Background Characterization of myocardial structural changes in heart failure (HF) with preserved ejection fraction (HFpEF) has been hindered by limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction and myocardial fibrosis may contribute to HFpEF pathophysiology. Methods and Results We identified HFpEF patients (n=124) and age-appropriate control patients (non-cardiac death, no HF diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. Using whole field digital microscopy and automated analysis algorithms in full thickness left ventricular (LV) sections, microvascular density (MVD), myocardial fibrosis and their relationship were quantified. Subjects with HFpEF had heavier hearts (median 538 g; 169% of age/sex/body size expected heart weight vs. 335 g; 112% in controls), more severe CAD (65% with ≥ one vessel with >50% diameter stenosis in HFpEF vs 13% in controls), more LV fibrosis (median % area fibrosis, 9.6 vs. 7.1) and lower MVD (median 961 vs. 1316 vessels per mm2) than control (p <0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r = − 0.28, p=0.004) and HFpEF (r = − 0.26, p=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis and MVD were similar in HFpEF patients with vs without CAD. Conclusions In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction and myocardial fibrosis than controls. Each of these findings may contribute to the LV diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.

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Objective Determine the frequency of left ventricular (LV) amyloid in heart failure with preserved ejection fraction (HFpEF). Background LV amyloid deposition can cause diastolic dysfunction and HFpEF. Methods Autopsy LV specimens from patients with ante-mortem diagnosis of HFpEF without clinically apparent amyloid (n=109) and Control subjects (n=131) were screened with sulfated alcian blue and subsequent Congo red staining with micro-dissection for mass spectrometry-based proteomics to determine amyloid type. Fibrosis was assessed with quantitative whole-field digital microscopy. Results Presence of wtTTR amyloid was associated with age at death and male sex; but the age-and sex-adjusted prevalence of wtTTR amyloid was higher in HFpEF than Control (Odds ratio 3.8, 95% confidence interval 1.5–11.3; p=0.03). Among HFpEF patients, moderate or severe interstitial wtTTR deposition, consistent with senile systemic amyloidosis as the primary etiology of HFpEF, was present in five (5%) patients (80% male), with mild interstitial and/or variable severity of intramural coronary vascular deposition in 13 (12%). While wtTTR deposition was often mild, adjusting for age and presence of HFpEF, wtTTR amyloid was associated with more fibrosis (p=0.005) and lower age, sex, and body size-adjusted heart weight (p=0.04). Conclusion Given the age- and sex-independent association of HFpEF and wtTTR deposition and an emerging understanding of the pathophysiology of the amyloidoses, the current findings support further investigation of the role of wtTTR in the pathophysiology of HFpEF.

Background Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular (CV) structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental CV structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Methods and Results Comorbidity adjusted CV structural and functional parameters scaled to independently generated and age appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/gender-matched healthy (CON, n=193) and hypertensive (HTN, n=386) controls. Within HFpEF patients, body size and concomitant comorbidity adjusted CV structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes and renal dysfunction) were each associated with unique clinical, structural, functional and prognostic profiles. However, after accounting for age, gender, body size and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic and vascular dysfunction were consistently observed in HFpEF compared to CON and HTN. Conclusions Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically-targeted therapies in this disease.

This follow-up study of LM surgical treatments shows excellent outcomes for wide excision and MMS. Because this is a nonrandomized retrospective study, no direct comparisons between the 2 treatments can be made. When recurrences occurred, repeat surgery, either standard excision or MMS, was usually sufficient to provide definitive cure.

Background: Cellulitis is common and recurs in some patients. The study described herein derived a predictive model for the recurrence of lower extremity cellulitis in a population-based cohort. Methods: We conducted a retrospective, populationbased cohort study using the Rochester Epidemiology Project. We reviewed the medical records of Olmsted County, Minnesota, residents with lower extremity cellulitis occurring from January 1, 1999, to June 30, 2000. Univariate and multivariate Cox proportional hazards analyses were performed to evaluate risk factors in patients who experienced recurrent lower extremity cellulitis within 2 years. A predictive model was developed to estimate risk of recurrence based on a score of risk factors identified by multivariate analysis. Results: A total of 209 episodes met the definition of lower extremity cellulitis. Thirty-five patients (16.7%) experienced recurrence within 2 years. Multivariate analysis identified tibial area involvement, prior malignancy, and dermatitis affecting the ipsilateral limb as independent risk factors for recurrence, with hazard ratios of 5.02, 3.87, and 2.99 (PϽ.01), respectively. A score calculated from these variables (a count of 0, 1, 2, or 3) was developed to measure risk of recurrence. Based on the predictive model, the estimated probability of recurrence (95% confidence interval [CI]) within 2 years was 5.0% (95% CI, 1.6%-8.2%), 17.3% (95% CI, 11.1%-23.0%), 50.6% (95% CI, 34.2%-63.0%), or 92.8% (95% CI, 51.9%-98.9%) for a score of 0, 1, 2 or 3, respectively. Conclusions: We derived a model including tibial area involvement, history of cancer, and dermatitis to predict recurrence of lower extremity cellulitis. Potential interventions can be incorporated into treatment to diminish the proclivity for recurrence in high-risk patients.

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SummaryBackground Brachioradial pruritus (BRP) is a fascinating condition that is seen increasingly often, but any additional data from retrospective observational studies can still enhance our understanding. Objectives To review our experience at the Mayo Clinic with patients presenting with BRP. Methods We retrospectively reviewed the clinical records of patients diagnosed with BRP between 1999 and 2011. Results In total, 111 patients (80 female, 72%) had been diagnosed with BRP. Their mean age was 59 years, range 12-84 years. Symptoms were bilateral in 84 (75Á7%). Fifty-four patients (48Á6%) reported prolonged exposure to the sun, and 16 had a history of neck concerns. Forty-five (40Á5%) had undergone imaging studies of the neck; of these, eight had foraminal stenosis, six had protrusion of the intervertebral disk and six had stenosis of the spinal canal; 10 had more than one cervical abnormality. Thirty-one patients had been referred to neurology; eight of these had BRP attributed to a radiculopathy or peripheral neuropathy. Several topical and oral medications were prescribed. Seventy-five patients had a follow-up; of these, nine (12%) had complete resolution, 13 (17%) had improvement, four (5%) showed no change and 49 (65%) had no mention of BRP. Conclusions Brachioradial pruritus presented most commonly in female patients and was observed over a wide age range. Although a third of patients with imaging studies had cervical abnormalities, the significance of these findings is unclear, as no structural causes of BRP were found in most cases. Some treatments were more successful than others.