INSIDE THIS ISSUE OF JACC
Inside This Issue of JACC
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Clinical Trial
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Darapladib Significantly Lowers Lp-PLA2 Activity.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a biomarker of cardiovascular risk that contributes to the proatherosclerotic tendencies of oxidized low-density lipoprotein. This placebo-controlled, dose-ranging study examined the effects of darapladib, a selective Lp-PLA2 inhibitor, on biomarkers of cardiovascular risk, but was too short to identify any clinical benefit. Darapladib inhibited Lp-PLA2 activity by up to 66% for the highest dose. Interleukin-6 and high-sensitivity C-reactive protein were also substantially lowered. No major safety concerns were noted. Darapladib appears to produce a sustained inhibition of plasma Lp-PLA2 activity in patients receiving atorvastatin; further studies will determine if this results in better outcomes. See pages 1632 and
1642. See figure.
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Heart Failure
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Weak Diaphragms May Contribute to Fatigue and Vasoconstriction in CHF Patients.
Previous research has demonstrated that the inspiratory muscles of the diaphragm may shift to anaerobic metabolism when they become fatigued. Through the inspiratory muscle metaboreflex, this may lead to shunting of blood from other vascular beds to the diaphragm. Chiappa and colleagues hypothesized that this reflex may be accentuated in patients with chronic heart failure (CHF) and could be overcome through training of these muscles. Inspiratory muscle fatigue was induced by having subjects breathe through a small tube during hand exercise while measuring blood flow to the calf and forearm. Experiments were repeated after 4 weeks of inspiratory muscle training. Subjects with CHF showed marked vasoconstriction during exercise, which was attenuated after the respiratory training. This study provides evidence of abnormal activity of the inspiratory muscle metaboreflex in patients with CHF and suggests that it can be attenuated by training of the inspiratory muscles. See pages 1663 and
1672.
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Heart Rhythm Disorders
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Registry of ICD Implants in Pediatric and Congenital Heart Patients.
Berul and colleagues retrospectively obtained data from 4 pediatric centers, aiming to identify implant characteristics, shock frequency, and complication rates for pediatric or adult patients with congenital heart disease (CHD) who received implantable cardioverter-defibrillators (ICDs). They identified 443 patients, with a median age of 16 years; 69% had structural heart disease and the others had electrical anomalies. One-half of patients received the device for primary prevention. Twenty-six percent received appropriate shocks, and 21% received inappropriate shocks, mainly due to lead failure (14%). The authors conclude that children and CHD ICD recipients have significant appropriate and inappropriate shocks; the number of inappropriate shocks may be reduced by better device programming, medical management, patient compliance, and reducing the lead failure rate. See page 1685.
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Heart Rhythm Disorders
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Mitral Annuloplasty May Frequently Result in Functional Mitral Stenosis.
When patients referred for coronary artery bypass graft surgery are found to have mitral regurgitation, many have advocated simultaneous placement of a mitral valve annuloplasty (MVA) ring. By convention, the size of the ring is usually 2 to 4 mm smaller than the pre-surgical intertrigonal width. Magne and colleagues performed resting and dobutamine stress echocardiography and 6-min walk test (6MWT) in 24 patients without recurrent mitral regurgitation after restrictive MVA. Compared to a matched control group, MVA patients had higher transmitral pressure gradients, higher pulmonary artery pressures, and reduced 6MWT distance. These results suggest that performing a restrictive MVA in patients with ischemic mitral regurgitation may create a functional mitral stenosis that may impair functional capacity. See pages 1692 and
1702. See figure.
Related Articles
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The Effect of Darapladib on Plasma Lipoprotein-Associated Phospholipase A2 Activity and Cardiovascular Biomarkers in Patients With Stable Coronary Heart Disease or Coronary Heart Disease Risk Equivalent: The Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
- Emile R. Mohler, III, Christie M. Ballantyne, Michael H. Davidson, Markolf Hanefeld, Luis M. Ruilope, Joel L. Johnson, Andrew Zalewski for the Darapladib Investigators
J. Am. Coll. Cardiol. 2008 51: 1632-1641.
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Treating Residual Cardiovascular Risk: Will Lipoprotein-Associated Phospholipase A2 Inhibition Live Up to Its Promise?
- Wolfgang Koenig
J. Am. Coll. Cardiol. 2008 51: 1642-1644.
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Inspiratory Muscle Training Improves Blood Flow to Resting and Exercising Limbs in Patients With Chronic Heart Failure
- Gaspar R. Chiappa, Bruno T. Roseguini, Paulo J.C. Vieira, Cristiano N. Alves, Angela Tavares, Eliane R. Winkelmann, Elton L. Ferlin, Ricardo Stein, and Jorge P. Ribeiro
J. Am. Coll. Cardiol. 2008 51: 1663-1671.
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Improving Exercise Tolerance in Chronic Heart Failure: A Tale of Inspiration?
- Jerome L. Fleg
J. Am. Coll. Cardiol. 2008 51: 1672-1674.
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Results of a Multicenter Retrospective Implantable Cardioverter-Defibrillator Registry of Pediatric and Congenital Heart Disease Patients
- Charles I. Berul, George F. Van Hare, Naomi J. Kertesz, Anne M. Dubin, Frank Cecchin, Kathryn K. Collins, Bryan C. Cannon, Mark E. Alexander, John K. Triedman, Edward P. Walsh, and Richard A. Friedman
J. Am. Coll. Cardiol. 2008 51: 1685-1691.
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Restrictive Annuloplasty for Ischemic Mitral Regurgitation May Induce Functional Mitral Stenosis
- Julien Magne, Mario Sénéchal, Patrick Mathieu, Jean G. Dumesnil, François Dagenais, and Philippe Pibarot
J. Am. Coll. Cardiol. 2008 51: 1692-1701.
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Restrictive Annuloplasty for Ischemic Mitral Regurgitation: Too Little or Too Much?
- Thomas H. Marwick
J. Am. Coll. Cardiol. 2008 51: 1702-1703.
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