Dear Editor,Previous studies indicated an association of biomarkers reflecting collagen turnover with heart failure.P < .05.Our study includes all 354 participants with suspected heart failure from the HOMAGE‐HULL subcohortP = .019) and MMP‐1 , but not PICP . Figure S2 displays the correlation between the eight urinary biomarkers and the three serum biomarkers. There were 33 heart failure deaths during a median follow‐up of 6.4 years (interquartile range 4.9‐7.0 years). Figure P < .001) for the urinary classifier, and fourfold higher for the serum classifier .These biomarkers were combined into a “urinary” and a “serum” classifier, respectively, whose components are listed in Table S3. We first verified that the association between the two classifiers and adverse outcome was independent of the other, and neither classifier was associated with noncardiovascular death (Table S4). There was no overlap between fragments associated with heart failure death and those associated with noncardiovascular death . We stratified the patients into quartiles by classifier scores. In analyses adjusted for the six cofounders and NT‐proBNP, increasing classifier score was associated with a higher incidence of heart failure death Figure . The incTo the best of knowledge, our study is the first one investigating a large number of collagen I fragments (N = 293) with a focus on collagen degradation. We observed that patients who died from heart failure exhibited (i) specific changes in urinary COL1A1 fragments including an increase in abundance of terminal fragments and, conversely, a decrease in central fragments and (ii) an increase in serum collagen degradation biomarkers, but no significant change in the collagen synthesis biomarker. Both urinary collagen I fragments and serum collagen I degradation biomarkers can independently predict adverse cardiovascular outcomes.12 rendering collagen fibers more resistant to degradation.13 Since the impact of modification is expected to be more pronounced in the central, rigid part and reduced in the terminal regions , collagen fragments from the central part of COL1A1 are reduced in the group with poor cardiovascular outcomes, indicating reduced degradation of this part of the collagen molecule as a result of increased cross‐linking. This hypothesis also fits with the observed upregulation of MMP‐1: to counteract the attenuation of collagen degradation by cross‐linking, protease activity is upregulated. Study limitations include that we could not test the observation and the classifiers in an independent cohort. Additionally, due to lack of power, we could not account for the multiple testing of 293 fragments or assess the presence of other fibrotic diseases that might affect collagen levels. However, it should be noted that there were no reported signs of fibrotic diseases in the participants.We hypothesize that the observed pattern Figure  is a conIn conclusion, our results indicate that attenuation of collagen degradation may be responsible for progressive fibrosis in heart failure, with cross‐linking of collagen fibers potentially being a major cause. Urinary markers of collagen I turnover might be a valuable prognostic tool for fibrotic heart disease, possibly enabling the monitoring of treatments targeting fibrosis.Harald Mischak is the co‐founder and co‐owner of Mosaiques Diagnostics GmbH. Tianlin He and Agnieszka Latosinska are employed by Mosaiques Diagnostics GmbH. The Research Institute Alliance for the Promotion of Preventive Medicine (JAS) received a nonbinding grant from Omron Healthcare Inc. Ltd., Kyoto, Japan. All other authors declared no conflict of interest.The study complied with the Helsinki declaration for research in humans. Participants provided informed written consent for their data and biological samples to be stored and analyzed. The Ethics Committee of the University of Aachen approved the secondary use of anonymized data and the biomarker measurements (number EK163/19).Supporting InformationClick here for additional data file.


To evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI).A total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year.p = 0.015) and STR (ST-segment resolution) > 70%  were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months  and 1 year . IMR was negatively correlated with LVEF at 3 months  and 1 year .The ratio of TMPG  3 (85.7% vs. 52%, The IMR showed significant negative correlation with the LVEF value after primary PCI. The high IMR is a strong predictor of heart failure within 1 year after anterior myocardial infarction. Acute ST-segment elevation myocardial infarction (STEMI) is one of the most common causes of death in both the developed and developing world . ImmediaThe current study represents a retrospective analysis of patients with acute arterial wall STEMI. Patients were prospectively enrolled in Nanjing Drum Tower Hospital from June 2015 to July 2016 . Details about the RCT trial have been reported previously . The tarBefore PCI, all the patients took aspirin 300 mg and P2Y12 (clopidogrel 600 mg or ticagrelor 180 mg). Coronary angiography was performed using standard techniques and the final decision for PCI was at the discretion of the operators. In brief, a guide catheter (5F to 7F) was used to engage the coronary artery, and a pressure–temperature sensor guidewire was used to measure physiologic indices. After wire crossing, 6F Export AP  thrombus aspiration was performed on high thrombus burden patients. Immediately after successful implantation of drug-eluting stents (DES), TIMI and TMPG were recorded at 30 frames per second. The index of microcirculatory resistance (IMR) was detected by fractional flow reserve (FFR) detector .Maximal hyperemia was induced by adenosine (140 µg/kg/min) intravenously administered into the median cubital vein. A 0.014-in floppy Certus Pressure Wire  and modified Pressure Wire-4 software  were used to measure distal coronary pressure and temperature. We placed a pressure wire into the distal LAD and administered ATP to the Pa 15% decline. Pd, Pa, and FFR were measured and 3 consecutive thermodilution curves were obtained by brisk injection of 3 ml of room temperature saline into the coronary artery, thereby enabling the calculation of mean transit time (Tmin). IMR was calculated by Pd × Tmin . IMR > 4Standard therapy for coronary heart disease was administered before and after the procedure accordingly , β-blocker, statin). Clinical events were obtained at outpatient clinic visits or by telephone contact when needed. The primary outcome was the all-cause mortality or any revascularization events. The secondary endpoint was 1-year MACE, defined as a composite of worsened heart failure, recurrent angina pectoris, recurrent acute myocardial infarction, or cardiac death.40 U group is 44.16 , and loss of follow-up is 0.1, then 9 subjects per group would be needed. All discrete or categorical variables are presented as numbers and relative frequencies (proportions), which were compared with the chi-square test or Fisher’s exact test, as appropriate. Continuous variables are presented as the mean ± SD or median (interquartile range) according to their distributions, which were compared with Student’s t test. Nonnormally distributed continuous variables were compared with the Kruskal–Wallis test. Correlations between variables were expressed with Pearson r. Cox proportional hazard regression models were used to determine predictors of the clinical end points. Statistical analysis was performed with Prism 7, and p < 0.05 was considered statistically significant.In addition to the study design, the key factor that will influence the power of the retrospective analysis is the sample size. In this research, we have estimated that if the median EF value at 1 year in IMR > 40 U group is 40.13  and that in ≤ A total of 53 anterior wall STEMI patients who were followed up without any death for 1 year were included in the present analysis  and a higher STR > 70% ratio  among patients with low IMR  and balloon dilation between the two groups, except for a significantly higher percentage of TMPG 3  or 1 month . However, the EF value in the low IMR group was significantly higher than that in the high IMR group at 3 months  and 1 year  after PCI  and 1 month  but had a negative correlation with LVEF at 3 months  and 1 year   at 24 h . However, there were 7 patients diagnosed with heart failure, which was classified II according to NYHA classification. A higher cumulative incidence of heart failure occurred in the IMR > 40 U group than in the ≤ 40 U group at the 1-year follow-up (p = 0.011). This result suggested that a higher IMR was associated with heart failure  There is a significant negative correlation between IMR and LVEF in patients with anterior wall STEMI at three months and 1-year after primary PCI; (2) The IMR is an independent predictor of heart failure at 1-year after primary PCI.The purpose of pPCI in acute STEMI was to improve myocardial perfusion and cardiac function . HoweverIMR is an invasive, readily available, quantitative and reproducible, wire-based measure of the minimal achievable coronary microvascular function that exploits the ability of one of the commercially available pressure wire systems to measure both coronary pressure and flow , 13. In There are some other predictors of post -PCI EF in ant MI patients. Hayıroğlu and colleagues assessed the prognostic value of precordial total Q wave amplitude to precordial total R wave amplitude ratio (Q/R) on 354 patients with first acute anterior MI treated with primary PCI, which indicated that Q/R is an independent prognostic factor for in-hospital mortality, cardiogenic shock and MACE . Syntax Some studies found that the CK peak concentration with an IMR value below 40 U was relatively low, the ventricular wall motion score could be significantly improved at 3 months, and better clinical prognosis was shown in the short-term follow-up , 18. PreWe further analyzed the correlation between IMR and LVEF values, and the study showed that IMR and EF values were negatively correlated at 3 months and 1 year after PCI, with statistically significant differences, which was consistent with research of McGeoch  showing Finally, IMR is useful for the early identification of long-term microvascular dysfunction in patients with acute STEMI. Current evidence supports the feasibility of studies using IMR as a predictor of microvascular dysfunction and as a measure of treatment effect. The results of this study confirm that IMR can predict the long-term cardiac systolic function of acute anterior wall myocardial infarction, and the optimization of an emergency PCI strategy based on IMR can improve microcirculatory function, thus improving the long-term cardiac systolic function. These data illustrate an insight from measuring IMR as a tool to guide the stratification of patients for adjunctive therapeutic strategies in acute ST-segment elevation myocardial infarction.The results of our study show a significant negative correlation of IMR and LVEF after primary PCI during long term follow-up. Patients with IMR > 40 U are at increased risk of the development of heart failure with in first one year after anterior wall STEMI, which indicated that high IMR may be a useful independent predictor for post-myocardial infarction cardiac function.


Huangqi Jianzhong Tang (HQJZT) is a traditional Chinese herbal formula consisting of seven different herbs: Radix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. The present study aims to evaluate the possible effects of HQJZT on cardiac function in acute myocardial infarction (AMI) and related mechanism. AMI model was established by ligation of the left anterior descending coronary artery followed by one-week HQJZT treatment. Survival rate was calculated. Rat heart function was assessed by heart performance analysis system. 5-Triphenyltetrazolium chloride (TTC) staining was used to observe myocardial infarct size. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and western blot were applied to evaluate tissue apoptotic level. Treatment with high dose of HQJZT improved cardiac function, reduced infarct size, number of apoptotic cells and expression of apoptotic proteins, Bax (a proapoptotic protein), and increased expression of antiapoptotic protein, Bcl2. However, enalapril (an angiotensin-converting enzyme inhibitor) treatment did not show marked improvement of these parameters. Our present data suggest that HQJZT has potential therapeutic effects to improve cardiac function by regulation of apoptotic signaling pathway. Heart failure is the terminal stage of cardiovascular disease. Most of the myocardial infarction (MI) cases will finally develop into heart failure. MI has become one of the main causes of death in patients with cardiovascular diseases. The common consequence of MI is cardiac tissue death induced by heart dysfunction , 2. As sTCM has long history of more than 2000 years and has gained widespread clinical applications, including in treatment of cardiovascular disorders , 7. AlthRadix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. It has been recorded on a classic TCM masterpiece “Jin Gui Yao Lue” (Synopsis of Prescriptions of the Golden Chamber), which was written by a TCM master, Zhang Zhong-Jing . HQJZT is mainly used for the treatment of chronic gastrointestinal diseases such as chronic gastritis, peptic ulcers, inﬂammatory bowel disease, autonomic dystonia, chronic hepatitis, and chronic nephritis [α-induced myocardial fibrosis in myocardial ischemia rats [Huangqi Jianzhong Tang (HQJZT) is a traditional Chinese herbal formula consisting of seven different herbs: ephritis . Basic rephritis –14. Sincmia rats . Dang Gumia rats ; Shu-maimia rats , 18. HowHQJZT was composed of seven dried raw herbs  preparedTen-week-old male Sprague-Dawley rats were purchased from Shanghai Laboratory Animal Center . Rats were housed in optimal conditions with standard hygiene, kept at a temperature of 25°C with a 12/12 light/dark cycle, fed with standard rat chow and water ad libitum. The experiments were performed in accordance with the National Institutes of Health Guidelines for the Use of Laboratory Animals , which were in accordance with the guidelines for the care and use of animals established by Soochow University of Animal Care and Use Committee . Sodium pentobarbital anesthesia was used in all surgeries, and all efforts were made to minimize animal suffering.n = 30) or with HQJZT solution for 1.44 g/kg/day  or 5.76 g/kg/day , or treated with Enalapril . Dose of Enalapril applied in the present observation was based on previous observation, which was demonstrated to improve cardiac function in chronic left ventricular dysfunction rat model [n = 10). Treatment period lasted for one week. Rats have then undergone cardiac function examination; after that, rats were sacrificed, and hearts were harvested for further analysis. Finally, each group included 10 rats.The model was performed as in our previous report . Brieflyat model . The dosp/dt max), the left ventricular end-diastolic pressure (LVEDP), etc.One week later, rats were anesthetized with sodium pentobarbital ; hemodynamic parameters were measured with a heart performance analysis system . Left femoral artery and right common carotid artery were isolated. A polystyrene PE-50 catheter  was inserted into the left ventricle via right common carotid artery, and the other end was connected to the measurement system. The major parameters of cardiac function were derived or calculated from the continuously obtained pressure signal, including systolic arterial pressure (SAP), the rate of maximum positive and negative left ventricular pressure development , rats were sacrificed, and their hearts were excised immediately and perfused with Evans blue  via the coronary artery. Hearts were transversely cut into 1-2 mm slices along the ligation point, placed in 1.25% 2,3,5-triphenyltetrazolium chloride  solution in PBS, incubated for 10 min at 37°C. The infarct tissue appeared white (not stained by TTC) and the normal tissue was red (stained by TTC); the samples were recorded by using a digital light microscope . The ratio of myocardial infarct area (white part) to whole section area (left and right ventricle section) was calculated using NIH image software .μm slices. Apoptotic cells were detected by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay kit  according to the manufacturer's instructions. Total number of 1,000 cells was counted; the mean percentage of TUNEL-positive cell was calculated.Rat hearts were sampled and fixed with 3.7% paraformaldehyde in PBS, embedded in paraffin, and cut into 5 g for 10 min at 4°C. Target proteins were separated by SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membranes . The membranes were blocked in 5% nonfat milk in PBS and 0.1% Tween-20 at room temperature. The blots were then incubated with primary antibody: anti-Bcl-2 antibody , anti-Bax antibody , anti-Caspase-3 antibody , or anti-GAPDH  for 2 h at room temperature or at 4°C overnight. Membranes were then washed for 15 minutes using TBS-T, three times. Washing was done to remove excess antibody before incubation for 1 minute with chemiluminescent reagents . Membranes were subsequently exposed to X-ray film. Immunoreactive bands were detected by analysis of X-ray films using the software Image J . The quantity of target proteins was normalized to GAPDH expression.Myocardial tissues were homogenized with radioimmunoprecipitation assay (RIPA) buffer  containing phenylmethanesulfonyl fluoride . Homogenates were centrifuged at 12,000 × P value <0.05 was considered statistically significant.The SPSS 18.0 software  was used for statistical analysis. Data are presented as the mean ± standard error mean (SEM). Grouped data was analyzed using a two-way or one-way analysis of variance followed by the Student–Newman–Keuls test for each group. A P < 0.05). There was no significant difference among all groups subjected to AMI  and mean arterial pressure (MAP), dp/dtmax . One-weePmax: the maximum of left ventricular pressure development; Pmin: the minimum of left ventricular pressure development; Pmean: the mean of ventricular pressure development; LVEDP: left ventricular end-diastolic pressure; +dp/dtmax: rates of maximum positive left ventricular pressure development; and −dp/dtmax: rates of maximum negative left ventricular pressure development. Sham represents without ligation of the left descending coronary artery group (n = 10), AMI represents acute myocardial infraction group (n = 10), AMI + low dose represents acute myocardial infarction treated with low dose of HQJZT group (n = 10), AMI + high dose represents acute myocardial infarction treated with high dose of HQJZT group (n = 10), and AMI + enalapril represents acute myocardial infarction treated with enalapril group (n = 10). ∗P < 0.05 compared with sham group. #P < 0.05 compare with AMI group.HR: heart rate; RRI: the R-R interval; SAP: systolic arterial pressure; DAP: diastolic arterial pressure; MAP: mean arterial pressure; PP: pulse pressure; P=0.088). These results suggest that HQJZT ameliorates cardiomyocyte injury and improves cardiac recovery. In addition, HQJZT showed better effect than enalapril during early phase of cardiac infarction injury.Cardiomyocyte injury is characterized by myocardial infarct size. To determine whether HQJZT attenuates cardiomyocyte injury, the ratio of infarct size to whole section was calculated. AMI group showed that the ratio of infarct size to whole section was 15.79 ± 0.92%. Treatment with low-dose HQJZT significantly reduced the ratio to 11.72 ± 1.82%; treatment with high-dose HQJZT further decreased the ratio to 3.30 ± 0.59% . HoweverTUNEL staining results showed that there were still large amounts of apoptotic cells after one-week AMI. Treatment with low-dose or high-dose HQJZT significantly reduced the percentage of TUNEL-positive cell. Enalapril treatment also reduced the percentage of TUNEL-positive cell . These rBcl-2 and Bax genes are reported to play a crucial role in cell survival or death after apoptotic stimuli. Caspase-3 is also an important component of the apoptotic signaling pathway. The effects of HQJZT on Bcl-2, Bax, and Caspase-3 expression in myocardial tissues were analyzed by western blot. AMI significantly reduced the expression of Bcl-2 protein and increased the expressions of Bax and Caspase-3 proteins. Treatment with high dose of HQJZT increased the expression of Bcl-2 when compared with AMI group  and decrIn our present study, we clearly demonstrate that HQJZT improves cardiac function and reduces myocardial infarction injury. The related mechanism may be through regulation of cell apoptosis cascades (increase of Bcl-2 and decrease of Bax and Caspase-3 expression).Radix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. Each has been widely used in traditional Chinese medicine for treatment of various diseases. Radix Astragali injection has been demonstrated to improve immune function in patients with congestive heart failure (CHF); it was proposed to be taken as an important auxiliary treatment for CHF [Radix Astragali on patients with chronic viral hepatitis B [Radix Paeoniae Alba has been used to treat coronary heart disease [Ramulus Cinnamomi was applied for treatment with hysteromyoma [Fructus Jujubae fruits on dyslipidemia in obese adolescents has been investigated, showing potential favorable effects on serum lipid profile [Fructus Jujubae was also observed [Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle has effects with respect to increasing muscle mass and suppressing the percentage of body fat in elderly populations [Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle has been used in the treatment of seasonal influenza [Rhizoma Zingiberis Recens on depressed patients [Saccharum Granorum has been shown to improve the gastrointestinal tolerability of miglustat and reduce the magnitude of changes in body weight, particularly if initiated at or before the start of therapy [HQJZT used in the present study is composed of seven herbs:  for CHF . Effectsatitis B , primaryatitis B , and sysatitis B  have bee disease  and prim disease . Ramuluseromyoma , and it eromyoma . The eff profile . Antiepiobserved . Oil froulations . Glycyrrnfluenza  and Parknfluenza . Clinicapatients  and postpatients . Sacchar therapy . The abop/dtmax) was improved after one-week treatment with HQJZT (low dose or high dose, p/dtmax; even though it markedly reduced tissue injury, our present study at least proves that HQJZT improves cardiac performance in cardiac infarction model, which is maybe dose dependent.It is well known that myocardial infarction inevitably results in damage of heart tissue and reduction of heart function ,39. FromTraditionally, it has been well recognized that cellular response to myocardial infarction is highly related to the activation of apoptotic signaling pathway . VariousIn the present study, we applied enalapril as a positive control; however, although enalapril treatment also improves the cardiac function, compared with the HQJZT, it shows less effectiveness. In addition, enalapril treatment does not show reduction in cardiac tissue injury. It should be noted that enalapril has been widely demonstrated to play a protective role in cardiac infarction model, although our present study shows less effectiveness compared with HQJZT; it may be due to the dose applied in the present study; this dose of Enalapril has been demonstrated to improve hemodynamic parameters in chronic left ventricular dysfunction rat model . It alsoIn conclusion, our present observation demonstrates that HQJZT improves cardiac function and ameliorates cardiac injury, which may be through the regulation of apoptotic signaling pathway.


Systolic left ventricular ejection fraction (LVEF) is a strong prognosticator after acute myocardial infarction (AMI). Currently, section summation of contiguous cardiac magnetic resonance (CMR) short axis steady-state free precession (SSFP) images is the reference standard for measuring LVEF.However, the use of standard CMR LVEF measurement in the early postinfarction phase is limited by the time need of image acquisition in multiple breath-holds, which is frequently not well tolerated by critically ill patients. Additional time is needed for calculating LVEF by summation of discs by semi-automated post-processing tools.Cine imaging accelerated by Temporal Parallel Acquisition Technique (TPAT) allows for the acquisition of multiple cine images in a single breath-hold. LVEF calculation from TPAT images in short an long axis orientation can be performed by a novel software tool applying four dimensional guide point modeling ventricular function analysis (4DVF). As 4DFV is based on geometric assumptions of a normal heart, it is unclear whether 4DFV is applicable to patients with AMI.To compare 4D guide-point modeling LVEF analysis of TPAT images with standard LVEF analysis in patients with AMI.27 consecutive patients  underwent CMR on a 1.5 Tesla MRI scanner  within 1 to 15 (mean 4) days after AMI.The CMR protocol included SSFP cine imaging  in 7–16 (mean 13) breath-holds and inversion recovery (IR) delayed enhancement imaging following gadolinium contrast administration.Contiguous short axis cine images were analyzed by standard left ventricular function (LVF) analysis and the disc summation method .Additionally, two long axis and four short axis cine images were acquired in a single breath-hold using a TPAT accelerated SSFP sequence . The resulting cine images were used for 4-dimensional guide point modeling LVF analysis .Both LVEF calculation methods were performed by two independent observers, and the duration of analysis was recorded.Mean infarct size was 17 ± 12% of left ventricular mass. 6 ± 3 (range 1 to 12) LV myocardial segments were affected by wall motion abnormalities. 11 patients had anterior, 16 inferior wall myocardial infarction. A strong correlation of EF values from 4DVF with standard LVF analysis was observed . The results for observer A are shown in Table 4DVF guide point modeling is a time saving alternative to standard LVF analysis. On the basis of images acquired in a single breath-hold, it yields results that are in good accordance with standard LVF analysis.A protocol combining TPAT accelerated single breath-hold imaging and 4DVF image processing may be potentially useful for the rapid assessment of LV function in critically ill patients following acute myocardial infarction.


Durable left ventricular assist device therapy has improved survival in patients with advanced heart failure refractory to conventional medical therapy, although the readmission rates due to device-related comorbidities remain high. Left ventricular assist devices are designed to support a failing left ventricle through relief of congestion and improvement of cardiac output. However, many patients still have abnormal hemodynamics even though they may appear to be clinically stable. Furthermore, such abnormal hemodynamics are associated with an increased risk of future adverse events including recurrent heart failure, gastrointestinal bleeding, stroke, and pump thrombosis. Correction of residual hemodynamic derangements post-implantation may be a target in improving longitudinal clinical outcomes during left ventricular assist device support. Automatic and timely device speed adjustments considering a patients’ hemodynamic status  are potential improvements in forthcoming devices. Despite considerable improvement in available heart failure-specific medical therapies including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone antagonists, angiotensin receptor-neprilysin inhibitors, and arginine vasopressin type II receptor antagonists, morbidity and mortality in patients with advanced heart failure remain exceedingly high .In addition to mechanical circulatory support technologies including the intra-aortic balloon pump, extra-corporeal membrane oxygenation, and percutaneous axial-flow left ventricular assist device (LVAD), cardiac replacement therapy (heart transplantation and durable LVAD) remains the gold-standard therapy for those with refractory stage D heart failure . Given tLVAD therapy improves survival in patients with advanced heart failure compared to medical therapies alone ,5; howevLVADs correct hemodynamic derangements by mechanically unloading the failing left ventricle that decreases intra-cardiac pressure and subsequently increasing systemic circulation that increases total cardiac output. However, one report showed that many LVAD patients have abnormal hemodynamics despite appearing clinically stable in the ambulatory setting . FurtherDurable LVAD technology is improving, from para-corporeal models to the implantable and smaller iterations, including both pulsatile and continuous-flow types. Notably, the dominant types in the current era are implantable continuous-flow devices  12]. Th. Th12]. 2. Notably, we can measure directly or calculate various other hemodynamic parameters using right heart catheterization, as discussed later.Nevertheless, our group recently found that many LVAD patients had abnormal hemodynamics despite showing no apparent clinical symptomology . Here, wParticularly, many LVAD patients seem to have inappropriately elevated central venous pressure indicative of sub-clinical right heart failure ,14. LVADFor several reasons, we believe that invasive right heart catheterization should be routinely performed following LVAD implantation . First, Our team recently demonstrated that the presence of abnormal hemodynamics post-LVAD implantation, even without heart failure symptoms, was associated with future instances of clinical volume overload and heart failure recurrence . As one Optimal device positioning also affects the device’s ability to effectively unload the left ventricle, with malposition of the inflow cannula associated with an increased risk of future heart failure exacerbations . LateralBleeding, particularly gastrointestinal bleeding, is among the most common comorbidities during LVAD support with an estimated incidence of 25% . Some gaThe mechanism of gastrointestinal bleeding is multifactorial . In addiThe most apparent risk factor for LVAD-associated stroke is uncontrolled systemic blood pressure . This rePump thrombosis is one of the major causes of device malfunction that requires device exchange . AbnormaSeveral unique hemodynamic patterns vary by disease state including right heart failure, pulmonary hypertension, and aortic insufficiency.We should state at first that there is no comprehensive and consistently agreed-upon definition of right heart failure . Right hAs mentioned above, right heart failure remains a highly morbid complication of contemporary LVAD therapy. Despite the pump’s purpose to restore systemic perfusion in the failing heart by unloading the left ventricle, adverse right ventricular remodeling resulting from longstanding left ventricular failure is common and challenging to correct by durable mechanical circulatory support alone. Following LVAD implantation, right ventricular preload dramatically increases due to improved systemic circulation. The right ventricle, however, is often unprepared for this drastic increase in flow due to maladaptive structural changes from the afterload of a chronically failing left heart. As a result, right heart failure can become apparent both early and in later periods following LVAD implantation. Furthermore, a decrease in the size of the left ventricle due to mechanical unloading also facilitates a geometrical unbalance between the left and the right ventricle, resulting in further impairment of normal right ventricular contractile mechanics .Elevated central venous pressures in the setting of normal pulmonary capillary wedge pressure are one of the hallmarks of right heart failure and tend to be difficult to correct alone through mechanical unloading . Right hInvasive right heart catheterization provides the clinician valuable information regarding right ventricular performance. Pulmonary artery pulsatility index, which is calculated as a pulse pressure of the pulmonary artery divided by the central venous pressure, is a recently proposed index of right ventricular function , with a Many patients with advanced heart failure have secondary pulmonary (combined pre and post-capillary) hypertension due to chronically elevated left-sided filling pressures . HoweverAortic insufficiency is a unique and progressive comorbidity during long-term LVAD support. Continuous left ventricular unloading leads to aortic valve closure and pressure increases in the aortic root via the outflow graft. This can lead to valvular degeneration, and subsequent continuous and eccentric valvular regurgitation . Aortic The severity of aortic insufficiency is assessed usually using conventional color Doppler echocardiography for visual estimation. Accurate quantification is challenging given non-physiologic continuous and eccentric regurgitant flow. Our group recently proposed several methods to more accurately quantify the severity of aortic insufficiency .First, we can estimate the degree of aortic insufficiency using a device flow monitor, which is equipped in the HeartWare LVAD . This stSecond, we can quantify the severity of aortic insufficiency using Doppler echocardiography obtained at outflow graft  53]. Th. Th53]. As discussed above, abnormal hemodynamics are associated with various adverse clinical outcomes during LVAD support. Furthermore, there are several hemodynamically unique comorbidities during LVAD support which have unique and specific management strategies.2. We simultaneously perform echocardiography to assess for aortic valve opening, to understand the interventricular septum position, and to determine the presence of mitral valve regurgitation at each speed interval . It. It61]. The CardioMEMS device might have the potential to be utilized in LVAD patients to monitor and adjust device parameters in response to hemodynamic status . This isReDS is another promising tool to noninvasively estimate intra-thoracic fluid levels , which mThe HeartWare LVAD provides an estimated instantaneous flow waveform that shows insights into patients and device properties. For example, low pulsatility and low mean flow indicate hypovolemia, whereas low pulsatility and high mean flow let us detect suspected device thrombosis. High pulsatility and low mean flow might indicate continuous suction, whereas high pulsatility and high mean flow indicate volume overload. LVAD flow is determined by the pressure difference between the aorta and left ventricle at a fixed device speed. When aortic pressure is assumed to be constant at the diastole phase, LVAD flow is dependent on left ventricular pressure. When left ventricular pressure increases, LVAD flow often increases. Given this mechanism, pulmonary capillary wedge pressure can be estimated by the slope of LVAD flow at the end-diastolic phase  66]. We. We66]. Future advances in durable mechanical support may include a smart pump concept, which can automatically adjust device speed by continuously monitoring hemodynamic data points. For example, a novel smart pump might automatically measure the HeartWare LVAD flow slope and adjust its rotational speed considering estimated intra-cardiac pressure . If the Despite durable LVAD support, many patients can have abnormal hemodynamics due to a variety of clinical conditions even when clinically stable. LVAD therapy has improved survival in patients with advanced heart failure, though considerable limitations remain including unacceptably high readmission rates due to these various comorbidities, including volume overload and hemocompatibility-related adverse events. Assessment and optimization of hemodynamics might be one of the modifiable targets which could reduce the burden of these common post-implant complications. Interventions to optimize the hemodynamic status by adjustments of device speed and medications might improve clinical outcomes, though further large-scale prospective randomized control trials are needed to study these interventions. In the interim, noninvasive methods that estimate hemodynamics, including CardioMEMS, ReDS, and HartWare LVAD waveform analyses, may prove to be useful in more precisely guiding daily LVAD management.


This study was conducted to detect the association between radiologic features of CT pulmonary angiography (CTPA) and pulmonary embolism severity index (PESI).P value < 0.05 was considered as statistically significant.A total of 150 patients with a definite diagnosis of PE entered the study. The CTPA feature including obstruction index, pulmonary trunk size, presence of backwash contrast, septal morphology, right ventricular (RV) and left ventricular (LV) dimensions, and RV/LV ratio were examined. The severity of the PE was estimated using PESI. The association between CTPA indices and PESI was measured. Statistical analysis was conducted using the SPSS software. r = 0.45, P < 0.05). Moreover, PESI was significantly higher in patients with a more dilated pulmonary trunk . The backwash contrast and abnormal septal morphology were significantly more common among patients with higher PESI (P < 0.05). However, no significant correlation was detected between RV, LV, RV/LV, and PESI. The most predictor of high-risk PE was dilated pulmonary trunk with an odds ratio of 4.4.A positive correlation was detected between the obstruction index and PESI (Higher Obstruction index, dilated pulmonary trunk, presence of backwash contrast, and an abnormal septal morphology can be associated with a higher PESI. Pulmonary embolism (PE) is a type of thromboembolism that refers to obstruction of the main pulmonary artery or its branches. PE may cause various clinical presentations and even death. To reduce the morbidity and mortality caused by PE, an efficient diagnostic approach is needed for quick detection of the pathology in patients with suspected PE .Computerized tomography pulmonary angiography (CTPA) is the gold standard technique in detecting PE with high sensitivity and specificity . Since CPE can cause an increase in right ventricular (RV) afterload and dilation of RV. It may lead to a decreased LV function and output and a decrease in coronary artery supply. The reduction of blood flow to the coronary artery can cause RV dysfunction . RadioloDespite some studies conducted on the predictive value of CTPA indices on PE outcomes, the association between several CTPA measures of RV function and PE severity is still controversial. In this study, we aimed to detect the correlation between these indices and pulmonary embolism severity index (PESI) in patients diagnosed with PE.This was a retrospective cohort study that was conducted on patients with a diagnosis of PE in CTPA who were referred to the Radiology Department of Al-Zahra hospital, Isfahan University of Medical Sciences, Isfahan, Iran, between April 2018 and May 2019. Patients with age > 18 years, no history of thromboembolism, thrombolytic, and anticoagulant use were included in the study.The study was approved by the ethics committee of the Radiology Department, Isfahan University of Medical Sciences, Isfahan, Iran. The purpose of the study was described to patients, and all participants provided written consent to participation.All images were obtained using a 128-section multi-detector CT scanner based on the standard CTPA protocol for PE  and 20 s after administration of 100 ml contrast media at a rate of 5 ml/sec.CTPA indexes including obstruction index, RV and LV dimension, RV/LV ratio, pulmonary trunk size, presence of backwash contrast, septal bowing, and location of embolism were evaluated. The obstruction index was measured using the Qandali score . RV and Pulmonary embolism severity index (PESI) was used to estimate the 30-day outcome and was obtained by summing the patient’s age in years and point assigned for each of the 10 predictors as follows: 10 points for male sex, 30 points for a history of cancer, 10 points for a history of heart failure, 10 points for a history of chronic lung disease, 20 points for tachycardia (pulse rate ≥ 110/min), 30 points for systolic blood pressure < 100 mmHg, 20 points for tachypnea (respiratory rate ≥ 30/min), 20 points for temperature < 36 °C, 60 points for an altered mental status, and 20 points for arterial oxygen saturation < 90% [t test, and chi-square test were used to perform the analyses. Odds Ratio (OR) was reported for the effective variables. P < 0.05 was considered as the statistical significance level.All statistical analyses were performed using the SPSS software, version 21 . The mean ± standard deviation (SD) value was used for the analyses of quantitative variables. Frequency and percentage were used to represent qualitative variables. Pearson correlation, independent sample In this study, 150 patients including 97 (64.7%) males and 53 (35.3%) females entered the study. The patients aged from 12 to 91 years old with a mean ± SD of 56.9 ± 17.9 years. The calculated PESI was ranged from 11 to 170 with a mean ± SD of 90.0 ± 30.1. None of the patients had hemodynamic instability and massive PE. Based on American Heart Association (AHA) classification, 90 (60%) and 60 (40%) patients had sub-massive and low-risk PE, respectively.r = 0.45, P < 0.001), and patients with high-risk PE had significantly higher PESI than those with low-risk PE (P < 0.05) . The high-risk PE was significantly more common among patients with a dilated pulmonary artery  . An increase in the PESI was detected with the increase in pulmonary trunk size (P = 0.778), LV (P = 0.595), RV/LV (P = 0.857), troponin level (P = 0.141), and D-dimer level (P = 0.846).RV/LV ranged from 0.53 to 13.28 with a mean of 1.01 ± 1.07. The mean troponin and D-dimer serum levels were 78.74 ± 145.26 and 3806.42 ± 12446.37, respectively. No correlation was detected between PESI and RV (P < 0.05) (Table P < 0.05) with a higher rate of backwash contrast in patients with high-risk PE.Backwash contrast into IVC was detected among 67 (44.7%) of individuals. PESI was significantly higher in patients with backwash contrast than those without a backwash contrast (5) Table . The preP < 0.05).Interventricular septum bowed to the right side in 91 (60.7%) of patients, while bowing to left, and straight septum was detected in 5 (3.3%) and 54 (36.0%) of individuals, respectively. The frequency of patients with abnormal interventricular septal morphology was significantly higher among patients with high-risk PE (P < 0.05). However, no significant difference was detected between PESI in PEs located in the main and lobar pulmonary arteries (P = 0.233).PESI was significantly lower in patients with segmental artery PE than those with lobar or main artery PE (This study was conducted on 150 patients with an approved PE diagnosis to detect the CTPA indices indicating the PE with higher PESI. We found the obstruction index, the pulmonary trunk size, the presence of backwash contrast into IVC, and the abnormal septal morphology as predictive factors of higher PESI. We also investigated the dilated pulmonary trunk as the most effective predictor.Among the signs included in the study, backwash contrast was significantly correlated with PESI. The result, in concordance with other studies, reported the presence of mentioned sign as a risk factor for mortality –13. The In this study, an abnormal septal morphology was significantly more common among patients with a high-risk PE. Interventricular septal morphology is caused by an increase of right ventricular pressure secondary to PE. It sometimes causes a leftward shift of interventricular septum that may lead to a decrease in left ventricular filling and a reduction of cardiac output, causing right ventricular wall ischemia, impaired heart function, and a poor prognosis for patients with PE .In the present study, pulmonary trunk size was positively correlated with PESI. Patients with high-risk PE had significantly higher pulmonary trunk diameter. In this study, the value of 29 mm was established for the maximal value for normal pulmonary artery diameter. Also, we found that the dilated pulmonary artery had the highest OR = 4.4 in comparison with other predictors including abnormal septal morphology or the presence of backwash contrast. It suggests the idea that pulmonary trunk size can be used as a factor in prediction of patients with high-risk PE. The association between pulmonary artery diameter and short-term clinical outcomes was observed in a report of Lyhne et al. However, they did not report the pulmonary artery diameter as a strong predictor of PE outcomes .There are many studies on the association between RV/LV ratio and PE outcomes. RV/LV ratio greater than 0.9 in the short axis was proposed as a sign of poor outcome and a higher 30-day risk of mortality –19. HoweIn addition to clinical symptoms and imaging features, there are many laboratory tools that are frequently utilized in patients with suspected PE, including arterial blood gas, brain natriuretic peptide, troponin, and D-dimer. These tests are not diagnostic, but they may have some prognostic values , 25. In Although this study identified CTA indices related to higher PESI in patients with stable hemodynamic, it cannot be generalized to all patients with PE. None of the participants in this study had a massive PE. Another study is needed to identify the predictive features of CTA in patients with hemodynamic instability.In conclusion, this study suggests the CTPA indices including obstruction index, presence of backwash contrast, dilated pulmonary trunk, and presence of an abnormal septal bowing as indicators of high PESI. The physicians can use these imaging features to distinguish high-risk patients and make effective therapeutic managements.


LVEF increased from 34.1 ± 8.6% to 38.0 ± 10.0% (p = 0.031) and 6MWD increased from 393.4 ± 95.9 m to 432.8 ± 93.3 m (p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers—serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6 ± 82.6 U.CARR to 346.5 ± 56.9 U.CARR ( Astaxanthin, a carotenoid like β-carotene and lycopene, is widely distributed in nature, especially in deep-red-colored natural sea products such as salmon, salmon roe, shrimp, and crab . As humaIn patients with HF, oxidative stress worsens the progression of HF . TherefoWe enrolled patients with systolic HF at Juntendo University Hospital  if they met the following criteria: men and women aged ≥20 years, patients with HF due to ischemic or non-ischemic cardiomyopathy, patients with an LV ejection fraction (LVEF) <50% on echocardiography, patients labeled as New York Heart Association (NYHA) functional class ≥II, and patients with a stable clinical status evidenced by the absence of symptoms related to the acute exacerbation of HF. Exclusion criteria were as follows: patients who cannot perform a 6-min walk test; those who cannot answer the questionnaire without assistance; current smokers; patients with acute coronary syndrome or that have had cardiac surgery during the previous 4 weeks; patients with organic valvular heart diseases, chronic inflammatory diseases, chronic lung diseases, or malignancies; and patients under dialysis. This prospective observational pilot study (UMIN-ID: 000014088) was approved by the Juntendo University Hospital Institutional Review Board (#14-019), and complied with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.On the morning of the day before starting astaxanthin supplementation, height and weight were measured, body mass index (BMI) was calculated, blood pressure and heart rate were measured, and venous blood samples were obtained after an overnight fast. The estimated glomerular filtration rate (eGFR) based on serum creatinine level was assessed . Plasma To assess cardiac function, cardiac chamber quantification using 2-dimensional echocardiography was performed according to American Society of Echocardiography guidelines  on the dIn this prospective small uncontrolled pilot study, once daily for 3 months, patients orally ingested a commercially available astaxanthin supplement containing 12 mg of astaxanthin, 40 mg of tocotorienol, and 30 mg of L-ascorbic acid 2-glucoside . The patients visited our HF clinic every month, and no changes in the other medications were allowed during the study period. Measurements of BMI, blood pressure, and heart rate were performed at every clinic visit. Blood and urine sampling, echocardiography, and 6-min walk test were repeated at a follow-up visit 3 months after starting astaxanthin supplementation.p value < 0.05 indicated statistical significance. Analyses were performed by SPSS 23.0 .Because there were no data regarding the effects of astaxanthin supplement on patients with HF, we did not calculate a specific sample size and instead conducted the present study as a pilot study. Nevertheless, we planned to perform analyses once ≥15 patients had completed their 3-month follow-up period. Values are expressed as mean ± SD for normally distributed data or median [interquartile range] for non-normally distributed data. Correlations between the baseline HF-related parameters  and oxidative stress/inflammatory markers  were assessed using the Pearson and Spearman correlation coefficients for normally and non-normally distributed data, respectively. Differences between baseline and follow-up measurements were compared using paired t-test for normally distributed data or Wilcoxon signed-rank test for non-normally distributed data. Changes in parameters from baseline to 3 months  were calculated as Δ = [ − ] and expressed as %Δ [Δ/ × 100] except for plasma astaxanthin concentration because astaxanthin was not detected at baseline in most participants. Relationships across changes or percent changes in parameters were assessed using Pearson correlation coefficient for normally distributed data and using Spearman correlation coefficient for non-normally distributed data. A r = −0.516; p = 0.041), whereas no such correlations were observed between the baseline dROM and BNP levels or 6MWD . In addition, no significant correlations were found between the other oxidative stress/inflammatory markers  and the baseline HF-related parameters .Overall, 19 eligible patients were enrolled, all of whom had been diagnosed as having HF and treated for at least 6 months at enrollment. All the other medications remained unchanged during the study period. Three patients were excluded, two because of lost follow-up records and one because of worsening spinal stenosis at follow-up that caused difficulty during the 6MWD test. Thus, data of 16 patients were analyzed. Characteristics of these patients are summarized in p < 0.001). No complaints or adverse events related to astaxanthin administration were observed. From baseline to 3 months, dROM decreased significantly .A significant correlation was found between the baseline dROM level and the %Δ in dROM level , whereasp-values regarding relationships between Δ in astaxanthin levels, %Δ in inflammatory and oxidative stress markers, and %Δ in cardiac functions from baseline to 3 months are shown in Correlation coefficients and Findings of the present prospective small uncontrolled study provide several novel insights into the effects of astaxanthin supplementation on patients with HF. First, augmented baseline oxidative stress level as expressed by increased dROM level was associated with impaired LV systolic function at baseline. Second, 3-month daily oral administration of a commercially available astaxanthin supplement significantly increased the blood concentration of astaxanthin in the HF patients. Third, the dROM results showed a decrease in blood oxidative stress after the 3-month astaxanthin supplementation, whereas the 8-OHdG results showed no decrease in urinary oxidative stress. Fourth, the higher the baseline oxidative stress level, the greater the reduction of blood oxidative stress. Fifth, the serum inflammatory markers did not change after the supplementation. Sixth, improved LV systolic function was observed after the 3-month supplementation. Seventh, exercise tolerance improved after the 3-month supplementation. Finally, significant correlations were observed between the reduction in oxidative stress and the improvement in both the LV systolic function and degree of LV remodeling. These findings suggest that 3-month astaxanthin supplementation improves LV systolic function and exercise tolerance possibly due to the reduction in oxidative stress.Following 3-month oral administration of a commercially available astaxanthin supplement containing 12 mg of astaxanthin, plasma concentration of astaxanthin was 133.7 [122.1] ng/mL. This value is comparable to the plasma astaxanthin concentration observed in a previous study in which plasma concentration of astaxanthin was measured following the 3-week oral administration of 5 mg and 20 mg of astaxanthin in otherwise healthy overweight and obese subjects . In thatPark et al. reported that astaxanthin supplementation for 8 weeks reduced plasma levels of oxidative stress markers such as 8-OHdG and 8-isoprostane in healthy young women . In addiIn one randomized, placebo-controlled, double-blind clinical trial, effects of astaxanthin on surrogate markers of atherosclerosis and arterial stiffness—including aortic pulse wave velocity, augmentation index, brachial forearm reactivity, and carotid artery intima-media thickness—were assessed in kidney transplant recipients . Such paIn terms of exercise tolerance, astaxanthin supplementation may improve 6MWD possibly due to improvement of cardiac function. However, as mentioned earlier, astaxanthin may have a direct effect on skeletal muscles, as evidenced in mice . In a raOur study is subject to some limitations. First, because this was an observational study without control groups, no causal relationship between astaxanthin supplementation and improvements in cardiac function and exercise tolerance was proven. Second, although we found a significant correlation between the reduction in oxidative stress markers and the improvements in cardiac function, the variability of the oxidative stress measurements over time may play some roles. In addition, the improvement in cardiac function may have initially occurred through a mechanism independent of the suppression of oxidative stress. Further, the reduction in dROM level may have occurred as a result of improved cardiac function. Third, the astaxanthin supplement used in the present study containing 40 mg of tocotorienol and 30 mg of L-ascorbic acid 2-glucoside in addition to 12 mg of the astaxanthin. Because both tocotorienol and L-ascorbic acid 2-glucoside also have antioxidant properties, they may too have the potential to reduce dROM and subsequently improve cardiac function. However, because astaxanthin has a stronger antioxidant effect , we beliIn conclusion, this pilot study found that after 3 months of astaxanthin supplementation, the levels of the oxidative stress markers decreased and improvements were observed in both cardiac contractility and exercise tolerance in the HF patients with LV systolic dysfunction. In addition, improvements in cardiac function correlated significantly with the suppression of oxidative stress, suggesting that suppression of HF-associated oxidative stress by astaxanthin supplementation may have therapeutic potential for improving underlying cardiac dysfunction and impaired exercise capacity.


Adults with congenital heart disease represent a complex and growing patient population. By virtue of their variant anatomy and the complex surgical repair often required in infancy, these patients are at risk of developing unique atrial and ventricular arrhythmias throughout their lifetimes. Electrophysiologists involved in the care of these patients should have a detailed understanding of their underlying anatomy and any prior surgical procedures to guide procedural planning and should have knowledge of the range of possible arrhythmia mechanisms that may differ from patients without structural heart disease. Despite this complexity, standard mapping techniques and electrophysiologic maneuvers may still be used to elucidate arrhythmia mechanisms, map tachycardia circuits, and guide catheter ablation. We report a case of two different macroreentrant right atrial tachycardias that were successfully ablated in a patient with congenitally-corrected transposition of the great arteries. As the morphologic right ventricle (RV) supplies oxygenated blood to the systemic circulation and the morphologic left ventricle (LV) supplies deoxygenated blood to the pulmonary circulation, patients are not typically cyanotic. However, cc-TGA is frequently associated with other congenital cardiac defects, including ventricular septal defects (VSDs) (60%–80%), pulmonary stenosis (30%–50%), and conduction system abnormalities (15%–50%). was transferred to our hospital following an episode of syncope and tachycardia. On the day of her presentation, she reported showering and experiencing a sudden onset of chest pain, palpitations, shortness of breath, headaches, and vision changes. This was accompanied by syncope. Her family also reported an episode of near-syncope approximately two weeks before this event; at the time, it was attributed to summer heat and underhydration. At an outside facility, her heart rate was recorded as 238 bpm and an electrocardiogram (ECG) confirmed a diagnosis of SVT. A dose of atenolol 12.5 mg was given, which resulted in brief periods of sinus rhythm, followed by the resumption of sustained SVT. She was also given three boluses of adenosine  without tachycardia termination. She was finally given an intravenous dose of 5 mg metoprolol, after which point, she converted to sinus rhythm. She was then transferred to our pediatric intensive care unit (ICU).A 15-year-old female with a medical history of cc-TGA, perimembranous VSD status following surgical closure, severe tricuspid regurgitation status following right atriotomy and mechanical tricuspid valve replacement, and pulmonary valvar and subvalvar stenosis status following LV-to–pulmonary artery (PA) extracardiac conduit with subsequent thrombosis On initial examination, she was afebrile and hemodynamically stable with a blood pressure of 113/65 mmHg and a heart rate of 120 bpm. Her cardiac examination revealed a resting tachycardia with a regular rhythm. She had a grade 3 harsh systolic ejection murmur at the left sternal border, normal mechanical valve click, and prominent apical heave. Her physical examination was otherwise unremarkable. Laboratory data on admission including serum chemistries, complete blood count, thyroid function studies, and cardiac biomarkers were unremarkable.. A transthoracic echocardiogram showed expected postsurgical changes related to her congenital heart disease (CHD) and a normally functioning tricuspid valve prosthesis. She also demonstrated underlying moderate systemic RV enlargement with RV systolic dysfunction.A review of her initial ECG demonstrated suspected atrial tachycardia with 1:1 AV conduction and baseline right bundle branch block . Atrial and ventricular activations were dissociated during tachycardia, excluding orthodromic reciprocating tachycardia and making AV-node reentry less likely.Given her history of complex CHD and highly symptomatic SVT, she was referred for invasive electrophysiologic study. At baseline, she had no evidence of dual AV nodal physiology on either decremental atrial pacing or during the measurement of the antegrade AV-nodal effective refractory period. The location of the AV nodal complex was usually situated. Retrograde atrial activation was decremental and concentric. Burst pacing from the RA appendage induced SVT (with a tachycardia cycle length of 262 ms) ® catheter  using the Carto® 3 electroanatomic mapping system . Propagation mapping was consistent with counterclockwise cavomitral isthmus– dependent atrial flutter . A ThermoCool SmartTouch® ablation catheter  was positioned in the cavomitral isthmus and entrainment from this location yielded concealed fusion and a postpacing interval equal to the tachycardia cycle length .High-density mapping of the RA was performed during tachycardia with the PentaRayAblation was performed during tachycardia in a slightly lateral location along the cavomitral isthmus to create a continuous lesion from the mitral annulus to the inferior vena cava. It was noted during catheter manipulation along this region that the curvature of the mitral annulus was demonstrably less convex than as is typically appreciated during cavotricuspid isthmus ablation. Tachycardia terminated during radiofrequency (RF) energy delivery, but pacing from the proximal coronary was suggestive of residual conduction through the isthmus. A series of consolidation lesions were delivered, yielding widely split double potentials, and bidirectional block was demonstrated using differential pacing. Repeat mapping was also performed during proximal coronary sinus (CS) pacing, which demonstrated “high-to-low” activation, consistent with block across the isthmus.. This tachycardia was hemodynamically unstable and required synchronized direct current cardioversion. The cavomitral isthmus was remapped during proximal CS pacing, which demonstrated persistent conduction block. Tachycardia was re-induced and persisted with 2:1 AV conduction. Activation mapping was again performed with the multipolar mapping catheter, which demonstrated a macro-reentrant atrial tachycardia originating from the RA free wall .Following this, low-dose isoproterenol was initiated. Burst pacing was again performed, which induced SVT with a slightly different atrial activation sequence (tachycardia cycle length: 236 ms) and 1:1 AV conduction With manipulation of the bipolar voltage calipers, several small channels were identified that corresponded to areas of slow conduction identified during activation mapping. Entrainment was performed in this region, yielding concealed fusion with a postpacing interval minus the tachycardia cycle length equal to 21 ms. RF application here resulted in tachycardia termination. A series of consolidation lesions were placed in areas where low bipolar voltage corresponded to arrhythmogenic channels identified in the propagation map. These were mainly located in areas of putative scar border zone and diastolic activity during tachycardia along the RA free wall. Afterward, extensive atrial burst pacing both during isoproterenol infusion and washout failed to induce any further SVT. She returned to the pediatric ICU without complications, recovering well. She was started on atenolol 25 mg once daily and discharged home the following day on her chronic medical regimen. She showed no subsequent SVT at six months of follow-up.5 Furthermore, the complex anatomic arrangement of conduction systems within the cc-TGA heart may lead to normal, anterior, or dual AV nodal systems, adding to variability in arrhythmia presentation.6 Our patient’s particular subset of associated congenital defects and surgical history makes her condition exceptionally rare.Patients with cc-TGA are rare, accounting for just 0.05% of all patients with CHD.10 Of significant concern among all types of CHD is the recurrence of previously ablated or the appearance of new atrial arrhythmias. Newer mapping methods, including the use of high-density mapping, reduce the number of lesions  required in ablation, which is likely to limit the likelihood of the creation of new arrhythmia substrate. Recurrence generally occurs within the first year after ablation (88%); those who do not experience a recurrence within this time period have a 91% chance of long-term cure.11The success of catheter ablation in adolescents and adults with CHD has improved significantly over time, likely related to advances in high-density mapping technology and ablation techniques.12 Reports of tachyarrhythmia treatment in the cc-TGA patient are sporadic, making it difficult to generalize about likely arrhythmia mechanisms.17 Studies focused upon atrial tachycardia in surgically repaired CHD do not typically carry sample sizes large enough to demonstrate isolated unique findings in the cc-TGA patient. In one study examining atrial tachycardia following the surgical repair of CHD, two of two patients with cc-TGA showed intra-atrial reentrant tachycardia (IART), whereas only three of six patients with dextro-transposition of the great arteries (d-TGA) displayed IART. This result may be linked to the particular type of procedure performed; while all six d-TGA patients underwent either a Mustard or Senning procedure, cc-TGA patients in this study received excision of subvalvular pulmonary stenosis, which possibly contributed to the arrhythmogenic substrate.18The overall prevalence of atrial tachycardia in patients with a transposition complex is 28%, although less is specifically known about the cc-TGA population.20 In general, typical atrial flutter using the cavotricuspid isthmus is the most common atrial arrhythmia mechanism in adult CHD patients,20 likely due to an increased degree of conduction delay through the crista terminalis and prolongation of atrial muscle refractoriness caused by atrial dilation and remodeling.23 While our patient’s systemic venous AV valve was a mitral valve , ablation of the initial atrial tachycardia was successful by transecting the cavomitral isthmus, suggesting that the underlying arrhythmia substrate is likely similar to that of anatomically normal patients with typical atrial flutter. As such, typical differential pacing maneuvers can be adopted to confirm conduction block as was the case in our patient.In patients with biventricular physiology following surgical repair of complex congenital cardiac lesions, the two most important anatomic obstacles allowing for RA macro-reentry are the tricuspid annulus and right atriotomy.24 Importantly, the atrial activation sequence during tachycardia cannot reliably distinguish between tachycardia mechanisms unless multiple RA catheters are used. Thus, electroanatomic activation mapping and entrainment mapping are important tools for defining the arrhythmia mechanism as well as identifying critical components of the reentrant circuits that are amenable to ablation. In our patient, the initial tachycardia was confirmed to be a cavomitral isthmus–dependent flutter by activation and entrainment mapping.As seen in the present case, IART is the next most common atrial arrhythmia mechanism in patients with prior surgery for CHD.Meanwhile, the second atrial tachycardia had a similar activation sequence but showed essentially vertical activation in the CS recordings. Typically, this is suggestive of a focal left atrial tachycardia, peri-mitral reentry, or roof-dependent flutter. However, as noted above, mapping and entrainment maneuvers identified this tachycardia as IART using the lateral atriotomy. There are several possible explanations for these disparate findings. In general, left atrial activation depends upon conduction over Bachmann’s bundle, through the interatrial septum, and through the CS musculature. In normal subjects, early activation is often noted in the distal CS due to Bachmann’s bundle connections near the base of the left atrial appendage. In this patient, slow conduction through the CS muscle and interatrial septum during IART may have allowed for a relatively greater contribution from Bachmann’s bundle to left atrial activation. Additionally, the tendon of Todaro and crista terminalis create natural barriers to conduction into the lower RA and, in the setting of altered intra-atrial conduction due to prior cardiac surgery, this may have preferentially directed activation through Bachmann’s bundle, leading to the resulting CS recordings seen in this case.24 Thus, voltage mapping can also be used to identify the critical circuit isthmus. The bipolar electrogram amplitude used to define scar varies: while many studies to date have defined scar as areas with a bipolar voltage of less than 0.1 mV, Nakagawa et al. only considered true scar as areas with no electrogram recorded above background noise, which can be as low as 0.03 mV. In the small study by Nakagawa et al., nearly half of successful ablation sites (7/15) were located in areas that would otherwise have been defined as “nonconducting scar” using a definition of bipolar voltage being less than 0.1 mV.25 Of obvious importance when using this approach is the assessment of the background noise present during mapping, which can vary significantly from laboratory to laboratory and which is affected by many external factors including cabling through the laboratory, proximity to alternating current power sources, and patient warming devices. In the present case, we were able to manipulate the voltage calipers in the mapping system to identify channels of relatively lower voltage coursing through the scar, which allowed us to create a complete line of block through the scar and prevent further SVT. Notably, using this approach, the absolute bipolar voltage below which the “scar” is annotated was less important than the relative voltage traversing between the putative slow-conduction channels and normal tissue. Channels identified in this manner can be compared to the activation map of the tachycardia to determine which channels may form critical circuit elements.The arrhythmia substrate in IART likely relies on low-voltage “channels” coursing through the scar that allow for the slow conduction required for sustained reentry.We report a rare case of a cc-TGA patient with prior tricuspid valve replacement and RV outflow tract surgery in whom multiple atrial tachycardias causing syncope were successfully treated with catheter ablation. The combinatorial use of activation, entrainment, and voltage mapping may assist in the ablation of atrial arrhythmias in complex CHD, whereas high-density mapping can be used to augment the understanding of a tachycardia’s endocardial activation sequence and scar border zones. In the cc-TGA patient, an awareness of inherent anatomical nuances coupled with the potential for multiple tachycardia mechanisms is essential to periprocedural planning and successful mapping and ablation.


Ventricular fibrillation (VF) and sudden cardiac death (SCD) are predominantly caused by channelopathies and cardiomyopathies in youngsters and coronary heart disease in the elderly. Temporary factors, e.g., electrolyte imbalance, drug interactions, and substance abuses may play an additive role in arrhythmogenesis. Ectopic automaticity, triggered activity, and reentry mechanisms are known as important electrophysiological substrates for VF determining the antiarrhythmic therapies at the same time. Emergency need for electrical cardioversion is supported by the fact that every minute without defibrillation decreases survival rates by approximately 7%–10%. Thus, early defibrillation is an essential part of antiarrhythmic emergency management. Drug therapy has its relevance rather in the prevention of sudden cardiac death, where early recognition and treatment of the underlying disease has significant importance. Cardioprotective and antiarrhythmic effects of beta blockers in patients predisposed to sudden cardiac death were highlighted in numerous studies, hence nowadays these drugs are considered to be the cornerstones of the prevention and treatment of life-threatening ventricular arrhythmias. Nevertheless, other medical therapies have not been proven to be useful in the prevention of VF. Although amiodarone has shown positive results occasionally, this was not demonstrated to be consistent. Furthermore, the potential proarrhythmic effects of drugs may also limit their applicability. Based on these unfavorable observations we highlight the importance of arrhythmia prevention, where echocardiography, electrocardiography and laboratory testing play a significant role even in the emergency setting. In the following we provide a summary on the latest developments on cardiopulmonary resuscitation, and the evaluation and preventive treatment possibilities of patients with increased susceptibility to VF and SCD. Ventricular fibrillation (VF) is an emergency condition that, without immediate treatment, leads to death. In the event of this malignant ventricular arrhythmia chaotic, disorganized electrical activity appears in the ventricular myocardium. In such cases the heart is unable to transport blood effectively, which leads to circulatory collapse, clinical death, and if left unattended, biological death. Sudden cardiac death (SCD) is a leading death cause all over the world, affecting some 5 million people a year  with a lThe most common factors that may contribute to the development of VF are acquired risk factors, e.g., ischemic heart disease, cardiomyopathies, electrolyte imbalances, certain drug therapies affecting myocardial repolarization, and less frequently inherited disorders, e.g., ion channel abnormalities (channelopathies), congenital valvular diseases, and coronary artery anomalies. Table 1 KCNQ1 or the KCNH2 (hERG) genes have been clarified. These genes encode the potassium channels responsible for the slow (IKs) and rapid component (IKr) of the delayed rectifier repolarising potassium current, respectively. Beyond KCNQ1 (LQT1) and KCNH2 (LQT2), SCN5A (LQT3) is the third most frequently affected gene that plays a role in the genesis of LQTS. Mutation of the SCNA5 contributes to an increase in the depolarising sodium inward current leading to the consequent prolongation of the QT interval , are important pathogenetic factors . In 70% interval . Furtherinterval . In the  to CPVT . The Bru to CPVT . Nearly en found . Howeverebatable . The higpatients . Severalpatients  Arrhythmpatients . The sinpatients .to) are also different. These dissimilarities can form a transmural voltage gradient during the activation of the ventricular myocardium. As a result, increased ventricular electrical anisotropy and an enhanced ventricular arrhythmia vulnerability may appear (to and delayed rectifier potassium currents (IKr and IKs currents of K channels encoded by KCNH2 and KCNQ1 genes) that may enhance the effect of proarrhythmic factors  (to) and the decrease of rapid and slow components of the delayed rectifier currents  can contribute to the prolongation of APD. Regarding HF, the overexpression of HCN2 and HCN4 genes can appear resulting in an increased pacemaker current (If) not only in the SA node, but in the ventricular tissue, too. The electrical remodeling of the heart can lead to a reduced ventricular repolarization reserve, increasing the risk of ventricular arrhythmias based on triggered activity, ectopic automaticity, and reentry mechanisms (ATP channels) localized in the sarcolemmal membrane may be activated by metabolic stress or ischemia causing the shortening of APD, preventing the heart from calcium overload and contraction abnormalities. Moreover, myocardial hypertrophy and ischemia can increase the expression levels of Kir 6.1 and Kir 6.2 KATP channels, leading to an increased risk for ventricular dysrhythmias based on heterogeneous shortening of the AP  as a compensatory mechanism in order to prevent the prolongation of repolarization. Furthermore, congenital alterations in ion currents of the myocardium, heart failure, cardiac hypertrophy, bradycardia, increased sympathetic activation, female gender, recent pharmacological conversion from atrial fibrillation to sinus rhythm, use of diuretics, hypokalemia, hypomagnesemia, administration of class IA, IC or III antiarrhythmic drugs or agents with IKr blocking effect can decrease repolarization reserve. Co-occurence of certain conditions which affect more than one type of ion currents involved in regular repolarization may critically reduce repolarization reserve and can result in proarrhythmia  heterogeneity and secondary anisotropy of the ventricular myocardium play a crucial role in the genesis of VF. The monophasic action potentials (MAPs) characterising the electrical feature of a myocardial cell in the endocardial, mid-myocardial, and epicardial layers differ from each other, where types and expression levels of potassium channels responsible for transient outward currents (Iy appear . Anisotry appear . The macy appear . Scars ay appear . In the y appear  Heart fac drugs) . In the c drugs) . In the chanisms . ATP-senf the AP . In 1998rhythmia .ectopic automaticity, reentry and triggered activity (due to early and late afterdepolarizations)  Figure 1zations) .Ectopic automaticity is the result of spontaneous diastolic depolarization, where current of injury  due to acute ischemic damage is an important provoking mechanism   .Triggered activity may also appear as a consequence of early (EAD) or delayed afterdepolarization (DAD). EAD is caused by the early reactivation of L-type Ca-channels, a consequence of a decrease in repolarising potassium currents or an increase in the activity of positive currents toward the intracellular space  may be of help in predicting life-threatening ventricular dysrhythmias and clarifying the underlying arrhythmia mechanism. Holter ECG may be useful in arrhythmia risk stratification . Echocardiography is widely used to determine structural and functional abnormalities of the heart. Accumulation of connective tissue in the left ventricle (scar burden) and fatty tissue in the right ventricle (ARVD) can be examined by MRI. Coronary CT angiography and coronarography may be of help to recognize coronary artery disease as a possible underlying arrhythmogenic factor. Electrophysiological testing is suitable for the examination of VT/VF inducibility and for the definition of the arrhythmia foci. Serum level of certain biomarkers may also be taken into consideration as part of ventricular arrhythmia risk assessment .Considering laboratory biomarkers, in addition to the now more widely used NT-proBNP and the high-sensitive troponin T, osteopontin, galectin-3, and soluble ST2 can also be applied to determine the arrhythmia vulnerability of the ventricular myocardium . NT-proBLeft ventricular ejection fraction (EF) measured during echocardiography is suitable for predicting malignant ventricular arrhythmia and, according to current knowledge, is the only echocardiographic parameter with predictive value for an increased risk of sudden cardiac death in the case of ischemic heart disease and left ventricular dysfunction . EchocarAnother opportunity is to perform a cardiac MR, which thanks to its high resolution gives a more precise picture of wall motion disorders, is suitable for performing more refined volumetric measurements and provides a better approximation of the left ventricular mass than echocardiography, is at the same time much more expensive, less accessible, and may requires the administration of a contrast agent. It is of outstanding value in the diagnostics of patients with arrhythmogenic right ventricular dysplasia, in assessing the tissue structure of the ventricular wall .Determining the respective parameters of a 12-lead surface ECG is an inexpensive, easy to perform and reproducable method, which can be widely used in the everyday clinical practice for predicting ventricular arrhythmias.Short QT interval  and long QT interval  involve a confirmed increased risk of sudden cardiac death  can be determined manually or by means of a computer software. Generally, 30 consecutive QT intervals in leads II and V5 are measured . IncreasT wave peak-to-end interval (Tpe) and the arrhythmogeneity index  are also suitable for estimating the danger of ventricular arrhythmias . The norT wave alternans is yet another electrocardiographic parameter that represents beat-to-beat changes in T wave morphology. Its examination may be suitable for expressing the spatial heterogeneity of ventricular repolarization  as well  are immediate high-quality chest compression as well as early defibrillation, which latter plays a key role in terminating these arrhythmias Figure 2Survival rate by early defibrillation in the case of resuscitation performed by lay people is 37.4% . The necAn improvement in the chance of long-term survival and the least neurological damage were found in the case when the initial rhythm observed on site was ventricular fibrillation . AnotherResearch findings in recent years have confirmed that a most decisive element of successful resuscitation is high-quality chest compression interrupted for the briefest possible time . Due to According to the international resuscitation recommendation currently in force, the European Resuscitation Council ALS protocol, the application of mechanical devices is recommended if the sustainment of high-quality chest compressions is required for a longer time, e.g. during transportation, for a hypothermic patient or in the case of PCI during ongiong CPR .There are currently two major types of mechanical devices available in trade, LUCAS (Lund University Cardiopulmonary Assist System) and AutoPulse (Load distributing band CPR). LUCAS is a system operating based on a piston principle and also plays a role in the active decompression of the chest; a silicone ring is to be pressed against the patient’s chest, which thereafter exercises pressure in a depth of 5–6 cm with a frequency of 100/min, and helps the relaxation of the chest wall as well . In the One of the greatest doubts arising in relation to the devices was potential injuries they could cause, but as has been confirmed by several autopsy findings, mechanical devices have not caused either other types of, or more serious or frequent injuries than manual chest compression. The most frequent injury they caused was similarly rib fracture .In another study in relation to resuscitation performed using a LUCAS-2 mechanical chest compression device has similarly shown favourable results. The data of altogether 287 patients were investigated who suffered out-of-hospital non-traumatic circulatory collapse, out of which resuscitation using a LUCAS-2 device was performed in 55 cases, while manual chest compression was carried out in the others. Return of spontaneous circulation (ROSC) happened in 37% of the cases; in a slightly higher rate in the mechanical group (p = 0.072). Also, in cases of prolonged resuscitation, success rate was higher in the mechanical group (p<0.05). The number of traumatic injuries was not higher in the LUCAS-2 compared to the manual group .The prognosis and long-term outcome of resuscitated patients who survived aborted cardiac death are significantly influenced by comorbidities , the extent of potential left ventricular hypertrophy and the mechanism of ventricular arrhythmogenesis. Koldobskiy et al. found that kidney failure, immunosuppression and obesity negatively influenced the outcome of resuscitation . HerlitzIn addition to the application of a mechanical device, a new opportunity for prehospital emergency diagnostics available is to perform echocardiography. This may help identify some of the reversible reasons (4H-4T) causing circulatory collapse and improve the efficiency of chest compression. For the confirmation of the further roles and efficiency of echocardiography during resuscitation as well as its effect on the outcome, further studies are requried .ex vivo and in vitro investigations. Epinephrine shortens sinus cycle length, decreases the effective refractory period of the ventricular myocardium and may also lead to increased atrial and ventricular automaticity and conduction abnormalities. Epinephrine was reported to be able to generate sinus tachycardia, supraventricular, and ventricular arrhythmias in a dose-dependent manner , and by increasing K+ currents β-adrenoceptor antagonists cause negative chronotropy. Their classification is based on their chemical structure, βselectivity and pharmacokinetic properties. There are two subtypes of both α- and β-adrenoceptors. They have distinct distribution and density in different tissues. β1-receptors have a more intense presence in the heart and β2-receptors have a higher density in the smooth muscles and in the bronchi, however α1-, β1-, and β2-adrenoceptors occur on the surface of the cardiomyocytes. β-adrenoceptor antagonists mainly act on β1-and β2-adrenoceptors  has a more pronounced β1-selectivity especially in low doses. In this group bisoprolol is known as the most cardioselective agent with explicit antiarrhythmic activity. Third generation β-adrenoceptor antagonists  has an additional vasodilating effect, hence they are usually ordered as antiarrhythmics mainly in hypertensive patients , while L-sotalol inhibits both IKr current and β-adrenoceptors . Quinidine is a class IA antiarrhythmic drug, that blocks α-adrenoceptors, muscarinic acetylcholine receptors and several types of voltage gated K channels beyond Kv1.5 Na channel. It reduces the frequency of impulse generation by prolonging spontaneous diastolic depolarization and elevates the threshold potential of action potentials. Oral quinidine is recommended for patients with ICD due to BrS, ERS, or IVF, while it decreases the number of ICD shocks and it also improves ICD-free survival .Amiodarone is an iodinated benzofuran, which was originally developed for the treatment of angina pectoris. Amiodarone prolongs the action potential duration and increases the refractory period of the atrial and ventricular myocardium, the AV-node and the Purkinje system . AmiodarA synthetic amiodarone analogue, dronedarone is not iodinated, as it has been designed for avoiding the side effects of amiodarone. Dronedarone blocks L-type Ca, K, and Na channels. In animal studies the antiarrhythmic effect of dronaderone on the ventricular myocardium has been described . AdditioTaking all the available data into consideration it can be concluded that currently there is no appropriate antiarrhythmic agent that can safely prevent VF and would significantly improve the long-term outcome of patients with life-threatening ventricular arrhythmias .In the case of refractory VF (refibrillation), the resuscitation recommendation suggests administering shocks of growing intensity up to 360 J . In caseRegarding long-term treatment of malignant ventricular arrhythmias, the application of implantable cardioverter defibrillator (ICD) is an important element, which releases an antitachycardia pacing or an electric shock at the occurrence of the rhythm disturbance Figure 3+ currents. It has the same positive effects as amiodarone, but it is known to cause less proarrhythmic effect. Additionally, azimilide has not been proven to reduce left ventricular systolic function during long-term antiarrhythmic treatment (+ current) were also described, but less antiarrhythmic and mortality reducing effects were verified compared to amiodarone and sotalol  as well. Tang et al. examined 1798 patients, half of whom were grouped, in a randomized way, into the category ‘only ICD’, while the other half into the category ICD complemented by CRT. In the course of the 40-month examination period they found that the relative risk of cardiovascular death in the CRT group fell by 24% compared to the ‘only ICD’ group, and the frequency of hospitalization was also signifcantly lower .The European Society of Cardiology has issued recommendations for subcutaneous ICDs as well. The malfunctioning of these devices develops rarely, although the application of ATP or cardiac resynchronization is not available.The implantation of ICD’s is mainly performed as secondary prevention combined with β-adrenoceptor antagonist therapy  for patients who suffered malignant ventricular arrhythmia episodes . For theThe administration of β-adrenoceptor antagonists has especially great significance in the case of congenital heart disease patients and primary ion channel diseases. Both the short- and long-term survival of inherited long QT syndrome patients is clearly positively influenced β-adrenoceptor antagonist therapy unless it is the LQT3 type. The suggested β-adrenoceptor antagonists are propranolol (2–4 mg/kg/die) or the long-acting nadolol (1.5 mg/kg/die), while other β-adrenoceptor antagonists, e.g., metoprolol or atenolol seem to be ineffective in this particular indication. Regarding LQT3, drugs decreasing the late sodium current, e.g., flecainide, dofetilide, mexiletine, or ranolazine can be administered . Wilde eACE-inhibitors and aldosterone antagonists (eplerenone), which protect from ventricular arrhythmias associated to ischemic heart disease primarily, reduce the heterogeneity of APD and left ventricular reverse remodelling and lower the risk of sudden cardiac death . It was The angiotensin-receptor blocker candesartan was proven, based on the CHARM low LVEF study published in 2004, to signifcantly reduce overall mortality as well as cardiovascular mortality when added to the base therapy of chronic heart failure patients with left ventricular EF of lower than 40% . The samStatins are inhibitors of the hydroximethylglutaryl coenzyme A reductase, i.e., they reduce the serum cholesterole level, in addition to which, thanks also to their pleiotropic effect, they reduce the likelihood of malignant ventricular arrhythmias. The DEFINITE study examined 229 non-ischemic heart disease patients undergoing ICD therapy where the administration of statins significantly reduced ventricular arrhythmogenesis and sudden cardiac death compared to patients without statin administration .++ currents may be administered as part of the long-term therapy. Morita et al. found that the late type Na channel blocker ranolazine reduced repolarization heterogeneity, and increased the threshold potential value required for the development of VF. In addition, its non-selective blocking property on L-type Ca channels and IKr, IKs currents was detected, too. Ranolazine is also effective in the case of VF with underlying reentry mechanism (Furthermore, in the case of arrhythmias triggered by EADs, inhibitors of the L-type Caechanism  and has echanism . Howeverechanism .The cyclin-dependent kinase inhibitor roscovitine, originally developed as a chemotherapeutic agent, accelerated the inactivation of L-type Ca channels in the course of model experiments, thereby reducing the likelihood of the development of ventricular arrhythmias . FurtherIn the cases of recurrent or refractory VF and ICD storms secondary to repeated VF episodes, ablation of VF triggers and substrates have to be taken into consideration. In these circumstances electrophysiological testing, and intracardiac mapping are performed . In ordeIn VF patients with ischemic heart disease, non-ischemic cardiomyopathies, valvulopathies, amyloidosis, long QT syndromes and IVF, short-coupling triggering ventricular premature beats originating from the Purkinje system were identified and ablated . In 2011Sudden cardiac death is a leading death cause in developed countries, its fast and effective treatment as well as prevention are therefore high priority tasks. There are several non-invasive diagnostic opportunities serving the timely detection of diseases increasing susceptibility to inherited and acquired ventricular arrhythmia, and earliest possible detection is followed, as part of a long-term therapeutic strategy, by the assessment and application of drug and device therapy on an individual basis. In the case of cardiopulmonary resuscitation early defibrillation in addition to minimally interrupted chest compression has been proven to improve the outcome of patients. Radiofrequency ablation of VF triggers and substrates is also a feasible and emerging therapeutical opportunity.All authors confirm that they have read and approved the paper and they have met the criteria for authorship. ZS: wrote the manuscript. DU: took part in preparing the manuscript. TÖ: took part in preparing the manuscript. VS: took part in preparing the manuscript. PN: prepared and reviewed the manuscript before publication.This work was funded by GINOP-2.3.2-15-2016-00062.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.