Phenotypic characterization of primary cardiac fibroblasts from patients with HFpEF.

Heart failure is a leading cause of hospitalizations and mortality worldwide. Heart failure with a preserved ejection fraction (HFpEF) represents a significant clinical challenge due to the lack of available treatment modalities for patients diagnosed with HFpEF. One symptom of HFpEF is impaired diastolic function that is associated with increases in left ventricular stiffness. Increases in myocardial fibrillar collagen content is one factor contributing to increases in myocardial stiffness. Cardiac fibroblasts are the primary cell type that produce fibrillar collagen in the heart. However, relatively little is known regarding phenotypic changes in cardiac fibroblasts in HFpEF myocardium. In the current study, cardiac fibroblasts were established from left ventricular epicardial biopsies obtained from patients undergoing cardiovascular interventions and divided into three categories: Referent control, hypertension without a heart failure designation (HTN (-) HFpEF), and hypertension with heart failure (HTN (+) HFpEF). Biopsies were evaluated for cardiac myocyte cross-sectional area (CSA) and collagen volume fraction. Primary fibroblast cultures were assessed for differences in proliferation and protein expression of collagen I, Membrane Type 1-Matrix Metalloproteinase (MT1-MMP), and α smooth muscle actin (αSMA). Biopsies from HTN (-) HFpEF and HTN (+) HFpEF exhibited increases in myocyte CSA over referent control although only HTN (+) HFpEF exhibited significant increases in fibrillar collagen content. No significant changes in proliferation or αSMA was detected in HTN (-) HFpEF or HTN (+) HFpEF cultures versus referent control. Significant increases in production of collagen I was detected in HF (-) HFpEF fibroblasts, whereas significant decreases in MT1-MMP levels were measured in HTN (+) HFpEF cells. We conclude that epicardial biopsies provide a viable source for primary fibroblast cultures and that phenotypic differences are demonstrated by HTN (-) HFpEF and HTN (+) HFpEF cells versus referent control.

Pathophysiology and Pathogenesis of Marfan Syndrome.

Marfan syndrome (MFS) is a systemic connective tissue disorder that is inherited in an autosomal dominant pattern with variable penetrance. While clinically this disease manifests in many different ways, the most life-threatening manifestations are related to cardiovascular complications including mitral valve prolapse, aortic insufficiency, dilatation of the aortic root, and aortic dissection. In the past 30 years, research efforts have not only identified the genetic locus responsible but have begun to elucidate the molecular pathogenesis underlying this disorder, allowing for the development of seemingly rational therapeutic strategies for treating affected individuals. In spite of these advancements, the cardiovascular complications still remain as the most life-threatening clinical manifestations. The present chapter will focus on the pathophysiology and clinical treatment of Marfan syndrome, providing an updated overview of the recent advancements in molecular genetics research and clinical trials, with an emphasis on how this information can focus future efforts toward finding betters ways to detect, diagnose, and treat this devastating condition.

Successful Repair of Type A Aortic Dissection in an Octogenarian With Double Aortic Arch.

An 80-year-old woman was transferred to our institution with a subacute type A aortic dissection and a previously undiagnosed double aortic arch. The patient underwent successful repair with aortic valve resuspension, ascending aortic replacement, and repair of the proximal right-sided arch. This is the first reported case of a type A dissection associated with a double aortic arch in the United States.

A novel, catheter-based approach to left ventricular assist device deactivation after myocardial recovery.

We describe a case of catheter-based embolization and deactivation of a left ventricular assist device using an Amplatzer plug for a patient demonstrating myocardial recovery after diagnosis of nonischemic cardiomyopathy. This procedure can provide a minimally invasive, low morbidity solution for patients wishing to be separated from left ventricular assist device support who want to avoid invasive surgery for device removal.

Regression of cardiac amyloid after autologous stem-cell transplantation.

Primary cardiac amyloid has a dismal prognosis and most treatments are experimental with highly variable results. Although autologous stem-cell transplant in conjunction with high-dose chemotherapy has yielded regression of amyloid in other body tissues, the presence of cardiac involvement contraindicates stem-cell transfer due to high treatment mortality. We describe the successful treatment of cardiac amyloid using autologous stem-cell transplantation and the resultant regression of the cardiac amyloid.