Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole.

AIMS: To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…<1 h, 1 h…<24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. METHODS AND RESULTS: In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…<1 h, 99.6% (253/254) for episodes 1 h…<24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA2DS2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. CONCLUSION: A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.

Impact of lockdown during COVID-19 pandemic on physical activity and arrhythmia burden in heart failure patients.

BACKGROUND: Restricted outdoor activity during COVID-19 related lockdown may accelerate heart failure (HF) progression and thereby increase cardiac arrhythmias. We analyzed the impact of March/April 2020 lockdown on physical activity and arrhythmia burden in HF patients treated with cardiac resynchronization therapy (CRT) devices with daily, automatic remote monitoring (RM) function. METHODS: The study cohort included 405 HF patients enrolled in Observation of Clinical Routine Care for Heart Failure Patients Implanted with BIOTRONIK CRT Devices (BIO|STREAM.HF) registry in 16 countries, who had left ventricular ejection fraction (LVEF) ≤40% (mean 28.2 ± 6.6%) and NYHA class II/III/IV (47.9%/49.6%/2.5%) before CRT pacemaker/defibrillator implantation. The analyzed RM data comprised physical activity detected by accelerometer, mean heart rate and nocturnal rate, PP variability, percentage of biventricular pacing, atrial high rate episode (AHRE) burden, ventricular extrasystoles and tachyarrhythmias, defibrillator shocks, and number of implant interrogations (i.e., follow-ups). Intraindividual differences in RM parameters before (4-week period) versus during (4-week period) lockdown were tested for statistical significance and independent predictors were identified. RESULTS: There was a significant relative change in activity (mean -6.5%, p < .001), AHRE burden (+17%, p = .013), and follow-up rate (-75%, p < .001) during lockdown, with no significant changes in other RM parameters. Activity decreased by ≥8 min/day in 46.5% of patients; predictors were higher LVEF, lower NYHA class, no defibrillator indication, and more activity before lockdown. AHRE burden increased by ≥17 min/day in 4.7% of patients; predictors were history of atrial fibrillation, higher LVEF, higher body mass index, and activity decrease during lockdown. CONCLUSION: Unfavorable changes in physical activity, AHRE burden, and follow-up rate were observed during lockdown, but not in ventricular arrhythmia.

Patient selection criteria and midterm clinical outcome for MitraClip therapy in patients with severe mitral regurgitation and severe congestive heart failure.

AIMS: The implantation of a MitraClip (MC) is a new treatment modality for severe mitral regurgitation (MR) in patients whose condition is inoperable or who are at high conventional operative risk. This study reports the follow-up data of patients implanted with an MC in our heart centre to find selection criteria for this procedure in patients with severe congestive heart failure. METHODS AND RESULTS: This study included 163 implantation procedures in 157 patients between March 2009 and November 2012. The severe MR was caused by functional or organic valve disease. The patients had no surgical treatment option or dramatically increased surgical operative risk due to reduced LVEF or concomitant diseases. Three (2%) implantation procedures were unsuccessful. Eleven (7%) patients died during the first 30 days after MC implantation, and 9 (6%) additional patients died during the first 6 months, both groups mainly due to severe, therapy-resistant end-stage heart failure. The 111 patients who were followed up showed significant improvement in NT-proBNP, LVEF, NYHA class, 6 min walk test, and quality of life. Ten (6%) patients needed conventional heart surgery despite high operative risk due to persistent symptomatic MR after MC implantation. CONCLUSION: The interventional implantation of an MC is a new treatment for severe MR with acceptable periprocedural risk and results in clinical improvement in the majority. Patients with end-stage heart failure and an NT-proBNP value >10 000 pg/mL have a high mortality despite MC implantation, and their treatment should be based on a very individualized decision. Based on this experience, a clinical algorithm for patient selection is proposed.

Baseline vectorcardiography as a predictor of invasively determined acute hemodynamic response to cardiac resynchronization therapy.

AIMS: Identifying potential responders to cardiac resynchronization therapy (CRT) may be sometimes difficult and time consuming. Searching for a simple method, we chose vectorcardiography (VCG) for our study. The aim was to evaluate whether a VCG parameter can be used to predict invasively measured acute hemodynamic changes after CRT onset. METHODS AND RESULTS: Baseline VCG data were prospectively recorded just before initiation of CRT in a series of 126 consecutive patients (♂74 %, DCMP 60 %, ICMP 40 %, NYHA class III 100 %, QRS width 161 ± 27 ms, LV-EF 25 ± 6.5 %) prior to implantation at our specialized center. The time interval (TI) between the maximum vector and the end of the vector loop (initial description by Koglek W.) was correlated with acute hemodynamic change after CRT onset. Positive response to CRT was defined as an increase in dp/dt max >10 % or pulse pressure >5 %. According to these invasive hemodynamic parameters, 25 patients (20 %) were defined as non-responders. Using ROC analysis, the threshold value of the TI for responders was found to be 64 ms. TI is a predictor of acute hemodynamic response with a sensitivity of 96 %, a specificity of 76 %, a positive predictive value of 94 %, and a negative predictive value of 79 %. More non-responders are identified by TI than by using conventional QRS width in the 12-lead surface ECG. CONCLUSION: TI is a new method of evaluation based on baseline VCG analysis. It may be a useful diagnostic test for predicting acute hemodynamic response to CRT.

Long-term outcome of cardiac contractility modulation in patients with severe congestive heart failure.

AIMS: Cardiac contractility modulation (CCM) is a new form of electrical therapy in patients with congestive heart failure. Recently published clinical studies provide evidence of safety and improvements of exercise tolerance and quality of life. In this study, we investigated the impact of CCM on cardiac and all-cause mortality. METHODS AND RESULTS: Fifty-four consecutive patients (age 63 ± 10 years, 91% male, left ventricular ejection fraction 23 ± 6%, baseline peak oxygen consumption 10.0 ± 4.8 mL/min/kg, N-terminal pro-B-type natriuretic peptide 5194 pg/mL, New York Heart Association III/IV) who underwent implantation of an Optimizer system (IMPULSE Dynamics, Orangeburg, NY, USA) at our centre between June 2003 and June 2010 were analysed retrospectively. Patients were followed every 3 months at our outpatient clinic. This study determined long-term outcomes of patients receiving CCM therapy. Twenty-four (44%) patients died during the follow-up period, which included 19 cardiac deaths (3 sudden cardiac deaths and 16 terminal cardiac pump failure deaths). The Kaplan-Meier analysis calculated a median survival time of 992 days (33.1 months) and a mean death rate of 18.4% per year. All-cause mortality for these patients was precisely predicted by the Seattle Heart Failure Model. CONCLUSION: Cardiac contractility modulation appears to be a safe therapeutic option for advanced heart failure patients who have no other therapeutic options. Symptomatic improvement by CCM has been shown in earlier studies but our observational study suggests, for the first time, that there is no adverse effect of CCM on long-term survival.

Cardiac contractility modulation electrical signals improve myocardial gene expression in patients with heart failure.

OBJECTIVES: The objective of this study was to test whether cardiac contractility modulation (CCM) electric signals induce reverse molecular remodeling in myocardium of patients with heart failure. BACKGROUND: Heart failure is associated with up-regulation of myocardial fetal and stretch response genes and down-regulation of Ca(2+) cycling genes. Treatment with CCM signals has been associated with improved symptoms and exercise tolerance in heart failure patients. We tested the impact of CCM signals on myocardial gene expression in 11 patients. METHODS: Endomyocardial biopsies were obtained at baseline and 3 and 6 months thereafter. The CCM signals were delivered in random order of ON for 3 months and OFF for 3 months. Messenger ribonucleic acid expression was analyzed in the core lab by investigators blinded to treatment sequence. Expression of A- and B-type natriuretic peptides and alpha-myosin heavy chain (MHC), the sarcoplasmic reticulum genes SERCA-2a, phospholamban and ryanodine receptors, and the stretch response genes p38 mitogen activated protein kinase and p21 Ras were measured using reverse transcription-polymerase chain reaction and bands quantified in densitometric units. RESULTS: The 3-month therapy OFF phase was associated with increased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase, and p21 Ras and decreased expression of alpha-MHC, SERCA-2a, phospholamban, and ryanodine receptors. In contrast, the 3-month ON therapy phase resulted in decreased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase and p21 Ras and increased expression of alpha-MHC, SERCA-2a, phospholamban, and ryanodine receptors. CONCLUSIONS: The CCM signal treatment reverses the cardiac maladaptive fetal gene program and normalizes expression of key sarcoplasmic reticulum Ca(2+) cycling and stretch response genes. These changes may contribute to the clinical effects of CCM.

First use of cardiac contractility modulation (CCM) in a patient failing CRT therapy: clinical and technical aspects of combined therapies.

Cardiac contractility modulating (CCM) signals delivered by the OPTIMIZER System are being investigated as a treatment for medically refractory heart failure. Previous chronic studies of CCM have excluded patients with prolonged QRS and a cardiac resynchronization therapy (CRT) device. However, symptoms persist in more than 25% of these CRT patients. CCM may offer a therapeutic option for these non-responders. Here we report the first use of CCM signals in a patient who did not respond to treatment with a CRT-D device. We show that the implantation is technically feasible, that the OPTIMIZER and CRT-D devices can coexist without interference and that acute haemodynamic and clinical improvements can be observed. The results suggest that systematic investigation of CCM treatment in CRT non-responders is warranted.