Jürgen Kuschyk

Extent of late gadolinium enhancement detected by cardiovascular magnetic resonance correlates with the inducibility of ventricular tachyarrhythmia in hypertrophic cardiomyopathy

BackgroundMyocardial fibrosis is frequently identified in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the role of myocardial fibrosis detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) as a potential arrhythmogenic substrate in HCM. We hypothesized that the extent of LGE might be associated with the inducibility of ventricular tachyarrhythmias (VT) during programmed ventricular stimulation (PVS).MethodsWe evaluated retrospectively LGE CMR of 76 consecutive HCM patients, of which 43 presented with one or more risk factors for sudden cardiac death (SCD) and were therefore clinically classified as high-risk patients. Of these 43 patients, 38 additionally underwent an electrophysiological testing (EP). CMR indices and the extent of LGE, given as the % of LV mass with LGE were correlated with the presence of risk factors for SCD and the results of EP.ResultsHigh-risk patients had a significant higher prevalence of LGE than low-risk patients (29/43 [67%] versus 14/33 [47%]; p = 0.03). Also the % of LV mass with LGE was significantly higher in high-risk patients than in low-risk patients (14% versus 3%, p = 0.001, respectively). Of the 38 high- risk patients, 12 had inducible VT during EP. LV function, volumes and mass were comparable in patients with and without inducible VT. However, the % of LV mass with LGE was significantly higher in patients with inducible VT compared to those without (22% versus 10%, p = 0.03). The prevalence of LGE was, however, comparable between HCM patients with and those without inducible VT (10/12 [83%] versus 15/26 [58%]; p = 0.12). In the univariate analysis the % of LV mass with LGE and the septal wall thickness were significantly associated with the high-risk group (p = 0.001 and 0.004, respectively). Multivariate analysis demonstrated that the extent of LGE was the only independent predictor of the risk group (p = 0.03).ConclusionsThe extent of LGE in HCM patients correlated with risk factors of SCD and the likelihood of inducible VT. Furthermore, LGE extent was the only independent predictor of the risk group. This supports the hypothesis that the extent of fibrosis may serve as potential arrhythmogenic substrate for the occurrence of VT, especially in patients with clinical risk factors for SCD.

Insights into the location of type I ECG in patients with Brugada syndrome: Correlation of ECG and cardiovascular magnetic resonance imaging

BACKGROUND Brugada syndrome is characterized by ST-segment abnormalities in V1-V3. Electrocardiogram (ECG) leads placed in the 3rd and 2nd intercostal spaces (ICSs) increased the sensitivity for the detection of a type I ECG pattern. The anatomic explanation for this finding is pending. OBJECTIVE The purpose of the study was to correlate the location of the Brugada type I ECG with the anatomic location of the right ventricular outflow tract (RVOT). METHODS Twenty patients with positive ajmaline challenge and 10 patients with spontaneous Brugada type I ECG performed by using 12 right precordial leads underwent cardiovascular magnetic resonance imaging (CMRI). The craniocaudal and lateral extent of the RVOT and maximal RVOT area were determined. Type I ECG pattern and maximal ST-segment elevation were correlated to extent and maximal RVOT area, respectively. RESULTS In all patients, Brugada type I pattern was found in the 3rd ICS in sternal and left-parasternal positions. RVOT extent determined by using CMRI included the 3rd ICS in all patients. Maximal RVOT area was found in 3 patients in the 2nd ICS, in 5 patients in the 4th ICS, and in 22 patients in the 3rd ICS. CMRI predicted type I pattern with a sensitivity of 97.2%, specificity of 91.7%, positive predictive value of 88.6%, and negative predictive value of 98.0%. Maximal RVOT area coincided with maximal ST-segment elevation in 29 of 30 patients. CONCLUSION RVOT localization determined by using CMRI correlates highly with the type I Brugada pattern. Lead positioning according to RVOT location improves the diagnosis of Brugada syndrome.

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.

Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide

BACKGROUND The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. OBJECTIVE Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. METHODS Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and T(peak)-T(end) intervals were analyzed before and during rufinamide treatment. RESULTS The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). T(peak)-T(end) intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. CONCLUSION QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations notwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings.

Efficacy and survival in patients with cardiac contractility modulation: Long-term single center experience in 81 patients

AIMS To analyze long-term efficacy and survival in patients with chronic heart failure treated with cardiac contractility modulation. METHODS 81 patients implanted with a CCM device between 2004 and 2012 were included in this retrospective analysis. Changes in NYHA class, ejection fraction (EF), Minnesota Living with Heart Failure Questionnaire, NT-proBNP and peak VO₂ were analyzed during a mean follow up of 34.2 ± 28 months (6-123 months). Observed mortality rate was compared with that predicted by the MAGGIC Score. RESULTS Patients were 61 ± 12 years old with EF 23 ± 7%. Heart failure was due to ischemic (n=48, 59.3%) or idiopathic dilated (n=33, 40.7%) cardiomyopathy. EF increased from 23.1 ± 7.9 to 29.4 ± 8.6% (p<0.05), mean NT-proBNP decreased from 4395 ± 3818 to 2762 ± 3490 ng/l (p<0.05) and mean peak VO2 increased from 13.9 ± 3.3 to 14.6 ± 3.5 ml/kg/min (p=0.1). The overall clinical responder rate (at least 1 class improvement of NYHA within 6 months or last follow-up) was 74.1%. 21 (25.9%) patients died during follow up, 11 (52.4%) due to cardiac conditions and 10 (47.6%) due to non-cardiac conditions. Mortality rates at 1 and 3 years were 5.2% and 29.5% compared to mortality rates estimated from the MAGGIC risk score of 18.4% (p<0.001) and 40% (p=ns), respectively. Log-Rank analysis of all events through 3 years of follow-up, however, was significantly less than predicted (p=0.022). CONCLUSIONS CCM therapy improved quality of life, exercise capacity, NYHA class, EF and NT-proBNP levels during long-term follow up. Mortality rates appeared to be lower than estimated from the MAGGIC score.

Characteristics and long-term outcome of right ventricular involvement in Takotsubo cardiomyopathy

OBJECTIVE Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy (SCM) resembles a reversible cardiomyopathy that is characterized by localized wall motion abnormalities in the absence of stenotic coronary vascular disease. Patients typically present with apical ballooning of the left ventricle (LV), however the right ventricle (RV) is also affected in up to 50.0% of patients. Long-term prognosis of classical SCM resembles that of patients after ST elevation myocardial infarction. Data on long-term prognosis of biventricular compared to classical SCM is controversial. The aim of this study was therefore to analyze patients with biventricular SCM regarding in-hospital outcome and long-term prognosis. MATERIALS AND METHODS 114 consecutive patients with SCM were retrospectively analyzed. 88 patients presented with classical SCM, 26 patients (22.8%) were diagnosed with biventricular SCM. Follow-up was conducted for a total of 4.4years. Mean age was 67.1years with 83.3% of patients being female. The primary endpoint was a composite of all-cause mortality, recurrence of SCM and re-hospitalization due to heart failure. RESULTS Although patients with biventricular SCM presented with a tendency towards an increased rate of cardiogenic shock (30.8% vs. 15.9%; p=0.09) and significantly more usage of inotropic support upon hospital admission (34.6% vs. 13.6%; p=0.01), there was no difference concerning the primary endpoint in both groups (50.0% vs. 44.3%; p=0.31). Furthermore, there was no difference in mortality both in-hospital (7.7% vs. 7.9%; p=0.66) and during long-term follow-up (27.3% vs. 23.1%; p=0.46). CONCLUSION Patients with biventricular SCM have the same in-hospital and long-term outcome compared to classical SCM.

Prevalence, Clinical Characteristics, and Predictors of Patients with Thromboembolic Events in Takotsubo Cardiomyopathy

Background Several acute complications related to takotsubo cardiomyopathy (TTC) have been documented recently. However, the incidence and clinical significance of acute thromboembolic events in TTC is not well established. Methods A detailed investigation of the clinical characteristics and in-hospital complications of 114 consecutive patients diagnosed with TTC between January 2003 and September 2015 was carried out. This study was initiated to reveal the predictors, clinical significance, and short-term and long-term outcomes of patients with TTC associated with acute thromboembolic events on index presentation. Results The incidence of acute thromboembolic events related to TTC was around 12.2%, and these included ventricular thrombi, cerebrovascular events, retinal and brachial artery pathologies, renal, splenic, and aortic involvement. The most frequent complication on initial presentation was cardiogenic shock (20%) accompanied with pulmonary congestion (20%). Interestingly, patients experiencing thromboembolic events had higher C-reactive protein (CRP) levels as compared to the non-thromboembolic group (P = 0.02). Certain thromboembolic events were characterized by the presence of ST-segment elevation in electrocardiogram (P 0.02). Chest pain was the primary symptom in these patients (P 0.09). Furthermore, there was significant right ventricular involvement (as assessed by transthoracic echocardiography) in patients presenting with an acute thromboembolic event (P 0.08). A Kaplan–Meier analysis indicated a significantly higher mortality rate over a mean follow-up of three years in the thromboembolic group than the non-thromboembolic group (log-rank, P = 0.02). Conclusions Our results confirmed the relative common occurrence of thromboembolic events in the setting of TTC. Inflammation might play an important role in the development of thromboembolic events, and a right ventricular involvement and ST-segment elevation could be positive predictors for this occurrence. In order to circumvent the risk of a negative outcome, it is recommended that an anticoagulation therapy be initiated in all high-risk patients.

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.

Right ventricular dysfunction, late gadolinium enhancement, and female gender predict poor outcome in patients with dilated cardiomyopathy

AIMS Dilated cardiomyopathy (DCM) shows a variable disease course and is associated with significant morbidity and mortality. So far, left ventricular function (LVF) is the major determinant for risk stratification. However, since it has shown to be a poor guide to individual outcome, we studied the prognostic value of cardiovascular magnetic resonance imaging (CMR) parameters, late gadolinium enhancement (LGE) and epicardial adipose tissue (EAT). METHODS AND RESULTS 140 patients with DCM underwent late gadolinium enhancement (LGE) CMR. During a median follow-up of 3 years, 22 patients (16%) died and another 51 (36%) were hospitalized due to congestive heart failure (CHF). Female gender and right ventricular ejection fraction (RV-EF) below the median of 38% were independent predictors of all-cause mortality in multivariable analysis. In patients who were hospitalized due to CHF, RV-EF below the median of 38% was the only independent predictor in multivariable analysis. When patients where further stratified according to systolic LV-EF, the prognostic value of RV-EF to predict mortality and cardiac morbidity remained unchanged. Looking at DCM patients who died during follow-up compared to those who were hospitalized due to CHF, the former presented with a higher prevalence of LGE as well as reduced indexed EAT. CONCLUSION Female gender, RV-EF and the presence of LGE are of prognostic importance in patients with DCM. Therefore, the present study underlines the role of CMR as an important tool for risk stratification in patients with DCM.