Reviews & Analysis

In this Viewpoint, Dr Xavier and colleagues discuss the rationale behind their choice to perform a study on a cardiovascular Polypill in the setting of primary prevention, and behind the drug combinations used in The Indian Polycap study. Results of The Indian Polycap study will be available in April 2009.

The pharmaceutical development of a cardiovascular polypill presents several unique challenges. In this Review, Dr Guglietta and Dr Guerrero highlight important considerations regarding the selection of the type and number of components, the type of pharmaceutical formulation, and approval by regulatory agencies.

Secondary prevention of ischemic heart disease could have a huge impact on the global epidemic of cardiovascular disease. Here Ginés Sanz and Valentin Fuster consider the value of a 'polypill' for secondary prevention, examine the most efficacious combination of agents and explore whether widespread use could improve adherence and improve treatment affordability in low-income countries.

The pericardium, myocardium, coronary arteries and pulmonary arteries are the main cardiac targets for disease in people who are infected with HIV. Mpiko Ntsekhe and Bongani Mayosi discuss the cardiac manifestations of HIV in sub-Saharan Africa, where approximately 70% of the 34 million people worldwide with HIV and AIDS live.

Drs Rosenson and Pitt review the pathophysiological mechanisms for the increased cardiovascular risk associated with elevated triglycerides, and provide a rationale for the need to conduct a randomized clinical trial of statin therapy versus combined statin and fibrate therapy in patients with acute coronary syndromes.

The authors highlight the benefits of using a beating-heart technique during surgical correction of myocardial bridging in this 10-year-old patient with nonobstructive hypertrophic.cardiomyopathy.

Treatment of patients with amyloidosis is centered on reducing the supply of the respective amyloid fibril precursor protein. This Case Study describes a patient with cardiac acquired monoclonal immunoglobulin-light-chain amyloidosis, who also has an incidental amyloidogenic transthyretin Val122Ile mutation, and illustrates the crucial need to characterize the presence, extent and—most importantly—fibril type of amyloid deposits in patients with amyloidosis.

The Polypill for prevention of cardiovascular disease was first proposed in 2003 and results of the first trials are eagerly anticipated. Regulatory agencies face the challenge of deciding which studies should be requested to meet reasonable demands regarding efficacy and safety of the Polypill in the intended (high-risk) target population. In this Viewpoint, Dr Forslund highlights the important issues that should be considered when generating these regulatory recommendations.

Atrial fibrillation and heart failure share many common risk factors, and are often seen together in an individual patient. Each of these conditions alone can cause the development and worsening of the other. In this article, Morrison et al. discuss the clinical and pathological relationships between these two conditions, review current treatment strategies, and propose areas for future research that will help define the optimal therapeutic approach for patients with concurrent atrial fibrillation and heart failure.

Reduced adiponectin levels have been shown to correlate with increased risk of cardiovascular disease in obese individuals and in patients with diabetes and hyperglycemia. In this Review, Drs Goldstein, Scalia and Ma discuss the various signaling pathways that mediate adiponectin's protective effects in the vasculature and the myocardium.

Thirteen years after his seminal Review on flow-mediated endothelial mechanotransduction, Peter Davies reviews the complex spatiotemporal shear stress characteristics that can predict atherosclerosis susceptibility. He also examines endothelial flow-induced responses—collectively known as mechanotransduction—and the spatially decentralized mechanism of endothelial mechanotransduction.

Mills et al. explore the preclinical and clinical evidence and examine the potential pathways through which air pollution—an important and modifiable determinant of cardiovascular disease—mediates adverse cardiovascular effects. Understanding the mediators and mechanisms will enable the development of strategies to reduce the impact of air pollution on cardiovascular disease.

In this thought-provoking Viewpoint and accompanying clinical vignettes, Sengupta and colleagues posit that clinicians should be aware of obstructive sleep apnea in patients with hypertrophic obstructive cardiomyopathy. They hypothesize that this sleep disorder could be the reason cardiomyopathy symptoms remain despite therapy and could also contribute to a raised gradient seen in some patients.

Aspirin can effectively prevent arterial thrombosis; however, its efficacy is limited as it inhibits the synthesis of only one platelet agonist (thromboxane A₂). Here Raju and colleagues review agents that target ADP-mediated platelet activation. They examine controversies and unresolved issues associated with clopidogrel—the optimum loading dose, duration of treatment and incomplete platelet inhibition—and the new ADP-receptor antagonists prasugrel, AZD6140 and cangrelor, and explore their potential relative to each other and to clopidogrel.

Vascular complications following cancer treatment are relatively common, particularly in patients with advanced stages of cancer. In this Review, Dr Daher and Dr Yeh describe the vascular complications of treatment with 5-fluorouracil, bevacizumab, and several new tyrosine kinase inhibitors, with special emphasis on thrombotic complications and hypertension.

Atrial fibrillation is characterized by structural remodeling of the atrial myocardium—a slow process that comprises morphological changes that affect atrial myocardial architecture and atrial ultrastructure. Here Corradi et al. examine the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and explore how the pathogenetic mechanisms involved in AF could lead to new treatments.

Patient-prosthesis mismatch (PPM) is common after aortic valve replacement and has been shown to be associated with poor hemodynamic and symptomatic status, a high rate of cardiac events, and increased mortality. In this article, Philippe Pibarot and Jean G. Dumesnil highlight the importance of defining and recognizing PPM and its clinical impact. They also assert that, because PPM is a predictable and modifiable risk factor, it is vital to identify susceptible patients and to apply preventive strategies to avoid PPM or reduce its severity.

Ramcharitar and colleagues present an interesting case of a patient with drug-refractory hypertrophic obstructive cardiomyopathy and NYHA class II–III heart failure who was treated with septal coil embolization. This article demonstrates, for the first time, the acute changes in hemodynamics that occur following septal coil embolization, and shows that this treatment is a viable alternative to percutaneous coronary intervention.

Several chemotherapeutic agents, including newer drugs, can have toxic cardiac effects. In this month's Case Study, To and colleagues present their patient who had capecitabine-induced cardiogenic shock. They examine the best course of action for this serious complication of chemotherapy.