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INSIDE THIS ISSUE

Inside This Issue

	Quarterly Focus Issue: Heart Failure

Top Quarterly Focus Issue: Heart... Cardiovascular Risk Cardiac Surgery

Thomas G. Di Salvo, Michael A. Acker, G. William Dec, John G. Byrne

Di Salvo and colleagues review the physiology and structure of the mitral valve that leads to mitral regurgitation in a significant proportion of patients with left ventricular dysfunction. Treatments for this condition range from medical therapy to cardiac resynchronization therapy to surgical therapy with either mitral valve repair or replacement. Recent trials provide evidence for a beneficial effect of surgery on left ventricular remodeling and functional capacity. However, these trials did not randomize patients to surgical or medical therapy. This paper ends by proposing an integrated approach to management that focuses on optimizing medical and device-based therapies before referring patients for isolated mitral valve surgery.

State-of-the-Art Paper.   Glucose, Obesity, Metabolic Syndrome, and the Risk of HF

283

Tamara B. Horwich, Gregg C. Fonarow

Horwich and Fonarow review the epidemiologic evidence showing that the incidence of heart failure (HF) continues to rise. The data linking the increasingly prevalent metabolic risk factors, glucose, diabetes, obesity, and the metabolic syndrome, with the risk of HF is reviewed. For instance, in a cohort study of almost 50,000 adult patients with (predominantly type 2) diabetes, each 1% increase in glycosylated hemoglobin was associated with an 8% increased risk of HF hospitalization or HF death. The pathophysiologic mechanisms underlying these relationships are reviewed, especially the fact that the heart may become less energy efficient in the setting of insulin resistance, which may increase susceptibility to injury. Finally, the potential for risk factor modification and other preventive therapies to curb the rising incidence of HF is reviewed.

Clinical Research.   Significant Geographic Disparities in Hospitalization Rates for HF

294

Michele Casper, Isaac Nwaise, Janet B. Croft, Yuling Hong, Jing Fang, Sophia Greer

Casper and colleagues reviewed Medicare billing information to determine if there were geographic disparities in heart failure (HF) hospitalization rates among Medicare beneficiaries in the U.S. The average annual age-adjusted HF hospitalization rate was 21.5 per 1,000 Medicare beneficiaries, and ranged from 7 to 61 per 1,000 among counties in the U.S. There was a clear east-west gradient, with the highest hospitalization rates primarily along the lower Mississippi River Valley and the Ohio River Valley, including the Appalachian region. This data may help health professionals decide where to focus when they design policies and programs to reduce cardiovascular morbidity.

Clinical Research.   Diastolic Dysfunction and the Risk of HF in Diabetic Patients

300

Aaron M. From, Christopher G. Scott, Horng H. Chen

The ratio of the early passive transmitral inflow velocity (E) and the pulsed tissue Doppler velocity of the medial mitral annulus (e') is a reliable and continuous index of left ventricular filling pressure. From and colleagues followed almost 2,000 subjects with diabetes who had an echocardiogram that included the E/e' ratio with diastolic dysfunction defined as a mitral E/e' ratio >15. Those with diastolic dysfunction were almost twice as likely to develop heart failure (HF) even after adjusting for multiple HF risk factors. Every 1-U increase in the mitral E/e' ratio increased the risk of HF by 3%. Furthermore, those with diastolic dysfunction had a higher mortality and higher risk of developing atrial fibrillation compared with those with a normal E/e' ratio. This study confirms that pre-clinical diastolic dysfunction as manifested by echo is prevalent in diabetic patients and is associated with increased heart failure.

Editorial Comment: Barry Greenberg, p. 306

Clinical Research.   Common Geriatric Comorbidities Substantially Affect HF Mortality
309

Sarwat I. Chaudhry, Yongfei Wang, Thomas M. Gill, Harlan M. Krumholz

Chaudhry and colleagues investigated whether the common geriatric conditions of dementia and mobility disability affect short- (30-day) and long-term (5-year) mortality after a hospitalization for heart failure (HF). Mobility disability was defined as requiring assistance (from a device or from another person) or being unable to walk. The mean age of subjects included in the analysis was 80 years; 10% had dementia and 39% had mobility disability. Dementia and mobility disability were among the top predictors of short- and long-term mortality, with an odds ratio similar to those seen for elevated creatinine, a history of aortic stenosis, and a prior history of HF. These results show that geriatric conditions are strongly and independently associated with short- and long-term mortality among older patients with HF.

Editorial Comment: Lakshmi Venkitachalam, John A. Spertus, p. 317

Clinical Research.   Mutation in Alpha-Tropomyosin Linked to Familial DCM

320

Neal K. Lakdawala, Lisa Dellefave, Charles S. Redwood, Elizabeth Sparks, Allison L. Cirino, Steve Depalma, Steven D. Colan, Birgit Funke, Rebekah S. Zimmerman, Paul Robinson, Hugh Watkins, Christine E. Seidman, J. G. Seidman, Elizabeth M. McNally, Carolyn Y. Ho

Lakdawala and colleagues performed direct sequencing of 6 sarcomere genes in 334 probands with dilated cardiomyopathy (DCM). A novel D230N missense mutation in the gene encoding alpha-tropomyosin (TPM1) was identified in 2 large unrelated families and was strongly linked to the likelihood of developing DCM. In vitro studies demonstrated major inhibitory effects on sarcomere function with reduced Ca²⁺ sensitivity, maximum activation, and Ca²⁺ affinity compared with wild-type TPM1. These results from genetic segregation and functional analyses conclusively establish a pathogenic role for TPM1 mutations in DCM.

Editorial Comment: Jil C. Tardiff, p. 330

Clinical Research.   Natural History of Stress Cardiomyopathy (Tako-Tsubo)

333

Scott W. Sharkey, Denise C. Windenburg, John R. Lesser, Martin S. Maron, Robert G. Hauser, Jennifer N. Lesser, Tammy S. Haas, James S. Hodges, Barry J. Maron

Stress cardiomyopathy (SC) is a recently recognized condition characterized by transient cardiac dysfunction with ventricular ballooning, commonly known as tako-tsubo cardiomyopathy. Sharkey and colleagues report their experience with 136 consecutive patients with SC. Patients were predominantly female (96%), with a wide range of ages. In 89% of patients, there was an identifiable precipitating event, either intense emotional stress or a physical event such as the administration of sympathomimetic drugs or a surgical procedure. Eighteen percent were taking beta-blockers at the time of their SC event. Five percent had recurrent SC events. This large cohort helps to define both the precipitating events and the clinical course of these patients.

	Cardiovascular Risk

Top Quarterly Focus Issue: Heart... Cardiovascular Risk Cardiac Surgery

 
Cardiovascular Risk.   High ABI Is Associated With Increased LV Mass

342

Joachim H. Ix, Ronit Katz, Carmen A. Peralta, Ian H. de Boer, Matthew A. Allison, David A. Bluemke, David S. Siscovick, João A. C. Lima, Michael H. Criqui

Ix and colleagues investigated the relationship between ankle brachial index (ABI) and left ventricular (LV) mass. A high ABI (>1.4) indicates stiff peripheral arteries; a low ABI (<0.9) is linked to occlusive peripheral arterial disease. Almost 5,000 subjects enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) had both cardiac magnetic resonance and ABI measurements; many also had measurements of carotid intima-media thickness (cIMT) and coronary artery calcification (CAC). Compared to subjects with intermediate ABI, LV mass was higher with either low or high ABI. Adjustment for cIMT and CAC substantially attenuated the association of low ABI with LV mass, but not the association with high ABI. These results suggest that high ABI may lead to increased LV mass through nonatherosclerotic pathways.

Cardiovascular Risk.   ED Associated With Cardiovascular Risk, But Does Not Improve the FRS
350

Andre B. Araujo, Susan A. Hall, Peter Ganz, Gretchen R. Chiu, Raymond C. Rosen, Varant Kupelian, Thomas G. Travison, John B. McKinlay

Erectile dysfunction (ED) and cardiovascular disease (CVD) share pathophysiological mechanisms, but whether ED improves risk stratification over the Framingham Risk Score (FRS) is unknown. For this prospective study of 1,709 men, ED was measured by self reports. ED was associated with CVD incidence controlling for age (hazard ratio [HR]: 1.42) and age and traditional CVD risk factors (HR: 1.41), as well as age and FRS (HR: 1.40). Despite these significant associations, ED did not improve reclassification beyond the FRS. ED is associated with increased CVD incidence, but does not improve the prediction of who will or will not develop CVD beyond that offered by traditional risk factors.

Cardiovascular Risk.   Obesity Impairs Function of EPCs

357

Nana-Maria Heida, Jan-Peter Müller, I-Fen Cheng, Maren Leifheit Nestler, Vivien Faustin, Joachim Riggert, Gerd Hasenfuss, Stavros Konstantinides, Katrin Schäfer

Heida and colleagues investigated the viability of endothelial progenitor cells (EPCs) isolated from the peripheral blood of obese (body mass index 35 kg/m²) nondiabetic individuals and compared it to lean volunteers. Obese persons were re-examined 6 months later after weight loss. EPCs from obese individuals showed reduced adhesive, migratory, and angiogenic capacity, and mice treated with "obese" EPCs showed reduced EPC homing to ischemic hindlimbs. After weight loss, EPC function improved. These results show that obesity is associated with a reversible functional impairment of EPCs.

	Cardiac Surgery

Top Quarterly Focus Issue: Heart... Cardiovascular Risk Cardiac Surgery

 
Cardiac Surgery.   Improved Outcomes With Freestyle Versus Homograft Aortic Root Replacement

368

Ismail El-Hamamsy, Lucy Clark, Louis M. Stevens, Zubair Sarang, Giovanni Melina, Johanna J. M. Takkenberg, Magdi H. Yacoub

This study randomized 166 patients undergoing aortic valve surgery with root replacement to either a homograft or a Freestyle (Medtronic Inc., Minneapolis, Minnesota) aortic root replacement. The homograft is obtained either at autopsy or from patients undergoing heart transplantation; the Freestyle is porcine. Median follow-up was 7.6 years. There was no difference in mortality, but there were significantly fewer reoperations needed with the Freestyle root replacement (100% vs. 90%). Freedom from aortic valve dysfunction was 86% for Freestyle bioprostheses versus 37% for homografts. In this population, Freestyle aortic root replacement is superior to homografts.

Editorial Comment: John A. Elefteriades, p. 377

Related Articles

Mitral Valve Surgery in Advanced Heart Failure

Thomas G. Di Salvo, Michael A. Acker, G. William Dec, and John G. Byrne
J. Am. Coll. Cardiol. 2010 55: 271-282. [Abstract] [Full Text] [PDF]

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