Prolonged QRS Complex Research Articles

Prevalence of electrocardiographic markers associated with myocardial fibrosis in masters athletes: a cohort study

ObjectivesMyocardial fibrosis (MF) is associated with an increased predisposition to adverse cardiac events. The accumulation of high-volume and high-intensity exercise over an extended duration potentially increases the risk of MF....

Evolving trends of pharmaceutical poisonings associated with QRS complex prolongation

Introduction Tricyclic antidepressants often cause drug-induced QRS complex prolongation in overdose but are now less commonly prescribed. We sought to determine, among a contemporary cohort of patients, the pharmaceuticals independently associated with QRS complex prolongation in acute overdose. Methods We performed secondary analysis of data from the Toxicology Investigators Consortium (ToxIC) Core Registry. We included adult patients presenting from January 2016 through March 2023 with acute or acute-on-chronic pharmaceutical exposures. The primary outcome was QRS complex prolongation >0.12 s. Secondary outcomes included cardiac arrest, death, ventricular dysrhythmia, intensive care unit admission, initiation of vasopressors, and treatment with sodium bicarbonate. We used a multivariable logistic regression model with QRS complex prolongation as the outcome and individual pharmaceuticals of interest as independent variables. We assessed yearly trends of the contribution of relevant pharmaceuticals to QRS complex prolongation since 2016. Results Of 11,945 patients in the total cohort (median age 37 years, 6,652 [55.7%] female), 366 (3.1%) developed QRS complex prolongation. Of 9,417 patients included in the model, 290 (3.1%) developed QRS complex prolongation. Amitriptyline, nortriptyline, doxepin, imipramine, noxiptiline, bupropion, flecainide, carvedilol, propranolol, diphenhydramine, and lamotrigine poisonings were independent predictors of QRS complex prolongation. Flecainide poisoning conferred the greatest odds of QRS complex prolongation (OR 574.1; 95% CI: 88.3–12,747). The contribution of tricyclic antidepressants to QRS complex prolongation decreased from 38.8% to 17.6% of all patients with QRS complex prolongation from 2016 to 2022. In 2022, the proportion of QRS complex prolongation from diphenhydramine (20.6%) surpassed that of tricyclic antidepressants. Discussion This study provides insights into contemporary pharmaceutical poisoning associated with QRS complex prolongation. Tricyclic antidepressants remain clinically relevant exposures but are no longer the most common cause of drug-induced QRS complex prolongation. Conclusions Bupropion, diphenhydramine, and antidysrhythmics are increasingly common causes of QRS complex prolongation, each associated with numerous severe outcomes in poisoning. Greater safety measures to protect patients from cardiovascular toxicity from these pharmaceuticals are warranted.

Beating the heart failure odds: long-term survival after myocardial ischemia in juvenile rainbow trout.

Salmonid fish include some of the most valued cultured fish species worldwide. Unlike most other fish, the hearts of salmonids, including Atlantic salmon and rainbow trout, have a well-developed coronary circulation. Consequently, their hearts' reliance on oxygenation through coronary arteries leaves them prone to coronary lesions, believed to precipitate myocardial ischemia. Here, we mimicked such coronary lesions by subjecting groups of juvenile rainbow trout to coronary ligation, assessing histomorphological myocardial changes associated with ischemia and scarring in the context of cardiac arrhythmias using electrocardiography (ECG). Notable ECG changes resembling myocardial ischemia-like ECG in humans, such as atrioventricular blocks and abnormal ventricular depolarization (prolonged and fragmented QRS complex), as well as repolarization (long QT interval) patterns, were observed during the acute phase of myocardial ischemia. A remarkable 100% survival rate was observed among juvenile trout subjected to coronary ligation after 24 wk. Recovery from coronary ligation occurred through adaptive ventricular remodeling, coupled with a fast cardiac revascularization response. These findings carry significant implications for understanding the mechanisms governing cardiac health in salmonid fish, a family particularly susceptible to cardiac diseases. Furthermore, our results provide valuable insights into comparative studies on the evolution, pathophysiology, and ontogeny of vertebrate cardiac repair and restoration.NEW & NOTEWORTHY Juvenile rainbow trout exhibit a remarkable capacity to recover from cardiac injury caused by myocardial ischemia. Recovery from cardiac damage occurs through adaptive ventricular remodeling, coupled with a rapid cardiac revascularization response. These findings carry significant implications for understanding the mechanisms governing cardiac health within salmonid fishes, which are particularly susceptible to cardiac diseases.

The role of QRS complex prolongation in predicting severe toxicity in single-xenobiotic overdose

Objective The QRS complex duration is commonly used to prognosticate severity, predict outcomes, and indicate treatment in overdose. However, literature to support this practice is mixed in tricyclic antidepressant overdoses and absent in non-tricyclic antidepressant overdoses. Our objective was to assess the validity of QRS complex duration as a prognostic marker in overdose. Methods This was a secondary analysis of cases reported to the Toxicology Investigators Consortium between January 1, 2010, and December 31, 2022. Cases were assessed to determine the six xenobiotics most associated with QRS complex prolongation. All cases involving these six xenobiotics, regardless of QRS complex duration, constituted the study cohort. Inclusion criteria were cases of patients older than 12 years old with single-xenobiotic exposures. Clinical outcomes evaluated were seizure, ventricular dysrhythmia, metabolic acidosis, and death. Results Of 94,939 total cases, diphenhydramine, amitriptyline, bupropion, quetiapine, nortriptyline, and cocaine were most associated with QRS complex prolongation. Inclusion criteria were met by 4,655 cases of exposure to these xenobiotics. QRS complex prolongation was associated with increased odds ratio of seizure in all included xenobiotics, of ventricular dysrhythmia in all included xenobiotics except nortriptyline, and of metabolic acidosis or death in all included xenobiotics except nortriptyline and quetiapine. A normal QRS complex duration had a negative predictive value of greater than or equal to 93.0 percent of developing metabolic acidosis and 98.0 percent of developing a ventricular dysrhythmia or death from the xenobiotics studied. Discussion This study demonstrates that patients with QRS complex prolongation from all six xenobiotics studied had an increased prevalence and odds of developing severe outcomes. Furthermore, patients who did not develop QRS complex prolongation were unlikely to develop a ventricular dysrhythmia, metabolic acidosis, or death. These findings were noted in six xenobiotics that mechanistically can cause QRS complex prolongation through sodium channel or gap junction inhibition. Conclusion Identification of patients at risk for severe outcomes after overdose can be aided by measuring the QRS complex duration. If prospectively validated, these outcomes have implications on risk stratification, disposition level of care, and appropriateness of treatments.

CDR1as promotes arrhythmias in myocardial infarction via targeting the NAMPT-NAD+ pathway

Cardiac ventricular arrhythmia triggered by acute myocardial infarction (AMI) is a major cause of sudden cardiac death. We have reported previously that an increased serum level of circular RNA CDR1as is a potential biomarker of AMI. However, the possible role of CDR1as in post-infarct arrhythmia remains unclear. This study in MI mice investigated the effects and underlying mechanism of CDR1as in ventricular arrhythmias associated with MI. We showed that knockdown of CDR1as abbreviated the duration of the abnormally prolonged QRS complex and QTc intervals and decreased susceptibility to ventricular arrhythmias. Optical mapping demonstrated knockdown of CDR1as also reduced post-infarct arrhythmia by increasing the conduction velocity and decreasing dispersion of repolarization. Mechanistically, CDR1as led to the depletion of NAD+ and caused mitochondrial dysfunction by directly targeting the NAMPT protein and repressing its expression. Moreover, CDR1as aggravated dysregulation of the NaV1.5 and Kir6.2 channels in cardiomyocytes, a change which was alleviated by the replenishment of NAD+. These findings suggest that anti-CDR1as is a potential therapeutic approach for ischemic arrhythmias.

Overlapping and Distinct Features of Cardiac Pathology in Inherited Human and Murine Ether Lipid Deficiency.

Inherited deficiency in ether lipids, a subgroup of glycerophospholipids with unique biochemical and biophysical properties, evokes severe symptoms in humans resulting in a multi-organ syndrome. Mouse models with defects in ether lipid biosynthesis have widely been used to understand the pathophysiology of human disease and to study the roles of ether lipids in various cell types and tissues. However, little is known about the function of these lipids in cardiac tissue. Previous studies included case reports of cardiac defects in ether-lipid-deficient patients, but a systematic analysis of the impact of ether lipid deficiency on the mammalian heart is still missing. Here, we utilize a mouse model of complete ether lipid deficiency (Gnpat KO) to accomplish this task. Similar to a subgroup of human patients with rhizomelic chondrodysplasia punctata (RCDP), a fraction of Gnpat KO fetuses present with defects in ventricular septation, presumably evoked by a developmental delay. We did not detect any signs of cardiomyopathy but identified increased left ventricular end-systolic and end-diastolic pressure in middle-aged ether-lipid-deficient mice. By comprehensive electrocardiographic characterization, we consistently found reduced ventricular conduction velocity, as indicated by a prolonged QRS complex, as well as increased QRS and QT dispersion in the Gnpat KO group. Furthermore, a shift of the Wenckebach point to longer cycle lengths indicated depressed atrioventricular nodal function. To complement our findings in mice, we analyzed medical records and performed electrocardiography in ether-lipid-deficient human patients, which, in contrast to the murine phenotype, indicated a trend towards shortened QT intervals. Taken together, our findings demonstrate that the cardiac phenotype upon ether lipid deficiency is highly heterogeneous, and although the manifestations in the mouse model only partially match the abnormalities in human patients, the results add to our understanding of the physiological role of ether lipids and emphasize their importance for proper cardiac development and function.

Bimodal distribution of QRS complex duration in patients with dilated cardiomyopathy undergoing an ICD implant procedure

Abstract Background/Introduction In patients with heart failure with reduced ejection fraction (HFrEF), QRS duration is of the uttermost importance. Substantial proportion of patients with HFrEF and sufficiently prolonged QRS complex, especially those with left bundle branch block (LBBB), may significantly benefit from cardiac resynchronization therapy. Purpose The aim of the study was to analyse the distribution of the QRS durations in patients with HFrEF undergoing ICD implant procedure to better understand the phenomenon of QRS prolongation. Methods All patients undergoing the implant procedure in our centre between January 2017 and December 2021 for HFrEF caused by coronary artery disease (CAD) or dilated cardiomyopathy (DCM) were analysed for the inclusion into the study. The exclusion criteria were (1) coincidence of CAD with DCM, (2) upgrade from any other cardiac rhythm management device, (3) unavailability of the ECG recording or ECG recording with insufficient quality before the implant procedure, (4) more than one ventricular premature beat in the recording. The study used automatically measured QRS duration by Mortara EKG machines (299 recordings with ELI350, 98 with ELI380, and 10 with ELI250). Statistical analysis was performed in R software [1] with the function locmodes for the visualisation of probability density and excess mass test [2] for assessing statistical significance, both from the multimode package. Results The study included 407 patients. In 113 patients with DCM and 177 patients with CAD, the implantation was based on primary prevention (PP) indications, and 24 and 93 patients with DCM and CAD were implanted for secondary prevention (SP) indications. The distribution of QRS durations in the CAD-PP, as well as CAD-SP was unimodal (p=ns). In the DCM-PP group, the distribution was bimodal (p=0.012), in the DCM-SP group, the trend was non-significantly bimodal (p=0.076). Both DCM groups taken together had clearly bimodal distribution (p=0.002 – probability density curve according to locmodes function in the figure). The values between 139 and 142 ms were not present in this group. Below this border zone, two other patients fulfilled the criteria of LBBB, both with the duration close to the border zone (137 and 138 ms). Above this zone, 8 patients had right bundle branch block, the rest had LBBB. Conclusions Bimodal distribution of QRS duration values in patients with DCM supports the idea of sudden change of left bundle conduction rather than slow progression of local changes. In CAD, scars and other local impairments in conduction may hide these changes and no clear border zone can be set. With the well-known differences in the measurements of main ECGmachine manufacturers, criteria for bundle branch block in DCM could be set with high accuracy. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Charles University Research Program “Cooperatio – Cardiovascular Science” and the Ministry of Health of the Czech Republic Conceptual Development of Research Organization

Common electrocardiogram manifestations in electrolyte imbalance

Abnormalities in serum electrolyte levels and impaired electrolyte homeostasis may aberrate cardiac conduction by altering cardiac ion current kinetics. Oftentimes, the bedside electrocardiogram (ECG) can render expeditious insight and prompt emergency therapy while laboratory investigations of fluid, acid-base and electrolyte imbalances are underway for establishing a definitive diagnosis. The most frequent electrolyte aberrations affecting the ECG include disturbances of potassium, calcium, and magnesium concentrations. Electrolyte dyshomeostasis impacts the depolarization and repolarization phases of action potential in cardiomyocytes by modifying potentials across their cell membranes. Further, individual electrolyte disturbances often have wide-ranging consequences due to their effect on one another. Serum potassium concentration changes can cause considerable repercussions on myocyte conduction and potentially resulting in ECG changes. The ECG changes in hypokalemia mimic those of myocardial ischemia. With severe hypokalemia, the telltale ECG change is the development of U waves. In hyperkalemia, the primary ECG manifestation is T wave tenting, that is seen as a symmetrical narrowing or peaking but with oftentimes a wide deflection and high amplitude. With very severe hyperkalemia, a slurring “sine-wave” appearance may be observed on the ECG due to significant prolongation and widening of QRS complex and subsequent fusion with the T wave. Hyper-and hypo-calcemia mainly change the action potential span (phase 2), which causes either shrinking (in hypercalcemia) or extension (in hypocalcemia) of the QT interval. The effect on the QT interval is mainly the result of an alteration of the ST-segment time span. Both situations can impact T wave structure. No classic ECG presentation is observed in hypo-or hyper-states of magnesium. Bedside electrocardiography serves as an important aid in forming diagnoses and managing patients presenting with electrolytic dyshomeostasis.

Body mass index, lipid profile, and hypertension contribute to prolonged QRS complex

QRS prolongation is one of the most common findings in patients with underlying cardiac diseases. Recent studies have shown that QRS prolongation can be accompanied by obesity, hypertension, and hyperlipidemia, which are known risk factors for cardiovascular events. This study aimed to evaluate how obesity, hypertension, and hyperlipidemia could affect QRS duration. A total of 4033 eligible subjects aged between 35 and 70 years were included from the Persian Cohort Study in Mashhad. ECG intervals, blood pressures, lipid profile, and BMI measures were obtained at the time of enrolment. Multiple regression analysis was performed to assess the relationship between QRS duration and BMI, hypertension, and lipid profile. This study population consisted of 2047 females and 1986 males with a mean age of 46.05±9.50 years. Higher BMI values and heart rate were observed in women (27.12±4 and 74.66±8.54; P<0.001), while height, weight, and QRS duration showed a significant increase in men (172.60±7.18, 79.44±12.55, and 97±11.05; P<0.001). Except for total cholesterol (P=0.317), blood pressures and lipid profile differed significantly among women and men (P<0.001). Furthermore, univariate analyses indicated that QRS duration was associated with age, sex, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), systolic blood pressure, diastolic blood pressure, categorical blood pressure, categorical BMI, and continuous BMI. On the backward multivariate model, TG, LDL, HDL, DBP, SBP, categorical blood pressure, categorical BMI, and continuous BMI were independently correlated with QRS duration. Hypertension, increased BMI, and high levels of LDL, TG, and lower HDL, as well-known risk factors of cardiovascular disease, were associated with prolonged QRS duration. These findings could be beneficial in future investigations regarding establishing the underlying heart problems.

Protein Kinase C-Mediated Hyperphosphorylation and Lateralization of Connexin 43 Are Involved in Autoimmune Myocarditis-Induced Prolongation of QRS Complex.

Myocarditis is a serious and potentially life-threatening disease, which leads to cardiac dysfunction and sudden cardiac death. An increasing number of evidence suggests that myocarditis is also a malignant complication of coronavirus pneumonia, associated with heart failure and sudden cardiac death. Prolonged QRS complexes that are related to malignant arrhythmias caused by myocarditis significantly increase the risk of sudden cardiac death in patients. However, the molecular mechanisms are not fully known at present. In this study, we identify protein kinase C (PKC) as a new regulator of the QRS complex. In isolated hearts of normal rats, the PKC agonist, phorbol-12-myristate-13-acetate (PMA), induced prolongation of the QRS complex. Mechanistically, hyperphosphorylation and lateralization of connexin 43 (Cx43) by PKC induced depolymerization and internalization of Cx43 gap junction channels and prolongation of the QRS duration. Conversely, administration of the PKC inhibitor, Ro-32-0432, in experimental autoimmune myocarditis (EAM) rats after the most severe inflammation period still significantly rescued the stability of the Cx43 gap junction and alleviated prolongation of the QRS complex. Ro-32-0432 reduced phosphorylation and blocked translocation of Cx43 in EAM rat heart but did not regulate the mRNA expression level of ventricular ion channels and the other regulatory proteins, which indicates that the inhibition of PKC might have no protective effect on ion channels that generate ventricular action potential in EAM rats. These results suggest that the pharmacological inhibition of PKC ameliorates the prolongation of the QRS complex via suppression of Cx43 hyperphosphorylation, lateralization, and depolymerization of Cx43 gap junction channels in EAM rats, which provides a potential therapeutic strategy for myocarditis-induced arrhythmias.

Transcription factor Meis1 act as a new regulator of ischemic arrhythmias in mice

IntroductionThe principal voltage-gated Na+ channel, NaV1.5 governs heart excitability and conduction. NaV1.5 dysregulation is responsible for ventricular arrhythmias and subsequent sudden cardiac death (SCD) in post-infarct hearts. The transcription factor Meis1 performs a significant role in determining differentiation fate and regenerative capability of cardiomyocytes. However, the functions of Meis1 in ischemic arrhythmias following myocardial infarction (MI) are still largely undefined. ObjectivesHere we aimed to study whether Meis1 could act as a key regulator to mediate cardiac Na+ channel and its underlying mechanisms. MethodsHeart-specific Meis1 overexpression was established by AAV9 virus injection in C57BL/6 mice. The QRS duration, the incidence of ventricular arrhythmias and cardiac conduction velocity were evaluated by ECG, programmed electrical stimulation and optical mapping techniques respectively. The conventional patch clamp technique was performed to explore the INa characteristics of isolated mouse ventricular myocytes. In vitro, Meis1 was also overexpressed in hypoxic-treated neonatal cardiomyocytes. The analysis of immunoblotting and immunofluorescence were used to detect the changes in the expression of NaV1.5 in each group. ResultsWe found that forced expression of Meis1 rescued the prolongation of QRS complex, produced anti-arrhythmic activity and improved epicardial conduction velocity in infarcted mouse hearts. In terms of mechanisms, cardiac electrophysiological changes of MI mice can be ameliorated by the recovery of Meis1, which is characterized by the restoration of INa current density and NaV1.5 expression level of cardiomyocytes in the marginal zone of MI mouse hearts. Furthermore, in vitro studies showed that Meis1 was also able to rescue hypoxia-induced decreased expression and dysfunction of NaV1.5 in ventricular myocytes. We further revealed that E3 ubiquitin ligase CDC20 led to the ubiquitination and degradation of Meis1, which blocked the transcriptional regulation of SCN5A by Meis1 and ultimately led to the electrophysiological remodeling in ischemic-hypoxic cardiomyocytes. ConclusionCDC20 mediates ubiquitination of Meis1 to govern the transcription of SCN5A and cardiac electrical conduction in mouse cardiomyocytes. This finding uncovers a new mechanism of NaV1.5 dysregulation in infarcted heart, and provides new therapeutic strategies for malignant arrhythmias and sudden cardiac death following MI.

Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.

POTENTIAL ROLE OF GLP-1 RECEPTOR AGONIST IN A RAT MODEL OF CARDIO-RENAL SYNDROME TYPE-3: EFFECTS ON OXIDATIVE, INFLAMMATORY AND INOS EXPRESSION AXIS

Background: Acute renal and cardiac diseases are common encounters in hospitalized and non-hospitalized patients. Kidney and heart pathology are continuously interrelated. The impact of acute kidney injury (AKI) on the cardiac function is demonstrated in both preclinical and clinical studies and is termed cardio-renal syndrome type 3.Aim of the work: The aim of this work is to establish an animal model of cardio-renal syndrome type 3, and to study the effect of glucagon-like peptide-1 receptor (GLP-1R) agonist “liraglutide” on this condition.Materials and methods: Sixty male Wistar rats were used in this study and were divided into six groups (10 per group). Group 1: control, Group 2: low dose liraglutide-treated rats(L-lira). Group 3: high dose liraglutide-treated rats (H-lira). Group 4: Gentamicin (GM) treated rats. Group 5: low dose liraglutide- and GM-treated rats (L-lira-GM). Group 6: high dose liraglutide- and GM-treated rats (H-lira-GM). Liraglutide was given daily by subcutaneous injection for three weeks. GM was injected intraperitoneally (IP) starting from day 15 to day 21.Results: GM treatment was associated with histopathological injuries of both renal and cardiac tissues, in addition to significant elevation of renal biomarkers (serum urea and creatinine) as well as cardiac biomarkers (cardiac troponin I (TnI), creatine kinase (CK-MB) and lactate dehydrogenase (LDH). ECG showed prolongation of QRS complex, Q-T and Q-Tc interval, in addition to increased T wave voltage. There was significant increase in the relative weight of the right ventricle and the absolute and relative weights of left ventricles and the whole heart of the GM group. Moreover, GM injection resulted in a significant increase in oxidative and inflammatory markers (MDA, NO, IL-1beta, IL-6 and TNF-α) and diminished antioxidants GSH, SOD, and catalase, in the serum as well as in renal and cardiac tissues. GLP-1R agonist administration before GM injection normalized all the measured parameters only in the high dose group. Liraglutide evidently prevented upregulation of the inducible nitric oxide synthase (iNOS) gene expression in both renal and cardiac tissue of GM-treated animals.Conclusion: GM injected rats exhibited renal and cardiac structural and functional damage. The GLP-1R agonist, liraglutide protects both the kidney and the heart through antioxidant and anti-inflammatory effects. In addition, it downregulates the iNOS expression in renal and cardiac tissues, thus decreasing production of nitric oxide (NO).

Predictors of Pacemaker Insertion Post-Sutureless (Perceval) Aortic Valve Implantation

The use of rapid deployment sutureless aortic valve replacement (AVR) has become a viable alternative to conventional AVR especially in intermediate and high-risk patients. However, sutureless AVR has been associated with increased rates of permanent pacemaker (PPM) implantation compared with conventionally implanted aortic valve prostheses. The aim of this study was to determine predictive factors for complete heart block requiring insertion of a PPM post-AVR with a Perceval S sutureless valve (LivaNova, London, UK). Such knowledge will help to improve patient counselling, selection and management of patients undergoing sutureless AVR. A retrospective cohort study assessed all patients who underwent insertion of the Perceval sutureless aortic valve prosthesis between July 2015 and September 2019. Medical records were reviewed for demographic, preoperative electrocardiograph (ECG), and operative features related to postoperative PPM implantation and follow-up in the electrophysiology clinic. One hundred and thirty (130) patients without pre-existing PPM underwent sutureless AVR (66.9% male, average age 74.4±6.6 years). Fifty-seven (57) underwent concomitant cardiac surgical procedures. Eight (8) patients underwent redo cardiac surgery. Nineteen (19) of the 130 (14.6%) patients required insertion of a PPM during their postoperative course. Factors associated with PPM insertion were right bundle branch block (overall n=15, PPM vs No PPM: 8/19 vs 7/111 [42.1 % vs. 6.31 %; p<0.01]), longer QRS duration 113.32ms±22.24 ms vs 100.52±20.96 ms (p=0.017) and longer PR Interval 185.166±42.38 ms vs 169.23±25.70 ms (p=0.03). Insertion of rapid deployment sutureless aortic valves in the setting of pre-existing right bundle branch block, prolonged QRS complex and longer PR intervals is associated with increased risk of postoperative PPM requirement. These factors should be considered when preoperatively counselling and postoperatively managing patients when balloon expandable sutureless valves are used.

Fast delivery of flecainide via the pulmonary (bolus) or intravenous (rapid infusion) routes reduces atrial fibrillation conversion dose and minimizes negative inotropic burden

Abstract Background/Introduction The negative inotropic effect of certain antiarrhythmic drugs limits their use for acute cardioversion of new-onset paroxysmal atrial fibrillation (AF). Purpose In an intact porcine model of AF, we examined the effects of pulmonary and intravenous (IV) administration of flecainide on left ventricular (LV) contractility, i.e., LV dP/dt max, at doses that are effective in converting AF to sinus rhythm. The magnitude of the decrease in LV dP/dt max and time that it remained below baseline, measured by the area under the curve (AUC), is referred to as negative inotropic burden. Methods Flecainide was delivered via intratracheal administration at 1.5 mg/kg bolus and compared to IV infusion at 1.0 mg/kg over 2 min (lower-dose, rapid) and 2.0 mg/kg over 10 min (ESC guideline) in 11 closed-chest, anesthetized Yorkshire pigs. These doses of flecainide have been shown effective in converting AF to sinus rhythm. Catheters were fluoroscopically positioned in the right atrium for pacing at 140 beats/min and in the LV to measure QRS complex duration and contractility (LV dP/dt). Intratracheal flecainide was delivered via a catheter positioned at the bifurcation of the main bronchi. Results The peak plasma levels (Cmax values) were similar but the AUC of plasma concentrations over time was greater for the higher-dose, slow IV infusion of flecainide than for either intratracheal instillation (by 32%) or lower-dose, rapid IV infusion (by 88%). Based on AUCs of LV dP/dt max (figure, left panel), the negative inotropic burden is 3.1- to 3.8-fold greater for the higher IV (1006% • min) than for the lower IV (323%·min) or the intratracheal doses (263% • min). There was a corresponding inverse increase in the AUC of QRS complex prolongation. The decrease in LV dP/dt max (Δ%) was correlated with the prolongation of the QRS complex (Δms) (y = −1.4337x + 3.6613, r2=0.69, p&amp;lt;0.0001) (figure, right panel). Conclusion Rapid delivery of pulmonary or IV flecainide reduces the dose of drug required to achieve Cmax levels associated with conversion of AF. The attendant decrease across time in exposure of the ventricles to flecainide reduces QRS complex prolongation and the accompanying negative inotropic burden. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): InCarda Therapeutics, Inc.

The effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet.

Metabolic syndrome represents one of the major health, social and economic issues nowadays, and affects more than 25% people worldwide. Being a multifactorial health problem, metabolic syndrome clusters various features, such as obesity, dyslipidemia, hyperglycemia and hypertension. Each of these disturbances represents a risk factor for developing cardiovascular disease. Moreover, patients with metabolic syndrome are more likely to suffer from depression, thus treatment with antidepressants (e.g. venlafaxine) is often neccessary. However, many of the antidepressants themselves may contribute to worsening or even development of the metabolic syndrome, thus creating a “vicious circle”. The aim of this work was to investigate on the animal model of metabolic syndrome, i.e. on hypertriacylglycerolemic rats fed high-fat-fructose diet (HFFD): 1) the effect of a change in diet from HFFD to a standard diet (SD) and the effect of venlafaxine treatment, 2) during HFFD, 3) as well as during a changed diet to SD. We focused on biometric parameters, blood pressure and selected ECG parameters. We observed the reversibility of the present metabolic and cardiovascular changes by switching the HFFD to SD in the last 3 weeks of the experiment. Switch to the standard diet led to decrease of body weight, even in the presence of venlafaxine. Administration of venlafaxine caused the decrease of heart weight/body weight index in rats fed with HFFD compared to the untreated group fed with HFFD for 8 weeks. Blood pressure, which was increased in the HFFD group showed a tendency to decrease to control values after switching to the standard diet . Administration of venlafaxine led to significant increase in all parameters of blood pressure when rats were fed with HFFD throughout the whole experiment. In untreated rats fed with HFFD for 8 weeks, we observed a shorter PQ interval and prolonged QRS complex as well as QTc interval compared to untreated rats with diet switched to SD. This effect was potentiated by venlafaxine administered not only during HFFD but even after switch to SD. Our results point to the fact that metabolic syndrome is clearly affecting the function of the cardiovascular system by modifying blood pressure and electrical activity of the heart. Moreover, administration of venlafaxine may lead to worsening of the observed changes, especially in the presence of high-fat-fructose diet.

TCAS-ASSOCIATED WITH PERSISTENT WIDE COMPLEX VENTRICULAR TACHYCARDIA

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Amitriptyline is a tricyclic antidepressant (TCA) that has been used for over 50 years. TCAs are notorious for cardiotoxicity and neurotoxicity, and it is widely used medication for suicide. The incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) is approximately 4% in TCA overdose patients. It is mostly noted in patients with severe acidosis, hypotension, and prolonged QRS duration. Here, we present a patient with prolonged wide-complex ventricular tachycardia secondary to amitriptyline overdose. CASE PRESENTATION: A 50 year old female with history of Ehlers-Danlos syndrome and fibromyalgia was brought to the ED by her husband because of a reported seizure at home. Pertinent home medications included Amitriptyline, fentanyl patch, and hydromorphone. Patient denied any prior history of heart disease or neurological problems. On arrival to the ED, Glasgow Coma Scale was 3. Pertinent vital signs were blood pressure of 61/35 mmHg. The patient was emergently intubated. ECG on admission showed slow wide complex VT (80 bpm with QRS duration 217 msec. Admission labs showed elevated anion gap metabolic acidosis. Lactic acid was 20.0 mmol/L. ABG post intubation showed pH 7.17, pCO2 44, pO2 240 with base excess of -12. Urine toxicology demonstrated TCAs and opiates. Naloxone 4 mg IV was given twice with no improvement in symptoms. Repeat ECG 2 hours later showed wide complex ventricular tachycardia 158 bpm with QRS prolongation 178 msec. This was initially thought to be sinus tachycardia with prolonged QRS complex. ICU was consulted and the patient was immediately cardioverted upon arrival to the MICU. Sinus rhythm was achieved, but the patient remained tachycardic. EEG was obtained which confirmed 7 left and 5 right mid-temporal lobe seizures. Patient was started on bicarbonate gtt and Ativan gtt. ECG and ABG were obtained every 4 hours. Her QRS duration normalized and the acidosis has resolved after 12 hours. Brain MRI with and without contrast did not show any acute intracranial pathology. The patient was discharged home safely after a 7-day hospitalization. DISCUSSION: TCAs have been used for over 50 years for the treatment of depression and neuropathic pain. It has many side effects including cardiotoxic and neurotoxic adverse outcomes. The severity of cardiotoxic effects are also imperative to recognize; particularly, it is important to suspect TCA toxicity in a patient with persistent wide complex ventricular tachycardia. Patients with VT secondary to TCA overdose, should promptly treated with the ACLS protocol. These patients should be closely monitored in the ICU and should receive sodium bicarbonate gtt, ABG, and EKG every four hours. CONCLUSIONS: Early recognition and aggressive intervention is warranted in patients presenting with TCA overdose in order to improve patient outcomes. Reference #1: Goldberg RJ, Capone RJ, Hunt JD. Cardiac complications following tricyclic antidepressant overdose. Issues for monitoring policy. JAMA 1985; 254:1772. Reference #2: Khandker Mohammad Nurus Sabah, Abdul Wadud Chowdhury, Mohammad Shahidul Islam, Bishnu Pada Saha, Syed Rezwan Kabir, and Shamima Kawser. Amitriptyline-induced ventricular tachycardia: a case report. BME Res Notes. 2017;10:286. https://doi.org/10.1186/s13104-017-2615-8 DISCLOSURES: No relevant relationships by Abdisamad Ibrahim, source=Web Response No relevant relationships by Mohamed Labedi, source=Web Response No relevant relationships by Ruby Maini, source=Web Response No relevant relationships by Nitin Tandan, source=Web Response

Cardiac resynchronization therapy in patients with chronic heart failure: the view of a therapist, cardiologist

The prevalence of the chronic heart failure is increasing due to the success of cardiology and the increase in life expectancy of the population. A greater number of patients live up to the clinically pronounced stages of the chronic heart failure. This issue leads to an increasing in the absolute number of the patients in whom there is a lack of efficacy of optimally prescribed drug therapy. These patients are considering initiating cardiac resynchronization therapy (CRT). CRT is recommended for the patients with chronic heart failure II-IV functional class with severe left ventricular systolic dysfunction and prolonged QRS complex. Despite careful selection of patients for CRT implantation, the device does not lead to the expected result in one third of cases. To increase the effectiveness of this intervention, the procedure should be performed in accordance with current guidelines only for compliant patients who have been at least 3 months on selected optimal drug therapy, should use the optimal strategies and modes of stimulation and the adequate drug support after the intervention. The number of patients with long-term use of CRT is constantly growing. More and more patients with installed devices come into the field of vision of general practitioners and cardiologists of ambulatory clinics and hospitals, for whom it is extremely important to understand the specifics of the methods and tactics of managing such patients. This publication is dedicated to this.

A case of wide complex tachycardia in wolff-parkinson-white syndrome

The manifestation of atrial flutter, particularly with 1:1 conduction, is rare in patients with ventricular preexcitation secondary to Wolff-Parkinson-White Syndrome (WPW). Very few cases have been reported in the literature. We present a 40-year old male with a history of untreated WPW who presented with severe chest pain and shortness of breath. He was found to have a rapid, regular, wide complex tachycardia. He underwent successful synchronized cardioversion, in which the patient converted tonormal sinus rhythm with classic WPW waveform characteristics, including a shortened PR interval and prolonged QRS complex with a slurred upstroke. Surprisingly, a subsequent electrophysiology study revealed atrial flutter, with bystander conduction of 1:1 atrial flutter being the most likely cause of the patient’s presenting symptoms, and a posteroseptal accessory pathway consistent with the diagnosis of WPW. While considerably rarer than ventricular tachycardia or AVRT, it is nevertheless important for clinicians to consider atrial flutter with 1:1 conduction as a potential diagnosis in patients with WPW presenting with wide complex tachycardia.

A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in advanced gastrointestinal cancer patients with cancer cachexia.

BackgroundCancer cachexia is characterized by weight loss and is associated with increased morbidity and mortality in patients with cancer. Anamorelin (ONO‐7643; ANAM) is a novel and selective ghrelin receptor agonist that improves appetite, lean body mass (LBM), body weight, and anorexia.MethodsThis multicenter, open‐label, single‐arm study investigated the efficacy and safety of 100 mg anamorelin in 50 Japanese patients with advanced and unresectable gastrointestinal (colorectal, gastric, or pancreatic) cancer. ANAM was administered once daily over 12 weeks. The primary endpoint was the proportion of patients that maintained or gained LBM over the course of the study. Secondary endpoints included changes in LBM, body weight, quality of life (QoL), and nutritional status biomarkers.ResultsThe proportion of patients who responded to treatment was 63.3% (95% CI, 48.3%‐76.6%), with a least square mean ± SE change in LBM and body weight from baseline of 1.89 ± 0.36 kg and 1.41 ± 0.61 kg, respectively. Appetite‐related questions on the QoL questionnaire showed that ANAM improved appetite. Adverse events occurred in 79.6% of patients, and the most common treatment‐related adverse events were increased γ‐glutamyl transpeptidase (8.2%), diabetes mellitus (6.1%), hyperglycemia (6.1%), and prolonged QRS complex (6.1%).ConclusionsANAM improved anorexia and patients' nutritional status, resulting in rapid increases in LBM and body weight in patients with advanced gastrointestinal cancer who had cancer cachexia. ANAM treatment was well tolerated over 12 weeks. ANAM is a potential clinically beneficial pharmacotherapeutic option for patients with advanced gastrointestinal cancer who have cancer cachexia.