Intracardiac Conduction Research Articles

Echocardiographic Diagnostics of Myocardial Infarction in Newborns

Early and correct diagnostics of myocardial infarction in newborns is impossible without modern instrumental methods, among which echocardiography is the leading one. Hypokinesia, akinesia or dyskinesia of local segments of the heart ventricular wall is determined with echocardiography. We examined a 3-days-old baby with circulatory failure requiring cardiotonic support. On auscultation there was a heart murmur. It was an intracardiac conduction disoder and infarction-like changes on ECG, however, a convincing evidence to interpret the patient’s condition as myocardial infarction has not been received. Therefore, it was decided to conduct echocardiography. According to the results of echocardiography the presence of hyperechogenic diskinetic locus in the apical segment of the right ventricle (post-infarction scar), a local pericardial effusion in the same projection, hyperechogenic movable mass (thrombus) in the apical segment of the right ventricle were determined that together with the results of the ECG allowed us to set diagnosis myocardial infarction. Transthoracic echocardiography is one of highly informative methods; the data obtained allowed to correctly interpret the clinical picture of heart failure and to reveal the cause of the patien’st dependance on cardiotonic support.

TCT-63 Objective Assessment of Intracardiac Conduction to Guide Permanent Pacemaker Implantation Following Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy

TCT-63 Objective Assessment of Intracardiac Conduction to Guide Permanent Pacemaker Implantation Following Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy

Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers.

In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane).

Risk-benefit assessment of ivabradine in the treatment of chronic heart failure.

Heart rate is not only a major risk marker in heart failure but also a general risk marker. Within the last few years, it has been demonstrated that reduction of resting heart rate to <70 bpm is of significant benefit for patients with heart failure, especially those with impaired left ventricular systolic function. Ivabradine is the first innovative drug synthesized to reduce heart rate. It selectively and specifically inhibits the pacemaker If ionic current, which reduces cardiac pacemaker activity. Therefore, the main effect of ivabradine therapy is a substantial lowering of heart rate. Ivabradine does not influence intracardiac conduction, contractility, or ventricular repolarization. According to the European Society of Cardiology guidelines, ivabradine should be considered in symptomatic patients (New York Heart Association functional class II–IV) with sinus rhythm, left ventricular ejection fraction ≤35%, and heart rate ≥70 bpm despite optimal treatment with a beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and a mineralocorticoid receptor antagonist. As shown in numerous clinical studies, ivabradine improves clinical outcomes and quality of life and reduces the risk of death from heart failure or cardiovascular causes. Treatment with ivabradine is very well tolerated and safe, even at maximal recommended doses.

Cardiotoxicity and oncological treatments.

Cardiotoxic and other side effects limit the usefulness of treatments for cancer. This article is based on pertinent articles that were retrieved by a selective search in PubMed and other databases, and on the guidelines of the European Society of Cardiology, the Association of Scientific Medical Societies in Germany, and the European Society of Medical Oncology. Prospective studies have shown that some treatments for cancer are cardiotoxic. The heart damage that they cause can manifest itself as arrhythmia, arterial hypertension, thromboembolism, angina pectoris, myocardial infarction, or heart failure. It has been observed that potentially lethal complications can arise as late as 40 years after treatment of the original cancer. The anthracycline drug doxorubicin, given in a dose of 500 mg/m2 of body surface area, has been found to cause cardiac complications in 4-36% of the patients treated with it. Trastuzumab and epirubicin cause dose-limiting cardiac events in 1.7-5% of patients, depending on the dosage. Paclitaxel causes bradycardia, intracardiac conduction block, or arrhythmia in 0.5% of patients. 18% of patients treated with sunitimib or sorafenib have clinical manifestations relating to the heart (angina pectoris, dyspnea). 5-fluorouracil can cause angina pectoris at the beginning of treatment and rarely causes myocardial infarction. Cardiac radiation therapy, a form of treatment practiced in earlier decades, can cause cardiac complications 20 years after the event. The opportunity to prevent cardiac complications of anthracycline drugs with dexrazoxane is decidedly limited, but initial studies have shown that treatment with beta-blockers and ACE inhibitors lessens the likelihood of cardiotoxic side effects. When cardiac complications arise, the generally applicable rules for the treatment of each type of cardiac problem should be followed. The oncological treatment protocol should be adjusted or switched to one that is less damaging to the heart. Treating physicians need to be thoroughly acquainted with the cardiotoxic effects of anti-cancer drugs so that they can diagnose them early on and avoid jeopardizing the overall success of treatment.

Flecainide-Induced Myoclonus

Flecainide is a class 1c antiarrhythmic that acts by blocking sodium channels to reduce intracardiac conduction and is used mainly in the treatment of supraventricular arrhythmias. Dizziness, visual disturbances, headache, and nausea are commonly associated with flecainide, but severe central nervous system toxicity is rare. Here, we report the case of a 71-year-old woman with a history of renal transplantation who developed severe myoclonus 24 hours after being started on flecainide, 100 mg 2 times a day, because of atrial fibrillation. This symptom completely disappeared once the drug was removed. Only 2 patients presenting with flecainide-induced myoclonus have been previously reported. Although the exact pathophysiologic explanation of this phenomenon remains unclear, it is well known that the susceptibility to severe flecainide toxicity is increased in patients with chronic kidney disease.

Electrophysiologically competent skeletal myoblast based engineered tissue constructs show cardiac-like force generation

Introduction: Previously, we demonstrated that skeletal myoblast (SM) based engineered tissue constructs (ETC) applying specific culture conditions can augment the intra-cardiac conduction system, i.e. for the treament of AV conduction block. However, the mechanical and contractile properties of SM based ETC remain largely unexplored. Here, we present force measurement analyses of ETC as an essential prerequisite for potential treatment of the failing heart.

ECG Phenomena: Pseudopreexcitation and Repolarization Disturbances Resembling ST-Elevation Myocardial Infarction Caused by an Intraatrial Rhabdomyoma in a Newborn

As is known from other reports, a rhabdomyoma or tumor metastasis may alter intracardiac electrical conduction, producing electrical phenomena like pseudopreexcitation or repolarization disturbances resembling ST-elevation myocardial infarction or Brugada's syndrome. We present a newborn with a giant atrial rhabdomyoma and additionally multiple ventricular rhabdomyomas. He presented with several electrocardiogram (ECG) phenomena due to tumor-caused atrial depolarization and repolarization disturbances. Except from the cardiac tumors, the physical status was within normal range. Initial ECG showed a rapid atrial tachycardia with a ventricular rate of 230 bpm, which was terminated by electrical cardioversion. Afterwards, the ECG showed atrial rhythm with frequent atrial premature contractions and deformation of the PR interval with large, broad P waves and loss of discret PR segment, imposing as pseudopreexcitation. The following QRS complex was normal, with seemingly abnormal ventricular repolarization resembeling ST-elevation myocardial infarction. The atrial tumor was resected with consequent vast atrial reconstruction using patch plastic. The ventricular tumors were left without manipulation. After surgery, pseudopreexcitation and repolarization abnormalities vanished entirely and an alternans between sinus rhythm and ectopic atrial rhythm was present. These phenomena were supposably caused by isolated atrial depolarization disturbances due to tumor-caused heterogenous endocardial activation. The seemingly abnormal ventricular repolarization is probably due to repolarization of the atrial mass, superimposed on the ventricular repolarization. Recognizably, the QRS complex before and after surgical resection of the rhabdomyoma is identical, underlining the atrial origin of the repolarization abnormalities before surgery.

Omega-3 in Antiarrhythmic Therapy

Omega-3 (n-3 polyunsaturated fatty acids) has demonstrated its ability to reduce global mortality, obtaining an indication for the prevention of sudden death in patients with myocardial infarction of the anterior wall. These observations have led to the design of several clinical studies aimed at demonstrating the potential antiarrhythmic effect of omega-3. These studies have given contradictory results, probably due to differences in the populations and doses used. Observations supporting the use of omega-3 as antiarrhythmic agents come from a study in patients with post-ischaemic dilatative cardiomyopathy and carriers of implantable cardioverter defibrillators (ICDs), without cardiovascular events in the last 12 months. In this population a combination of nutraceuticals containing omega-3 (Ritmonutra®) has been able to reduce the number of ventricular and supraventricular arrhythmias without modification of the left ventricle function. Specifically, a 46% reduction of premature ventricular contractions (BEV), 54.2% of premature supraventricular contractions (BESV), 48% of BESV run and 33% of sustained or non-ventricular tachycardia were observed (all significant, p < 0.0001).In a following study, the antiarrhythmc effect of Ritmonutra® was evaluated by Holter ECG for 24 hours in patients with essential hypertension, without ischaemia, preserved left ventricular function and positive anamnesis for arrhythmia. The results showed that omega-3 treatment produced a significant reduction of ventricular and supraventricular arrhythmias compared with placebo, without modification of heart rate, intra-cardiac conduction and contractility.A recent meta-analysis of studies conducted on omega-3 and possible reduction of cardiovascular events concluded that no significant beneficial effects are related to omega-3 treatment on reducing death for all cardiovascular events. Do these conclusions exclude omega-3 as an anti-arrhythmic?We currently have no antiarrhythmic therapies showing a clear reduction of mortality, with the exception of amiodarone and β-blockers (β-adrenoceptor antagonists). This consideration is even more important for treatment of arrhythmias in healthy subjects, when the first goal is the relief of symptoms and improvement in quality of life. Keeping these last points in mind, the answer to the previous question is a loud 'NO', also taking into account the fact that omega-3, in contrast to the other antiarrhythmics, do not negatively affect myocardial contractility.

Brugada pattern masquerading as ST-segment elevation myocardial infarction in flecainide toxicity

Flecainide (a class 1c antiarrhythmic) produces a dose-dependent decrease in intracardiac conduction. Its well known common electrocardiographic effects are prolongation of PR and QT intervals and the QRS complex duration. We report a case of flecainide toxicity in an elderly female who presented with a type 1 Brugada pattern who essentially had a previously normal ECG pattern on therapeutic dose of flecainide therapy. The case describes a rare electrocardiographic abnormality induced by flecainide toxicity which otherwise could be easily misinterpreted as a ST-segment elevation myocardial infarction (STEMI) without lack of expertise and high clinical suspicion.

Altered sinoatrial node function and intra-atrial conduction in murine gain-of-function Scn5a+/ΔKPQ hearts suggest an overlap syndrome

Mutations in SCN5A, the gene encoding the pore-forming subunit of cardiac Na+ channels, cause a spectrum of arrhythmic syndromes. Of these, sinoatrial node (SAN) dysfunction occurs in patients with both loss- and gain-of-function SCN5A mutations. We explored for corresponding alterations in SAN function and intracardiac conduction and clarified possible mechanisms underlying these in an established mouse long QT syndrome type 3 model carrying a mutation equivalent to human SCN5A-ΔKPQ. Electrophysiological characterizations of SAN function in living animals and in vitro sinoatrial preparations were compared with cellular SAN and two-dimensional tissue models exploring the consequences of Scn5a+/ΔKPQ mutations. Scn5a+/ΔKPQ mice showed prolonged electrocardiographic QT and corrected QT intervals confirming long QT phenotypes. They showed frequent episodes of sinus bradycardia, sinus pause/arrest, and significantly longer sinus node recovery times, suggesting compromised pacemaker activity compared with wild-type mice. Electrocardiographic waveforms suggested depressed intra-atrial, atrioventricular node, and intraventricular conduction in Scn5a+/ΔKPQ mice. Isolated Scn5a+/ΔKPQ sinoatrial preparations similarly showed lower mean intrinsic heart rates and overall slower conduction through the SAN to the surrounding atrium than did wild-type preparations. Computer simulations of both single SAN cells as well as two-dimensional SAN-atrial models could reproduce the experimental observations of impaired pacemaker and sinoatrial conduction in terms of changes produced by both augmented tail and reduced total Na+ currents, respectively. In conclusion, the gain-of-function long QT syndrome type 3 murine Scn5a+/ΔKPQ cardiac system, in overlap with corresponding features reported in loss-of-function Na+ channel mutations, shows compromised SAN pacemaker and conduction function explicable in modeling studies through a combination of augmented tail and reduced peak Na+ currents.

Surface and intracardiac ECG for discriminating conduction disorders after CoreValve implantation

BackgroundTranscatheter aortic valve implantation (TAVI) has been developed to minimize operative morbidity and mortality in high-risk symptomatic patients unfit for open surgery. With the proximity of the aortic valve annulus to the conduction system there is, however, an unknown risk of conduction disturbances necessitating monitoring and often cardiac pacing.Materials and methodsWe enrolled 50 consecutive patients from January 2007 to 2008 in our prospective evaluation of conduction disturbances measured by surface and intracardiac ECG recordings. Baseline parameters, procedural characteristics as well as twelve-lead surface ECG and intracardiac conduction times were revealed pre-interventionally, after TAVI and at 7-day follow-up.ResultsTAVI was performed successfully in all patients. During 7 days of follow-up the rate for first-degree AV block raised from 14% at baseline to 44% at day 7 (p < 0.001), while rates for type II second- and third-degree were 0 versus 8% (p < 0.001) and 0 versus 12% (p < 0.001), respectively. Similarly, the prevalence of new left bundle branch block (LBBB) rose from 2 to 54% (p < 0.001). Intracardiac measurements revealed a prolongation of both AH and HV interval from 123.7 ± 41.6 to 136.6 ± 40.5 ms (p < 0.001) and from 54.8 ± 11.7 to 71.4 ± 20.0 ms (p < 0.001), respectively. Pacemaker implantation at a mean follow-up of 4.8 ± 1.2 days was subsequently performed in 23 patients (46%) due to complete AV block (12%) and type II second-degree AV block (8%) while another 13 patients (26%) received a pacemaker for the combination of new LBBB with marked HV prolongation. The high rate of first-degree AV block was primarily driven by an increase in HV interval.ConclusionCardiac conduction disturbances were common in the early experience with CoreValve implantation necessitating close surveillance for at least 1 week.

Aortic stiffness is increased in acromegaly regardless the method of assessment

acid prevents atrial fibrillation associated with heart failure in a rabbit model. Am J Physiol Heart Circ Physiol 2011;300:H1814–21. [19] Michellucci A, Toso A, Mezzani A, et al. Noninvasive recording of sinus node activity by Pwave triggered SAECG. Validation using direct intra-atrial recording of sinus node electrogram. Am J Noninvasive Cardiol 1993;7:132–7. [20] Ehlert F, Gaur A, Steinberg JS. Correlation of the P-wave signal-averaged electrocardiogram to intra-cardiac atrial conduction. Circulation 1996;94:I-70. [21] Nomura M, Kawano T, Nakayasu K, Nakaya Y. The effects of losartan on signalaveraged P wave in patients with atrial fibrillation. Int J Cardiol 2008;126:21–7. [22] Chen J, Shearer GC, Chen Q, et al. Omega-3 fatty acids prevent pressure overloadinduced cardiac fibrosis through activation of cyclic GMP/protein kinase G signaling in cardiac fibroblasts. Circulation 2011;123:584–93. [23] Ciulla MM, Paliotti R, Esposito A, et al. Effects of antihypertensive treatment on ultrasound measures of myocardial fibrosis in hypertensive patients with left ventricular hypertrophy: results of a randomized trial comparing the angiotensin receptor antagonist, candesartan and the angiotensin-converting enzyme inhibitor, enarapril. J Hypertens 2009;27:626–32.

Revision Points and Remaining Issues to be Solved in the Updated Guidelines for Treatment of Chronic Heart Failure

Heart failure (HF) is a leading cause of morbidity and mortality in developed countries and afflicts more than 55 million people in the united states. Patients with chronic HF manifests progressive cardiac dysfunction that is characterized by either reduced systolic and diastolic left ventricular function, or both of it, with ventricular remodeling, arrhythmia, and intracardiac conduction disturbances. A growing body of evidence indicates that combination of pharmacological and non-pharmacological therapies had been significantly contributed to the improved morbidity and mortality of HF in the last decade. Reflecting those advances in HF-therapy, guidelines for treatment of chronic heart failure (JCS2010) has been updated at the end of year 2010. The new version of the guidelines includes updated information for device therapy for cardiac arrhythmia [implantable cardioverter defibllirator (ICD) and ablation therapy], respiratory support therapy for sleep disordered breathing, cardiac resynchronization therapy(CRT) for patients with wide QRS, surgical intervention for severe congestive heart failure, and newly developed left ventricular assist devices. In addition, disease management program and protocols of exercise and Waon therapy for HF patients were revised or newly added into the guideline. In this Symposium, I will review these revision points and remaining issues to be solved for treatment of chronic heart failure.

Ivabradine added to guidelines-based therapy in systolic heart failure patients

Raised resting heart rate is a risk factor for morbidity and mortality in a patient with heart disease [1]. Several patients with heart failure show increased heart rate even if treated with beta-blockers. Furthermore, most patients are intolerant to these drugs. Ivabradine is a selective inhibitor of the If current in the sinoatrial node, resulting in heart rate reduction without affecting myocardial contractility and intracardiac conduction. This pure negative chronotropic effect was previously evaluated in patients with stable angina pectoris. Previously randomised clinical studies demonstrate that ivabradine reduces the heart rate and the risk of angina attacks, and improves exercise capacity, without affecting cardiovascular death and hospital admission for heart failure [2–4].

Ivabradine: Just another New Pharmacological Option for Heart Rate Control?

Ivabradine (IVB) is a heart rate lowering agent that acts via selective inhibition of the pacemaker funny current in sinoatrial nodal P cells, thus, reducing heart rate at rest and during exercise with minimal effect on myocardial contractility, blood pressure, and intracardiac conduction. IVB exerts no effect on external respiratory function parameters and it may also play a role in patients with concurrent chronic obstructive pulmonary disease. This property constitutes an important advantage over β-blockers. IVB acts by reducing the heart rate in a mechanism different from β-blockers, calcium channel blockers or late sodium channel blockers, three commonly prescribed antianginal drugs. As clinical trials have shown, it is remarkably well-tolerated and offers an alternative for patients who cannot take β-blockers. The combination of IVB and atenolol at commonly used doses in patients with chronic stable angina produced additional efficacy with no untoward effect on safety or tolerability. Additionally, side effects are rare and largely limited to a luminous phenomenon or phosphenes. This sensation is thought to be due to a block of Ih in the retina, a current very similar to cardiac If channels. IVB is contraindicated in patients with sick sinus syndrome or sinus node dysfunction and in patients taking hepatic inhibitors of Cytochrome P450 family 3, subfamily A, polypeptide 4 (abbreviated CYP3A4), with exception of omeprazole or lansoprazole. This review briefly summarizes the main studies regarding this drug.

HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG), echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG), echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

A Case of Refractory Heart Failure Successfully Managed by Optimization of the Intra-Cardiac Conduction Delays Using Smart Delay

Background: Optimal atrial-ventricular (AV) and intra-ventricular (VV) conduction delay setting is mandatory for maintaining left ventricular pump function in patients who have undergone cardiac resynchronization therapy (CRT). Echocardiography is considered the gold standard of timing optimization but is a time-consuming procedure.Purpose: We report an interesting case of refractory heart failure who were successfully managed by algorithmic AV and VV delay programming using Smart Delay algorithm.Case: A 54-year-old female patient. The patient was diagnosed as NYHA III degree heart failure in September 2008, CRT-D was implanted in October 2008. In late December 2009, the patient was diagnosed as NYHA IV degree heart failure, and the patient was transferred to our hospital for the treatment of arrhythmias and heart failure.Therapy: optimization of the intra-cardiac conduction delays was achieved using Smart Delay algorithm (paced AV 160 to 180 msec, sensed AV 160 to 180 msec, and BIV pacing to LV pacing), which resulted in a prompt increase in her stroke volume from 46 to 80 ml with consequent improvement in heart failure symptoms.Conclusion: We experienced a case of refractory heart failure successfully managed by optimization of the intra-cardiac conduction delays using Smart Delay.

Precision of a Parabolic Optimum Calculated from Noisy Biological Data, and Implications for Quantitative Optimization of Biventricular Pacemakers (Cardiac Resynchronization Therapy)

In patients with heart failure and disordered intracardiac conduction of activation, doctors implant a biven- tricular pacemaker (“cardiac resynchronization therapy”, CRT) to allow adjustment of the relative timings of activation of parts of the heart. The process of selecting the pacemaker timings that maximize cardiac function is called “optimization”. Although optimization—more than any other clinical assessment—needs to be precise, it is not yet conventional to report the standard error of the optimum alongside its value in clinical practice, nor even in research, because no method is available to calculate precision from one optimization dataset. Moreover, as long as the determinants of precision remain unknown, they will remain unconsidered, preventing candidate haemodynamic variables from being screened for suitability for use in optimization. This manuscript derives algebraically a clinically-applicable method to calculate the precision of the optimum value of x arising from fitting noisy biological measurements of y (such as blood flow or pressure) obtained at a series of known values of x (such as atrioventricular or interventricular delay) to a quadratic curve. A formula for uncertainty in the optimum value of x is obtained, in terms of the amount of scatter (irreproducibility) of y, the intensity of its curvature with respect to x, the width of the range and number of values of x tested, the number of replicate measurements made at each value of x, and the position of the optimum within the tested range. The ratio of scatter to curvature is found to be the overwhelming practical determinant of precision of the optimum. The new formulae have three uses. First, they are a basic science for anyone desiring time-efficient, reliable optimization protocols. Second, asking for the precision of every reported optimum may expose optimization methods whose precision is unacceptable. Third, evaluating precision quantitatively will help clinicians decide whether an apparent change in optimum between successive visits is real and not just noise.