Combining home monitoring temporal trends from implanted defibrillators and baseline patient risk profile to predict heart failure hospitalizations: results from the SELENE HF study.

AIMS: We developed and validated an algorithm for prediction of heart failure (HF) hospitalizations using remote monitoring (RM) data transmitted by implanted defibrillators. METHODS AND RESULTS: The SELENE HF study enrolled 918 patients (median age 69 years, 81% men, median ejection fraction 30%) with cardiac resynchronization therapy (44%), dual-chamber (38%), or single-chamber defibrillators with atrial diagnostics (18%). To develop a predictive algorithm, temporal trends of diurnal and nocturnal heart rates, ventricular extrasystoles, atrial tachyarrhythmia burden, heart rate variability, physical activity, and thoracic impedance obtained by daily automatic RM were combined with a baseline risk-stratifier (Seattle HF Model) into one index. The primary endpoint was the first post-implant adjudicated HF hospitalization. After a median follow-up of 22.5 months since enrolment, patients were randomly allocated to the algorithm derivation group (n = 457; 31 endpoints) or algorithm validation group (n = 461; 29 endpoints). In the derivation group, the index showed a C-statistics of 0.89 [95% confidence interval (CI): 0.83-0.95] with 2.73 odds ratio (CI 1.98-3.78) for first HF hospitalization per unitary increase of index value (P < 0.001). In the validation group, sensitivity of predicting primary endpoint was 65.5% (CI 45.7-82.1%), median alerting time 42 days (interquartile range 21-89), and false (or unexplained) alert rate 0.69 (CI 0.64-0.74) [or 0.63 (CI 0.58-0.68)] per patient-year. Without the baseline risk-stratifier, the sensitivity remained 65.5% and the false/unexplained alert rates increased by ≈10% to 0.76/0.71 per patient-year. CONCLUSION: With the developed algorithm, two-thirds of first post-implant HF hospitalizations could be predicted timely with only 0.7 false alerts per patient-year.

Appropriate implantable cardioverter-defibrillator interventions in cardiac resynchronization therapy-defibrillator (CRT-D) patients undergoing device replacement: time to downgrade from CRT-D to CRT-pacemaker? Insights from real-world clinical practice in the DECODE CRT-D analysis.

Aim: Ventricular tachycardia (VT)/ventricular fibrillation (VF) occurrence after cardiac resynchronization therapy-defibrillator (CRT-D) replacement is unknown; hence, there is no practical guideline to recommend either CRT-D or CRT-pacemaker at the time of device replacement. We observed the 1-year VT/VF occurrence after CRT-D replacement in a subanalysis of the Detect Long-term Complications after ICD Replacement (DECODE) registry. Methods and results: A total of 332 consecutive patients who had undergone CRT-D replacement from 2013 to 2015 were enrolled in 36 Italian centres. The primary endpoint was the number of patients with any appropriate implantable cardioverter-defibrillator (ICD) interventions during 12-month follow-up. The secondary endpoint comprised death from any cause and appropriate ICD interventions. At replacement, 214 (64.5%) patients had a left ventricular ejection fraction ≤ 35% and 138 (41.6%) patients had a secondary prevention indication for ICD. Seventy (21.1%) patients had no longer indication to ICD therapy. During a median follow-up period of 406.5 (362-533) days, VT/VF requiring therapy delivery occurred in 57 (17%) patients, specifically in 7% of those who no longer had an ICD indication. On multivariate analysis, number of criteria for ICD replacement independently predicted appropriate ICD intervention during follow-up [hazard ratio (HR) = 1.62, 95% confidence interval (CI) 1.07-2.46; log-rank P = 0.02]. The combined endpoint of death from any cause or appropriate ICD therapy occurred in 76 (23%) patients. Only NYHA class remained associated with this combined endpoint (HR = 1.97, 95% CI 1.23-3.14; P = 0.005). Conclusions: The DECODE registry showed the 'real-world' experience of CRT-D recipients approaching device replacement, in which 7% of patients who no longer had an indication for ICD therapy experienced appropriate ICD interventions.

Access to magnetic resonance imaging of patients with magnetic resonance-conditional pacemaker and implantable cardioverter-defibrillator systems: results from the Really ProMRI study.

Aims: The Really ProMRI study evaluates magnetic resonance imaging (MRI) access for patients with cardiac implantable electronic devices (CIEDs) as well as the performance of magnetic resonance (MR)-conditional leads when undergoing MRI. Methods and results: Patients either with an MR-conditional pacemaker or implantable defibrillator (ICD) system or with at least a component (device or one or more leads) from an MR-conditional system, were asked to fill in a questionnaire when they were referred to a MR scan. The rate of prescription, denial, or execution of MR examinations was evaluated in a 1-year follow-up visit. In total, 555 patients [median age (interquartile range) 72.2 (62.2-78.6); 72% male] were enrolled, 49% (270) with a pacemaker, 51% (285) with an ICD system. Five-hundred and ten patients completed the follow-up period. A total of 37 MRI referrals were reported in 35 patients, with a consequent event rate of 7.0/100 patient-years (CI, 4.9-9.7). Fourteen were denied, while 23 [66%; (CI, 48-81%)] were performed. The number of patients with MR referrals was not statistically different between pacemaker and ICD groups (21 vs. 14; P = 0.178). The rate of scans performed was higher in the pacemaker subjects (19/23 vs. 4/14, P = 0.003), while it was similar between patients with or without a complete MR-conditional system (19/30 vs. 4/7, P = 0.606). Conclusion: In this study, we reported a 7.0/100 patient-year's event rate of MR prescriptions in CIED patients. Many examinations were denied, despite MR-conditional systems, especially in ICD patients. Regulatory and cultural changes are needed to allow wider access to MR imaging in CIED patients with MR-conditional systems.

The economic impact of battery longevity in implantable cardioverter-defibrillators for cardiac resynchronization therapy: the hospital and healthcare system perspectives.

AIMS: Patients receiving cardiac resynchronization therapy defibrillators (CRT-Ds) are likely to undergo one or more device replacements, mainly for battery depletion. We assessed the economic impact of battery depletion on the overall cost of CRT-D treatment from the perspectives of the healthcare system and the hospital. We also compared devices of different generations and from different manufacturers in terms of therapy cost. METHODS AND RESULTS: We analysed data on 1792 CRT-Ds implanted in 1399 patients in 9 Italian centres. We calculated the replacement probability and the total therapy cost over 6 years, stratified by device generation and manufacturer. Public tariffs from diagnosis-related groups were used together with device prices and hospitalization costs. Generators were from 3 manufacturers: Boston Scientific (667, 37%), Medtronic (973, 54%), and St Jude Medical (152, 9%). The replacement probability at 6 years was 83 and 68% for earlier- and recent-generation devices, respectively. The need for replacement increased total therapy costs by more than 50% over the initial implantation cost for hospitals and by more than 30% for healthcare system. The improved longevity of recent-generation CRT-Ds reduced the therapy cost by ∼6% in both perspectives. Among recent-generation CRT-Ds, the replacement probability of devices from different manufacturers ranged from 12 to 70%. Consequently, the maximum difference in therapy cost between manufacturers was 40% for hospitals and 19% for the healthcare system. CONCLUSIONS: Differences in CRT-D longevity strongly affect the overall therapy cost. While the use of recent-generation devices has reduced the cost, significant differences exist among currently available systems.

The Italian subcutaneous implantable cardioverter-defibrillator survey: S-ICD, why not?

AIMS: A recommendation for a subcutaneous-implantable cardioverter-defibrillator (S-ICD) has been added to recent European Society of Cardiology Guidelines. However, the S-ICD is not ideally suitable for patients who need pacing. The aim of this survey was to analyse the current practice of ICD implantation and to evaluate the actual suitability of S-ICD. METHODS AND RESULTS: The survey 'S-ICD Why Not?' was an independent initiative taken by the Italian Heart Rhythm Society (AIAC). Clinical characteristics, selection criteria, and factors guiding the choice of ICD type were collected in consecutive patients who underwent ICD implantation in 33 Italian centres from September to December 2015. A cardiac resynchronization therapy (CRT) device was implanted in 39% (369 of 947) of patients undergoing de novo ICD implantation. An S-ICD was implanted in 12% of patients with no CRT indication (62 of 510 with available data). S-ICD patients were younger than patients who received transvenous ICD, more often had channelopathies, and more frequently received their device for secondary prevention of sudden death. More frequently, the clinical reason for preferring a transvenous ICD over an S-ICD was the need for pacing (45%) or for antitachycardia pacing (36%). Nonetheless, only 7% of patients fulfilled conditions for recommending permanent pacing, and 4% of patients had a history of monomorphic ventricular tachycardia that might have been treatable with antitachycardia pacing. CONCLUSION: The vast majority of patients needing ICD therapy are suitable candidates for S-ICD implantation. Nevertheless, it currently seems to be preferentially adopted for secondary prevention of sudden death in young patients with channelopathies.

Longevity of implantable cardioverter-defibrillators for cardiac resynchronization therapy in current clinical practice: an analysis according to influencing factors, device generation, and manufacturer.

AIMS: Device replacement at the time of battery depletion of implantable cardioverter-defibrillators (ICDs) may carry a considerable risk of complications and engenders costs for healthcare systems. Therefore, ICD device longevity is extremely important both from a clinical and economic standpoint. Cardiac resynchronization therapy defibrillators (CRT-D) battery longevity is shorter than ICDs. We determined the rate of replacements for battery depletion and we identified possible determinants of early depletion in a series of patients who had undergone implantation of CRT-D devices. METHODS AND RESULTS: We retrieved data on 1726 consecutive CRT-D systems implanted from January 2008 to March 2010 in nine centres. Five years after a successful CRT-D implantation procedure, 46% of devices were replaced due to battery depletion. The time to device replacement for battery depletion differed considerably among currently available CRT-D systems from different manufacturers, with rates of batteries still in service at 5 years ranging from 52 to 88% (log-rank test, P < 0.001). Left ventricular lead output and unipolar pacing configuration were independent determinants of early depletion [hazard ratio (HR): 1.96; 95% 95% confidence interval (CI): 1.57-2.46; P < 0.001 and HR: 1.58, 95% CI: 1.25-2.01; P < 0.001, respectively]. The implantation of a recent-generation device (HR: 0.57; 95% CI: 0.45-0.72; P < 0.001), the battery chemistry and the CRT-D manufacturer (HR: 0.64; 95% CI: 0.47-0.89; P = 0.008) were additional factors associated with replacement for battery depletion. CONCLUSION: The device longevity at 5 years was 54%. High left ventricular lead output and unipolar pacing configuration were associated with early battery depletion, while recent-generation CRT-Ds displayed better longevity. Significant differences emerged among currently available CRT-D systems from different manufacturers.

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.

Long-term complications related to biventricular defibrillator implantation: rate of surgical revisions and impact on survival: insights from the Italian Clinical Service Database.

BACKGROUND: Long-term data on device-related untoward events in patients receiving defibrillators for resynchronization therapy (CRT-D) are lacking. We quantified the frequency of repeat invasive procedures and the nature of long-term complications in current clinical practice and examined possible predictors of device-related events and their association with long-term patient outcome. METHODS AND RESULTS: We analyzed data from 3253 patients who underwent de novo successful implantation of CRT-D and were followed up for a median of 18 months (25th to 75th percentiles: 9 to 30) in 117 Italian centers. Device-related events were reported in 416 patients, and, specifically, surgical interventions for system revision were described in 390 patients. Four years after the implantation procedure, 50% of patients underwent surgical revision for battery depletion and 14% for unanticipated events. For comparison, at 4 years battery depletion occurred in 10% and 13% of patients who received single- and dual-chamber defibrillators at the study centers, and unanticipated events were reported as 4% and 9%, respectively. In CRT-D, infections occurred at a rate of 1.0%/y, and the risk of infections increased after device replacement procedures (hazard ratio, 2.04; 95% confidence interval, 1.01 to 4.09; P=0.045). Left ventricular lead dislodgements were reported at a rate of 2.3%/y and were predicted by longer fluoroscopy time and higher pacing threshold on implantation. Device-related events were not associated with a worse clinical outcome; indeed, the risk of death was similar in patients with and without surgical revision (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.47; P=0.682). CONCLUSIONS: In current clinical practice device-related events are more frequent in CRT-D than in single- or dual-chamber defibrillators, and are frequently managed by surgical intervention for system revision. However, a worse clinical outcome is not associated with these events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01007474.

Impact of incomplete revascularization following OPCAB surgery.

BACKGROUND AND AIM OF THE STUDY: The aim of this study was to evaluate the early and mid-term off-pump coronary artery bypass surgery (OPCAB) results in a single surgical unit, assessing the impact of completeness of revascularization. METHODS: Three hundred and twelve patients underwent OPCAB between August 2000 and January 2005. In-hospital data were collected prospectively for all patients undergoing OPCAB. Complete revascularization (CR) was derived by comparing significantly stenotic vessels at cardiac catheterization with surgically grafted coronary vessels. Grafting of all the significantly stenotic coronary vessels was considered CR. In-hospital outcomes were compared between patients with CR and incomplete revascularization (IR). A multivariate analysis based on the Cox proportional hazards regression model was performed. RESULTS: Patients receiving IR (105 patients, 43.7%) presented a worse preoperative risk profile then those having CR (mean Euroscore 6.8 +/- 2.9 vs. 4.3 +/- 2.8, p < 0.0001). IR was not associated with a higher incidence of early adverse events. Five-year freedom from death and major adverse cardiac events (MACE) were 0.88 (0.02 SE) and 0.86 (0.03 SE), respectively. Complete revascularization was protective for mid-term unstable angina recurrence [heart rate (HR) = 0.24, 95% confidence interval (CI) 0.10 to 0.58], acute myocardial infarction (HR = 0.25, 95% CI 0.09 to 0.73), all-cause repeat revascularization (HR = 0.35, 95% CI 0.13 to 0.90), and MACE (HR = 0.2, 95% CI 0.1 to 0.5). CONCLUSION: Our study suggests that, although incomplete revascularization may not result in increased short-term morbidity and mortality, it increases the incidence of mid-term MACE.

Cardiac resynchronization therapy modifies the neurohormonal profile, hemodynamic and functional capacity in heart failure patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to improve the clinical status and survival in congestive heart failure (CHF) patients, but little is known about its influence on neurohormonal profile. METHODS: Heart failure patients treated with CRT for moderate/severe heart failure were studied with echocardiography, cardiopulmonary test, and neurohormonal profile [brain natriuretic peptide (BNP), endothelin (END), big endothelin (big-END), epinephrine (EPI), tumor necrosis factor-alpha (TNF-alpha)] at baseline and after 1 year from the pacemaker implantation. RESULTS: 120 NYHA II-IV patients entered this study, all with an indication to CRT; 100 agreed to be implanted (group A), whereas 20 refused, identifying a control group (group B). In group A NYHA class (from 3.15+/-0.49-1.15+/-0.49, p=0.001), left ventricular ejection fraction (from 19.6+/-4.95-35.6+/-5.95%, p=0.001), severity of mitral regurgitation (from 13.3+/-4.19-6.09+/-4.11 cmq, p=0.001), and peak VO(2) (from 9.68+/-4.61-13.35+/-3.32 mL/kg/min, p=0.001) improved at 1-year follow-up. In the neurohormonal profile only plasma BNP (from 185.1+/-185.9-110.2+/-137.5 pg/mL, p=0.03) and big-END (from 1.8+/-1.5-0.87+/-0.7 fmol/mL, p=0.007) were reduced significantly. None of these parameters significantly changed in the control group at 1-year follow-up. CONCLUSIONS: In patients with moderate/severe heart failure, CRT improved clinical status and the functional parameters modifying the neurohormonal profile at 1-year follow-up.

Myocardial scar and insulin resistance predict cardiovascular events in severe ischaemic myocardial dysfunction: a perfusion-metabolism positron emission tomography study.

BACKGROUND: Clinical outcome can be predicted by metabolism-perfusion positron emission tomography (PET) in patients with severe ischaemic left ventricular dysfunction. This study determined whether the amount of viable or non-viable myocardium detected with a PET scan or clinical-functional parameters might predict cardiovascular events. METHODS: All patients had previous myocardial infarction (>6 months previously) and left ventricular ejection fraction (LVEF) <40%. Metabolism-perfusion PET, echocardiogram and coronary angiography were provided. All subjects underwent short euglycaemic-hyperinsulinaemic clamp before the metabolism study. The dysfunctioning segment was defined as hibernating myocardium when metabolism was normal-moderately reduced with impaired perfusion (mismatch flow-metabolism). Cardiac death, hospital admission for myocardial infarction or heart failure were considered cardiovascular events. RESULTS: Ninety-three patients (71 males, aged 64.2 years) were studied. The LVEF was 30.2+/-7.7%; 48 (51.6%) suffered an anterior myocardial infarction. Fifty-three (54.1%) subjects were treated with coronary revascularization; all had optimal medical therapy. Cardiovascular events occurred in 20/93 patients at 1-year follow-up (event group). Age (P=0.7), diabetes mellitus (P=0.6) and rate of coronary revascularization (P=0.3) were not different in the two groups. Patients who experienced cardiovascular events had larger non-viable myocardium (5.8+/-2.7 vs. 4.1+/-2.6, P=0.01), lower metabolic rate glucose (1.3+/-0.6 vs. 1.7+/-0.7 ml . kg . min, P=0.04) but similar hibernating myocardium (1.6+/-1.6 vs. 1.7+/-2, P=0.8) and baseline LVEF (28.1+/-4.8 vs. 30.7+/-8.3%, P=0.08). Having more then five non-viable segments and a metabolic rate for glucose of <0.9 mg . kg . min predicted a worse prognosis (P=0.04, log rank, 3.89; and P=0.004, log rank, 8.1, respectively). CONCLUSION: Non-viable myocardium revealed with PET predicts mid-term clinical prognosis. Insulin resistance seems to influence the outcome.

Prognostic Value of Different Allelic Polymorphism of Aldosterone Synthase Receptor in a Congestive Heart Failure European Continental Ancestry Population.

Aldosterone synthase (CYP11B2) is as an 9-exon gene on chromosome 8q22 and exists as a common single nucleotide polymorphism C-T transition for position -344. The aim of this study was to assess the -344T/C polymorphism of the aldosterone synthase promoter in a European continental ancestry congestive heart failure (CHF) population. METHODS: Patients discharged after an acute decompensation were enrolled and underwent echocardiography, determination of BNP, evaluation of non-invasive cardiac outputs and determination of -344 T/C SNP in the aldosterone synthase gene. RESULTS: 175 patients (137 male; age 69.9 ± 10.2 years) were enrolled. The genotype distribution of -344 T/C SNP demonstrated a TT genotype in 61 patients (34.9%), CT in 80 (45.7%) and finally CC in 34 (19.4%) CHF patients. According to presence of C allele, CHF patients were divided into C group (-CT/CC genotype, 114 subjects) and T Group (-TT genotype, 61 subjects). The two groups did not differ in term of age, non-invasive cardiac output at rest, creatinine level or end-systolic or diastolic left ventricle diameter, LVEF and BNP. In group C patients in comparison than in group T a higher degree of disability (Barthel Index p = 0.004), NYHA class (p = 0.02) and a lower cardiac index (p = 0.01) emerged. Moreover, the two groups showed a similar clinical outcome (death for any cause/hospital readmission for CHF) at 48 month follow-up (p = 0.16; log-rank 1.99). CONCLUSIONS: In European continental ancestry patients the C allele (CC or CT) at -344T/C SNP in the aldosterone synthase gene does not significantly influence clinical prognosis of CHF.

Placebo or trimetazidine (99m)Tc tetrofosmin myocardial SPECT and low-dose dobutamine echocardiography in hibernating myocardium.

BACKGROUND: Trimetazidine (TMZ) improves (99m)Tc sestamibi uptake in myocardial single photon emission tomography (SPECT). This study compared TMZ (99m)Tc tetrofosmin SPECT and low-dose dobutamine echocardiography (LDDE) as predictors of functional recovery of hibernating myocardium after coronary revascularization. METHODS: Thirty-one patients with prior myocardial infarction and left ventricular dysfunction underwent coronary angiography, LDDE, placebo SPECT and TMZ SPECT. Echocardiographic follow-up was obtained at 2/6 months; the clinical follow-up lasted 2 years. RESULTS: Twenty-three (74.2%) patients (195 dysfunctioning left ventricular segments) were revascularized. TMZ improved (99m)Tc tetrofosmin uptake (p = 0.0001) as well as LVEF at gated SPECT (p = 0.04). At 2-months, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated (LDDE 71.9, 78.7, 71, 79.5; placebo SPECT 66.2, 75.6, 65.4, 76.3; TMZ SPECT 79.2, 67.7, 61.6, 83.3, respectively). The specificity improved in placebo and TMZ SPECT (82.1 and 78.7%) at 6-months follow-up. Two patients (2/23) with hibernating myocardium treated with revascularization and three (3/4) treated medically died a cardiac death (p = 0.0016, log rank 12.89). None (0/4) without viability died during the 2-year follow-up (p = 0.6, log rank 0.28). CONCLUSIONS: The addition of TMZ to (99m)Tc tetrofosmin SPECT improved diagnostic accuracy. The importance of hibernating myocardium revascularization was confirmed.

Estrogen receptor-alpha polymorphisms and angiographic outcome after coronary artery stenting.

OBJECTIVE: Because of the receptor-mediated antiproliferative effects of estradiol on vascular smooth muscle cells, our study aimed at identifying a role of PvuII and XbaI polymorphisms of the alpha-estrogen receptor (alphaER) gene in the occurrence of restenosis after coronary stent implantation (in-stent restenosis [ISR]). METHODS AND RESULTS: In 858 patients (148 women), 955 lesions were treated with stent implantation, and the PvuII C/T and XbaI G/A polymorphisms of the alphaER gene were determined. Quantitative angiography was performed before and after stenting and at 6-month follow-up. The allelic frequencies were similar between sexes (C/T allele, 0.43/0.57 and 0.44/0.56; P=0.9; G/A allele, 0.35/0.65 and 0.38/0.62; P=0.8; in women and men, respectively). A significantly higher ISR rate in women than in men homozygous for the T-allele of the PvuII polymorphism (42.6% versus 26.9%, P=0.03) or the G-allele of the XbaI polymorphism (41.2% versus 19.4%, P=0.04) was observed. At multivariate analysis, T/T genotype was the only independent predictor of ISR in women but not in men (odds ratio, 1.5; 95% CI, 1.0 to 2.1; P=0.03). XbaI polymorphism was no longer associated with ISR in both sexes. CONCLUSIONS: Women homozygous for the T-allele of the PvuII polymorphism of the alphaER gene treated with coronary stent implantation have a higher risk of ISR than men.

Characterization of ventricular activation pattern and acute hemodynamics during multipoint left ventricular pacing.

BACKGROUND: Multipoint left ventricular (LV) pacing (MultiPoint Pacing [MPP], St Jude Medical, Sylmar, CA) in a single coronary sinus branch has been introduced as a novel means of cardiac resynchronization therapy (CRT). It is speculated that MPP improves LV function by capturing a larger LV tissue area, resulting in uniform wavefront propagation throughout the ventricles, in comparison to conventional biventricular pacing (BIV). OBJECTIVE: The purpose of this study was to evaluate MPP by means of contact mapping and hemodynamic measures to understand the underlying mechanisms and effects. METHODS: Ten patients with non-ischemic cardiomyopathy (mean age 69 ± 9 years; 6 men (60%); New York Heart Association heart failure class II or III; QRS duration 173 ± 20 ms; LV ejection fraction 27% ± 5%) received a CRT-defibrillator capable of MPP. After the implantation procedure, an acute pacing protocol was implemented, including 2 BIV and up to 9 MPP interventions. In all pacing interventions, LV electrical activation patterns and hemodynamics (dP/dtmax) were evaluated, and for each patient, both the resulting measures were compared between MPP and BIV interventions. RESULTS: Compared with BIV, MPP resulted in an increase in LV dP/dtmax (30% ± 13% vs. 25% ± 11%; P = .041), a reduction in QRS duration (22% ± 11% vs. 11% ± 11%; P = .01), and a decrease in total endocardial activation time (25% ± 15% vs. 10% ± 20%; P = .01). MPP resulted in a larger capture of LV mass during the first 25 ms (35% ± 22% vs. 16% ± 8%; P = .005) and during the first 50 ms (78% ± 27% vs. 60% ± 23%; P = .03) of pacing, suggesting a quicker wavefront propagation throughout the left ventricle. CONCLUSION: In this acute study, MPP in CRT improved both endocardial and surface electrical parameters and hemodynamics in comparison with BIV.

Selection of potential predictors of worsening heart failure: rational and design of the SELENE HF study.

BACKGROUND: Heart failure is a leading cause of hospitalization and a significant medical burden in our society. Implantable medical devices are nowadays established therapies in heart failure patients that not only provide cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICDs) therapy but are also able to continuously and remotely monitor diagnostic information of various physiologic parameters. The value of combining individual diagnostic variables to predict worsening of heart failure is still largely unclear but could eventually become a valuable tool towards a better heart failure management. METHODS: SELENE HF (Selection of potential predictors of worsening Heart Failure) is an observational, multicentre study designed to prospectively collect follow-up and home monitoring data trends from a population of individuals with ICDs with or without resynchronization therapy (CRT-D), to document heart failure hospitalizations and deaths and to correlate these events with Home Monitoring data in order to identify the combination with the greatest sensitivity and specificity in predicting heart failure events.The purpose of this study is to describe the design of the study focusing on the Heart Failure Predicting model and statistical approach that will be used to analyse the data. CONCLUSION: The results of the SELENE HF study could help to select and define potential predictors of worsening heart failure in patients with remotely monitored ICD or CRT-D devices. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01836510.

Effect of angiotensin-converting enzyme inhibition on restenosis after coronary stenting.

The Plasma level of angiotensin-converting enzyme (ACE) has been identified as a major risk factor for restenosis after coronary stent implantation in selected patients; ACE inhibition may therefore contribute to prevent its occurrence. The effect of oral ACE inhibition at conventional doses was analyzed retrospectively in a series of 897 patients with ischemia who received >or=1 coronary stent on 998 lesions and underwent angiographic follow-up; no exclusion criteria were introduced in this analysis. The restenosis rate in 282 patients (31.4%) taking ACE inhibitors was 36.6% compared with 22.9% in 615 non-ACE-inhibited patients (p = 0.00001, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.45 to 2.59), and the late loss in minimum lumen diameter was 1.25 +/- 0.8 versus 0.96 +/- 0.8 mm, respectively (p = 0.0001). During univariate analysis, a negative effect of the drug on restenosis was observed in all subgroups of patients (i.e., hypertensives, diabetics, women, and patients with previous myocardial infarction). Similar effects were observed independently of the ACE gene insertion/deletion polymorphism. During multivariate analysis, ACE inhibition was confirmed as an independent risk factor for restenosis (OR 1.84, 95% CI 1.35 to 2.51, p = 0.0001). Other predictors were the implantation of multiple stents (OR 2.41, 95% CI 1.60 to 3.64, p <0.0001), diabetes (OR 2.34, 95% CI 1.61 to 3.41, p <0.0001), and vessel reference diameter before angioplasty (OR 0.51, 95% CI 0.38 to 0.69, p <0.0001). Although unexplained and apparently contradictory, our data suggest that the use of conventional oral doses of ACE inhibitors in a "real-world" population who underwent coronary stent implantation increases the incidence of in-stent restenosis. Such a finding does not negate the known clinical benefits of ACE inhibitors, but it may deserve attention when a patient treated with ACE inhibitors becomes a candidate for stent implantation.

Comparison of frequency of insulin resistance after coronary stenting in patients with type 2 diabetes mellitus with versus without coronary restenosis.

The large incidence of restenosis after coronary angioplasty in diabetic patients renders this procedure less effective than in nondiabetics, and insulin resistance could be a relevant cause of restenosis in such patients. This study assessed insulin resistance and biologic markers of metabolic control in type 2 diabetic patients treated with stented angioplasty. Seventy-four patients were studied prospectively. Biochemical determinations, insulin tolerance test results, and the rate constant for plasma glucose disappearance (K(itt)%) were obtained. The angiographic outcome of angioplasty was assessed by quantitative coronary analysis at baseline and at 6 months in 64 patients (86%). Patients with restenosis had smaller minimum luminal diameters after stenting (2.8 +/- 0.5 vs 3.04 +/- 0.5 mm, p = 0.05), were more often hypertensive (97% vs 79%, p = 0.02) and treated with angiotensin-converting enzyme inhibitors (53% vs 23%, p = 0.02), and had smaller K(itt)% (2.9 +/- 1.6%/min vs 3.7 +/- 1.4%/min, p = 0.04) and larger titers of growth hormone (1.36 +/- 1.5 vs 0.68 +/- 0.6 ng/ml, p = 0.02).

Predicting cardiac events with Tl201 dipyridamole myocardial scintigraphy in renal transplant recipients.

BACKGROUND: Renal transplant recipients should be screened for coronary artery disease. The purpose of this study was to evaluate the usefulness of thallium-201 dipyridamole myocardial perfusion single-photon emission computed tomography (SPECT) to predict major cardiac events in these patients. METHODS AND RESULTS: Eighty-two consecutive patients (61 males) in hemodialysis (HD) treatment, awaiting renal transplantation, underwent dipyridamole Tl-201 SPECT for pretransplant risk stratification. SPECT semiquantitative analysis showed a normal perfusion pattern in 52 patients (group A) and fixed defects in 9 (group B). Reversible perfusion defects were found in 21 (group C). Cardiac death, myocadial infarction, and unstable angina were sought as cardiac events. During a follow-up lasting 28.3 +/- 21.6 months, three patients of group A died for a non-cardiac cause. In group C, six patients (28.6%) had a cadiac event: one had a non-q wave myocardial infarction after renal transplantation; five were admitted with unstable angina. No cardiac events were observed in groups A and B (p = 0.0001). SPECT semiquantitative analysis showed that a summed difference score > or = 3 significantly increased the risk of cardiac events (odds ratio 4.5, C.I. 2.5-8.1). CONCLUSION: Cardiac events were only observed in HD patients with Tl-201 SPECT dipyridamole reversible defects (group C). A normal pattern or a fixed defect in Tl-201 dipyridamole SPECT in HD patients identified a good long-term prognosis.

The usefulness of adenosine 99mTc tetrofosmin SPECT for the diagnosis of left anterior descending coronary artery disease in patients with chest pain and left bundle branch block.

OBJECTIVES: The aim of this study was to assess the usefulness of 99mTc tetrofosmin single photon emission computed tomography (SPECT) for the diagnosis of left anterior descending (LAD) coronary artery disease in 60 subjects with left bundle branch block (LBBB) admitted for chest pain. METHODS AND RESULTS: Adenosine 99mTc tetrofosmin SPECT, transthoracic echocardiogram and coronary angiography were performed, by protocol, in 60 non-infarcted consecutive patients. The mean left ventricular ejection fraction (LVEF) was 41.6 +/- 10.8%. A significant angiographic disease of the LAD was found in 15 (25%) patients. The sensitivity and the specificity of SPECT was found to be 75% and 89%, respectively; the positive predictive value (PPV) was 70% with a negative predictive value (NPV) of 91%. During the adenosine infusion the QRS complex width reduced from 131.3 +/- 29.6 ms to 125.5 +/- 28.6 ms in the patients without LAD involvement (P = 0.008) but remained unchanged in LAD disease patients (P = 0.1). Combining SPECT information and QRS analysis the sensitivity increased to 87% with unchanged specificity, the PPV was 74% and the NPV resulted 95%. At 2-year follow-up 13 (22%) patients experienced a cardiac event. Using Kaplan-Meier analysis, an LVEF of < or = 35% was the only predictor of cardiac events (P = 0.01, log-rank 6.2). CONCLUSIONS: A quarter of patients with LBBB complaining of chest pain had LAD coronary disease. The highly negative predictive value of adenosine SPECT could help in the exclusion of LAD disease, especially when the SPECT image is combined with the QRS analysis.