Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial.

BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing)  trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSION: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Conduction latency in left bundle branch pacing in heart failure patient.

Since the introduction of left bundle branch pacing (LBBP), a search for precise parameters confirming successful capture of conduction system was conducted. Most of the proposed electrocardiographic criteria refer to patients with narrow QRS complexes. We present a patient with heart failure in whom cardiac resynchronization was achieved using conduction system pacing. While measuring left ventricular activation time, an isoelectric interval of 74 ms between stimulus and R-wave appeared resulting in prolongation of V6 RWPT to 124 ms. Considering the immediate narrowing of QRS complexes following LBBP, the observed latency most probably reflects prolonged conduction time through the His-Purkinje system.

[Treatment with cardiac electronic implantable devices]. / Therapie mit kardialen elektronischen implantierbaren Devices.

Cardiac device therapy provides not only treatment options for bradyarrhythmia but also advanced treatment for heart failure and preventive measures against sudden cardiac death. In heart failure treatment it enables synergistic reverse remodelling and reduces pharmacological side effects. Cardiac resynchronization therapy (CRT) has revolutionized the treatment of reduced left ventricular ejection fraction (LVEF) and left bundle branch block by decreasing the mortality and morbidity with improvement of the quality of life and resilience. Conduction system pacing (CSP) as an alternative method of physiological stimulation can improve heart function and reduce the risk of pacemaker-induced cardiomyopathy. Leadless pacers and subcutaneous/extravascular defibrillators offer less invasive options with lower complication rates. The prevention of infections through preoperative and postoperative strategies enhances the safety of these therapies.

[New frontiers in pacing: from myocardial pacing to conduction system pacing]. / Nuove frontiere dell'elettrostimolazione: dal pacing del miocardio comune al pacing del sistema di conduzione.

For many years, cardiac pacing has been based on the stimulation of right ventricular common myocardium to correct diseases of the conduction system. The birth and the development of cardiac resynchronization have led to growing interest in the correction and prevention of pacing-induced dyssynchrony. Many observational studies and some randomized clinical trials have shown that conduction system pacing (CSP) can not only prevent pacing-induced dyssynchrony but can also correct proximal conduction system blocks, with reduction of QRS duration and with equal or greater effectiveness than biventricular pacing. Based on these results, many Italian electrophysiologists have changed the stimulation target from the right ventricular common myocardium to CSP. The two techniques with greater clinical impact are the His bundle stimulation and the left bundle branch pacing. The latter, in particular, because of its easier implantation technique and better electric parameters, is spreading like wildfire and is representing a real revolution in the cardiac pacing field. However, despite the growing amount of data, until now, the European Society of Cardiology guidelines give a very limited role to CSP.

Implication of geriatric nutritional risk index on treatment response and long-term prognosis in patients with cardiac resynchronization therapy.

PURPOSE: Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). METHODS: Patients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. RESULTS: Totally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52-67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04-1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93-0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95-0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). CONCLUSION: Higher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.

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.

Enhancing cardiac pacing strategies: a review of conduction system pacing compared with right and biventricular pacing and their influence on myocardial function.

Traditional right ventricular pacing (RVP) has been linked to the deterioration of both left ventricular diastolic and systolic function. This worsening often culminates in elevated rates of hospitalization due to heart failure, an increased risk of atrial fibrillation, and increased morbidity. While biventricular pacing (BVP) has demonstrated clinical and echocardiographic improvements in patients afflicted with heart failure and left bundle branch block, it has also encountered significant challenges such as a notable portion of non-responders and procedural failures attributed to anatomical complexities. In recent times, the interest has shifted towards conduction system pacing, initially, His bundle pacing, and more recently, left bundle branch area pacing, which are seen as promising alternatives to established methods. In contrast to other approaches, conduction system pacing offers the advantage of fostering more physiological and harmonized ventricular activation by directly stimulating the His-Purkinje network. This direct pacing results in a more synchronized systolic and diastolic function of the left ventricle compared with RVP and BVP. Of particular note is the capacity of conduction system pacing to yield a shorter QRS, conserve left ventricular ejection fraction, and reduce rates of mitral and tricuspid regurgitation when compared with RVP. The efficacy of conduction system pacing has also been found to have better clinical and echocardiographic improvement than BVP in patients requiring cardiac resynchronization. This review will delve into myocardial function in conduction system pacing compared with that in RVP and BVP.

Different methods of 3D QRS area calculation from vectorcardiographic X, Y, and Z Leads.

3DQRSarea is a strong marker for cardiac resynchronization therapy and can be obtained by taking the (i) summation or the (ii) difference of the areas subtended by positive and negative deflections in X, Y, Z vectorcardiographic electrocardiogram (ECG) leads. We correlated both methods with the instantaneous-absolute-3D-voltage-time-integral (VTIQRS-3D). 3DQRSarea consistently underestimated the VTIQRS -3D, but the summation method was a closer and more reliable approximation. The dissimilarity was less apparent in left bundle branch block (r2 summation .996 vs. difference .972) and biventricular paced ECGs (r2 .996 vs. .957) but was more apparent in normal ECGs (r2 .988 vs. .653).

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.