Impact of Pulmonary Hypertension on Survival Following Device Closure of Atrial Septal Defects.

Pulmonary hypertension (PH), defined as mean pulmonary arterial pressure ≥25 mm Hg, may be a complication of a secundum atrial septal defect (ASD). This study sought to evaluate the impact of PH at time of ASD device closure on patient survival. A prospectively collected database of ASD closures was utilized. Patients were stratified by age above and below the cohort median (48 years). Survival was analyzed by preprocedural PH status, age cohort, and echocardiographic resolution of PH at 3 months postdevice closure. PH was present in 48 of 228 patients (21.1%) and was more common in the older cohort (31.3% vs 10.6%, p <0.01). ASD size was unrelated to the presence of PH (p = 0.33). Older patients had more medical co-morbidities including diabetes (p = 0.02), hyperlipidemia (p <0.01), and systemic hypertension (p <0.01) compared with younger patients. PH did not impact survival in patients ≤48 years, but PH was associated with fivefold increased risk of death in patients >48 years (p < 0.01). Patients with preprocedural PH and RVSP ≥40 mm Hg at 3-month follow-up continued to have an increased risk of mortality (p <0.01), whereas those with resolution of PH had similar survival to those without PH at time of closure. In conclusion, PH is common in adults with unrepaired ASDs and appears unrelated to defect size. PH in older adults and its persistence closure are strong predictors of a worsened clinical outcome. These patients may benefit from additional risk assessment and advanced medical therapies to mitigate this risk.

Pro-Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (HFpEF). In this study we tested the hypothesis that pro-inflammatory biomarkers are elevated in patients with acutely decompensated HFpEF (AD-HFpEF) compared with patients with stable HFpEF (S-HFpEF). METHODS AND RESULTS: Using a post hoc analysis the serum biomarkers tumor necrosis factor-alpha, high-sensitivity C-reactive protein interleukin 6 and pentraxin 3 (PTX3) and clinical, demographic, echocardiographic-Doppler and clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD-HFpEF or S-HFpEF. Compared to S-HFpEF, AD-HFpEF patients had higher levels of PTX3 (3.08 ng/mL versus 1.27 ng/mL, P<0.0001), interleukin-6 (4.14 pg/mL versus 1.71 pg/mL, P<0.0001), tumor necrosis factor-alpha (11.54 pg/mL versus 8.62 pg/mL, P=0.0015), and high-sensitivity C-reactive protein (11.90 mg/dL versus 3.42 mg/dL, P<0.0001). Moreover, high-sensitivity C-reactive protein, interleukin-6 and PTX3 levels were significantly higher in AD-HFpEF compared with S-HFpEF patients admitted for decompensated HF within the previous year. PTX3 was positively correlated with left atrial volume index (r=0.41, P=0.0017) and left ventricular mass (r=0.26, P=0.0415), while tumor necrosis factor-alpha was inversely correlated with E/A ratio (r=-0.31, P=0.0395). CONCLUSIONS: Levels of pro-inflammatory biomarkers are strikingly higher in AD-HFpEF compared with S-HFpEF patients. PTX3 and tumor necrosis factor-alpha are correlated with echocardiographic-Doppler evidence of diastolic dysfunction. Taken together these data support the concept that a heightened pro-inflammatory state has a pathophysiologic role in the development of AD-HFpEF.

Impact of diabetes in patients with pulmonary hypertension.

Diabetes complicates management in a number of disease states and adversely impacts survival; how diabetes affects patients with pulmonary hypertension (PH) has not been well characterized. With insulin resistance having recently been demonstrated in PH, we sought to examine the impact of diabetes in these patients. Demographic characteristics, echo data, and invasive hemodynamic data were prospectively collected for 261 patients with PH referred for initial hemodynamic assessment. Diabetes was defined as documented insulin resistance or treatment with antidiabetic medications. Fifty-five patients (21%) had diabetes, and compared with nondiabetic patients, they were older (mean years ± SD, 61 ± 13 vs. 56 ± 16; [Formula: see text]), more likely to be black (29% vs. 14%; [Formula: see text]) and hypertensive (71% vs. 30%; [Formula: see text]), and had higher mean (±SD) serum creatinine levels (1.1 ± 0.5 vs. 1.0 ± 0.4; [Formula: see text]). Diabetic patients had similar World Health Organization functional class at presentation but were more likely to have pulmonary venous etiology of PH (24% vs. 10%; [Formula: see text]). Echo findings, including biventricular function, tricuspid regurgitation, and pressure estimates were similar. Invasive pulmonary pressures and cardiac output were similar, but right atrial pressure was appreciably higher (14 ± 8 mmHg vs. 10 ± 5 mmHg; [Formula: see text]). Despite similar management, survival was markedly worse and remained so after statistical adjustment. In summary, diabetic patients referred for assessment of PH were more likely to have pulmonary venous disease than nondiabetic patients with PH, with hemodynamics suggesting greater right-sided diastolic dysfunction. The markedly worse survival in these patients merits further study.

Phototargeting human periodontal pathogens in vivo.

The effects of blue light at 455 nm were investigated on the bacterial composition of human dental plaque in vivo. Eleven subjects who refrained from brushing for 3 days before and during phototherapy participated in the study. Light with a power density of 70 mW/cm(2) was applied to the buccal surfaces of premolar and molar teeth on one side of the mouth twice daily for 2 min over a period of 4 days. Dental plaque was harvested at baseline and again at the end of 4 days from eight posterior teeth on both the exposed side and unexposed sides of the mouth. Microbiological changes were monitored by checkerboard DNA probe analysis of 40 periodontal bacteria. The proportions of black-pigmented species Porphyromonas gingivalis and Prevotella intermedia were significantly reduced on the exposed side from their original proportions by 25 and 56 %, respectively, while no change was observed to the unexposed side. Five other species showed the greatest proportional reduction of the light-exposed side relative to the unexposed side. These species were Streptococcus intermedius, Fusobacterium nucleatum ss. vincentii, Fusobacterium nucleatum ss. polymorphum, Fusobacterium periodonticum, and Capnocytophaga sputigena. At the same time, the percentage of gingival areas scored as being red decreased on the side exposed to light from 48 to 42 %, whereas the percentage scored as red increased on the unexposed side from 53 to 56 %. No adverse effects were found or reported in this study. The present study proposes a new method to modify the ecosystem in dental plaque by phototherapy and introduces a new avenue of prophylactic treatment for periodontal diseases.

Migraine headaches following mitral valvuloplasty: Koch's postulates finally satisfied?

The relationship between patent foramen ovale and migraine headache is a topic surrounded by much controversy. We present the case of a 45-year-old woman who underwent successful percutaneous mitral balloon valvuloplasty for rheumatic mitral valve stenosis, but had an immediate postprocedural course complicated by refractory migraine headaches. Interestingly, resolution of her headaches coincided with the spontaneous closure of the interatrial communication created during valvuloplasty. This suggests interatrial flow as an important trigger for migraine headaches in this patient.

Photodynamic therapy for endodontic disinfection.

The aims of this study were to investigate the effects of photodynamic therapy (PDT) on endodontic pathogens in planktonic phase as well as on Enterococcus faecalis biofilms in experimentally infected root canals of extracted teeth. Strains of microorganisms were sensitized with methylene blue (25 microg/ml) for 5 minutes followed by exposure to red light of 665 nm with an energy fluence of 30 J/cm2. Methylene blue fully eliminated all bacterial species with the exception of E. faecalis (53% killing). The same concentration of methylene blue in combination with red light (222 J/cm2) was able to eliminate 97% of E. faecalis biofilm bacteria in root canals using an optical fiber with multiple cylindrical diffusers that uniformly distributed light at 360 degrees. We conclude that PDT may be developed as an adjunctive procedure to kill residual bacteria in the root canal system after standard endodontic treatment.

Phototargeting oral black-pigmented bacteria.

We have found that broadband light (380 to 520 nm) rapidly and selectively kills oral black-pigmented bacteria (BPB) in pure cultures and in dental plaque samples obtained from human subjects with chronic periodontitis. We hypothesize that this killing effect is a result of light excitation of their endogenous porphyrins. Cultures of Prevotella intermedia and P. nigrescens were killed by 4.2 J/cm2, whereas P. melaninogenica required 21 J/cm2. Exposure to light with a fluence of 42 J/cm2 produced 99% killing of P. gingivalis. High-performance liquid chromatography demonstrated the presence of various amounts of different porphyrin molecules in BPB. The amounts of endogenous porphyrin in BPB were 267 (P. intermedia), 47 (P. nigrescens), 41 (P. melaninogenica), and 2.2 (P. gingivalis) ng/mg. Analysis of bacteria in dental plaque samples by DNA-DNA hybridization for 40 taxa before and after phototherapy showed that the growth of the four BPB was decreased by 2 and 3 times after irradiation at energy fluences of 4.2 and 21 J/cm2, respectively, whereas the growth of the remaining 36 microorganisms was decreased by 1.5 times at both energy fluences. The present study suggests that intraoral light exposure may be used to control BPB growth and possibly benefit patients with periodontal disease.