Ventricular Arrhythmias in the Patient with a Structurally Normal Heart.

Ventricular arrhythmias (VAs) are among the most common cardiac rhythm disturbances encountered in clinical practice. Patients presenting with frequent ventricular ectopy or sustained ventricular tachycardia represent a challenging and worrisome clinical scenario for many practitioners because of concerning symptoms, frequent associated acute hemodynamic compromise, and the adverse prognostic implications inherent to these cases. While an underlying structural or functional cardiac abnormality, metabolic derangement, or medication toxicity is often readily apparent, many patients have no obvious underlying condition, despite a comprehensive diagnostic evaluation. Such patients are diagnosed as having an idiopathic VA, which is a label with specific implications regarding arrhythmia origin, prognosis, and potential for pharmacologic and invasive management. Further, a subset of patients with otherwise benign idiopathic ventricular ectopy can present with polymorphic ventricular tachycardia and ventricular fibrillation, adding a layer of complexity to a clinical syndrome previously felt to have a benign clinical course. Thus, this review seeks to highlight the most common types of idiopathic VAs with a focus on their prognostic implications, underlying electrophysiologic mechanisms, unique electrocardiographic signatures, and considerations for invasive electrophysiologic study and catheter ablation. We further address some of the data regarding idiopathic ventricular fibrillation with respect to the heterogeneous nature of this diagnosis.

Inappropriate sinus tachycardia-symptom and heart rate reduction with ivabradine: A pooled analysis of prospective studies.

BACKGROUND: Inappropriate sinus tachycardia (IST) is debilitating despite available treatment. Off-label use of ivabradine for IST prompted this systematic analysis of existing data quality and sample size estimates for adequately powered studies. OBJECTIVE: To determine clinical efficacy of ivabradine in IST from pooled prospective studies. METHODS: Analysis included ivabradine studies for IST participants without structural heart disease and with follow-up of ≥2 weeks. Heart rate and symptom reduction with ivabradine were estimated based on results of subjective change in symptoms assessed by various data instruments used in each study. Studies were assessed for quality using validated checklists. Sample sizes were calculated based on the magnitude of symptom reduction encountered after treatment with ivabradine. RESULTS: Nine studies met criteria, culminating in 145 patients pooled. Most patients were women (≥70%). Studies were small and not adequately powered, and all reported a decrease in maximum or mean resting heart rate or both, with complete or considerable amelioration of symptoms with ivabradine. Most studies had moderate quality with excellent consistency of study quality and narrow limits of agreement between the quality checklists. Sample size estimates for adequately powered studies with various placebo effects and comparisons with ß-blockade are reported. CONCLUSIONS: Ivabradine effectively reduces heart rate and symptoms in IST, but no study was adequately powered to account for the expected placebo effect on symptoms. A multicenter, randomized, placebo-controlled, active, comparative study with a ß-blocker is needed for confirmation. This is especially relevant given the ivabradine's potential teratogenic effect, as many IST patients are females of childbearing potential.

Drug Therapy for Stable Angina Pectoris.

Chronic stable angina pectoris refers to the predictable, reproducible occurrence of pressure or a choking sensation in the chest or adjacent areas caused by myocardial ischemia in association with physical or emotional stress, and cessation of exertion and or sublingual nitroglycerin invariably relieves the discomfort. It is a common presenting symptom of severe narrowing of one or more coronary arteries, non-obstructive coronary arteries, or even when the coronary arteries are angiographically normal. Patients often avoid activities which precipitate symptoms and have impaired quality of life. Most patients with angina pectoris can be managed with lifestyle changes, especially abstinence from smoking and regular exercise, and anti-anginal drugs. However, the choice of initial or combination antianginals as recommended in the guidelines is not evidence based. In addition, patients with stable angina due to coronary artery disease should also receive aspirin and a statin. Treatment of patients with angina and normal coronary arteries remains to be established. The aim of this article is to provide the readers not only with a guideline-based approach, which varies from one country to another, but also an individual-based approach, which takes into consideration circulatory status and the presence or absence of comorbidities in the treatment decision-making process. This manuscript primarily deals with drug therapy of stable angina pectoris and not coronary artery revascularization, which also provides angina relief but is usually reserved for patients who fail to respond to adequate drug therapy.

Atrial Fibrillation Catheter Ablation: Overcoming Complications and Improving Success.

Careful patient selection and optimization of the management of active medical conditions prior to proceeding with catheter ablation for atrial fibrillation (AF) is critical to reducing complications and improving ablation success. AF ablation performed on patients who have not been offered appropriate antiarrhythmic drug therapy must be tempered with the procedure risks, particularly for those patients having multiple comorbidities. The inability to comply with systemic anticoagulation for thromboembolic prophylaxis in AF is a contraindication to AF ablation, as premature termination of anticoagulation therapy can lead to catastrophic thromboembolic complications. Successful pulmonary vein isolation (PVI), the cornerstone of AF ablation, is demonstrated by entrance and exit block post ablation, with sustained absence of atrium-to-pulmonary vein conduction in both directions. Beyond PVI, there is no consensus for other endpoints for AF ablation, particularly in patients with persistent or longstanding persistent AF. Complications of PVI for AF have decreased in recent years as technology and knowledge in this field has evolved; however, the risks of cardiac tamponade, thromboembolic complications, esophageal injury, and pulmonary vein stenosis may still be formidable.

The risk of cardiovascular side effects with anti-anginal drugs.

INTRODUCTION: Angina pectoris is a common presenting symptom of underlying coronary artery disease or reduced coronary flow reserve. Patients with angina have impaired quality of life; and need to be treated optimally with antianginal drugs to control symptoms and improve exercise performance. A wide range of antianginal medications are approved for the treatment of angina, and often more than one class of antianginal drugs are used to adequately control the symptoms. This expert opinion highlights the likely cardiac adverse effects of available antianginal drugs, and how to minimize these in individual patients and especially during combination treatment. Areas covered: All approved antianginal drugs, including the older and newly approved medications with different mechanism of action to the older drugs as well as some of the unapproved herbal medications. The safety profiles and potential cardiac side effects of these medications when used as monotherapy or as combination therapy are discussed and highlighted. Expert opinion: Because of the different cardiac safety profiles and possible side effects, we recommend selection of initial drug or adjustment of therapy based on the resting heart rate; blood pressure, hemodynamic status; and resting left ventricular function, concomitant medications and any associated comorbidities.

Atrial fibrillation: mechanistic insights and treatment options.

Atrial fibrillation (AF) remains the most common clinically encountered arrhythmia. Unlike supraventricular arrhythmias that use a defined mechanism, AF involves a wide spectrum of arrhythmias from lone AF to paroxysmal to chronic AF. AF is an arrhythmia that may develop in several ways. Mechanical remodeling manifests as decreased atrial contractility and increased atrial compliance which leads to a stretch of the atrial myocardium. Atrial remodeling may also increase in atrial fibrosis which can slow conduction velocity and can shorten the refractory period in atria with long-standing AF. It is still unclear whether initiation of AF activates direct inflammatory effects or whether the presence of a pre-existing systemic inflammatory state promotes further persistence of AF. Currently, the patient population undergoing AF ablation has greatly expanded. Patients are older and have larger left atrial size and are more likely to have persistent/permanent AF. It is likely that AF comprises a spectrum of disease with no single mechanism adequate enough to comprehensively explain AF and its variability. The management of patients with AF involves elements of anticoagulation, rate control and rhythm control and such treatment strategies are not necessarily mutually exclusive of each other.

Transcatheter aortic valve replacement: a potential option for the nonsurgical patient.

With improved life expectancy, the incidence of aortic stenosis is rising. However, up to one-third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to a high operative mortality rate. Such patients can only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement. Clinical trials are investigating these devices in patients with severe aortic stenosis that have been denied surgery. Preliminary results from these trials suggest that transcatheter aortic valve replacement (TAVR) is not only feasible, but an effective way to improve symptoms. In this review, we describe the current technology and display available outcome data. Though technical challenges and operator learning curve limit optimal use of the current technology, continued experience and advancements in technology may one day make TAVR a viable alternative to traditional surgical aortic valve replacement.

Evidence for using clopidogrel alone or in addition to aspirin in post coronary artery bypass surgery patients.

Clopidogrel is recommended with aspirin for patients who undergo coronary artery bypass grafting (CABG) after non-ST elevation myocardial infarctions. Cardiothoracic surgeons widely use clopidogrel in addition to aspirin for post-CABG patients, including those with stable coronary artery disease. The aim of this study was to systematically review the published research to determine whether clopidogrel use after CABG is based on good trial data. Studies reporting safety and/or efficacy data for clopidogrel use with or without aspirin after on- or off-pump CABG were included. Fourteen studies met the inclusion criteria, of which 11 were reported trials and 3 are ongoing trials. Subgroup retrospective analyses of previously reported large trials of patients presenting with acute coronary syndromes (n = 1) or patients with stable coronary artery disease (n = 3) did not show a clear clinical benefit of clopidogrel when given in addition to aspirin after CABG. In contrast, there was a trend toward increased major and minor bleeding after the use of clopidogrel plus aspirin. Two small prospective trials providing data on surrogate end points and 5 small trials involving off-pump CABG patients were not of good quality to draw meaningful conclusions. In conclusion, summarized data based on subgroup analyses, surrogate end points, and observational cohort studies fail to demonstrate a clear beneficial effect of clopidogrel alone or in combination with aspirin on clinical outcomes after CABG.

The heterogeneous spectrum of the long QT syndrome.

The long QT syndrome affects predominantly younger people who demonstrate structurally normal hearts. The underlying defect in the long QT syndrome seems to be genetic mutations in the cardiac ionic channels responsible for generating action potentials. Genetic linkage mapping has identified six genes (designated LQT1-6) associated with the Romano-Ward syndrome; two of these genes (LQT1, LQT5) are associated with the Jervell and Lange-Nielsen syndrome. All of these genes encode potassium channels with the exception of LQT3, which encodes a sodium channel. Mutations affecting these channels will lead to a derangement in ionic flows across the cytoplasmic membranes of cardiac cells, thereby leading to prolongation of the cardiac action potential and lengthening of the QT interval on the surface electrocardiogram. Long QT syndrome is a cause of death in young, otherwise healthy individuals. The heterogeneity of the long QT syndrome also makes prognosis and risk stratification difficult. In patients with long QT syndrome genotypes 1 and 2, as well as during slower heart rates, men exhibited shorter mean QTc interval durations than did women; thus, women possess a predilection for developing torsades de pointes. In female probands with the congenital long QT syndrome, the postpartum period appears to confer a significant risk for experiencing a cardiac event. The study determined that certain combinations, such as exhibiting a QTc of 500ms or more, along with the presence of LQT1, LQT2, and LQT3 (with male gender), conferred a 50% or greater risk of a first cardiac event. Based on the observation that physical exertion and emotional stress are significant triggers for cardiac events in the setting of congenital long QT syndrome (specifically the LQT1 and LQT2 genotypes), avoidance of competitive sports seems to be a prudent lifestyle modification. This heterogeneity stems from the presence of different mutations in the genes that encode cardiac ion channels. The triggering events, prognosis, and risk stratification of the patient with long QT syndrome appear to be influenced by the underlying genotype. The primary treatment of congenital long QT syndrome, i.e., beta-blockade therapy with internal cardioverter defibrillator therapy, appears to be useful in a subset of patients.

Relationship of mitral annular remodeling to severity of chronic mitral regurgitation.

HYPOTHESES: (1) Mitral regurgitation (MR) severity is directly associated with mitral annular remodeling as evidenced by mitral annular enlargement. (2) Increasing severity of chronic MR will result in symmetric enlargement of the mitral annulus as measured by annular shape indices. BACKGROUND: Limited data exist on mitral annular remodeling for patients with MR. Identification of annular changes may be important in aiding surgical repair. METHODS: The mitral annulus was measured in several planes using transthoracic echocardiography in 173 patients: trace to no MR (34), mild MR (48), moderate MR (45), and severe MR (46). Patients were subgrouped by mechanism of MR and annular shape indices were determined. RESULTS: With increasing MR severity, there was a corresponding symmetric increase in all systolic and diastolic measurements, but no significant differences in annular shape indices between subgroups by MR severity or by MR mechanism. CONCLUSIONS: Mitral annular remodeling is symmetric, regardless of degree or mechanism of MR.

Myocardial first-pass perfusion assessment using rotational long-axis MRI.

PURPOSE: To study a first-pass myocardial perfusion imaging method, such that long-axis imaging slices are obtained rotationally around the short-axis centroid of the left ventricular cavity, in order to improve myocardial coverage and better delineate the basal and apical myocardium. MATERIALS AND METHODS: This rotational long-axis (RLA) method was examined in 12 volunteers and compared to the perfusion images from conventional parallel short-axis (PSA) acquisitions in terms of the contrast to noise ratio (CNR), relative signal upslope and myocardial coverage. Both RLA and PSA first-pass perfusion images were acquired on each volunteer with otherwise identical imaging parameters using the partial Fourier saturation recovery steady state gradient echo sequence with refocused magnetization (TrueFISP) technique. RESULTS: Compared to PSA, RLA perfusion images with identical imaging parameters on the same subject exhibit an average of near 30% improvement in total myocardial area imaged. In addition, true basal and apical myocardium was seen on RLA, but not on PSA. The mean CNR and relative upslope were similar between the two techniques. CONCLUSIONS: This RLA perfusion imaging scheme is superior to the conventional PSA approach in terms of extent myocardial coverage and delineation of basal and apical regions of the left ventricle.

Quantitative breath-hold monitoring of myocardial gadolinium enhancement using inversion recovery TrueFISP.

The purpose of this work was to develop and evaluate the accuracy of a breath-hold IR-TrueFISP acquisition capable of monitoring gadolinium (Gd) concentrations through T1 measurements in the left ventricular blood pool and segments of the myocardium over an extended duration. Measurements using a phantom were performed to assess the accuracy of the technique. Accurate T1 measurements in the expected range after contrast agent administration were obtained with several theoretical formulations. Accurate T1 values before the administration of the contrast agent were obtained only when the incomplete recovery of magnetization during the delay time (TD) between imaging segments was incorporated into the observed signal intensity calculations. T1 measurements over a 1-hr time period were performed in four subjects with known myocardial infarctions. In this small study, Gd differences between recent and old myocardial infarctions were observed.

Congestive heart failure in the elderly: the Cardiovascular Health Study.

Congestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.