Economic analysis of remote monitoring of cardiac implantable electronic devices: Results of the Health Economics Evaluation Registry for Remote Follow-up (TARIFF) study.

BACKGROUND: Remote monitoring (RM) of cardiac implantable electronic devices has been demonstrated to improve outpatient clinic workflow and patient management. However, few data are available on the socioeconomic impact of RM. OBJECTIVE: The aim of this study was to assess the costs and benefits of RM compared with standard care (SC). METHODS: We used 12-month patient data from the Health Economics Evaluation Registry for Remote Follow-up (TARIFF) study (N = 209; RM: n = 102 (48.81%); SC: n = 107 (51.19%)). Cost comparison was made from 2 perspectives: the health care system (HCS) and patients. The use of health care resources was defined on the basis of hospital clinical folders. Out-of-pocket expenses were reported directly by patients. RESULTS: HCS perspective: The overall mean annual cost per patient in the SC group (€1044.89 ± €1990.47) was significantly higher than in the RM group (€482.87 ± €2488.10) (P < .0001), with a reduction of 53.87% being achieved in the RM group. The primary driver of cost reduction was the cost of cardiovascular hospitalizations (SC: €`886.67 ± €1979.13 vs RM: €432.34 ± €2488.10; P = .0030). Patient and caregiver perspective: The annual cost incurred by patients was significantly higher in the SC group than in the RM group (SC: €169.49 ± €189.50 vs RM: €56.87 ± €80.22; P < .0001). Patients' quality-adjusted life-years were not significantly different between the groups. Provider perspective: The total number of inhospital device follow-up visits was reduced by 58.78% in the RM group. CONCLUSION: RM of patients with cardiac implantable electronic devices (CIEDs) is cost saving from the perspectives of the HCS, patients, and caregivers. Introducing appropriate reimbursements will make RM sustainable even for the provider, i.e. the hospitals which provide the service and encourage widespread adoption of RM.

Impact of in-clinic follow-up visits in patients with implantable cardioverter defibrillators: demographic and socioeconomic analysis of the TARIFF study population.

PURPOSE: Remote monitoring of cardiac implantable electronic devices has been demonstrated to safely reduce frequency of hospital visits. Limited studies are available evaluating the economic impact. The aim of this article is to highlight the social impact and costs for the patients associated with hospital visits for routine device follow-up at the enrollment visit for the TARIFF study (NCT01075516). METHODS: TARIFF is a prospective, cohort, observational study designed to compare the costs and impact on quality of life between clinic-based and remote care device follow-up strategies. RESULTS: Two hundred nine patients (85.2 % males) were enrolled in the study; 153 patients (73.2 %) were retired, 36 (17.2 %) were active workers, 18 (8.6 %) were housewives, and 2 (1.0 %) were looking for a job. Among active workers, 63.9 % required time off from work to attend the hospital visit, while 67.0 % of all patients had to interrupt daily activities. The majority of patients spent half a day or more attending the visit. A carer accompanied 77 % of patients. Among carers, 36.6 % required time off from work, and 77.6 % had to interrupt daily activities. Median distance traveled was 36 km. The average cost of travel was 10 euros with 25 % of patients spending more than 30 euros. CONCLUSIONS: Data from patients enrolled in the TARIFF registry confirm that there are social and economic impacts to patients attending routine device checks in hospital which can be significantly reduced by using a remote monitoring strategy.

Low-dose dobutamine test associated with interventricular dyssynchrony: a useful tool to identify cardiac resynchronization therapy responders: data from the LOw dose DObutamine stress-echo test in Cardiac Resynchronization Therapy (LODO-CRT) phase 2 study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in patients with heart failure, but 30% to 50% of subjects are classified as nonresponders. Identifying responders remains a challenging task. AIMS: The LODO-CRT trial investigated the association between left ventricular contractile reserve (LVCR) and clinical and echocardiographic long-term CRT response. METHODS: This is a multicenter, prospective, observational study. Left ventricular contractile reserve was detected using a dobutamine stress echocardiography test, defined as an ejection fraction increase of >5 points. Clinical CRT response was defined as the absence of major cardiovascular events (ie, cardiovascular death or heart failure hospitalization). Echocardiographic response was defined as a left ventricle end-systolic volume reduction of >10%. RESULTS: A total of 221 CRT-indicated patients were studied (80% presented LVCR). During a mean follow-up of 15 ± 5 months, 17 patients died and 16 were hospitalized due to heart failure. The proportion of clinical responders was 155 (88%) of 177 and 33 (75%) of 44 (P = .036) in the groups with and without LVCR, respectively. Kaplan-Meier analysis showed a significant difference in cardiac survival/hospitalization between patients with and without LVCR. The proportion of echocardiographic responders was 144 (87%) of 166 and 16 (42%) of 38 in the groups with and without LVCR (P < .001), respectively; LVCR showed 90% sensitivity and 87% positive predictive value to prefigure echocardiographic CRT responders. Multivariable analysis identified LVCR and interventricular dyssynchrony as independent predictors of CRT response. The concomitant presence of both factors showed 99% specificity and 83% sensitivity in detecting responders. CONCLUSION: The presence of LVCR helps in predicting a clinical and echocardiographic CRT response. Concomitant assessment of LVCR and interventricular dyssynchrony accurately stratifies responder and nonresponder patients.

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.

A combined nucleic acid and protein analysis in Friedreich ataxia: implications for diagnosis, pathogenesis and clinical trial design.

BACKGROUND: Friedreich's ataxia (FRDA) is the most common hereditary ataxia among caucasians. The molecular defect in FRDA is the trinucleotide GAA expansion in the first intron of the FXN gene, which encodes frataxin. No studies have yet reported frataxin protein and mRNA levels in a large cohort of FRDA patients, carriers and controls. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 24 patients with classic FRDA phenotype (cFA), 6 late onset FRDA (LOFA), all homozygous for GAA expansion, 5 pFA cases who harbored the GAA expansion in compound heterozygosis with FXN point mutations (namely, p.I154F, c.482+3delA, p.R165P), 33 healthy expansion carriers, and 29 healthy controls. DNA was genotyped for GAA expansion, mRNA/FXN was quantified in real-time, and frataxin protein was measured using lateral-flow immunoassay in peripheral blood mononuclear cells (PBMCs). Mean residual levels of frataxin, compared to controls, were 35.8%, 65.6%, 33%, and 68.7% in cFA, LOFA, pFA and healthy carriers, respectively. Comparison of both cFA and pFA with controls resulted in 100% sensitivity and specificity, but there was overlap between LOFA, carriers and controls. Frataxin levels correlated inversely with GAA1 and GAA2 expansions, and directly with age at onset. Messenger RNA expression was reduced to 19.4% in cFA, 50.4% in LOFA, 52.7% in pFA, 53.0% in carriers, as compared to controls (p<0.0001). mRNA levels proved to be diagnostic when comparing cFA with controls resulting in 100% sensitivity and specificity. In cFA and LOFA patients mRNA levels correlated directly with protein levels and age at onset, and inversely with GAA1 and GAA2. CONCLUSION/SIGNIFICANCE: We report the first explorative study on combined frataxin and mRNA levels in PBMCs from a cohort of FRDA patients, carriers and healthy individuals. Lateral-flow immunoassay differentiated cFA and pFA patients from controls, whereas determination of mRNA in q-PCR was sensitive and specific only in cFA.

Efficacy of a tool combining guide-wire and stylet for the left ventricular lead positioning.

AIMS: The left ventricular (LV) lead for cardiac resynchronization therapy (CRT) is usually positioned in the coronary sinus via a stylet-guided or an 'over-the-wire' approach. Recently, a new tool has been developed, the Medtronic Attain Hybrid, that combines guide-wire and stylet features. We assessed its safety and efficacy in comparison with standard tools currently used in clinical practice. METHODS AND RESULTS: Patients undergoing standard CRT device implantation were enrolled in seven Italian centres. In the preliminary phase of the study (Phase I), data were collected during implantation procedures performed with standard tools (three patients per centre). Subsequently, the Attain Hybrid was made available in the centres and data were collected for all consecutive patients undergoing implantation during the following year. A learning phase was considered (Phase II), and the last three patients per centre (Phase III) were used for comparison with Phase I. One hundred and seventeen patients were enrolled: 21 patients in Phase I, 75 in Phase II, and 21 in Phase III. Rates of successful implantation were similar in Phases I and III (95 vs. 100%, P=1.000). The pre-defined target vein was reached in 15 (71%) patients in Phase I and in 21 (100%) patients in Phase III (P=0.021). In 10 (48%) procedures during Phase I, LV lead positioning necessitated switching from guide-wire to stylet; this proportion decreased during Phase III (14%, P=0.043). Mean LV positioning time was 16±7 min in Phase I and 11±6 min in Phase III (P=0.040). No adverse events or lead-related complications were detected on implantation or during a follow-up of 6±4 months. CONCLUSION: The Attain Hybrid is safe and effective. It significantly improves target vein accessibility and reduces procedural time in comparison with conventional tools.

Safety and performance of a system specifically designed for selective site pacing.

INTRODUCTION: In the right ventricle, selective site pacing (SSP) has been shown to avoid detrimental hemodynamic effects induced by right ventricular apical pacing and, in the right atrium, to prevent the onset of atrial fibrillation and to slow down disease progression. The purpose of our multicenter observational study was to describe the use of a transvenous 4-French catheter-delivered lead for SSP in the clinical practice of a large number of centers. METHODS: We enrolled 574 patients in whom an implantable device was indicated. In all patients, SSP was achieved by using the Select Secure System™ (Medtronic Inc., Minneapolis, MN, USA). RESULTS: In 570 patients, the lead was successfully implanted. In 125 patients, atrial SSP was performed: in 75 (60%) the lead was placed in the interatrial septum, in 31 (25%) in the coronary sinus ostium, and in 19 (15%) in the Bachman bundle. Ventricular SSP was undertaken in 138 patients: in 105 (76%) the high septal right ventricular outflow tract (RVOT) position was paced, in seven (5%) the high free-wall RVOT, in 25 (18%) the low septal RVOT, and in one (1%) the low free-wall RVOT. In the remaining 307 patients, the His zone was paced: in 87 (28%) patients, direct His-bundle pacing and in 220 (72%) patients para-hisian pacing was achieved. Adequate pacing parameters and a lead-related complication rate of 2.6% were recorded during a follow-up of 20 ± 10 months. CONCLUSIONS: Our results demonstrated that many sites, in the right atrium, in the right ventricle, and in His-bundle region, can be paced using the Select Secure System™.

Presence of left ventricular contractile reserve predicts midterm response to cardiac resynchronization therapy--results from the LOw dose DObutamine stress-echo test in Cardiac Resynchronization Therapy (LODO-CRT) trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selected patients with heart failure (HF). Nevertheless, the nonresponder rate remains high. The low-dose dobutamine stress-echo (DSE) test detects the presence of left ventricular (LV) contractile reserve (LVCR) in HF patients of any etiology and may be useful in predicting response to resynchronization. OBJECTIVE: The purpose of this study was to present the results of the LODO-CRT trial, which evaluated whether LVCR presence at baseline increases the chances of response to CRT. METHODS: LODO-CRT is a multicenter prospective study that enrolled CRT candidates according to guidelines. LVCR presence was defined as an LV ejection fraction increase >5 units during DSE test. CRT response is assessed at 6-month follow-up as an LV end-systolic volume reduction ≥10%. RESULTS: Two hundred seventy-one patients were enrolled. The DSE test was feasible without complications in 99% of patients. Nine patients died from noncardiac disease, and 31 presented inadequate data. Two hundred thirty-one patients were included in the analysis. Mean patient age was 67 ± 10 years; 95% were in New York Heart Association class III, and 42% had HF of ischemic etiology. Mean QRS and LV ejection fraction were 147 ± 25 ms and 27% ± 6%, respectively. LVCR presence was found in 185 subjects (80%). At follow-up, 170 (74%) patients responded to CRT, 145/185 in the group with LVCR (78%) and 25/46 (54%) in the group without LVCR. Difference in responder proportion to CRT was 24% (P <.001). Reported test sensitivity is 85%. CONCLUSION: The DSE test in CRT candidates is safe and feasible. LVCR presence at baseline increases the chances of response to CRT.

A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study.

AIMS: To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter-defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication. METHODS AND RESULTS: Prospective, controlled, parallel, multicentre, non-randomized study enrolling 324 primary prevention non-ischaemic HF patients implanted with CRT-D devices from 2004 to 2007: Protect group, 164 patients implanted with a Medtronic Insync III Protect device and Control group, 160 patients utilizing other Medtronic CRT-D devices. Efficacy was assessed by computing appropriate and inappropriate detections and therapies during follow-up; safety compared hospitalizations and syncopal events between groups. Ninety per cent of both ventricular and supraventricular tachyarrhythmias terminated within the 13-29 beat detection interval with the Protect algorithm. The Protect group showed a significantly better event-free survival to first delivered therapy for total (P = 0.0001), appropriately treated (P = 0.002), and inappropriately treated episodes (P = 0.017). The total number of delivered shocks was significantly lower in the Protect group (22 vs. 59, P < 0.0001). In the Protect group, a significantly reduced HF hospitalization (hazard ratio 0.38, 95% CI 0.15-0.98, P = 0.044) was observed without any increase of syncope or death. CONCLUSION: A simplified CRT-D device with fixed long detection reduced overall ICD therapy burden and HF hospitalizations without entailing any additional adverse events in primary prevention non-ischaemic HF patients.

Monitoring intrathoracic impedance with an implantable defibrillator reduces hospitalizations in patients with heart failure.

PURPOSE: Some implantable cardioverter-defibrillators (ICDs) are now able to monitor intrathoracic impedance. The aim of the study was to describe the use of such monitoring in clinical practice and to evaluate the clinical impact of the fluid accumulation alert feature of these ICDs. METHODS AND RESULTS: Five hundred thirty-two heart failure (HF) patients implanted with these ICDs were followed up for 11 +/- 7 months. A clinical event (CE) was deemed to have occurred if it resulted in hospitalization or milder manifestations of HF deterioration. Three hundred sixty-two acute decreases in intrathoracic impedance (Z events) occurred in 230 patients. Of these episodes, 171 (47%) were associated with a CE within 2 weeks of the Z event. In another 71 (20%) Z events, drug therapy was adjusted despite the absence of overt signs of clinical deterioration. The rate of unexplained Z events was 0.25 per patient-year and 25 hospitalizations were not associated with Z events. The audible alert was disabled in a group of 102 patients (OFF group). HF hospitalizations occurred in 29 (7%) patients in the ON group and 20 (20%, P < 0.001) patients in the OFF group. The rate of combined cardiac death and HF hospitalization was lower in patients with Alert ON (log-rank test, P = 0.007). CONCLUSIONS: The ICD reliably detected CE and yielded low rates of unexplained and undetected events. The alert capability seemed to reduce the number of HF hospitalizations by allowing timely detection and therapeutic intervention.

Electrical storm in patients with biventricular implantable cardioverter defibrillator: incidence, predictors, and prognostic implications.

BACKGROUND: The aim of the present study was to evaluate the incidence, predictors, and related outcomes of patients with heart failure (HF) treated with cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) who experienced electrical storm (ES). Electrical storm was defined as the occurrence of >or=3 episodes in 24 hours of sustained ventricular tachyarrhythmias. METHODS: A total of 631 patients with HF (90% male, mean 66+/-9 years) consecutively received a CRT-D device. At baseline, the mean left ventricular ejection fraction was 26%+/-7%, the QRS duration was 164+/-33 milliseconds, and the mean New York Heart Association class was 3.3+/-0.3. RESULTS: During a mean follow-up of 19+/-11 months, 2,419 ventricular tachyarrhythmia episodes were appropriately detected in 141 (22%) patients. Electrical storm occurred in 45 (7%) of 631 patients. Kaplan-Meier analysis and multivariable Cox regression showed that ES is more frequent in secondary prevention (hazard ratio 2.3, 95% CI 1.2-4.3, P=.015) and in nonischemic patients (hazard ratio 2.0, 95% CI 1.1-3.8, P=.028). In patients who presented ES, CRT was associated with only marginal nonsignificant improvements of New York Heart Association class and left ventricular ejection fraction. Hospitalizations and death due to HF were more frequent in patients with ES compared with those without ES, amounting to 16.8 (4.3) versus 8.6 (0.9) per 100 patient-years (P = .018) and 7.7 versus 2.7 per 100 patient-years (P=.014), respectively. CONCLUSIONS: Electrical storm affect only 7% of CRT-D recipients and occurred more frequently in nonischemic patients with HF with biventricular implantable cardioverter defibrillators implanted for secondary prevention. Electrical storm was associated with worse HF morbidity and mortality.

Antiarrhythmic effect of reverse ventricular remodeling induced by cardiac resynchronization therapy: the InSync ICD (Implantable Cardioverter-Defibrillator) Italian Registry.

OBJECTIVES: We investigated whether the reverse remodeling after cardiac resynchronization therapy (CRT) might reduce the occurrence of ventricular arrhythmias (VAs). BACKGROUND: It is currently debated whether CRT has an effect on the burden of VAs. METHODS: The study included 398 patients treated with a CRT defibrillator and with a follow-up of at least 12 months. Spontaneous VAs detected by the device were reviewed and validated. RESULTS: A significant reduction in VA episodes and shock therapies was evident during the follow-up with greater decrease after 1 month. After 6 months of CRT, 227 patients (57%) showed a reduction in end-systolic volume of >or=10% and were defined as "responders." The baseline characteristics were similar between the responders and the nonresponders. Nonetheless, the proportion of patients with recurrence of VA after 1 month of CRT was significantly lower in responders (32% vs. 43%, p = 0.024). Among baseline variables no parameters emerged as predictors of tachyarrhythmia recurrence. However, receiver-operating curve analysis recognized a reduction of left ventricular end-systolic volume at 6 months of 13% as the best cutoff to identify the reduction of VAs (with a sensitivity of 58% and a specificity of 54%). CONCLUSIONS: In patients treated with CRT defibrillators, a reduction in ventricular arrhythmic events occurs during the initial 12 months after implant and is correlated with the degree of ventricular remodeling induced by the therapy. Patients demonstrating reverse remodeling at midterm follow-up show a reduction in arrhythmias soon after the implant, pronounced improvements at long-term, and a better survival.

Implantable CRT device diagnostics identify patients with increased risk for heart failure hospitalization.

PURPOSE: To determine the association between device-determined diagnostic indices, including intrathoracic impedance, and heart failure (HF) hospitalization. METHODS: Clinical and device diagnostic data of 558 HF patients indicated for CRT-D therapy (In Sync Sentry, Medtronic Inc.) were prospectively collected from 34 centers. Device-recorded intrathoracic impedance fluid index threshold crossing event (TCE), mean activity counts, tachyarrhythmia events, night heart rate (NHR) and heart rate variability (HRV) were compared within patients with vs. without documented HF hospitalization. RESULTS: Mean follow-up was 326 +/- 216 days. Patients hospitalized for HF had significantly higher rates of TCE, a higher percentage of days with the thoracic impedance fluid index above the programmed threshold, a higher percentage of days with low activity, with low HRV or with high NHR. Multivariate analysis showed that TCE resulted in a 36% increased probability of HF hospitalization. Both TCE duration and patient activity were also significantly associated with hospitalization. Kaplan Meier analysis indicated that patients with more TCE events were significantly more likely to be hospitalized (log rank test, p = 0.005). CONCLUSIONS: Decreased intrathoracic impedance, low patient activity and low HRV were all independently associated with increased risk for HF hospitalization in HF patients treated with resynchronization therapy. Device-derived diagnostic data may provide valuable and reliable indices for the prognostic stratification of HF patients.

Persistent atrial fibrillation worsens heart rate variability, activity and heart rate, as shown by a continuous monitoring by implantable biventricular pacemakers in heart failure patients.

BACKGROUND: Atrial fibrillation (AF) induces loss of atrial contribution, heart rate irregularity, and fast ventricular rate. OBJECTIVES: The objectives of the study were to accurately measure AF incidence and to investigate the mutual temporal patterns of AF and heart failure (HF) in patients indicated to cardiac resynchronization therapy. METHODS: Four hundred ten consecutive patients (70% male, age 69 +/- 11) with advanced HF (NYHA = 3.0 +/- 0.6), low ejection fraction (EF = 27 +/- 9%), and ventricular conduction delay (QRS = 165 +/- 29 ms) received a biventricular pacemaker. Enrolled patients were divided into two groups: G1 = 249 patients with no AF history, G2 = 161 patients with history of paroxysmal/persistent AF. RESULTS: In a median follow-up of 13 months, AF episodes longer than 5 minutes occurred in 105 of 249 (42.2%) G1 patients and 76 of 161 (47.2%) G2 patients, while AF episodes longer than one day occurred in 14 of 249 (5.6%) G1 patients and in 36 of 161 (22.4%) G2 patients. Device diagnostics monitored daily values of patient activity, night heart rate (NHR), and heart rate variability (HRV). Comparing 30-day periods before AF onset and during persistent AF, significant (P < 0.0001) changes were observed in patient activity, which decreased from 221 +/- 13 to 162 +/- 12 minutes, and in NHR, which increased from 68 +/- 3 to 94 +/- 7 bpm. HRV significantly decreased (from 75 +/- 5 ms before AF onset to 60 +/- 6 ms after AF termination). NHR during AF was significantly (P < 0.01) and inversely correlated (R(2)= 0.73) with activity, with a significant lower activity associated with NHR >or= 88 bpm. CONCLUSION: AF is frequent in HF patients. Persistent AF is associated with statistically significant decrease in patient activity and HRV and NHR increase.

Results of the SCART study: selection of candidates for cardiac resynchronisation therapy.

OBJECTIVE: To prospectively determine whether prespecified electrocardiographic, echocardiographic and tissue Doppler imaging (TDI) selection criteria may predict a positive response to cardiac resynchronisation therapy (CRT). METHODS: In this multicentre, prospective, non-randomised study, 96 heart failure patients with New York Heart Association class III-IV symptoms, an ejection fraction of < or =35%, and at least one marker of ventricular dyssynchrony according to prespecified electrocardiographic, echocardiographic or TDI criteria were enrolled. The primary endpoint was an improvement in the clinical composite score at 6 months. RESULTS: At enrolment, 70 patients fulfilled the electrocardiographic criterion (QRS duration > or =150 ms), 77 patients showed echocardiographic signs of dyssynchrony, and 37 patients met the TDI dyssynchrony criteria. The overall responder rate was 78/96 (81%). In particular, the primary endpoint was reached in 68 patients who fulfilled the echocardiographic criteria as compared with 10 patients who did not (88 vs. 53%, P = 0.001). The patients who met the echocardiographic criteria showed a significant greater reduction in left ventricular end-systolic diameter (P = 0.029) and a higher improvement in quality of life (P = 0.017) than patients who did not. Neither electrocardiographic nor TDI criteria seemed to predict a positive response to CRT. CONCLUSIONS: In our patient population, mechanical indexes of dyssynchrony as assessed by echocardiography appeared to identify CRT responders. Although TDI is useful for evaluating ventricular dyssynchrony after CRT, the prespecified TDI inclusion criteria adopted in this investigation did not increase the number of CRT responders.

Comparison of the effects of cardiac resynchronization therapy in patients with class II versus class III and IV heart failure (from the InSync/InSync ICD Italian Registry).

Cardiac resynchronization therapy (CRT) is recommended for patients with New York Heart Association (NYHA) class III or IV heart failure and wide QRS complexes. The aim of this study was to compare the effects of CRT in patients in NYHA class II with those in NYHA class III or IV. Nine hundred fifty-two patients (188 in NYHA class II) consecutively implanted with biventricular devices and enrolled in a national observational registry were studied. Clinical outcomes were estimated after 12 months of CRT, and long-term survival was assessed. At a median follow-up of 16 months, significantly fewer major cardiovascular events were reported in patients in NYHA class II compared with NYHA class III or IV (rate 13 vs 23 per 100 patient-years of follow-up, p<0.001). The percentage of patients who improved in NYHA class status after 12 months of CRT was lower in those in class II than in those in class III or IV (34% vs 69%, p<0.001), whereas the absolute increase in the ejection fraction was similar (8+/-9% vs 9+/-11%, p=NS), as well as the reductions in end-diastolic diameter (-3+/-8 vs -3+/-8 mm, p=NS) and end-systolic diameter (-4+/-10 vs -6+/-10 mm, p=NS). The NYHA class II group experienced lower all-cause mortality (log-rank test p=0.018). In the 2 groups, patients with major cardiovascular events during follow-up exhibited less or no reverse remodeling compared with those with better long-term clinical outcomes. In conclusion, the results of this study indicate that CRT induced similar improvements in ventricular function in the 2 groups, whereas the improvement in functional status was significantly lower for patients in NYHA class II than for those in class III or IV. A positive effect of CRT on cardiac dimensions was associated with a long-term beneficial effect on disease progression in patients in NYHA class II.

Efficacy of cardiac resynchronization therapy in very old patients: the Insync/Insync ICD Italian Registry.

AIMS: To assess the effects of cardiac resynchronization therapy (CRT) in > or =80-year-old patients vs. patients <80 years, in terms of clinical, functional, and echocardiographic parameters after 12 month of CRT, survival, and incidence of arrhythmic events. METHODS AND RESULTS: The study population consisted of 1181 CRT patients (85 were > or =80 years old). They were enrolled in a national observational registry and underwent baseline evaluation and periodical follow-up visits. In the overall population, New York Heart Association class and ejection fraction (EF) improved and ventricular diameters decreased. Similar changes were observed in the two groups. In the study population, 157 patients died, 144 (13%) in the <80 years group and 13 (15%) in the > or =80 years group. There was a higher all-cause mortality (log-rank test, P = 0.015) among > or =80 years patients, with a trend towards higher sudden cardiac death (SCD) (P = 0.057), but similar non-SCD (P = 0.293). Using the combined endpoint of SCD or appropriate shock from a defibrillator for ventricular fibrillation, no significant differences resulted between groups (P = 0.455). In both groups, lower EF was associated with higher mortality. CONCLUSION: Cardiac resynchronization therapy demonstrated similar efficacy in patients aged > or =80 years and in those under 80, in terms of clinical and functional parameters and reverse remodelling. Similarly, CRT resulted in comparable effects on death for heart failure and on SCD.

Prediction of response to cardiac resynchronization therapy: the selection of candidates for CRT (SCART) study.

BACKGROUND: The aim of this study was to evaluate the ability of baseline clinical and echocardiographic parameters to predict a positive response to CRT. METHODS: We analyzed 6-month data from the first 133 consecutive patients enrolled in a multicenter prospective study. These patients had symptomatic heart failure (HF) refractory to pharmacological therapy (NYHA class II-IV), left ventricular ejection fraction (LVEF) < or =35%, and prespecified electrocardiographic, echocardiographic or tissue Doppler imaging markers of left ventricular (LV) dyssynchrony. RESULTS: After a follow-up period of 6 months, 1 patient died and 13 were hospitalized for worsening HF. There were significant (P < 0.01) clinical, functional, and echocardiographic improvements that included: New York heart Association Class, Quality-of-Life Score, QRS duration, LVEF, LV end-diastolic and end-systolic diameter (LVESD), and severity of mitral regurgitation A positive response was documented in 90/133 (68%) patients who presented an improved clinical composite score associated to an increase in LVEF > or = 5 units. A multivariate analysis identified that a smaller LVESD (OR = 0.957, 95% CI 0.920-0.996; P = 0.030) and longer interventricular mechanical delay (IVMD) (OR = 1.017, 95% CI 1.005-1.029, P = 0.007) as independent predictors of a positive response. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with IVMD > 44 ms (with a sensitivity of 66% and a specificity of 55%) or with LVESD < 60 mm (with a sensitivity of 66% and a specificity of 61%). CONCLUSIONS: Our results confirm the limited value of QRS duration in the selection of patients for CRT. A less-advanced stage of disease and echocardiographic evidence of interventricular dyssynchrony demonstrated to predict response to CRT, while intraventricular dyssynchrony did not predict response.

Long-term survival in patients treated with cardiac resynchronization therapy: a 3-year follow-up study from the InSync/InSync ICD Italian Registry.

BACKGROUND: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters. METHODS: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact. RESULTS: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06-2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24-6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively). CONCLUSIONS: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.

Characteristics of ventricular tachyarrhythmias occurring in ischemic versus nonischemic patients implanted with a biventricular cardioverter-defibrillator for primary or secondary prevention of sudden death.

OBJECTIVES: The InSync ICD Registry evaluated patients indicated for cardiac resynchronization therapy with defibrillation. BACKGROUND: Cardiac resynchronization therapy with defibrillation systems are prescribed for both primary and secondary prevention of sudden cardiac death in patients with heart failure with both ischemic and nonischemic etiology. The characterization of ventricular tachyarrhythmias detected by the ICD is not well known in these subpopulations. METHODS: We enrolled 421 patients with symptomatic heart failure despite optimized medical treatment, ventricular dyssynchrony, and primary or secondary ICD indications. An electrophysiologist reviewed all spontaneous episodes. Patients were grouped by etiology and ICD indications. RESULTS: The 421 patients included 292 ischemic (159 primary prevention) and 129 nonischemic (68 primary prevention) patients. In 19 +/- 11 months of follow-up, 110 patients (63 ischemic, 30 primary prevention and 47 nonischemic, 21 primary prevention) presented ventricular tachyarrhythmias, occurring in a ventricular tachycardia (VT) or a ventricular fibrillation zone (1382 and 456 events, respectively). The incidence of overall ventricular tachyarrhythmias in nonischemic patients in secondary prevention (35.7% at 1 year) was higher than in ischemic patients implanted for either indication (16.5% and 22.9% at 1 year, respectively). The incidence of self-terminating ventricular tachyarrhythmias was greater in patients with nonischemic heart disease, regardless of indication. Patients with ischemic heart disease in primary prevention had a lower occurrence of VTs, whereas nonischemic patients in primary prevention had faster VTs. CONCLUSIONS: Both rate of occurrence and characteristics of detected ventricular tachyarrhythmias vary according to underlying etiology and indication. Therefore, different device programming according to patient's profile is advisable to improve ventricular tachyarrhythmias management.