Local dose rate effects in implantable cardioverter-defibrillators with flattening filter free and flattened photon radiation.

PURPOSE: In the beam penumbra of stereotactic body radiotherapy volumes, dose rate effects in implantable cardioverter-defibrillators (ICDs) may be the predominant cause for failures in the absence of neutron-generating photon energies. We investigate such dose rate effects in ICDs and provide evidence for safe use of lung tumor stereotactic radioablation with flattening filter free (FFF) and flattened 6 Megavolt (MV) beams in ICD-bearing patients. METHODS: Sixty-two ICDs were subjected to scatter radiation in 1.0, 2.5, and 7.0 cm distance to 100 Gy within a 5â€¯× 5 cm2 radiation field. Radiation was applied with 6 MV FFF beams (constant dose rate of 1400 cGy/min) and flattened (FLAT) 6 MV beams (430 cGy/min). Local dose rates (LDR) at the position of all ICDs were measured. All ICDs were monitored continuously. RESULTS: With 6 MV FFF beams, ICD errors occurred at distances of 1.0 cm (LDR 46.8 cGy/min; maximum ICD dose 3.4 Gy) and 2.5 cm (LDR 15.6 cGy/min; 1.1 Gy). With 6 MV FLAT beams, ICD errors occurred only at 1 cm distance (LDR 16.8 cGy/min; 3.9 Gy). No errors occurred at an LDR below 7 cGy/min, translating to a safe distance of 2.5 cm (1.5 Gy) in flattened and 7 cm (0.4 Gy) in 6 MV FFF beams. CONCLUSION: A LDR in ICDs larger than 7 cGy/min may cause ICD malfunction. At identical LDR, differences between 6 MV FFF and 6 MV FLAT beams do not yield different rates of malfunction. The dominant reason for ICD failures could be the LDR and not the total dose to the ICD. For most stereotactic treatments, it is recommended to generate a planning risk volume around the ICD in which LDR larger than 7 cGy/min are avoided.

Predictors of positive response to beta-blockers for treatment of premature ventricular complexes.

BACKGROUND: The aim of the present study is to investigate the possible factors that might be predictive of effective antiarrhythmic effect of beta-blockers on premature ventricular complexes (PVC). METHODS: Data of 190 eligible consecutive patients to whom beta-blocker therapy had been initiated for treatment of PVC's were retrospectively evaluated. The Holter recording acquired before beta-blocker initiation and the first Holter acquired after beta blocker initiation during follow up was comprehensively evaluated for each patient. Parameters obtained from pre- and post-beta-blocker 24 h Holter recordings were compared with each other and possible predictors were evaluated for positive response to beta-blocker therapy. RESULTS: Sixty-one patients (32.1%) were observed to respond beta-blocker therapy with at least 50% reduction of daily PVC burden. Patients who responded to beta-blockers had significantly higher ratio of patients who had positive correlation between hourly heart rate and corresponding hourly PVC number (fast HR-PVC status) compared with non-responders (73.8% vs 48.1%, p < 0.001). Binary logistic regression analysis revealed PVC QRS width (Odds ratio: 0.971; p: 0.037) and fast HR-PVC status (Odds ratio: 2.935; p: 0.007) as the independent predictors of positive response to beta-blockers for treatment of PVC. CONCLUSION: Positive correlation between hourly heart rate and PVC incidence was found to be independent positive predictor and PVC QRS width was found to be independent negative predictor of beta-blocker success in our study. This observation might have important clinical implications to guide medical treatment of PVCs in clinical practice.

Incidence, mechanisms, and clinical impact of inappropriate shocks in patients with a subcutaneous defibrillator.

AIMS: Inappropriate shocks (IAS) remain a challenge for patients and physicians after implantation of the subcutaneous implantable cardioverter-defibrillator (S-ICD). The aims were to assess and characterize different patterns of IAS. METHODS AND RESULTS: Two hundred and thirty-nine patients were implanted with an S-ICD between 2010 and 2018 for primary and secondary prevention. Follow-up data of at least 6 months were analysed. During a mean follow-up of 34.9 ± 16.0 months, a total of 73 shocks occurred in 38 patients (6%). Forty-three (59%) shocks were considered appropriate due to ventricular tachycardia/ventricular fibrillation, while 30 (41%) were inappropriate and occurred in 19 patients (8%). Myopotentials/noise was the most frequent cause of inappropriate shocks (n = 8), followed by T-wave oversensing (n = 6) and undersensing of the QRS, resulting in adaptation of the automatic gain control and inappropriate shock (n = 5). Seventy-four percent of all IAS occurred on the primary vector, while no IAS occurred on the alternate vector. In seven of eight patients (88%), IAS related to myopotentials have occurred on the primary sensing vector. Multivariate analysis identified taller patients, primary sensing vector and first-generation S-ICD device as predictors for IAS. SMART pass effectively reduced the occurrence of IAS in the second-generation S-ICD system. CONCLUSION: Inappropriate therapies are less frequently observed on the alternate vector. The primary vector seems to be unfavourable with regard to oversensing caused by myopotentials. Inappropriate shocks were associated with an increased rate of rehospitalization but not mortality. These observations have implications for the prevention of inappropriate S-ICD shocks.

Clinical Profile and Long-Term Follow-Up of Children with Brugada Syndrome.

Brugada syndrome (BrS) is a rare channelopathy associated with sudden cardiac death (SCD). Although outcome data of adult cohorts are well known, information on children are lacking. The aim of the present study was to analyze the clinical profile, treatment approach and long-term outcome of children affected with BrS. After a systematic review of the literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Libary, Cinahl), data from a total of 4 studies which included 262 BrS patients were identified. The mean age of patients was 12.1 ± 5.5, 53.8% males and 19.8% spontaneous BrS type I. 80.2% of patients presented BrS ECG I after receiving sodium channel blockers. 76% of these patients were asymptomatic while only 17.9% suffered from recurrent syncope. Around 1.5% of the patients were admitted due to aborted SCD, and 3% suffered from atrial arrhythmias. Electrophysiological work-up was performed in 132 patients. Induction of ventricular tachycardia/ventricular fibrillation using programmed ventricular stimulation was inducible in 16 patients. 56 children received an ICD. 11 patients received quinidine. An electrical storm was documented in 1 patient. Appropriate shocks occured in 16% of the patients over a median follow-up period of 62.2 (54-64). ICD-related complications were observed in 11 patients (19.6%) with a predominance of inappropriate shocks and lead failure and/or fracture. Although BrS in the childhood is rare, diagnosis and management continues to be challenging. ICD therapy is an effective therapy in high-risk children with BrS, however, with relevant ICD-related complications.

Cardioprotective Effects of Dronedarone Mediated by the Influence on the Expression of Urokinase-Type Plasminogen Activator Receptor.

PURPOSE: Dronedarone is a multichannel-blocking antiarrhythmic drug for the treatment of atrial fibrillation. Observational data hypothesized a cardioprotective effect. In an in vitro endothelial cell-platelet model, we evaluated the molecular atheroprotective effects of dronedarone. METHODS: Following a 24-h incubation of human umbilical vein endothelial cells (HUVECs) with dronedarone (concentration 50, 100, and 150 ng/mL), they were then stimulated for 1 h with lipopolysaccharide (LPS) and were subsequently incubated in direct contact with thrombin-activated platelets. After incubation, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, urokinase-type plasminogen activator receptor (uPAR), and membrane type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. RESULTS: Preincubation with 150 ng/mL of dronedarone reduced the expression of uPAR on endothelial cells after proinflammatory stimulation with LPS and also by direct endothelial contact with activated platelets (p = 0.0038). In contrast, the expression of CD40L and CD62P on platelets after proinflammatory stimulation with thrombin was significantly increased through direct preincubation with 50/100/150 ng/mL of dronedarone. However, dronedarone had no effects on the expression of MT1-MMP and ICAM-1 in HUVECs. CONCLUSION: In this in vitro analysis, dronedarone directly increased platelet activation but showed significant direct effects on endothelial cells and indirect effects on platelets on selected markers of atherosclerosis.

Prevalence of malignant arrhythmia and sudden cardiac death in takotsubo syndrome and its management.

Aims: Recent studies have highlighted that takotsubo syndrome (TTS) is associated with a poor clinical outcome. Our study was conducted to determine the short- and long-term prevalence, recurrence rate and impact of life-threatening arrhythmias (LTA) on the clinical outcome of TTS. Methods and results: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The patient groups, divided according to the presence (n = 13, 11.4%) or absence (n = 101, 88.6%) of LTAs, were followed-up over a period of 3 years so as to determine the clinical outcome. Our analyses suggest that patients comprising the LTA group suffered significantly more often from an acute cardiovascular event including cases of a newly diagnosed atrial fibrillation (38.4% vs. 2.9%), cardiogenic shock with use of inotropic agents (53.8% vs. 14.8%) and cardiopulmonary resuscitation (61.5% vs. 1%). The short-term recurrence rate of a LTA episode was 15.3%, while the long-term recurrence rate of any LTA was around 5%. Whereas, in-hospital mortality was significantly higher in TTS associated with LTAs, the overall survival rate over 3 years was similar. A multivariate Cox regression analysis suggested atrial fibrillation, EF ≤ 35%, cardiogenic shock, and glomerular filtration rate <60 mL/min. as independent predictors of adverse outcome. Conclusion: The short- as well as the long-term prevalence and recurrence of LTAs in TTS patients is high. The long-term mortality rates were similar to the TTS patients presenting without any LTAs. LTAs in TTS could be triggered by a concomitant atrial fibrillation.

Clinical outcomes associated with catecholamine use in patients diagnosed with Takotsubo cardiomyopathy.

BACKGROUND: Recent hypotheses have suggested the pathophysiological role of catecholamines in the evolution of the Takotsubo syndrome (TTS). The extent of cardiac and circulatory compromise dictates the use of some form of supportive therapy. This study was designed to investigate the clinical outcomes associated with catecholamine use in TTS patients. METHODS: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The study-patients were subsequently classified into two groups based on the need for catecholamine support during hospital stay (catecholamine group n = 93; 81%, non-catecholamine group = 21; 19%). The primary end-point of our study was all-cause mortality. RESULTS: Patients receiving catecholamine support showed higher grades of circulatory and cardiac compromise (left ventricular ejection fraction (LVEF) 39.6% vs. 32.7%, p-value < 0.01) and the course of disease was often complicated by the occurrence of different TTS-associated complications. The in-hospital mortality (3.2% vs. 28.5%, p < 0.01), 30-day mortality (17.2% vs. 51.4%, p < 0.01) as well as long-term mortality (38.7% vs. 80.9%, p < 0.01) was significantly higher in the group of patients receiving catecholamine support. A multivariate Cox regression analysis attributed EF ≤ 35% (HR 3.6, 95% CI 1.6-8.1; p < 0.01) and use of positive inotropic agents (HR 2.2, 95% CI 1.0-4.8; p 0.04) as independent predictors of the adverse outcome. CONCLUSION: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTS patients receiving catecholamine support as compared to the other study-patients. These results need further evaluation in pre-clinical and clinical trials to determine if external catecholamines contribute to an adverse clinical outcome already compromised by the initial insult.

Therapy optimization in patients with heart failure: the role of the wearable cardioverter-defibrillator in a real-world setting.

BACKGROUND: The wearable cardioverter-defibrillator (WCD) has emerged as a valuable tool to temporarily protect patients at risk for sudden cardiac death (SCD). The aim of this study was to determine the value of the WCD for therapy optimization of heart failure patients. METHODS: One hundred five consecutive patients that received WCD between 4/2012 and 9/2016 were included in the study. All patients were followed for clinical outcome and echocardiographic parameters during WCD therapy and had continued follow-up after WCD therapy, irrespective of subsequent implantable cardioverter-defibrillator (ICD) implantation. RESULTS: The most common indication for WCD were newly diagnosed ischemic (ICM) or non-ischemic cardiomyopathy (NICM) with left ventricular ejection fraction (LVEF) ≤35%. Mean WCD wear time was 68.8 ± 50.4 days with a mean daily use of 21.5 ± 3.5 h. Five patients (4.8%) received a total of five appropriate WCD shocks. During WCD wear, patients with ICM and NICM showed significant improvement in LVEF, reducing the proportion of patients with a need for primary preventive ICD implantation to 54.8% (ICM) and 48.8% (NICM). An ICD was finally implanted in 51.4% of the study patients (24 trans-venous ICDs, 30 subcutaneous ICDs). After discontinuation of WCD therapy, all patients were followed for a mean of 18.6 ± 12.3 months. 5.6% of patients with implanted ICDs received appropriate therapies. No patient with subcutaneous ICD needed change to a trans-venous device. None of the patients without an implanted ICD suffered from ventricular tachyarrhythmias and no patient died suddenly. In patients with NICM a significant LVEF improvement was observed during long-term follow-up (from 34.8 ± 11.1% to 41.0 ± 10.2%). CONCLUSIONS: WCD therapy successfully bridged all patients to either LVEF recovery or ICD implantation. Following WCD, ICD implantation could be avoided in almost half of the patients. In selected patients, prolongation of WCD therapy beyond 3 months might further prevent unnecessary ICD implantation. The WCD as an external monitoring system contributed important information to optimize device selection in patients that needed ICD implantation.

Impact and management of left ventricular function on the prognosis of Takotsubo syndrome.

BACKGROUND: Early research has proposed that patients with Takotsubo syndrome (TTS) could have a higher mortality rate than the general population. Our study was conducted to determine the short- and long-term outcome of TTS patients associated with a significantly compromised left ventricular function on hospital admission. MATERIALS AND METHODS: Our institutional database constituted a collective of 112 patients diagnosed with TTS between 2003 and 2015. The patients were classified into two groups based on the left ventricular ejection fraction (LVEF), with those presenting with a LVEF > 35% on admission categorized into one group (n = 65, 58%) and those presenting with LVEF ≤ 35% (n=47, 42%) categorized into another group. The endpoint was the all-cause of mortality over a mean follow-up of 1529 ± 1121 days. RESULTS: Preliminary results indicated that patients with an EF ≤ 35% had a significantly greater risk of developing life-threatening arrhythmias, and were much more likely to suffer from cardiogenic shock. Patients often required varying forms of mechanical respiratory support. The in-hospital mortality, 30-day mortality, 1-year mortality and ongoing long-term mortality was significantly higher in TTS patients with an EF ≤ 35%. In a multivariate Cox regression analysis, an EF ≤ 35% (HR 3·3, 95% CI: 1·2-9·2, P < 0·05) was identified as a strong independent predictor of the primary endpoint. CONCLUSIONS: In-hospital events as well as short- and long-term mortality rates among TTS patients diagnosed with a significantly reduced LVEF on admission were significantly higher. There is an urgent need for randomized trials, which could help define uniform clinical management strategies for high risk TTS patients.

Systematic ajmaline challenge in patients with long QT 3 syndrome caused by the most common mutation: a multicentre study.

AIMS: Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K. METHODS AND RESULTS: Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study. Besides routine clinical work-up, ajmaline challenge was performed after informed consent. A total of 23 subjects (11 female, mean age 27 ± 14 years) from 4 unrelated families with a family history of sudden cardiac death and familial diagnosis of the SCN5A-E1784K mutation underwent ajmaline challenge and genetic testing. Sixteen subjects (9 female) were found to be heterozygous carriers of SCN5A-E1784K. Ajmaline challenge was positive in 12 out of the 16 (75%) mutation carriers, but negative in all non-carriers. Following ajmaline, a significant shortening of the rate-corrected JT (JTc) interval was observed in mutation carriers. The baseline JTc interval was significantly longer in mutation carriers with a positive ajmaline challenge compared with those with a negative one. CONCLUSION: Overlap of LQT3 and BrS in patients carrying the most common mutation is high. Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3.

Brugada syndrome: clinical presentation and genotype-correlation with magnetic resonance imaging parameters.

AIMS: The purpose of the this study was to evaluate a possible genotype-phenotype correlation in BrS patients and to analyze possible associations with clinical events in affected patients. SCN5A gene encodes the alpha-subunit of the voltage-gated sodium channel NaV1.5. Its mutations are associated with a broad spectrum of hereditary arrhythmias such as long-QT syndrome, cardiac conduction diseases, and Brugada syndrome (BrS). Experimental studies have shown an interaction between SCN5A and cellular cytoskeleton, explaining its functional role in cellular integrity of heart cells. METHODS AND RESULTS: Cardiovascular magnetic resonance was performed on 81 consecutive genetically screened BrS patients and 30 healthy controls. Left ventricular (LV) and right ventricular (RV) volumes and dimensions were assessed and compared with respect to the genotype. Brugada syndrome patients with an SCN5A mutation (16 patients; 20%) revealed significantly larger RV volumes, along with lower RV ejection fraction, than patients without a mutation or controls, indicating a more severe phenotype in patients with a mutation. Furthermore, patients with an SCN5A mutation showed significantly more often a spontaneous type 1 BrS-electrocardiogram (ECG). In multivariate analysis, the presence of a spontaneous type 1 BrS-ECG showed the strongest association with cardiac events. Receiver-operating characteristic curve analysis indicated good predictive performance of RV end-diastolic volume, RV end-systolic, and LV cardiac output (area under the curve = 0.81, 0.81, and 0.2), with respect to the presence of an SCN5A mutation. CONCLUSION: Brugada syndrome patients with an SCN5A mutation reveal distinct changes in RV volumes and function when compared with those without an SCN5A mutation. Furthermore, mutation-positive patients have a higher likelihood of a spontaneous type 1 BrS-ECG, which is associated with a higher incidence of clinical events. Cardiovascular magnetic resonance may provide additional insight to distinguish between SCN5A mutation-positive and -negative BrS patients.

Early repolarization pattern: a marker of increased risk in patients with catecholaminergic polymorphic ventricular tachycardia.

AIMS: The early repolarization pattern (ERP) has been shown to be associated with arrhythmias in patients with short QT syndrome, Brugada syndrome, and ischaemic heart disease. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome and related to malignant ventricular tachyarrhythmias in a structurally normal heart. The aim of this study was to evaluate the prevalence of ERP and clinical events in patients with CPVT. METHODS AND RESULTS: Digitalized resting 12-lead ECGs of patients were analysed for ERP and for repolarization markers (QT and Tpeak-Tend interval). The ERP was diagnosed as 'notching' or 'slurring' at the terminal portion of QRS with ≥0.1 mV elevation in at least two consecutive inferior (II, III, aVF) and/or lateral leads (V4-V6, I, aVL). Among 51 CPVT patients (mean age 36 ± 15 years, 11 males), the ERP was present in 23 (45%): strictly in the inferior leads in 9 (18%) patients, in the lateral leads in 9 (18%) patients, and in infero-lateral leads in 5 (10%) patients. All patients with ERP were symptomatic at presentation (23 of 23 patients with ERP vs. 19 of 28 patients without ERP, P = 0.003). Syncope was also more frequent in patients with ERP (18 of 23 patients with ERP vs. 11 of 28 patients without ERP, P = 0.005). CONCLUSION: A pathologic ERP is present in an unexpected large proportion (45%) of patients and is associated with an increased frequency of syncope. In patients with unexplained syncope and ERP at baseline, exercise testing should be performed to detect CPVT.

Septal myocardial scar burden predicts the response to cardiac contractility modulation in patients with heart failure.

We hypothesized that myocardial septal scarring, assessed by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE), at the site of cardiac contractility modulation (CCM) lead placement may predict treatment response. Eligible heart failure (HF) patients underwent LGE CMR imaging before CCM device implantation. The response to CCM therapy at follow-up was determined by a change in NYHA class and echocardiographic left ventricular ejection fraction (LVEF) assessment. Patients were classified as responders, if they showed an improvement in either NYHA class or improvement of LVEF by ≥ 5%. 58 patients were included. 67% of patients were classified as responders according to improved NYHA; 55% according to LVEF improvement. 74% of patients were responders if either NYHA class or LVEF improvement was observed. 90% of responders (according to NYHA class) showed septal LGE < 25% at septal position of the leads, while 44% of non-responders showed septal LGE > 25% (p < 0.01). In patients treated with CCM, an improvement of NYHA class was observed when leads were placed at myocardial segments with a CMR- LGE burden less than 25%.

Prediction of cardiac events with non-contrast magnetic resonance feature tracking in patients with ischaemic cardiomyopathy.

AIMS: The aim of this study was to evaluate the prognostic value of feature tracking (FT) derived cardiac magnetic resonance (CMR) strain parameters of the left ventricle (LV)/right ventricle (RV) in ischaemic cardiomyopathy (ICM) patients treated with an implantable cardioverter-defibrillator (ICD). Current guidelines suggest a LV-ejection fraction ≤35% as major criterion for ICD implantation in ICM, but this is a poor predictor for arrhythmic events. Supplementary parameters are missing. METHODS AND RESULTS: Ischaemic cardiomyopathy patients (n = 242), who underwent CMR imaging prior to primary and secondary implantation of ICD, were classified depending on EF ≤ 35% (n = 188) or >35% (n = 54). FT parameters were derived from steady-state free precession cine views using dedicated software. The primary endpoint was a composite of cardiovascular mortality (CVM) and/or appropriate ICD therapy. There were no significant differences in FT-function or LV-/RV-function parameters in patients with an EF ≤ 35% correlating to the primary endpoint. In patients with EF > 35%, standard CMR functional parameters, such as LV-EF, did not reveal significant differences. However, significant differences in most FT parameters correlating to the primary endpoint were observed in this subgroup. LV-GLS (left ventricular-global longitudinal strain) and RV-GRS (right ventricular-global radial strain) revealed the best diagnostic performance in ROC curve analysis. The combination of LV-GLS and RV-GRS showed a sensitivity of 85% and a specificity of 76% for the prediction of future events. CONCLUSIONS: The impact of FT derived measurements in the risk stratification of patients with ICM depends on LV function. The combination of LV-GLS/RV-GRS seems to be a predictor of cardiovascular mortality and/or appropriate ICD therapy in patients with EF > 35%.

Improvement in right ventricular systolic function after cardiac resynchronization therapy correlates with left ventricular reverse remodeling.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function in heart failure (HF). However, the effects of CRT on right ventricular (RV) systolic function are not fully understood. OBJECTIVE: We aimed to determine echocardiographic correlates of improvement in RV systolic function after CRT. METHODS: Fifty-four patients (61.9 ± 10.5 years; 43 men; LV ejection fraction 24.6 ± 4.0%; QRS duration > 120 ms) with HF were enrolled. Standard echocardiography, strain rate (SR), and tissue Doppler imaging were performed in all patients before and 6 months after CRT. Pulsed-wave TDI-derived systolic indices of RV included systolic (RV(S) ) and isovolumic velocity (RV(IVV)) and isovolumic acceleration (RV(IVA)). Response to CRT was defined as decline in LV end-systolic volume (LVESV) ≥ 10%. RESULTS: When indices of RV systolic function were assessed between responders and nonresponders, in responders (38 patients, 70.4%) RV end-diastolic diameters (RVD1-3), mid-RV strain, and mid-RV SR improved significantly (P < 0.01, for all). RV(S) (10.77 ± 4.29 vs 12.62 ± 4.10 cm/sec, P = 0.005), RV(IVV) (14.71 ± 5.88 vs 18.52 ± 6.62 cm/sec, P < 0.001), and RV(IVA) (1.69 ± 0.70 vs 2.39 ± 0.77 m/sec(2) , P < 0.001) significantly increased among responders. There was no significant change in these parameters among nonresponders. Pearson's analyses revealed moderate positive correlations between reduction of LVESV and ΔRV(IVV) (r = 0.467, P = 0.001) and ΔRV(IVA) (r = 0.473, P = 0.001), respectively. CONCLUSIONS: RV diameters and systolic indices after CRT improved only in the responder group. Improvement in RV systolic performance after CRT is correlated with the reduction of LVESV.

The reproducibility of heart rate recovery after treadmill exercise test.

BACKGROUND: Although predictive value of heart rate recovery (HRR) has been tested in large populations, the reproducibility of HRR in treadmill exercise test has not been assessed prospectively. This prospective study examined whether HRR index has test-retest stability in the short term. METHODS: A total of 52 healthy volunteers without cardiovascular risk factors (mean age, 30 ± 10 years, 30 females) underwent standardized graded treadmill exercise test, and the test was repeated on the 7th and the 30th days. The subjects' maximal heart rates and the decrease of heart rate from the peak exercise level to the level of 1, 2, 3, 4, and 5 minutes after the termination of the exercise were examined on each test, and heart rates for each minute from the first, second, and third tests were compared for each individual. RESULTS: The maximal heart rates on the 1st, 7th, and the 30th days were 179 ± 11, 177 ± 10, 178 ± 10 beats/min, respectively [P = 0.07, intraclass correlation coefficient (ICC) = 0.92], and the 1st minute HRR indices after peak exercise were 33 ± 10, 33 ± 10, 33 ± 11, respectively (P = 0.66, ICC = 0.88). There was no statistical difference in the 2nd, 3rd, 4th, and 5th minute heart rates of the recovery phase among the 1st, 7th, and 30th day treadmill exercise tests, either. CONCLUSION: Maximal heart rates and the decline of heart rate to the 5th minute on recovery phase after treadmill exercise test have short-term reproducibility.

Risk stratification of patients with Brugada syndrome: the impact of myocardial strain analysis using cardiac magnetic resonance feature tracking.

OBJECTIVE: This study evaluated the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in patients with Brugada syndrome (BrS) to detect subclinical alterations and predict major adverse events (MAE). METHODS: CMR was performed in 106 patients with BrS and 25 healthy controls. Biventricular global strain analysis was assessed using CMR-FT. Patients were followed over a median of 11.6 [8.8 ± 13.8] years. RESULTS: The study cohort was subdivided according to the presence of a spontaneous type 1 ECG (sECG) into sBrS (BrS with sECG, n = 34 (32.1%)) and diBrS (BrS with drug-induced type 1 ECG, n = 72 (67.9%)). CMR-FT revealed morphological differences between sBrS and diBrS patients with regard to right ventricular (RV) strain (circumferential (%) (sBrS -7.9 ± 2.9 vs diBrS - 9.5 ± 3.1, p = 0.02) and radial (%) (sBrS 12.0 ± 4.3 vs diBrS 15.4 ± 5.4, p = 0.004)). During follow-up, MAE occurred in 11 patients (10.4%). Multivariable analysis was performed to identify independent predictors for the occurrence of events during follow-up. The strongest predictive value was found for RV circumferential strain (OR 3.2 (95% CI 1.4 - 6.9), p = 0.02) and RVOT/BSA (OR 3.1 (95% CI 1.0 - 7.0), p = 0.03). CONCLUSIONS: Myocardial strain analysis detected early subclinical alterations, prior to apparent changes in myocardial function, in patients with BrS. While usual functional parameters were within the normal range, CMR-FT revealed pathological results in patients with an sECG. Moreover, RV circumferential strain and RVOT size provided additional prognostic information on the occurrence of MAE during follow-up, which reflects electrical vulnerability.

Extent of peri-infarct scar on late gadolinium enhancement cardiac magnetic resonance imaging and outcome in patients with ischemic cardiomyopathy.

BACKGROUND: Only a minority of patients who receive an implantable cardioverter-defibrillator (ICD) on the basis of left ventricular ejection fraction receive appropriate ICD therapy. Peri-infarct scar zone assessed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is a possible substrate for ventricular tachyarrhytmias (VTAs). OBJECTIVE: The aim of our prospective study was to determine whether LGE-CMR parameters can predict the occurrence of VTA in patients with ischemic cardiomyopathy (ICM). METHODS: Two hundred sixteen patients with ICM underwent CMR imaging before primary or secondary ICD implantation and were prospectively followed. We assessed CMR indices and CMR scar characteristics (infarct core and peri-infarct zone) to predict outcome and VTAs. RESULTS: Patients were followed up for 1497 days (interquartile range 697-2237 days). Forty-seven patients (21%) received appropriate therapy during follow-up. Patients with appropriate ICD therapy had smaller core scar (31.5% ± 8.5% vs 36.8% ± 8.9%; P = .0004) but larger peri-infarct scar (12.4% ± 2.6% vs 10.5% ± 2.9%; P = .0001) than did patients without appropriate therapy. In multivariate Cox regression analysis, peri-infarct scar (hazard ratio 1.15; 95% confidence interval 1.07-1.24; P = .0001) was independently and significantly associated with VTAs whereas left ventricular ejection fraction, right ventricular ejection fraction, core scar, and left atrial ejection fraction were not. CONCLUSION: Scar extent of peri-infarct border zone was significantly associated with appropriate ICD therapy. Thus, LGE-CMR parameters can identify a subgroup of patients with ICM and an increased risk of life-threatening VTAs.

Comparison of transvenous vs subcutaneous defibrillator therapy in patients with cardiac arrhythmia syndromes and genetic cardiomyopathies.

BACKGROUND: Inherited arrhythmia syndromes and genetic cardiomyopathies attribute in a significant proportion to sudden cardiac death. Implantable cardioverter defibrillators (ICDs) are the cornerstone in the prevention of sudden death in high-risk patients. However, ICD therapy is also associated with high rates of inappropriate shocks and/or device-related complications especially in young patients. OBJECTIVE: To determine the outcome of high-risk patients with inherited arrhythmia syndromes and genetic cardiomyopathies comparing two defibrillator technologies. METHOD: Between 2010 and 2018, 183 consecutive patients from two large German tertiary care centers were enrolled in the study. The majority of patients (83%) had either cardiac channelopathies or idiopathic ventricular fibrillation without cardiac structural abnormalities, while the remaining 17% had a genetic cardiomyopathy (HCM/ARVC). Eighty-six patients (47%) received a transvenous ICD (TV-ICD), while a subcutaneous ICD (S-ICD) was implanted in another 97 patients (53%). RESULTS: During a mean follow-up of 4.3 years, 30 patients had an appropriate ICD therapy (annual rate 3.8%). Fifteen patients experienced an inappropriate shock (annual rate 1.9%). Lead failure occurred in 17 (9%) patients and was less frequent in the S-ICD group (OR 0.48, 95%CI 0.38-0.62). Adverse defibrillator events, defined as a composite of inappropriate shocks and lead failure requiring surgical revision were significantly lower in the S-ICD group as compared to the TV-ICD group (OR 0.55, 95%CI 0.41-0.72). There was a non-significant trend towards lower appropriate shocks in the S-ICD group, that in combination with all-cause shocks yielded in a significantly higher freedom of any shock in the S-ICD group (RR 39%, p = 0.003). No deaths occurred during follow-up. CONCLUSION: The present data favor the use of the subcutaneous ICD for patients with inherited arrhythmia syndromes and genetic cardiomyopathies who do not need anti-bradycardia pacing.

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial. METHODS AND MATERIALS: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined. RESULTS: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference. CONCLUSIONS: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.