Benefits of upgrading right ventricular to biventricular pacing in heart failure patients with atrial fibrillation.

AIMS: Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm. METHODS AND RESULTS: Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26-7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02-0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07-0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16-0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference -49.21 mL; 95% CI -69.10 to -29.32; P < 0.001; interaction P = 0.21). CONCLUSION: In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR.

Benefits of upgrading right ventricular to biventricular pacing in heart failure patients with atrial fibrillation.

AIMS: Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm. METHODS AND RESULTS: Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26-7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02-0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07-0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16-0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference -49.21 mL; 95% CI -69.10 to -29.32; P < 0.001; interaction P = 0.21). CONCLUSION: In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

Clinical Impact of Digitalis Therapy in a Large Multicenter Cohort of CRT-Recipients.

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Key influences of VDD (DX) ICD selection: Results from a prospective, national survey.

BACKGROUND: To preserve the benefit of atrial sensing without the implantation of an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD) has been developed. The purpose of this nationwide survey was to provide an overview of the current key influences of device selection focusing on DX ICD and to test the applicability of a previously published decision-making flowchart of ICD-type selection. METHODS: An online questionnaire was sent to all implanting centers in Hungary. Eleven centers reported data from 361 DX ICD and 10 CRT-DX systems implantations between February 2021 and May 2023. RESULTS: The most important influencing clinical factors indicated by the participating doctors were elevated risk of atrial fibrillation (AF)/stroke (56%), risk of sinus/supraventricular tachycardias (SVT) (42%), and a potential need for CRT upgrade in the future (36%). The DX ICD was considered in the majority of cases instead of the VVI system (87%), and only in a small proportion instead of a DDD ICD (13%). 60% of the patients with DX ICDs were also included into remote monitoring-based follow-up. In 83% of the cases, good (>2 mV) or excellent (>5) atrial signal amplitude was recorded within 6 weeks after the implantation. CONCLUSION: In the current national survey, the most important influencing factors indicated by the implanters for selecting a DX ICD were the elevated risk of stroke or sinus/SVT and a potential need for CRT upgrade in the future. These findings support the use of a previously published decision-making flowchart.

The effect of kidney function on guideline-directed medical therapy implementation and prognosis in heart failure with reduced ejection fraction.

BACKGROUND: Kidney dysfunction (KD) is a main limiting factor of applying guideline-directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). HYPOTHESIS: We aimed to assess the success of optimization, long-term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + ßB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. METHODS: The data of 247 real-world, consecutive patients were analyzed who were hospitalized in 2019-2021 for HFrEF and then were followed-up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60-89, 45-59, 30-44, <30 mL/min/1.73 m2 ). Moreover, 1-year all-cause mortality and rehospitalization rates in KD subgroups were investigated. RESULTS: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p < .05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p < .05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One-year all-cause mortality (14%, 15%, 16%, 33%, 48%, p < .001), the ratio of all-cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p = .028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p = .001) were significantly higher in more severe KD categories. CONCLUSIONS: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up-titration of GDMT.

The Impact of Specialised Heart Failure Outpatient Care on the Long-Term Application of Guideline-Directed Medical Therapy and on Prognosis in Heart Failure with Reduced Ejection Fraction.

(1) Background: Besides the use of guideline-directed medical therapy (GDMT), multidisciplinary heart failure (HF) outpatient care (HFOC) is of strategic importance in HFrEF. (2) Methods: Data from 257 hospitalised HFrEF patients between 2019 and 2021 were retrospectively analysed. Application and target doses of GDMT were compared between HFOC and non-HFOC patients at discharge and at 1 year. 1-year all-cause mortality (ACM) and rehospitalisation (ACH) rates were compared using the Cox proportional hazard model. The effect of HFOC on GDMT and on prognosis after propensity score matching (PSM) of 168 patients and the independent predictors of 1-year ACM and ACH were also evaluated. (3) Results: At 1 year, the application of RASi, MRA and triple therapy (TT: RASi + ßB + MRA) was higher (p < 0.05) in the HFOC group, as was the proportion of target doses of ARNI, ßB, MRA and TT. After PSM, the composite of 1-year ACM or ACH was more favourable with HFOC (propensity-adjusted HR = 0.625, 95% CI = 0.401-0.974, p = 0.038). Independent predictors of 1-year ACM were age, systolic blood pressure, application of TT and HFOC, while 1-year ACH was influenced by the application of TT. (4) Conclusions: HFOC may positively impact GDMT use and prognosis in HFrEF even within the first year of its initiation.

[The effect of kidney function on the optimization of medical therapy and on mortality in heart failure with reduced ejection fraction]. / A vesefunkció hatása a gyógyszeres terápia optimalizálására és a mortalitásra csökkent ejekciós frakciójú szívelégtelenségben.

INTRODUCTION: Renal dysfunction is a main limiting factor of applying and up-titrating guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: Our retrospective monocentric observational study aimed to analyse the application ratio of combined neurohormonal antagonist therapy (RASi: ACEI/ARB/ARNI + ßB + MRA) and 12-month all-cause mortality differences in terms of renal dysfunction among HFrEF patients hospitalized for heart failure. METHOD: We retrospectively analysed the cohort of consecutive HFrEF patients, hospitalized at the Heart Failure Unit of our tertiary cardiological centre in 2019-2021. The application ratio of discharge triple therapy (TT) in five groups established on admission eGFR parameters, representing severity of renal dysfunction (eGFR≥90, eGFR = 60-89, eGFR = 45-59, eGFR = 30-44, eGFR<30 ml/min/1.73 m2) was investigated with chi-square test, while 12-month mortality differences were analysed with Kaplan-Meier method and log-rank test. RESULTS: 257 patients were included. Median eGFR was 57 (39-75) ml/min/1.73 m2, 54% of patients had eGFR<60 ml/min/1.73 m2. The proportion of patients in eGFR≥90, 60-89, 45-59, 30-44, <30 ml/min/1.73 m2 subgroups was 12%, 34%, 18%, 21%, 15%, respectively. 2% of patients were on dialysis. Even though the application rate of TT was notably high (77%) in the total cohort, more severe renal dysfunction led to a significantly lower implementation rate of TT (94%, 86%, 91%, 70%, 34%; p<0.0001): the application rate of RASi (100%, 98%, 96%, 89%, 50%, p<0.0001), ßB (94%, 88%, 96%, 79%, 68%; p = 0.003) and MRA therapy (97%, 99%, 98%, 94%, 82%; p = 0.001) differed significantly. 12-month all-cause mortality was 23% in the whole cohort. Mortality rates were higher in more severe renal dysfunction (3%, 15%, 22%, 31%, 46%; p<0.0001). CONCLUSION: Even though the proportion of patients on TT in the whole cohort was remarkably high, renal dysfunction led to a significantly lower application ratio of TT, associating with worse survival. Our results highlight that despite renal dysfunction the application of HFrEF cornerstone pharmacotherapy is essential. Orv Hetil. 2023; 164(35): 1387-1396.

Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis.

AIMS: This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades. METHODS AND RESULTS: PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76-0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80-0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79-1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96-1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time. CONCLUSION: The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.

Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial.

BACKGROUND AND AIMS: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. METHODS: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. RESULTS: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. CONCLUSIONS: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.

Editorial: Developments in cardiac implantable electronic device therapy: how can we improve clinical implementation?

CIED, cardiac implantable electronic devices; CRT, cardiac resynchronization therapy; CRT-D, cardiac resynchronization therapy defibrillator; EA, electroanatomical; ICD, implantable cardioverter defibrillator; LBB, left bundle branch; LBBAP, left bundle branch area pacing; LV, left ventricular; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; MRI, cardiac magnetic resonance imaging; S-ICD, subcutaneous defibrillator.

The Optimization of Guideline-Directed Medical Therapy during Hospitalization among Patients with Heart Failure with Reduced Ejection Fraction in Daily Clinical Practice.

INTRODUCTION: Hospitalization due to heart failure (HF) progression is associated with poor prognosis. This highlights the role of the implementation of guideline-directed medical therapy (GDMT) in improving the morbidity and mortality of patients with heart failure with reduced ejection fraction (HFrEF). There are limited data about the intrahospital applicability of GDMT in real-world circumstances. We aimed to assess retrospectively the use of cornerstone GDMT including RASi (ACEI/ARB/ARNI), ßB, MRA, and SGLT2i treatment in a consecutive real-world HFrEF patient population admitted with signs and symptoms of HF to the HF Unit of a Hungarian tertiary cardiac center between 2019 and 2021. The independent predictors of therapy optimization and the applicability of new HFrEF medication (ARNI, SGLT2i, vericiguat) were also investigated. METHODS: Statistical comparison of admission and discharge medication was accomplished with Fisher's exact test. The independent predictors of the introduction of triple therapy (RASi + ßB + MRA) were analyzed using univariate and multivariate logistic regression. The proportion of patients eligible for vericiguat based on the inclusion and exclusion criteria of the VICTORIA trial was also investigated, as well as the number of patients suitable for ARNI and SGLT2i, taking into account the contraindications of application contained in the ESC 2021 HF Guidelines. RESULTS: 238 patients were included. During hospitalization, the use of RASi (69% vs. 89%) (ACEI/ARBs [58% vs. 70%], ARNI [10% vs. 19%]), ßBs (69% vs. 85%), and MRAs (61% vs. 95%) increased significantly (p < 0.05) compared to at admission, and the use of SGLT2i (3% vs. 11%) also rose (p = 0.0005). The application ratio of triple (RASi + ßB + MRA; 43% vs. 77%) and quadruple (RASi + ßB + MRA + SGLT2i; 2% vs. 11%) therapy increased as well (p < 0.0001). The independent predictors of discharge application of triple therapy revealed through multivariate logistic regression analysis were age, duration of hospitalization, eGFR, NTproBNP, and presence of diabetes mellitus. Sixty-eight percent of the cohort would have been suitable for vericiguat, 83% for ARNI, and 84% for SGLT2i. CONCLUSION: High rates of application of disease-modifying drugs are achievable among hospitalized HFrEF patients in severe clinical condition; thus, awareness of the need for their initiation must be raised.

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

AIMS: The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies. METHODS AND RESULTS: This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%). CONCLUSION: When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02270840.

Association between electrical and mechanical remodeling after cardiac resynchronization therapy: systematic review and meta-analysis of observational studies.

Cardiac resynchronization therapy (CRT) may improve not only impaired left ventricular contractility but can also induce reverse remodeling of native conduction system. Measurement of intrinsic QRS complex width during follow-up is the simplest method to assess reverse electrical remodeling (RER). We aimed to provide a literature review and meta-analysis on incidence and impact of RER and its association with mechanical remodeling. A systematic review and random-effect meta-analysis of studies reporting data on RER was performed. A total of 16 studies were included in this meta-analysis with 930 patients undergoing CRT (mean age 64.0 years, 64.1% males). The weighted mean incidence of RER was 42%. Reverse mechanical remodeling assessed by echocardiography was more frequently observed in patients with RER compared to patients without RER (75.7% vs. 46.6%; odds ratio [OR] 3.7, 95% confidence interval [CI] 2.24-6.09, p < 0.01). Mechanical responders had a mean iQRS shortening of 7.7 ms, while mechanical non-responders experienced a mean widening of iQRS by 5.2 ms (p < 0.01). Clinical improvement was more frequent in patients with RER vs. patients without RER (82.9% vs. 49.0%; OR 5.26; 95% CI 2.92-9.48; p < 0.01). No significant difference in all-cause mortality between patients with and without RER was found. Mean difference between baseline intrinsic QRS and post-implantation paced QRS was significant in patients with later RER (21.2 ms, 95% CI 9.4-32.9, p < 0.01), but not in patients without RER (6.6 ms, 95% CI -2.2-15.4, p = 0.14). Gender, initial left bundle block morphology and heart failure etiology were found not to be predictive for RER. Our meta-analysis demonstrates that shortening of iQRS duration is a common finding during follow-up of patients undergoing CRT and is associated with mechanical reverse remodeling and clinical improvement. Clinical Trial Registration: Prospero Database-CRD42021253336.

Rationale and feasibility of the atrioventricular single-lead ICD systems with a floating atrial dipole (DX) in clinical practice.

Cardiac implantable electronic devices establish proper therapy for the prevention of sudden cardiac death, significantly reducing the morbidity and mortality of patients with arrhythmias and heart failure. It is well-known that the number of electrodes increases the risk of complications. To preserve the benefit of atrial sensing without the need to implant an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD lead) has been developed. Besides all of the potential benefits, the necessity of a reliable and stable atrial sensing via the floating dipole could be the main concern against the use of this lead type. In the current generation of DX devices, the specially filtered atrial signal seems to be high enough and stable over time, which is crucial in the early detection of atrial arrhythmias, discrimination between different forms of tachycardias in order to prevent inappropriate ICD therapy, and achieving an optimal atrioventricular and interventricular synchrony in patients with a two-lead CRT-DX system. The present review summarizes the benefits and potential drawbacks of the DX ICD systems based on the available literature, furthermore, proposes an evidence-based algorithm of ICD type selection.

Multiparameter diagnostic sensor measurements during clinically stable periods and worsening heart failure in ambulatory patients.

AIMS: This study aims to characterize the range of implantable device-based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events. METHODS AND RESULTS: The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT-D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT-proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P < 0.001), thoracic impedance (45.66 ± 8.78 Ohm vs. 50.33 ± 8.43 Ohm, P < 0.001), respiratory rate (19.09 ± 3.10 br/min vs. 17.66 ± 2.39 br/min, P = 0.002), night time heart rate (73.39 ± 8.36 b.p.m. vs. 69.56 ± 8.09 b.p.m., P = 0.001), patient activity (1.69 ± 1.84 h vs. 2.56 ± 2.20 h, P = 0.006), and HeartLogic index (11.07 ± 12.14 vs. 5.31 ± 5.13, P = 0.001). Sensor parameters measured worsening status leading up to HF events with recovery of values following treatment. CONCLUSIONS: Device-based physiologic sensors not only revealed progressive worsening leading up to HF events but also differentiated patients at increased risk of HF events when presumed to be clinically stable.

The impact of serum concentration-guided digoxin therapy on mortality of heart failure patients: A long-term follow-up, propensity-matched cohort study.

BACKGROUND: Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC-guided. AIM: To assess the impact of SDC-guided digoxin therapy on mortality in HFrEF patients. METHODS: Data of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC-guided (target SDC: 0.5-0.9 ng/mL). All-cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM). RESULTS: After 7.1 ± 4.7 years follow-up period (FUP) all-cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity-adjusted HR = 1.430; 95% CI = 1.134-1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all-cause mortality (HR = 1.750; 95% CI = 1.257-2.436, P = .001 and HR = 1.687; 95% CI = 1.153-2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827-1.570, P = .426), compared to digoxin nonusers. CONCLUSIONS: According to our propensity-matched analysis, SDC-guided digoxin therapy was associated with increased all-cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.

Novel two-lead cardiac resynchronization therapy system provides equivalent CRT responses with less complications than a conventional three-lead system: Results from the QP ExCELs lead registry.

INTRODUCTION: The novel two-lead cardiac resynchronization therapy (CRT)-DX system utilizes a floating atrial dipole on the implantable cardioverter-defibrillator lead, and when implanted with a left ventricular (LV) lead, offers a two-lead CRT system with AV synchrony. This study compared complication rates and CRT response among subjects implanted with a two-lead CRT-DX system to those subjects implanted with a standard three-lead CRT-D system. METHODS AND RESULTS: A total of 240 subjects from the Sentus QP-Extended CRT Evaluation with Quadripolar Left Ventricular Leads postapproval study were selected to identify 120 matched pairs based on similar demographic characteristics using a Greedy algorithm. The complication-free rate was evaluated as the primary endpoint. All-cause mortality, heart failure hospitalizations, device diagnostic data, New York Heart Association (NYHA) class improvement, and defibrillator therapy were evaluated from clinical data, in-office interrogations, and remote monitoring throughout the follow-up period. Complication-free survival favored the CRT-DX group with 92.5% without a major complication compared to 85.0% in the CRT-D cohort (P = .0495; 95% confidence interval: 0.1%-14.9%) over a mean follow-up of 1.3 and 1.4 years, respectively. Incidence of all-cause mortality, heart failure hospitalizations, NYHA changes at 6 months postimplant, and percent of LV pacing during CRT therapy were similar in both device cohorts. Inappropriate shocks were more frequent in the CRT-D cohort with 5.8% of subjects receiving an inappropriate shock vs 0.8% in the CRT-DX cohort. CONCLUSION: The results of this subanalysis demonstrate that the CRT-DX system can provide similar CRT responses and significantly fewer complications when compared to a similar cohort with a conventional three-lead CRT-D system.

Needle aspiration for treating iatrogenic pneumothorax after cardiac electronic device implantation: a pilot study.

PURPOSE: Pneumothorax (PTX) following cardiac implantable electronic device procedures is traditionally treated with chest tube drainage (CTD). We hypothesized that, in a subset of patients, the less invasive needle aspiration (NA) may also be effective. We compared the strategy of primary NA with that of primary CTD in a single-center observational study. METHODS: Of the 970 procedures with subclavian venous access between January 2016 and June 2018, 23 patients had PTX requiring intervention. Beginning with March 2017, the traditional primary CTD (9 cases) has been replaced by the "NA first" strategy (14 patients). Outcome measures were procedural success rate and duration of hospitalization evaluated both as time to event (log-rank test) and as a discrete variable (Wilcoxon-Mann-Whitney test). RESULTS: Needle aspiration was successful in 8/14 (57.1%) of the cases (95% CI 28.9-82.3%), whereas PTX resolved in all patients after CTD was 9/9 (100%, 95% CI 66.4-100.0%, p = 0.0481). Regarding length of hospital stay, intention to treat time to event analysis showed no difference between the two approaches (p = 0.73). Also, the median difference was not statistically significant (- 2.0 days, p = 0.17). In contrast, per protocol evaluation revealed reduced risk of prolonged hospitalization for NA patients (p = 0.0025) with a median difference of - 4.0 days (p = 0.0012). Failure of NA did not result in a meaningful delay in discharge timing as median difference was 1.5 days (p = 0.28). CONCLUSIONS: Our data suggest that in a number of patients iatrogenic PTX may be successfully treated with NA resulting in shorter hospitalization without the risk of meaningful discharge delay in unsuccessful cases.

Implantation of the Micra transcatheter pacing system: Single Polish center experience with the real costs of hospitalization analysis.

BACKGROUND: The Micra transcatheter pacing system (TPS) is a miniaturized, single-chamber pacemaker system. Study reported herein is an initial experience with implantation of the Micra TPS. METHODS: The leadless pacemaker was implanted in 10 patients with standard indications for a permanent pacemaker implantation. All hospitalization costs were calculated for all patients. RESULTS: The mean age of the patients was 75 ± 7.1 years, 6 were men and 4 were women. Four patients had permanent atrial fibrillation as the basal rhythm and 6 patients had sinus rhythm. All patients had at least one relative contraindication that precluded the use of a traditional pacing system. Mean intraoperative ventricular sensing amplitude was 10.6 ± 5.4 mV, impedance 843 ± 185 ohms, and pacing threshold at 0.24 ms was 0.56 ± 0.23 V. At discharge, those values were 13.9 ± 5.6 mV, 667 ± 119 ohms and 0.47 ± 0.17, respectively. The mean duration of implantation procedure was 82 min, while mean fluoroscopy time was 3.5 min. Two patients developed hematoma at the groin puncture site post-implantation. In 1 case there was a need for erythrocyte mass transfusion and surgical intervention. Mean total time of hospitalization was 26 days and time from procedure to discharge 12 days. Average cost of hospitalization per 1 patient was 11,260.15 EUR minimal cost was 9,052.68 EUR, while maximal cost was 16,533.18 EUR. CONCLUSIONS: Implantation of leadless pacemakers is feasible, safe and provides advantages over the conventional system. Hospitalization costs vary for individual patients in wide range.