-reactive protein and a multi-markers strategy: results of the CAMI-GUIDE study

AIMS Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can be offered therapy with implantable cardioverter defibrillators (ICDs). Whether plasma biomarkers can help risk stratify for SCD and ventricular arrhythmias (VT/VF) is unclear. METHODS AND RESULTS The primary objective of the CAMI-GUIDE study is to assess the predictive role of C-reactive protein for SCD or VT/VF in ischaemic patients with the ejection fraction <30% and ICDs. Secondary endpoints included all-cause mortality, hospitalizations, and death from heart failure. Additional analyses incorporated cystatin-C and NT-ProBNP in multi-marker approach for the prediction of adverse outcomes. A total of 300 patients were enrolled. All-cause mortality at 2 years was 22.6%, mortality from heart failure was 8.3%. Primary endpoint occurred in 17.3%. At a competing risk multivariable analysis adjusted for baseline variables, no significant difference in primary endpoint was found between patients with C-reactive protein ≤3 vs. >3 mg/L [heart rate (HR) 0.91 (0.50-1.64) P = 0.76], while C-reactive protein >3 mg/L was strongly associated with mortality due to heart failure [HR: 3.17 (1.54-6.54) P = 0.002]. NT-proBNP above median was significantly associated with the primary endpoint [adjusted HR: 1.46 (1.020-2.129) P = 0.042]. A risk function, including the three biomarkers, NYHA class and resting HR, allowed stratification of patient mortality risk from 5 to 50%. CONCLUSION C-reactive protein >3 mg/L is not associated with SCD or fast VT/VF, however, is a strong predictor of HF mortality. Biomarkers combined with clinical markers allow an excellent risk stratification of mortality at 2 years.

Cardiac pacing in patients with neurally mediated syncope and documented asystole: effectiveness analysis from the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) Registry

AIMS The randomized, double-blind Third International Study on Syncope of Uncertain Etiology (ISSUE-3) showed that dual-chamber permanent pacing was effective in reducing the recurrence of syncope in patients ≥ 40 years with severe asystolic, probably neurally mediated syncope (NMS), documented by implantable loop recorder (ILR). Analysis in ISSUE-3 was performed according to the intention-to-treat principle. In the present study, we performed an on-treatment analysis, which included additionally those non-randomized patients followed up in the ISSUE registry to evaluate in a better manner the effectiveness of cardiac pacing therapy. METHODS AND RESULTS Initially, 504 patients received an ILR, 162 (32%) patients had a diagnosis consistent with NMS within a mean observation period of 15 ± 11 months: 99 (19%) patients had documentation of syncope with ≥ 3 s asystole or ≥ 6 s asystole without syncope. Sixty patients affected by asystolic NMS received cardiac pacing therapy and 86 (33 asystolic and 53 non-asystolic NMS) were untreated; 16 patients were lost to follow-up. Paced and unpaced groups had similar clinical characteristics. During subsequent follow-up, syncope recurred in 10 paced (17%) and in 40 non-paced (46%) patients. At 21 months, the estimated product-limit syncope recurrence rates were 27% [95% confidence interval (CI) 15-47] and 54% (95% CI 43-67), respectively (P = 0.01). With cardiac pacing, the risk of recurrence was reduced by 57% (hazard ratio = 0.43, 95% CI = 0.2-0.8). Complications of pacemaker therapy were haemothorax at implantation in one patient and lead dislodgement that required correction in two patients. CONCLUSION Permanent cardiac pacing is effective in reducing recurrence of syncope in patients ≥ 40 years with severe asystolic possible NMS with a few complications. The study shows that 61% of patients with a diagnosis of NMS made by ILR received a pacemaker but 5.1 ILRs had to be implanted to find one patient who finally had a pacemaker implanted.

Optimization of cardiac resynchronization therapy: echocardiographic vs semiautomatic device algorithms.

Large evidence supports the importance of individualized optimization of cardiac resynchronization therapy in patients with congestive heart failure. The aim of this study was to compare a recently developed intracardiac electrogram (IEGM)-based method with the Doppler echocardiographic (ECHO)-based method to calculate optimal atrioventricular (AV) and interventricular (VV) delays. Ten male patients implanted with a St Jude Medical resynchronization device received AV and VV delay assessment with both the IEGM and the ECHO-based methods. Estimates of the optimal AV and VV delays assessed by the 2 tested methods proved highly comparable. No difference emerged between the IEGM (126.8+/-22.7) and the ECHO (127.3+/-19.8) AV delay values (P=.987). The VV delay suggested by ECHO was highly significantly correlated with the delays calculated by the IEGM method (35+/-27.6 vs 21.31+/-24.31; r(2)=0.78; P<.001). These preliminary data support the evidence that an IEGM based cardiac resynchronization optimization method may be as reliable as a complete ECHO assessment.

Hybrid right-left cardiac resynchronization therapy defibrillator implantation in persistent left superior vena cava.

Persistence of the left superior vena cava (PLSVC), observed in 0.3% of the general population as established by autopsy, is an anatomic variation particularly relevant when occurring in patients in need of a transvenous pacing. In this report, we describe a hybrid right-left cardiac resynchronization therapy defibrillator implantation approach in a patient with PLSVC. In our experience, the described approach proved feasible and safe, and may be considered an option in case of complex vein anatomy before referring for cardiac surgical implantation of a left ventricular lead.

Predictors of mortality and hospitalization for cardiac causes in patients with heart failure and nonischemic heart disease: a subanalysis of the ALPHA study.

Background: Several studies have searched for predictors of clinical outcome in patients with heart failure (HF). However, since they were collected in clinical trials, most data were subject to selection biases and do not specifically apply to patients with nonischemic heart disease. This study examined the impact of several variables on combined all‐cause mortality and hospitalization for cardiac causes, in consecutive ambulatory patients with HF included in the ALPHA registry.

'Sinus node' dysfunction associated with left atrial isomerism.

Introduction The eterotaxic syndromes encompass two main anatomic pictures: left and right atrial isomerism. They cause a distortion of the atria anatomy that may involve the conduction tissue. The prognosis is related to the severity of the intracardiac-associated defects. Case report We describe the case of a patient suffering from asymptomatic ‘sinus’ bradycardia since childhood, who was referred for pacemaker implantation, in which the diagnosis of left atrial isomerism was made. Conclusion The present paper may provide new insights on the clinical course of arrhythmic disorders, in particular among patients with congenital heart disease.