Abstract Background Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac ...involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. Objectives The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. Methods FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC . Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. Results Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. Conclusions Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.
Managing patients with cardiac implantable electrophysiological devices (CIED) infections can be challenging. The first step should be prevention, which involves patient selection, timing of ...implantation, and the procedure itself. After implantation, a high degree of suspicion should be applied in order to correctly diagnose patients with infected implanted devices. It is necessary to recognize that patients can present with a wide variety of signs and symptoms. Once diagnosed, the next step is determining if it is a local pocket infection or system infection. In almost every patient, in addition to antibiotics, complete removal of ALL hardware is required. Transvenous lead extraction is now safe and effective, but should only be performed at experienced centres with a practiced extraction team, all possible needed equipment, and cardiothoracic surgical backup. After extraction, the indication for CIED therapy should be re-evaluated to determine re-implantation is warranted. Timing of re-implantation depends on a variety of factors such as type of infection or valvular involvement and should be made in concordance with an infectious disease specialist. This review is aimed at introducing the steps needed to manage patients with infected cardiac devices.
Objectives The goal of this study was to establish a patient-specific human-induced pluripotent stem cells (hiPSCs) model of catecholaminergic polymorphic ventricular tachycardia (CPVT). Background ...CPVT is a familial arrhythmogenic syndrome characterized by abnormal calcium (Ca2+ ) handling, ventricular arrhythmias, and sudden cardiac death. Methods Dermal fibroblasts were obtained from a CPVT patient due to the M4109R heterozygous point RYR2 mutation and reprogrammed to generate the CPVT-hiPSCs. The patient-specific hiPSCs were coaxed to differentiate into the cardiac lineage and compared with healthy control hiPSCs-derived cardiomyocytes (hiPSCs-CMs). Results Intracellular electrophysiological recordings demonstrated the development of delayed afterdepolarizations in 69% of the CPVT-hiPSCs-CMs compared with 11% in healthy control cardiomyocytes. Adrenergic stimulation by isoproterenol (1 μM) or forskolin (5 μM) increased the frequency and magnitude of afterdepolarizations and also led to development of triggered activity in the CPVT-hiPSCs-CMs. In contrast, flecainide (10 μM) and thapsigargin (10 μM) eliminated all afterdepolarizations in these cells. The latter finding suggests an important role for internal Ca2+ stores in the pathogenesis of delayed afterdepolarizations. Laser-confocal Ca2+ imaging revealed significant whole-cell Ca2+ transient irregularities (frequent local and large-storage Ca2+ -release events, broad and double-humped transients, and triggered activity) in the CPVT cardiomyocytes that worsened with adrenergic stimulation and Ca2+ overload and improved with beta-blockers. Store-overload–induced Ca2+ release was also identified in the hiPSCs-CMs and the threshold for such events was significantly reduced in the CPVT cells. Conclusions This study highlights the potential of hiPSCs for studying inherited arrhythmogenic syndromes, in general, and CPVT specifically. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care, and aid in the development of new therapies.
Even after a successful ventricular tachycardia ablation (VTA), some patients have recurrent ventricular tachycardia (VT) during their follow-up. We assessed the long-term predictors of recurrent VT ...after having a successful VTA. The patients who underwent a successful VTA (defined as the non-inducibility of any VT at the procedure's end) in 2014-2021 at our center in Israel were retrospectively analyzed. A total of 111 successful VTAs were evaluated. Out of them, 31 (27.9%) had a recurrent event of VT after the procedure during a median follow-up time of 264 days. The mean left ventricular ejection fraction (LVEF) was significantly lower among patients with recurrent VT events (28.9 ± 12.67 vs. 23.53 ± 12.224,
= 0.048). A high number of induced VTs (>two) during the procedure was found to be a significant predictor of VT recurrence (24.69% vs. 56.67%, 20 vs. 17,
= 0.002). In a multivariate analysis, a lower LVEF (HR, 0.964;
= 0.037) and a high number of induced VTs (HR, 2.15;
= 0.039) were independent predictors of arrhythmia recurrence. The inducibility of more than two VTs during a VTA procedure remains a predictor of VT recurrence even after a successful VT ablation. This group of patients remains at high risk for VT and should be followed up with and treated more vigorously.
Objectives The aim of this study was to evaluate whether certain post-Maze left atrial (LA) contractile profiles may pose a risk for ischemic stroke. Background The mechanical contraction of the left ...atrium may be modified after the Maze procedure. Whether this imposes a risk for stroke, even in the presence of sinus rhythm and after removal of the LA appendage, is not known. Methods Clinical, surgery-related, and echocardiographic data from 150 patients who underwent radiofrequency and cryoablation Maze procedures without the use of atrial incisions between 2004 and 2009 and were in sustained sinus rhythm were collected and analyzed. The occurrence of stroke was evaluated by reviewing clinical records. All stroke events were adjudicated by a neurologist. Results At a mean follow-up time of 24.5 months, 15 patients (10%) had experienced ischemic strokes. Forty-seven patients (31%) had no evidence of LA mechanical contraction at 3 months after surgery (baseline assessment) and on follow-up echocardiography. Multivariate analysis showed that a lack of LA mechanical contraction at baseline was associated with a 5-fold increase in the risk for stroke (p = 0.02) during follow-up. Larger atria imposed a significant risk as well; LA volume index ≥33 ml/m2 was associated with a 3-fold risk increase (p = 0.03). These effects were maintained regardless of the lack of mechanical valve implantation and anticoagulation treatment. Conclusions Absence of LA contraction and LA volume index ≥33 ml/m2 result in a significant increase in the risk for thromboembolic stroke after the Maze procedure for patients in sinus rhythm.
Cardiac implantable electronic device (CIED) trans venous lead extraction (TLE) is technically challenging. Whether the use of a laser sheath reduces complications and improves outcomes is still in ...debate. We therefore aimed at comparing our experience with and without laser in a large referral center.
Information of all patients undergoing TLE was collected prospectively. We retrospectively compared procedural outcomes prior to the introduction of the laser sheath lead extraction technique to use of laser sheath.
During the years 2007-2017, there were 850 attempted lead removals in 407 pts. Of them, 339 (83%) were extracted due to infection, device upgrade/lead malfunction in 42 (10%) cases, and other (7%). Complete removal (radiological success) of all leads was achieved in (88%). Partial removal was achieved in another 6% of the patients. Comparison of cases prior to and after laser technique introduction, showed that with laser, a significantly smaller proportion of cases required conversion to femoral approach 31/275 (6%) laser vs. 40/132 (15%) non-laser; p<0.001. However, success rates of removal 259/275 (94%) vs. 124/132 (94%) respectively; p = 0.83 and total complication rates 35 (13%) vs. 19 (14%) respectively; p = 0.86 did not differ prior to and after laser use. In multivariate analysis, laser-assisted extraction was an independent predictor for no need for femoral extraction (OR = 0.39; 95% CI 0.23-0.69; p = 0.01).
Introduction of laser lead removal resulted in decreased need to convert to femoral approach, albeit without improving success rates or preventing major complications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heart transplantation (HT) in patients with prior cardiovascular implantable electronic devices (CIEDs) is becoming more common, in parallel with the increased use of CIEDs for patients with advanced ...heart failure. Complete removal of CIED components during HT is not always feasible, and it is thus surprising that the literature addressing the implications of retained CIED components is limited. Indeed, there are neither guidelines nor consensus regarding the need for removal of these CIED fragments. This issue is nonetheless becoming important in light of the increase in the percentage of HT candidates having CIEDs, on the one hand, and newer therapeutic immunosuppressive protocols with higher bacterial infection potential, on the other. Thus, with the aim to study the implications of retained CIED fragments as a step towards establishing a therapeutic approach for the unique population of HT recipients with CIED remnants, we present here a case series of HT patients with retained CIED fragments who developed complications of infections together with a review of the available literature.
Diabetes mellitus (DM) type 2 is an independent risk factor for atrial fibrillation (AF). Surgical ablation or "maze procedure" is an option for patients with AF undergoing concomitant or isolated ...cardiac surgery. The aim of this study was to evaluate the impact of DM type 2 on early and long-term outcomes of patients following surgical AF ablation.
We performed an observational cohort study in Israel's largest tertiary care center. All data of patients who underwent surgical AF ablation, between 2006 and 2021 were extracted from our departmental database. Patients were divided into Group I (non-diabetic patients) and Group II (DM type 2 patients). We compared the two groups with respect to freedom from recurrent atrial arrhythmia, and mortality rate.
The study population included 606 patients. Group I (non-DM patients), consisting of 484 patients, and Group II (DM type 2 patients), comprised 122 patients. Patients with DM were older, had more hypertension and incidence of cerebrovascular accident (CVA)/transient ischemic attack (TIA), higher EuroSCORE (p < .05 for all), and a longer bypass time-130 ± 40 vs. 122 ± 36 min (p = 0.028). The mean follow-up duration was 39.0 ± 22.7 months. Freedom from atrial fibrillation was similar between the non-DM and DM type 2 groups after a 1-year follow-up, 414 (88.2%) vs. 101 (87.1%) (p = 0.511), after a 3-year follow-up, 360 (86.3%) vs. 84 (79.9%) (p = 0.290) and after a 5-year follow-up, 226 (74.1%) vs. 55 (71.5%) (p = 0.622) respectively. Furthermore, 1- and 3-year mortality was similar between non-DM and DM type 2 groups, 2.5% vs. 4.9%, (p = 0.226) and 5.6% vs. 10.5% (p = 0.076) respectively. 5-year mortality was higher in Group II (DM type 2 patients) compared with Group I (non-DM patients), 11.1% vs. 23.4% (p = 0.009).
Surgical ablation had a high success rate, with freedom from recurrent atrial arrhythmia at 1- 3- and 5- years follow-up in both the DM type 2 and non-DM groups. Furthermore,1- and 3-year mortality after surgical ablation was also similar in both groups. However, 5-year mortality was higher in the DM type 2 group.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In a letter to the editor titled “How to improve clinical outcomes in patients with tachycardia-induced cardiomyopathy”, Dr. Naoya Kataoka and Dr. Teruhiko Imamura ...
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