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INSIDE THIS ISSUE

Inside This Issue

	State-of-the-Art Paper

Top State-of-the-Art Paper Viewpoint Clinical Research

Ara Tachjian, Viqar Maria, Arshad Jahangir

More than 15 million people in the U.S. consume herbal remedies or high-dose vitamins. The potential risk of adverse herb-drug-disease interactions in cardiac patients who may be taking multiple prescriptions is reviewed by Tachjian and colleagues. Despite the paucity of scientific evidence supporting the safety or efficacy of herbal products, they are widely promoted in the popular media with unsubstantiated health care claims. The possibility of harm caused either directly or through interactions with prescription medications is reviewed and suggestions for improving their safety are proffered.

	Viewpoint

Top State-of-the-Art Paper Viewpoint Clinical Research

 
Viewpoint.   More Evidence Needed to Guide Treatment of HFNEF
526

Walter J. Paulus, Joris J. M. van Ballegoij

Paulus and van Ballegoij explore the discrepancies in the literature showing positive effects of many interventions for patients with heart failure with reduced left ventricular ejection fraction (HFREF) but no significant benefit for those with heart failure and normal left ventricular ejection fraction (HFNEF). The patient recruitment criteria of 21 HFNEF trials are reviewed in reference to diagnostic guidelines for HFNEF as inclusion/exclusion criteria. Among these trials, left ventricular ejection fraction (LVEF) cut-off values ranged from 35% to 50%, with only 8 trials requiring an LVEF >50%. Only 1 trial specified a normal left ventricular (LV) end-diastolic dimension, and only 7 required evidence of diastolic LV dysfunction. Nonadherence to diagnostic guidelines may have blunted the possible benefit of intervention. Future HFNEF trials should adhere to diagnostic guidelines for HFNEF that require signs and/or symptoms of heart failure, evidence of normal systolic LV function, and evidence of diastolic dysfunction.

	Clinical Research

Top State-of-the-Art Paper Viewpoint Clinical Research

 
Interventional Cardiology.   Endovascular Stenting for Vertebral Artery Stenosis
538

J. Stephen Jenkins, Samir N. Patel, Christopher J. White, Tyrone J. Collins, John P. Reilly, Paul W. McMullan, Mark A. Grise, Arthur G. Grant, Stephen R. Ramee

Symptomatic vertebral artery stenosis (VAS) portends a 30% to 35% 5-year risk of stroke with medical therapy, but surgical bypass is rarely performed due to high morbidity and mortality. Jenkins and colleagues report their results with 105 consecutive symptomatic patients who underwent stent placement for extracranial (91%) and intracranial (9%) VAS. Procedural and clinical success was achieved in 100% and 90.5% of patients, respectively. At 1-year follow-up, 80% of patients remained symptom-free and only 5% had suffered a posterior circulation stroke. Stenting for symptomatic VAS can be safely performed and may offer a safer approach than either open surgical revascularization or medical therapy.

Interventional Cardiology.   ZES Noninferior to PES, But Results Are Mixed
543

Martin B. Leon, Laura Mauri, Jeffrey J. Popma, Donald E. Cutlip, Eugenia Nikolsky, Charles O'Shaughnessy, Paul A. Overlie, Brent T. McLaurin, Stuart L. Solomon, John S. Douglas, Jr, Michael W. Ball, Ronald P. Caputo, Ash Jain, Thaddeus R. Tolleson, Bernard M. Reen III, Ajay J. Kirtane, Peter J. Fitzgerald, Kweli Thompson, David E. Kandzari, for the ENDEAVOR IV Investigators

The ENDEAVOR IV trial is a prospective, randomized trial comparing a zotarolimus-eluting stent (ZES) with a paclitaxel-eluting stent (PES) for single de novo coronary artery lesions. The primary hypothesis was a noninferiority test with regard to 9-month target vessel failure (TVF), which was defined as cardiac death, myocardial infarction (MI), or target vessel revascularization. The ZES was found to be noninferior, with a TVF rate of 6.6% versus 7.1% for PES. However, there were differences in the particular end points, with fewer periprocedural MIs with ZES (0.5% vs. 2.2%), but a numerically higher rate of in-segment restenosis (15.3% vs. 10.4%). Based on the TVF end point, ZES is noninferior to PES, but more studies are needed to determine if the tradeoff between reduced periprocedural MI and higher restenosis is real, and ultimately beneficial for patients.

Editorial Comment: E. Magnus Ohman, Robert M. Califf, p. 555

Antiplatelet Therapy.   No Evidence of Platelet Hypersensitivity After Abrupt Cessation of Clopidogrel

558

Dirk Sibbing, Julia Stegherr, Siegmund Braun, Julinda Mehilli, Stefanie Schulz, Melchior Seyfarth, Adnan Kastrati, Nicolas von Beckerath, Albert Schömig

Clinical studies have reported a clustering of thrombotic events shortly after stopping clopidogrel treatment, suggesting that there may be a rebound phenomenon. Sibbing and colleagues studied this issue and whether tapering of the clopidogrel dose, rather than abrupt cessation, may be superior. Seventy patients who were finishing their clopidogrel therapy were randomized to either a tapering regimen for 4 weeks or to abruptly discontinue clopidogrel. Platelet aggregation (PA) was assessed with light transmission aggregometry and multiple electrode aggregometry weekly. PA was found to be similar after complete cessation of clopidogrel between both groups. The course of PA values after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon.

Cardiac Resynchronization Therapy.   Optimal LV Pacing Site Varies Unpredictably

566

Nicolas Derval, Paul Steendijk, Lorne J. Gula, Antoine Deplagne, Julien Laborderie, Frederic Sacher, Sebastien Knecht, Matthew Wright, Isabelle Nault, Sylvain Ploux, Philippe Ritter, Pierre Bordachar, Stephane Lafitte, Patricia Réant, George J. Klein, Sanjiv M. Narayan, Stephane Garrigue, Mélèze Hocini, Michel Haissaguerre, Jacques Clementy, Pierre Jaïs

Derval and colleagues used a micromanometer catheter to measure +dP/dt_max and other hemodynamic variables while subjects were paced through an endocardial pacing catheter placed at 11 specific points in the left ventricle (LV) and compared it to a traditional position in the coronary sinus (CS). Major interindividual and intraindividual variations of hemodynamic response depending on the LV pacing site were observed. Compared with baseline, LV DDD pacing at the best LV position significantly improved +dP/dt_max (+31%) and was superior to pacing the CS (+15%), or the latest activated LV wall as determined by tissue Doppler imaging (+11%). The pacing site is a primary determinant of the hemodynamic response to LV pacing, but determining the optimal site appears to require trial and error.

Editorial Comment: Jagmeet P. Singh, William T. Abraham, p. 576

Heart Rhythm Disorders.   Results From a Registry of Laser Lead Extractions
579

Oussama Wazni, Laurence M. Epstein, Roger G. Carrillo, Charles Love, Stuart W. Adler, David W. Riggio, Shahzad S. Karim, Jamil Bashir, Arnold J. Greenspon, John P. DiMarco, Joshua M. Cooper, John R. Onufer, Kenneth A. Ellenbogen, Stephen P. Kutalek, Sherri Dentry-Mabry, Carolyn M. Ervin, Bruce L. Wilkoff

Wazni and colleagues examined the safety and efficacy of laser-assisted lead extraction (LALE) in almost 1,500 consecutive patients at 13 centers. Leads were completely removed in 96%, with a 98% clinical success rate. Failure to achieve clinical success was more common in patients with a body mass index <25 kg/m² and in low extraction volume centers. Major adverse events in 20 patients were directly related to the lead extraction procedure (1.4%), including 4 deaths (0.28%). LALE is highly successful with a low procedural complication rate, but mortality from pocket infections or device-related endocarditis remains high.

Heart Rhythm Disorders.   Compound and Digenic Heterozygosity May Be Common in ARVC

587

Tianhong Xu, Zhao Yang, Matteo Vatta, Alessandra Rampazzo, Giorgia Beffagna, Kalliopi Pillichou, Steven E. Scherer, Jeffrey Saffitz, Joshua Kravitz, Wojciech Zareba, Gian Antonio Danieli, Alessandra Lorenzon, Andrea Nava, Barbara Bauce, Gaetano Thiene, Cristina Basso, Hugh Calkins, Kathy Gear, Frank Marcus, Jeffrey A. Towbin, for the Multidisciplinary Study of Right Ventricular Dysplasia Investigators

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is frequently the result of a mutation in 1 of the 7 genes encoding desmosomal proteins, with autosomal dominant inheritance, but reduced penetrance. Xu and colleagues sequenced the plakophilin-2 (PKP2) gene in 198 probands of families with ARVC. Twenty-one variants were found, with 19% of the probands having at least 1 variant. In 9 of the 38 (24%) probands, PKP2 variants were identified that were encoded in trans and, therefore, represent compound heterozygosity, or the inheritance of 2 distinct mutations. These 38 probands were also screened for other desmosomal mutations; second variants (digenic heterozygosity) were identified in 42%. These data suggest that the genetic basis of ARVC may require a "double-hit" with compound and digenic heterozygosity.

Cardiac Imaging.   MRI-Based Oximetry May Be Useful for Measuring Tissue Ischemia in Patients With PAD

598

Michael C. Langham, Thomas F. Floyd, Emile R. Mohler III, Jeremy F. Magland, Felix W. Wehrli

Magnetic resonance imaging (MRI)-based oximetry is a technique that can measure the fractional volume of deoxyhemoglobin in erythrocytes. Langham and colleagues tested if this technique could evaluate vascular function in the lower extremities by making direct time-course measurements of oxygen saturation in the femoral and popliteal arteries and veins during cuff-induced reactive hyperemia. Significantly longer washout time of the desaturated blood and a slower upslope of the return of oxygenated blood were observed in patients with peripheral arterial disease, compared with healthy subjects. Post-occlusive transient changes in venous blood oxygenation provide a measure of vascular competence.

Related Articles

Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases

Ara Tachjian, Viqar Maria, and Arshad Jahangir
J. Am. Coll. Cardiol. 2010 55: 515-525. [Abstract] [Full Text] [PDF]

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