Myocardial fibrosis occurs in a number of pathological processes, most commonly hypertension. Other disease states capable of producing cardiac fibrosis include hypereosinophilia, scleroderma, sarcoidosis, radiation and drug effects, viral myocarditis and inherited genetic mutations. Normal aging is also associated with a certain degree of interstitial fibrosis, but the degree of this nonpathological fibrosis is yet to be determined. Animal models of aging have shown alterations in collagen deposition 1, and studies involving human subjects and post-mortem examinations have documented increased fibrosis in the conduction system 2 and atria 3 with aging, but the true incidence of global myocardial fibrosis that can be expected in a healthy, normotensive elderly patient is not known.

The patient was a 73-year-old healthy African American female with no significant medical history. Notably, she was an avid athlete and power lifter, participated regularly in aerobic activity and traveled frequently. She presented initially with a 2-day history of sore throat and fever and acute onset of mental status changes. Upon arrival at the hospital she was found to be febrile, hypertensive, tachycardic and tachypneic and to have an elevated white blood cell count of 15.2 K/ul. Physical examination revealed no obvious source of infection, and EKG showed tachycardia but otherwise normal electrical activity. The patient rapidly decompensated and died despite resuscitative efforts. Pre-mortem blood samples were later found to be positive for group A beta-hemolytic Streptococci. Postmortem examination of the patient's medical records revealed no significant disease history. She had a favorable cholesterol profile, with total cholesterol of 183 mg/dl, triglycerides 66, LDL 98 and HDL 72. There was no history of hypertension or evidence of cardiac disease and no history of eosinophilia.

Autopsy was performed and revealed no pathological processes acutely related to death, including no signs of localized infection as the source of bacteremia. The patient was found to have cardiomegaly with a cardiac weight of 365 grams, left ventricular wall thickness of 1.8 mm and markedly decreased chamber volume. Histological examination showed wide distribution of interstitial myocardial fibrosis (Figures 1, 2 and 3). Fibrosis was present throughout the right and left ventricles in an inconsistent pattern and was more prevalent in the endomyocardium. The largest foci of fibrosis measured approximately 4 mm in greatest diameter, and approximately 25% of the myocardium was involved by some degree of fibrosis. A single foci of inflammatory infiltrate was noted, but was not located near an area of fibrosis. Microfiber disarray and septal hypertrophy were absent. The coronary arteries were notably patent with minimal atherosclerosis.

While the cardiac fibrosis in this patient was not the immediate cause of death, the findings of a diffuse distribution of patchy fibrosis and myocardial hypertrophy in a patient with no history of hypertension, hyperlipidemia or cardiac disease are puzzling. Some degree of fibrosis is expected in the healthy elderly myocardium, but likely to a smaller degree than seen in the present case. Myocardial hypertrophy in the elderly is most commonly a response to reduced vascular compliance, but in the absence of hypertension the degree of ventricular wall thickening and loss of chamber volume seen in this patient would not be expected. This patient's history of athletic activity, including power lifting, would support the finding of myocardial hypertrophy. Athletes are known to have physiological cardiac hypertrophy, but this is not usually associated with the development of fibrosis or chamber narrowing.

Fibrosis within the myocardium may be due to a variety of different pathological processes, and the pattern of fibrosis provides clues as to the underlying cause. Hypertensive cardiac fibrosis is classically perivascular with infiltration into the surrounding interstitium. A single large focus of fibrosis is consistent with remote myocardial infarction; hypereosinophilia and idiopathic restrictive cardiomyopathy produce fibrosis ranging from patchy subendocardial disease to diffuse full-thickness involvement. Radiation-induced fibrosis is often more severe in the right ventricle.

The true incidence and degree of age-related myocardial fibrosis is unknown; both animal and human models have documented its occurrence. Whether these age-related changes are due primarily to the diseases more frequently seen in the elderly, namely hypertension and inflammation, or arose de novo due to decreased collage breakdown is also uncertain. More recent reports of exercise-induced fibrosis raise the question of late pathological consequences of physical activity. Hypertension-related myocardial fibrosis is at least partly preventable with pharmacotherapy. Further understanding of the mechanisms associated with age- and exercise-induced fibrosis may likewise lead to the discovery of chemical pathways that can be pharmacologically altered, allowing for the prevention of cardiac dysfunction associated with fibrotic change.

angiotensin-converting enzyme (ACE); electrocardiography (EKG); extracellular-signal-related kinase (ERK); high-density lipoprotein (HDL); Jun N-terminal kinase (JNK); low-density lipoprotein (LDL); messenger ribonucleic acid (mRNA); nicotinamide adenine dinucleotide phosphate, reduced form (NADPH); renin-angiotensin-aldosterone system (RAAS); reactive oxygen species (ROS)

The author(s) declare that they have no competing interests.

SL and LH secured the case, conducted the literature review, and participated in the preparation of the manuscript. All authors read and approved the final manuscript.

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.