Erol Tülümen

Subcutaneous implantable cardioverter-defibrillator: First single-center experience with other cardiac implantable electronic devices

BACKGROUND The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an implantable device for antiarrhythmic therapy with no intravascular leads. OBJECTIVE The purpose of this study was to describe the technical feasibility of combining the S-ICD with other cardiac implantable electronic devices (CIEDs), including pacemakers with transvenous or epicardial electrodes. We also provide the first experience of combining an S-ICD with catheter-based therapies, including cardiac contractility modulation (CCM) and vagus nerve stimulation. METHODS Between July 2011 and November 2014, 6 patients received a CCM device and S-ICD, 3 patients with a single-chamber pacemaker using either transvenous or epicardial pacing electrodes received and S-ICD, and 1 patient with an implanted S-ICD received vagus nerve stimulation. In all patients, intraoperative S-ICD testing, crosstalk tests, and postoperative ergometric testing were performed. RESULTS In all 10 patients, device implantations were successfully performed without complications. S-ICD therapy was shown to be technically feasible with concomitant CIED. Mean follow-up was nearly 17 months. S-ICD testing and crosstalk testing before and during exercise enabled device programming across a broad range of test conditions and was associated with no subsequent evidence of adverse device interaction. None of the devices required permanent inactivation or removal, and no patient received an inappropriate shock. CONCLUSION In suitable patients, combining an S-ICD with CCM or pacemaker may provide an acceptable means to reduce the number of transvascular leads. S-ICD appeared safe with CCM over an intermediate follow-up period. Additional prospective randomized controlled trials examining S-ICD in conjunction with CIEDs are warranted.

Prevalence of cancer in Takotsubo cardiomyopathy: Short and long-term outcome

BACKGROUND Takotsubo Cardiomyopathy (TTC) is a transient disorder of ventricular wall dysfunction, mostly induced by physical or emotional stress. TTC may be associated with adverse cardiac events. The association of cancer and its clinical impact in TTC patients has not been described yet. METHODS In 114 consecutive patients presenting with TTC between January 2003 and September 2015, we studied the frequency of cancer diagnosis, and compared the clinical course and the occurrence of a clinical endpoint of cancer and non-cancer patients during a follow up of 4.2years. RESULTS Of the 114 patients, 16 (14.0%) had a malignancy already diagnosed at TTC, and further 11 patients received the diagnosis during follow up. Cancer patients had higher frequency of atrial fibrillation and lower hemoglobin levels at admission than patients without cancer. While the occurrence of in-hospital events was comparable, the diagnosis of cancer at TTC event or during follow up was predictive for a higher rate of the composite endpoint. In the Kaplan-Meier analysis, malignant diseases were strongly associated not only with overall mortality but also with worsened time of event-free survival during the long-term outcome. CONCLUSIONS Prevalence of malignant diseases is high in TTC patients, and is a risk factor for worse outcome. Screening for malignancies should be recommended in all patients presenting with TTC. Further studies are needed to define the association on molecular levels.

Simultaneous Non-Invasive Epicardial and Endocardial Mapping in Patients With Brugada Syndrome: New Insights Into Arrhythmia Mechanisms.

Background The underlying mechanisms of Brugada syndrome (BrS) are not completely understood. Recent studies provided evidence that the electrophysiological substrate, leading to electrocardiogram abnormalities and/or ventricular arrhythmias, is located in the right ventricular outflow tract (RVOT). The purpose of this study was to examine abnormalities of epicardial and endocardial local unipolar electrograms by simultaneous noninvasive mapping in patients with BrS. Methods and Results Local epicardial and endocardial unipolar electrograms were analyzed using a novel noninvasive epi‐ and endocardial electrophysiology system (NEEES) in 12 patients with BrS and 6 with right bundle branch block for comparison. Fifteen normal subjects composed the control group. Observed depolarization abnormalities included fragmented electrograms in the anatomical area of RVOT endocardially and epicardially, significantly prolonged activation time in the RVOT endocardium (65±20 vs 38±13 ms in controls; P=0.008), prolongation of the activation‐recovery interval in the RVOT epicardium (281±34 vs 247±26 ms in controls; P=0.002). Repolarization abnormalities included a larger area of ST‐segment elevation >2 mV and T‐wave inversions. Negative voltage gradient (−2.5 to −6.0 mV) between epicardium and endocardium of the RVOT was observed in 8 of 12 BrS patients, not present in patients with right bundle branch block or in controls. Conclusions Abnormalities of epicardial and endocardial electrograms associated with depolarization and repolarization properties were found using NEEES exclusively in the RVOT of BrS patients. These findings support both, depolarization and repolarization abnormalities, being operative at the same time in patients with BrS.

PQ segment depression in patients with short QT syndrome: A novel marker for diagnosing short QT syndrome?

BACKGROUND Patients with short QT syndrome (SQTS) have an increased risk for atrial tachyarrhythmias, ventricular tachyarrhythmias, and/or sudden cardiac death. PQ segment depression (PQD) is related to atrial fibrillation and carries a poor prognosis in the setting of acute inferior myocardial infarction and is a well-defined electrocardiographic (ECG) marker of acute pericarditis. OBJECTIVE To evaluate the prevalence of PQD in SQTS and to analyze the association with atrial arrhythmias. METHODS Digitalized 12-lead ECGs of SQTS patients were evaluated for PQD in all leads and for QT intervals in leads II and V5. PQD was defined as ≥0.05 mV (0.5 mm) depression from the isoelectric line. RESULTS A total of 760 leads from 64 SQTS patients (mean age 36 ± 18 years; 48 [75%] men) were analyzed. PQD was seen in 265 (35%) leads from 52 (81%) patients and was more frequent in leads II, V3, aVF, V4, and I (n = 43 [67%], n = 30 [47%], n = 27 [42%], n = 25 [39%], and n = 25 [39%], respectively). Nine of 64 (14%) patients presented with atrial tachyarrhythmias, and all of them had PQD. CONCLUSION Fifty-two of 64 (81%) patients with SQTS reveal PQD. As PQD is rarely observed in healthy individuals, this ECG stigma may constitute a novel marker for SQTS in addition to a short QT interval.

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.

Mitral annular plane systolic excursion is an easy tool for fibrosis detection by late gadolinium enhancement cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy

BACKGROUND Hypertrophic cardiomyopathy (HCM) causes various degrees of fibrosis resulting in left ventricular function impairment, which can be measured using mitral annular plane systolic excursion (MAPSE). AIMS To determine the values for septal, lateral and average MAPSE using cardiovascular magnetic resonance (CMR) in healthy controls and patients with HCM; and to investigate whether MAPSE correlated with the extent of fibrosis. METHODS Patients with HCM and healthy controls underwent CMR. RESULTS In 50 healthy controls, septal and lateral MAPSE were comparable and showed excellent intra- and inter-observer reliability. Patients with HCM had significantly reduced septal, lateral and average MAPSE compared to healthy controls. Furthermore, in patients with HCM, septal MAPSE measurements were significantly reduced compared to lateral ones. Correspondingly, the septal myocardial segments showed significantly more late gadolinium enhancement (LGE) than lateral ones. No significant differences were found between echocardiographic and CMR MAPSE measurements in healthy controls and patients with HCM. Patients who suffered a major adverse cardiac event or stroke revealed a significantly reduced MAPSE and a significantly greater LGE extent compared to event-free patients with HCM. CONCLUSIONS MAPSE measurement using CMR is feasible, reproducible and comparable to echocardiography in healthy controls and patients with HCM. The asymmetric and mainly septal distribution of myocardial hypertrophy and fibrosis detected by LGE in patients with HCM was reflected by significantly reduced septal versus lateral MAPSE. Therefore, reduced MAPSE seems to be an easily determinable marker of fibrosis accumulation leading to left ventricular mechanical dysfunction and also seems to have a prognostic implication.

Hyperthermia Influences the Effects of Sodium Channel Blocking Drugs in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Introduction Fever can increase the susceptibility to supraventricular and ventricular arrhythmias, in which sodium channel dysfunction has been implicated. Whether fever influences the efficacy of sodium channel blocking drugs is unknown. The current study was designed to investigate the temperature dependent effects of distinct sodium channel blocking drugs on the sodium currents in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Methods and Results hiPSC-CMs were generated from human skin fibroblasts of a healthy donor. The peak and late sodium currents (INa), steady-state activation, inactivation and recovery from inactivation of INa in hiPSC-CMs were analyzed using the whole-cell patch clamp technique. The effects of different concentrations of the antiarrhythmic drugs flecainide, lidocaine, ajmaline and the antianginal drug ranolazine on INa were tested at 36°C and 40°C. Increasing the temperature of the bath solution from 36°C to 40°C enhanced the inhibition of peak INa but reduced the inhibition of late INa by flecainide and lidocaine. By contrast, increasing the temperature reduced the effect of ajmaline and ranolazine on the peak INa but not late INa. None of the tested drugs showed temperature-dependent effects on the steady-state activation and inactivation as well as on the recovery from inactivation of INa in hiPSC-CMs. Conclusions Temperature variation from the physiological to the febrile range apparently influences the effects of sodium channel blockers on the sodium currents. This may influence their antiarrhythmic efficacy in patients suffering from fever.

Impact and Management of Left Ventricular Function on the Prognosis of Takotsubo Syndrome

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.

Long‐term results of combined cardiac contractility modulation and subcutaneous defibrillator therapy in patients with heart failure and reduced ejection fraction

Cardiac contractility modulation (CCM) is an electrical‐device therapy for patients with heart failure with reduced ejection fraction (HFrEF). Patients with left ventricular ejection fraction (LVEF) ≤35% also have indication for an implantable cardioverter‐defibrillator (ICD), and in some cases subcutaneous ICD (S‐ICD) is selected.

Automatic camera-based identification and 3-D reconstruction of electrode positions in electrocardiographic imaging.

Abstract Electrocardiographic imaging (ECG imaging) is a method to depict electrophysiological processes in the heart. It is an emerging technology with the potential of making the therapy of cardiac arrhythmia less invasive, less expensive, and more precise. A major challenge for integrating the method into clinical workflow is the seamless and correct identification and localization of electrodes on the thorax and their assignment to recorded channels. This work proposes a camera-based system, which can localize all electrode positions at once and to an accuracy of approximately 1±1 mm. A system for automatic identification of individual electrodes is implemented that overcomes the need of manual annotation. For this purpose, a system of markers is suggested, which facilitates a precise localization to subpixel accuracy and robust identification using an error-correcting code. The accuracy of the presented system in identifying and localizing electrodes is validated in a phantom study. Its overall capability is demonstrated in a clinical scenario.