Economic Considerations of Cardiovascular Implantable Electronic Devices for The Treatment of Heart Failure.

PURPOSE OF REVIEW: Heart failure (HF) is a major public health problem worldwide, affecting more than 64 million people [1]. The complex and severe nature of HF presents challenges in providing cost-effective care as patients often require multiple hospitalizations and treatments. This review of relevant studies with focus on the last 10 years summarizes the health and economic implications of various HF treatment options in Europe and beyond. Although the main cost drivers in HF treatment are clinical (re)admission and decompensation of HF, an assessment of the economic impacts of various other device therapy options for HF care are included in this review. This includes: cardiovascular implantable electronic devices (CIEDs) such as cardiac-resynchronisation-therapy devices that include pacemaking (CRT-P), cardiac-resynchronisation-therapy devices that include defibrillation (CRT-D), implantable cardioverter/defibrillators (ICDs) and various types of pacemakers. The impact of (semi)automated (tele)monitoring as a relevant factor for increasing both the quality and economic impact of care is also taken into consideration. Quality of life adjusted life years (QALYs) are used in the overall context as a composite metric reflecting quantity and quality of life as a standardized measurement of incremental cost-effectiveness ratios (ICER) of different device-based HF interventions. RECENT FINDINGS: In terms of the total cost of different devices, CRT-Ds were found in several studies to be more expensive than all other devices in regards to runtime and maintenance costs including (re)implantation. In the case of CRT combined with an implantable cardioverter-defibrillator (CRT-D) versus ICD alone, CRT-D was found to be the most cost-effective treatment in research work over the past 10 years. Further comparison between CRT-D vs. CRT-P does not show an economic advantage of CRT-D as a minority of patients require shock therapy. Furthermore, a positive health economic effect and higher survival rate is seen in CRT-P full ventricular stimulation vs. right heart only stimulation. Telemedical care has been found to provide a positive health economic impact for selected patient groups-even reducing patient mortality. For heart failure both in ICD and CRT-D subgroups the given telemonitoring benefit seems to be greater in higher-risk populations with a worse HF prognosis. In patients with HF, all CIED therapies are in the range of commonly accepted cost-effectiveness. QALY and ICER calculations provide a more nuanced understanding of the economic impact these therapies create in the healthcare landscape. For severe cases of HF, CRT-D with telemedical care seems to be the better option from a health economic standpoint, as therapy is more expensive, but costs per QALY range below the commonly accepted threshold.

Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients.

BACKGROUND: We analyzed the influence of the QRS duration (QRSd) to LV end-diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size. HYPOTHESIS: We proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate. METHODS: We enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non-LBBB and QRSd ≥150 milliseconds (n = 30) and non-LBBB and QRSd of 120-149 milliseconds (n = 24). RESULTS: Over a mean follow-up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all-cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024). CONCLUSION: Advanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small-body-size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT.

Outcomes of tricuspid regurgitation after lead extraction.

INTRODUCTION: Transvenous leads have been implicated in tricuspid valve (TV) dysfunction, but limited data are available regarding the effect of extracting leads across the TV on valve regurgitation. The aim of this study is to quantify tricuspid regurgitation (TR) before and after lead extraction and identify predictors of worsening TR. METHODS: We studied 321 patients who had echocardiographic data before and after lead extraction. TR was graded on a scale (0 = none/trivial, 1 = mild, 2 = moderate, 3 = severe). A change of >1 grade following extraction was considered significant. RESULTS: A total of 321 patients underwent extraction of a total of 338 leads across the TV (1.05 ± 0.31 leads across the TV per patient). There was no significant difference on average TR grade pre- and postextraction (1.18 ± 0.91 vs. 1.15 ± 0.87; p = 0.79). TR severity increased after extraction in 84 patients, but was classified as significantly worse (i.e., >1 grade change in severity) in only 8 patients (2.5%). Use of laser lead extraction was associated with a higher rate of worsening TR postextraction (44.0% vs. 31.6%, p = 0.04). CONCLUSION: In our single-center analysis, extraction of leads across the TV did not significantly affect the extent of TR in most patients. Laser lead extraction was associated with a higher rate of worsening TR after extraction.

Determination of sensed and paced atrial-ventricular delay in cardiac resynchronization therapy.

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.

Cardiac implantable electronic devices and bloodstream infections: management and outcomes.

BACKGROUND AND AIMS: Bloodstream infection (BSI) of any cause may lead to device infection in cardiac implantable electronic device (CIED) patients. Aiming for a better understanding of the diagnostic approach, treatment, and outcome, patients with an implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy and defibrillator (CRT-D) hospitalized with BSI were investigated. METHODS: This is a single-centre, retrospective, cohort analysis including consecutive ICD/CRT-D patients implanted between 2012 and 2021. These patients were screened against a list of all hospitalized patients having positive blood cultures consistent with diagnosed infection in any department of a local public hospital. RESULTS: The total cohort consisted of 515 patients. Over a median follow-up of 59 months (interquartile range 31-87 months), there were 47 BSI episodes in 36 patients. The majority of patients with BSI (92%) was admitted to non-cardiology units, and in 25 episodes (53%), no cardiac imaging was performed. Nearly all patients (85%) were treated with short-term antibiotics, whereas chronic antibiotic suppression therapy (n = 4) and system extraction (n = 3) were less frequent. Patients with BSI had a nearly seven-fold higher rate (hazard ratio 6.7, 95% confidence interval 3.9-11.2; P < .001) of all-cause mortality. CONCLUSIONS: Diagnostic workup of defibrillator patients with BSI admitted to a non-cardiology unit is often insufficient to characterize lead-related endocarditis. The high mortality rate in these patients with BSI may relate to underdiagnosis and consequently late/absence of system removal. Efforts to increase an interdisciplinary approach and greater use of cardiac imaging are necessary for timely diagnosis and adequate treatment.

Efficacy and safety of novel left ventricular pacing leads: 1-year analysis of the NAVIGATOR trial.

OBJECTIVES: Assess safety and performance of novel quadripolar preshaped left ventricular (LV) leads: NAVIGO 4LV 2D ('S shaped') and NAVIGO 4LV ARC ('U shaped'). METHODS: Patients indicated for cardiac resynchronisation therapy were enrolled in a multicentre, prospective, controlled study (NAVIGATOR, NCT03279484). Patients were implanted with either a NAVIGO 4LV 2D or ARC lead, and assessed at 10 weeks, 6, 12 and 24 months post-implant. Co-primary safety and performance endpoints were assessed at 10 weeks. Safety endpoint was the patients' rate free from lead-related complications. Performance endpoint was the rate of patients with successful lead performance, defined as LV pacing threshold ≤2.5 V at 0.5 ms on at least one pacing vector, and the absence of phrenic nerve stimulation at the final programmed configuration. Lead-related complications and electrical parameters were monitored throughout study. RESULTS: A NAVIGO 4LV lead was successfully implanted in 211 out of 217 patients (97.2%). The safety endpoint was met, with 100% and 96.1% of patients free from complications for NAVIGO 4LV 2D and ARC, respectively. The performance endpoint was met with 98.1% and 98.9% of patients with a successful lead performance for NAVIGO 4LV 2D and ARC, respectively. Over 12 months, the global complication-free rate for both leads was 97.1% (95% CI: 93.71% to 98.70%), with a mean pacing capture threshold of 1.23 V±0.73 V and a mean impedance of 951 Ω±300.1 Ω. CONCLUSION: A high implantation success rate and low complication rate was reported for the novel NAVIGO 4LV 2D and ARC leads, along with successful performance up to 12 months.

Association between QRS shortening and mortality after cardiac resynchronization therapy: Results from the DANISH study.

BACKGROUND: Changes in QRS duration (∆QRS) are often used in the clinical setting to evaluate the effect of cardiac resynchronization therapy (CRT), although an association between ∆QRS and outcomes is not firmly established. We aimed to assess the association between mortality and ∆QRS after CRT in patients from the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-Ischemic Systolic Heart Failure on Mortality) study. METHODS: We included all patients from DANISH who received a CRT device and had available QRS duration data before and after implantation. Cox proportional hazards models were used to assess associations between ∆QRS (post-CRT QRS minus pre-CRT QRS) and mortality. RESULTS: Complete data were available in 572 patients. Median baseline QRS duration was 160 ms (IQR [146;180]). Post-CRT QRS was recorded a median of 48 days (IQR [33;86]) after implantation, and the median ∆QRS was -14 ms (IQR [-38;-3]). During a median follow-up of 4.1 years (IQR [2.5;5.8]), 106 patients died. In crude Cox regression, all-cause mortality was reduced by 6% per 10 ms shortening of QRS (HR 0.94; CI: 0.88-1.00, p = 0.04). The effect did not remain significant after multivariable adjustment (HR 1.01, CI: 0.93-1.10, p = 0.77). Further, no association was found between ∆QRS and improvement of New York Heart Association functional class at 6 months (OR 1.03, CI: 0.96-1.10, p = 0.42). CONCLUSION: In a large cohort of patients with non-ischemic cardiomyopathy, reduction of QRS duration after CRT was not associated with changes in mortality during long-term follow-up.

Left ventricular lead placement in cardiac resynchronization therapy: Current data and potential explanations for the lack of benefit.

The present article reviews the literature on image-guided cardiac resynchronization therapy (CRT) studies. Improved outcome to CRT has been associated with the placement of a left ventricular (LV) lead in the latest activated segment free from scar. The majority of randomized controlled trials investigating guided LV lead implantation did not show superiority over conventional implantation approaches. Several factors may contribute to this paradoxical observation, including inclusion criteria favoring patients with left bundle branch block who already respond well to conventional anatomical LV lead implantation, differences in activation wavefronts during simultaneous right ventricular and LV pacing, incorrect definition of target regions, and limitations in coronary venous anatomy that prevent access to target regions that are detected by imaging. It is imperative that exclusion of patients lacking access to target regions from these studies would lead to larger benefit of image-guided CRT.

Cardiac resynchronization using fusion pacing during exercise.

INTRODUCTION: Fusion pacing requires correct timing of left ventricular pacing to right ventricular activation, although it is unclear whether this is maintained when atrioventricular (AV) conduction changes during exercise. We used cardiopulmonary exercise testing (CPET) to compare cardiac resynchronization therapy (CRT) using fusion pacing or fixed AV delays (AVD). METHODS: Patients 6 months post-CRT implant with PR intervals < 250 ms performed two CPET tests, using either the SyncAV™ algorithm or fixed AVD of 120 ms in a double-blinded, randomized, crossover study. All other programming was optimized to produce the narrowest QRS duration (QRSd) possible. RESULTS: Twenty patients (11 male, age 71 [65-77] years) were recruited. Fixed AVD and fusion programming resulted in similar narrowing of QRSd from intrinsic rhythm at rest (p = .85). Overall, there was no difference in peak oxygen consumption (V̇O2 PEAK , p = .19), oxygen consumption at anaerobic threshold (VT1, p = .42), or in the time to reach either V̇O2 PEAK (p = .81) or VT1 (p = .39). The BORG rating of perceived exertion was similar between groups. CPET performance was also analyzed comparing whichever programming gave the narrowest QRSd at rest (119 [96-136] vs. 134 [119-142] ms, p < .01). QRSd during exercise (p = .03), peak O2 pulse (mL/beat, a surrogate of stroke volume, p = .03), and cardiac efficiency (watts/mL/kg/min, p = .04) were significantly improved. CONCLUSION: Fusion pacing is maintained during exercise without impairing exercise capacity compared with fixed AVD. However, using whichever algorithm gives the narrowest QRSd at rest is associated with a narrower QRSd during exercise, higher peak stroke volume, and improved cardiac efficiency.

Utilization of the remote monitoring of cardiac implantable electronic devices in a diverse demographic cohort: Insights from a single-center observation.

BACKGROUND: Despite its clinical benefits, patient compliance to remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) varies and remains under-studied in diverse populations. OBJECTIVE: We sought to evaluate RM compliance, clinical outcomes, and identify demographic and socioeconomic factors affecting RM in a diverse urban population in New York. METHODS: This retrospective cohort study included patients enrolled in CIED RM at Montefiore Medical Center between December 2017 and May 2022. RM compliance was defined as the percentage of days compliant to RM transmission divided by the total prescribed days of RM. Patients were censored when they were lost to follow-up or at the time of death. The cohorts were categorized into low (≤30%), intermediate (31-69%), and high (≥70%) RM compliance groups. Statistical analyses were conducted accordingly. RESULTS: Among 853 patients, median RM compliance was 55%. Age inversely affected compliance (p < .001), and high compliance was associated with guideline-directed medical therapy (GDMT) usage and implantable cardioverter defibrillator (ICD)/cardiac resynchronization defibrillator (CRTD) devices. The low-compliance group had a higher mortality rate and fewer regular clinic visits (p < .001) than high-compliance group. Socioeconomic factors did not significantly impact compliance, while Asians showed higher compliance compared with Whites (OR 3.67; 95% CI 1.08-12.43; p = .04). Technical issues were the main reason for non-compliance. CONCLUSION: We observed suboptimal compliance to RM, which occurred most frequently in older patients. Clinic visit compliance, optimal medical therapy, and lower mortality were associated with higher compliance, whereas insufficient understanding of RM usage was the chief barrier to compliance.

The Micra Transcatheter Pacing System: past, present and the future.

Leadless permanent pacemakers represent an important innovation in cardiac device developments. Although transvenous permanent pacemakers have become indispensable in managing bradyarrhythmia and saving numerous lives, the use of transvenous systems comes with notable risks tied to intravascular leads and subcutaneous pockets. This drawback has spurred the creation of leadless cardiac pacemakers. Within this analysis, we compile existing clinical literature and proceed to evaluate the efficacy and safety of the Micra Transcatheter Pacing System. We also delve into the protocols for addressing a malfunctioning or end-of-life Micra as well as device extraction. Lastly, we explore prospects in this domain, such as the emergence of entirely leadless cardiac resynchronization therapy-defibrillator devices.

What is Micra? Micra is a type of leadless pacemaker. Leadless pacemakers are a relatively recent breakthrough in medical science. Regular pacemakers have wires that run into the heart and a battery tucked under the skin. They are crucial for treating slow heartbeats. However, they carry risks tied to the wire or batteries. The Micra is placed in the heart using a tiny cut near the groin. There is no wire left behind in the body. Using Micra can avoid the potential complications linked to regular pacemakers. Is Micra safe & effective? Scientists have found that Micra is effective in patients with appropriate heart rhythm issues. There seem to be fewer complications compared to the regular pacemakers. What does the future hold for Micra? There are concerns about what to do when the battery runs out. The technology and batteries in Micra are getting better. It is expected Micra will be used even more in the future.

Risk prediction of inappropriate implantable cardioverter-defibrillator therapy using machine learning.

We aimed to develop machine learning-based predictive models for identifying inappropriate implantable cardioverter-defibrillator (ICD) therapy. Our study included 182 consecutive cases (average age 62.2 ± 4.5 years, 169 men) and employed 14 non-deep learning models for prediction (hold-out method). These models utilized selected electrocardiogram parameters and clinical features collected after ICD implantation. From the feature importance analysis of the best ML model, we established easily calculable scores. Among the patients, 25 (13.7%) experienced inappropriate therapy, and we identified 16 significant predictors. Using recursive feature elimination with cross-validation, we reduced the features to six with high feature importance: history of atrial arrhythmia (Atr-arrhythm), ischemic cardiomyopathy (ICM), absence of diabetes mellitus (DM), lack of cardiac resynchronization therapy (CRT), V3 ST level at J point (V3 STJ), and V5 R-wave amplitudes (V5R amp). The extra-trees classifier yielded the highest area under receiver operating characteristics curve (AUROC; 0.869 on test data). Thus, the Cardi35 score was defined as [+ 5.5*Atr-arrhythm - 1.5*CRT + 1.0*V3STJ + 1.0*V5R - 1.0*ICM - 0.5*DM], which demonstrated a hazard ratio of 1.62 (P < 0.001). A cut-off value of the score + 5.5 showed high AUROC (0.826). The ML approach can yield a robust prediction model, and the Cardi35 score was a convenient predictor for inappropriate therapy.

Imaging in patients with cardiovascular implantable electronic devices: part 2-imaging after device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

Cardiac implantable electronic devices (CIEDs) improve quality of life and prolong survival, but there are additional considerations for cardiovascular imaging after implantation-both for standard indications and for diagnosing and guiding management of device-related complications. This clinical consensus statement (part 2) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients after implantation of conventional pacemakers, cardioverter defibrillators, and cardiac resynchronization therapy (CRT) devices. The document summarizes the existing evidence regarding the role and optimal use of various cardiac imaging modalities in patients with suspected CIED-related complications and also discusses CRT optimization, the safety of magnetic resonance imaging in CIED carriers, and describes the role of chest radiography in assessing CIED type, position, and complications. The role of imaging before and during CIED implantation is discussed in a companion document (part 1).

Indications for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Heart failure in patients with congenital heart disease (CHD) stems from unique causes compared with the elderly. Patients with CHD face structural abnormalities and malformations present from birth, leading to altered cardiac function and potential complications. In contrast, elderly individuals primarily experience heart failure due to age-related changes and underlying cardiovascular conditions. Cardiac resynchronization therapy (CRT) can benefit patients with CHD, although it presents numerous challenges. The complexities of CHD anatomy and limited access to appropriate venous sites for lead placement make CRT implantation demanding.

Techniques for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Cardiac resynchronization therapy (CRT) for congenital heart disease has shown promising suucess as an adjunct to medical therapy for heart failure. While cardiac conduction defects and need for ventricular pacing are common in congential heart disease, CRT indications, techniques and long term outcomes have not been well establaished. This is a review of the techniques nad short term outcomes of CRT for the following complex congenital heart disease conditions: single ventricle physiology, systemic right ventricle, and the subpulmonic right ventricle.