Amir Y. Shaikh

Chemotherapy-Induced Cardiotoxicity

Anthracycline-based chemotherapeutics have long been recognized as effective agents for treating a wide range of malignancies. However, their use is not without significant adverse cardiotoxic side effects. Strategies for prevention involve limiting free-radical production and subsequent cardiac myocyte damage. Dexrazoxane remains the most widely studied cardioprotective medication. Alternative agents may reduce cardiotoxicity but may still cause significant cardiovascular problems. The role of β-blockers and angiotensin-converting enzyme inhibitors in the treatment of heart failure is well proven. The role of these medications in the prevention and treatment of chemotherapy-induced cardiotoxicity is not well established.

Speckle echocardiographic left atrial strain and stiffness index as predictors of maintenance of sinus rhythm after cardioversion for atrial fibrillation: a prospective study

BackgroundEchocardiographic left atrial (LA) strain parameters have been associated with atrial fibrillation (AF) in prior studies. Our goal was to determine if strain measures [peak systolic longitudinal strain (LAS) and stiffness index (LASt)] changed after cardioversion (CV); and their relation to AF recurrence.Methods and results46 participants with persistent AF and 41 age-matched participants with no AF were recruited. LAS and LASt were measured before and immediately after CV using 2D speckle tracking imaging (2DSI). Maintenance of sinus rhythm was assessed over a 6-month follow up. Mean LAS was lower, and mean LASt higher, in participants with AF before CV as compared to control group (11.9 ± 1.0 vs 35.7 ± 1.7, p<0.01 and 1.31 ± 0.17 vs 0.23 ± 0.01, p<0.01, respectively). There was an increase in the mean LAS immediately after CV (11.9 ± 1.0 vs 15.9 ± 1.3, p<0.01), whereas mean LASt did not change significantly after CV (p=0.62). Although neither LAS nor LASt were independently associated with AF recurrence during the follow-up period, change in LAS after cardioversion (post-CV LAS – pre-CV LAS) was significantly higher among individuals who remained in sinus rhythm when compared to individuals with recurrent AF (3.6 ± 1.1 vs 0.4 ± 0.8, p=0.02).ConclusionsLAS and LASt differed between participants with and without AF, irrespective of the rhythm at the time of echocardiographic assessment. Baseline LAS and LASt were not associated with AF recurrence. However, change in LAS after CV may be a useful predictor of recurrent arrhythmia.

Newer anticoagulants in cardiovascular disease: a systematic review of the literature.

Vitamin K antagonists (VKAs) such as warfarin have traditionally been the major therapeutic option for anticoagulation in clinical practice. VKAs are effective and extensively recommended for the prevention of venous and arterial thromboembolism in cardiovascular disease. Despite its effectiveness, warfarin is limited by factors such as a narrow therapeutic index, drug-drug interactions, food interactions, slow onset and offset of action, hemorrhage, and routine anticoagulation monitoring to maintain therapeutic international normalized ratio. During the last 2 decades, the approval of anticoagulants, such as low-molecular-weight heparins, indirect factor Xa inhibitors (eg, fondaparinux), and direct thrombin inhibitors (eg, argatroban, lepirudin, and desirudin), have expanded the number of available antithrombotic compounds with additional targets within the anticoagulation pathway. Although these medications offer several potential therapeutic advantages, they all require parenteral or subcutaneous administration and are substantially more expensive than VKAs. Thus, VKAs, despite several limitations, have remained the major option for most patients requiring chronic anticoagulation. These limitations have prompted interest in the development of newer oral anticoagulants. Novel anticoagulants targeting inhibition of factor Xa and thrombin (factor IIa) have now been incorporated into clinical practice based on the results of large randomized clinical trials, with the recent U.S. Food and Drug Administration approval of dabigatran for stroke prevention in atrial fibrillation and rivaroxaban for deep vein thrombosis and stroke prevention in atrial fibrillation, with multiple other agents in various stages of development for these and other indications. This review discusses the pharmacological properties, clinical results, and therapeutic applications of novel and new anticoagulants, thereby providing an outline for the future of anticoagulation in cardiovascular disease.

Complications from catheter ablation of atrial fibrillation: a systematic review.

Atrial fibrillation (AF) is the most common arrhythmia requiring treatment that is encountered in clinical practice. Recent advances in the understanding of underlying mechanisms of AF have led to the increased use of catheter ablation (CA) as a treatment modality for paroxysmal, persistent, or long-standing persistent AF in patients with symptomatic AF despite treatment with antiarrhythmic medications. Because of the complexity in technique and anatomic location of the ablation sites, it is not surprising that CA of AF is associated with a greater risk of procedural complications compared with simpler cardiac ablation procedures. Major and minor complications, including life-threatening complications, have been described and quantified. This systematic review describes the potential risks of CA that have been reported over a period and provides insights into the evolving strategies to minimize these complications, thus making CA techniques safer and potentially more efficacious for AF.

Atrial Fibrillation and Hypertension: Mechanistic, Epidemiologic, and Treatment Parallels

Atrial fibrillation (AF) is an increasingly prevalent condition and the most common sustained arrhythmia encountered in ambulatory and hospital practice. Several clinical risk factors for AF include age, sex, valvular heart disease, obesity, sleep apnea, heart failure, and hypertension (HTN). Of all the risk factors, HTN is the most commonly encountered condition in patients with incident AF. Hypertension is associated with a 1.8-fold increase in the risk of developing new-onset AF and a 1.5-fold increase in the risk of progression to permanent AF. Hypertension predisposes to cardiac structural changes that influence the development of AF such as atrial remodeling. The renin angiotensin aldosterone system has been demonstrated to be a common mechanistic link in the pathogenesis of HTN and AF. Importantly, HTN is one of the few modifiable AF risk factors, and guideline-directed management of HTN may reduce the incidence of AF.

Atrial fibrillation and heart failure parallels: lessons for atrial fibrillation prevention.

Heart failure (HF) and atrial fibrillation (AF) are 2 of the most common cardiovascular diseases encountered in clinical practice, and the prevalence of these diseases continues to grow worldwide with the aging of the global population. While recognizing that AF is a heterogeneous disorder, we submit that the parallels between AF and HF may arise because many cases of AF and HF result from the cumulative exposure of the atria and ventricles to a common set of systemic cardiovascular risk factors. Over time, exposure to risk factors promotes development of atrial and ventricular structural and functional abnormalities through activation of several biologic pathways in concert: upregulation of neurohormonal signaling cascades, release of inflammatory mediators, programmed cell death, and fibrosis. Cardiac structural remodeling occurs in concert with electrophysiologic remodeling, both of which contribute to atrial and ventricular rhythm disturbances, including AF. AF and HF, instead of representing distinct disease processes, often represent different endpoints along a disease continuum. By reviewing some of the mechanistic parallels between AF and HF, we hope to emphasize the connection between established cardiovascular risk factors, cardiac remodeling and AF, with a view to promote strategies for AF prevention.

A Bridge Too Far? Findings of Bridging Anticoagulation Use and Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)

In the current issue of Circulation , Steinberg et al1 describe the use and outcomes associated with bridging anticoagulation (AC) in patients with atrial fibrillation (AF) in the contemporary Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF). Chronic oral anticoagulation (OAC) significantly reduces the risk of stroke or thromboembolism in patients with AF. Despite the growing population burden of AF,2 the increasing use of OAC, and the frequent need for cardiac and noncardiac procedures in this population, remarkably little contemporary data exist to help guide the clinician with respect to periprocedural AC decision making. Although guidelines exist on the topic, they are based on limited and largely observational data.3,4 Current guideline-supported periprocedural AC management supports the discontinuation of OAC and the use of short-acting AC, most commonly low-molecular-weight heparin or unfractionated heparin, to bridge AF patients at high risk for thromboembolic complications during the immediate pre- and postprocedure period (American College of Chest Physicians grade 2C; American Heart Association grade 1C).3,4 Article see p 488 “To bridge or not to bridge,” is a question often asked in clinical practice, with an estimated 250 000 patients on OAC undergoing cardiac and noncardiac procedures annually in North America.3 The authors are therefore to be congratulated for examining the topic of use and outcomes of bridging AC in an effort to better inform us and enhance the safety of our AF patients. Currently, the periprocedural management of patients who are receiving OAC is often informed by a clinician’s (1) assessment of patient risk for thromboembolism, (2) assessment of risk for perioperative bleeding, and (3) the type of procedure. Although CHADS2, CHA2DS2-VASc, HAS-BLED, and ATRIA scores are used in clinical practice to assess the risks of …

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid–femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02–1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01–1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63–0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02–1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF.

Association of Left Atrial Function Index With Late Atrial Fibrillation Recurrence after Catheter Ablation.

Although catheter ablation (CA) for atrial fibrillation (AF) is commonly used to improve symptoms, AF recurrence is common and new tools are needed to better inform patient selection for CA. Left atrial function index (LAFI), an echocardiographic measure of atrial mechanical function, has shown promise as a noninvasive predictor of AF. We hypothesized that LAFI would relate to AF recurrence after CA.

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

INTRODUCTION Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. METHODS One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI (>3 months post-PVI) over the 6-month follow-up period. RESULTS A BNP greater than or equal to 100 pg/dL (P=0.01) and AF recurrence within 3 months after PVI (P<0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P=0.001) and a net reclassification improvement of 60% (P=0.001) for all risk scores. CONCLUSIONS Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence.