Pulmonary hypertension and valvular heart disease.

Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients with left-sided heart disease, including valvular heart disease. In this context, elevated left atrial pressure primarily leads to the development of post-capillary PH. Despite the fact that repair of left-sided valvular heart disease by surgical or interventional approaches will improve PH, recent studies have highlighted that PH (pre- or post-interventional) remains an important predictor of long-term outcome. Here, we review the current knowledge on PH in valvular heart disease taking into account new hemodynamic PH definitions, and the distinction between post- and pre-capillary components of PH. A specific focus is on the precise characterization of hemodynamics and cardiopulmonary interaction, and on potential strategies for the management of residual PH after mitral or aortic valve interventions. In addition, we highlight the clinical significance of tricuspid regurgitation, which may occur as a primary condition or as a consequence of PH and right heart dilatation (functional). In this context, proper patient selection for potential tricuspid valve interventions is crucial. Finally, the article highlights gaps in evidence, and points toward future perspectives.

Pulmonary hypertension in HFpEF and HFrEF: Pathophysiology, diagnosis, treatment approaches.

Pulmonary hypertension (PH) is a frequent hemodynamic condition that is highly prevalent in patients with heart failure and reduced (HFrEF) or preserved ejection fraction (HFpEF). Irrespective of left ventricular EF, the presence of PH and right ventricular (RV) dysfunction are highly relevant for morbidity and mortality in patients with heart failure. While elevated left-sided filling pressures and functional mitral regurgitation primarily lead to post-capillary PH, current guidelines and recommendations distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH), the latter being defined by a pulmonary vascular resistance (PVR) of ≥3 Wood units. Here, we describe the pathophysiology and clinical relevance of these distinct entities, and report on the diagnostic work-up including remote pulmonary artery pressure (PAP) monitoring. Furthermore, we highlight strategies to manage PH and improve RV function in heart failure, which may include optimized management of HFrEF and HFpEF (medical and interventional), sufficient volume control, catheter-based mitral valve repair, and-in selected cases-targeted PH therapy. In this context, we also highlight gaps in evidence and the need for further research.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

[Chronic thromboembolic pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option - as PEA - is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.

[70-year-old woman with cardiac hypertrophy and severe pulmonary hypertension: pre- or postcapillary?]. / 70-jährige Patientin mit Myokardhypertrophie und schwerer pulmonaler Hypertonie: Prä- oder postkapillär?

HISTORY AND ADMISSION FINDINGS: A 70-year-old female patient was admitted with progressive dyspnea and peripheral edema. The patient had a medical history of myocardial hypertrophy, diastolic dysfunction and concomitant pulmonary hypertension (PH). INVESTIGATIONS: The physical exam was suggestive of cardiac decompensation. Echocardiography showed myocardial hypertrophy, an enlarged left atrium as well as enlarged right-sided heart chambers. A prominent tricuspid regurgitation jet was present, and the estimated systolic right ventricular pressure was 65 mmHg. Invasive hemodynamic measurements showed a marked pressure elevation in the pulmonary circulation (mean PAP 51 mmHg), combined with an elevated left ventricular end-diastolic pressure (LVEDP) of 30 mmHg and a profound increase in the transpulmonary gradient (TPG, 21 mmHg). TREATMENT AND COURSE: The synopsis of these findings led to the diagnosis of postcapillary PH with a prominent precapillary involvement and cardiac decompensation. Due to signs of volume overload, an adequate diuretic therapy was initiated. The patient was recompensated and lost 7 kg of weight, which was associated with substantial clinical improvement. At invasive follow-up hemodynamic measurement, the patient's PAP was substantially decreased and almost reached normal values. The previously diagnosed precapillary involvement had disappeared. CONCLUSION: PH is a frequent phenomenon in patients with systolic and diastolic heart failure, and might initially appear as a combination of pre- and postcapillary involvement. The patients' volume status has a major influence on pulmonary hemodynamics. An adequate therapy of the underlying heart failure, especially an adequate diuresis, may have marked beneficial effects on pulmonary hemodynamics. Hemodynamic measurements should always be performed in compensated status.

Historical contamination of the Anacostia River, Washington, D.C.

The tidal Anacostia River in Washington DC has long been impacted by various sources of chemical pollution over the past 200 years. To explore more recent inputs of various chemicals, six sediment cores were collected for dating and chemical analysis in the downstream section of the tidal Anacostia River. Profiles of contaminants in sediment cores can be useful in determining management direction and effectiveness of pollution controls over time. There were two main objectives for this investigation: (1) determine current sediment contaminant levels; (2) determine a historical perspective of the sediment changes in contamination using (137)Cs and (210)Pb dating. The determination of an age-depth relationship using (210)Pb and (137)Cs dating gave somewhat different results, suggesting that the assumptions of (210)Pb dating were not met. Using the (137)Cs horizon allowed an assignment of approximate sediment accumulation rates and hence an age-depth relationship to contaminant events in the upper portions of the cores. Total PAHs showed higher concentrations at depth and lower surface concentrations. In the upper sections, PAHs were a mixture of combustion and petrogenic sources, while at depth the signature appeared to be of natural origins. Total PCBs, DDTs and chlordane concentrations showed a maximum in recent sediments, decreasing towards the surface. PCBs had lower molecular weight congeners near the surface and higher molecular weights at depth. A phthalate ester, DEHP, appeared in the mid 1940-1950s, and decreased towards the surface. Trace elements fell roughly into three groups. Fe, Mn, and As were in approximately constant proportion to Al, except in some deeper, sandy sediments, where they showed enrichments linked to redox conditions. Ag, Cd, Cu, Hg, Pb, and Zn had low concentrations in the deepest sediments, high concentrations at mid-depths, and declines to intermediate levels at the surface. Ni and Cr followed neither of these patterns closely. We observed that many contaminants appeared in the Anacostia sediments at various times, and reached relatively high concentrations in the past, but are now showing declines in loadings. In some cases, such as PCBs, DDT, chlordane, and Pb from leaded gasoline, these declines can be clearly linked to the discontinuation of their use for environmental reasons. For other contaminants (e.g., PAHs, DEHP, selected metals) these declines are more likely the result of changes in production, usage and waste control.

The effects of copper pollution on fouling assemblage diversity: a tropical-temperate comparison.

BACKGROUND: The invasion of habitats by non-indigenous species (NIS) occurs at a global scale and can generate significant ecological, evolutionary, economic and social consequences. Estuarine and coastal ecosystems are particularly vulnerable to pollution from numerous sources due to years of human-induced degradation and shipping. Pollution is considered as a class of disturbance with anthropogenic roots and recent studies have concluded that high frequencies of disturbance may facilitate invasions by increasing the availability of resources. METHODOLOGY/PRINCIPAL FINDINGS: To examine the effects of heavy metal pollution as disturbance in shaping patterns of exotic versus native diversity in marine fouling communities we exposed fouling communities to different concentrations of copper in one temperate (Virginia) and one tropical (Panama) region. Diversity was categorized as total, native and non-indigenous and we also incorporated taxonomic and functional richness. Our findings indicate that total fouling diversity decreased with increasing copper pollution, whether taxonomic or functional diversity is considered. Both native and non-indigenous richness decreased with increasing copper concentrations at the tropical site whereas at the temperate site, non-indigenous richness was too low to detect any effect. CONCLUSIONS/SIGNIFICANCE: Non-indigenous richness decreased with increasing metal concentrations, contradicting previous investigations that evaluate the influence of heavy metal pollution on diversity and invasibility of fouling assemblages. These results provide first insights on how the invasive species pool in a certain region may play a key role in the disturbance vs. non-indigenous diversity relationship.

[Treatment of pulmonary arterial hypertension (PAH): recommendations of the Cologne Consensus Conference 2010]. / Therapie der pulmonal arteriellen Hypertonie (PAH): Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the treatment of PAH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.

Shellfish face uncertain future in high CO2 world: influence of acidification on oyster larvae calcification and growth in estuaries.

BACKGROUND: Human activities have increased atmospheric concentrations of carbon dioxide by 36% during the past 200 years. One third of all anthropogenic CO(2) has been absorbed by the oceans, reducing pH by about 0.1 of a unit and significantly altering their carbonate chemistry. There is widespread concern that these changes are altering marine habitats severely, but little or no attention has been given to the biota of estuarine and coastal settings, ecosystems that are less pH buffered because of naturally reduced alkalinity. METHODOLOGY/PRINCIPAL FINDINGS: To address CO(2)-induced changes to estuarine calcification, veliger larvae of two oyster species, the Eastern oyster (Crassostrea virginica), and the Suminoe oyster (Crassostrea ariakensis) were grown in estuarine water under four pCO(2) regimes, 280, 380, 560 and 800 microatm, to simulate atmospheric conditions in the pre-industrial era, present, and projected future concentrations in 50 and 100 years respectively. CO(2) manipulations were made using an automated negative feedback control system that allowed continuous and precise control over the pCO(2) in experimental aquaria. Larval growth was measured using image analysis, and calcification was measured by chemical analysis of calcium in their shells. C. virginica experienced a 16% decrease in shell area and a 42% reduction in calcium content when pre-industrial and end of 21(st) century pCO(2) treatments were compared. C. ariakensis showed no change to either growth or calcification. Both species demonstrated net calcification and growth, even when aragonite was undersaturated, a result that runs counter to previous expectations for invertebrate larvae that produce aragonite shells. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that temperate estuarine and coastal ecosystems are vulnerable to the expected changes in water chemistry due to elevated atmospheric CO(2) and that biological responses to acidification, especially calcifying biota, will be species-specific and therefore much more variable and complex than reported previously.

Cadmium distribution in coastal sediments and mollusks of the US.

Cadmium (Cd) concentrations in the coastal United States were assessed using the National Status and Trends (NS&T) Mussel Watch dataset, which is based on the analysis of sediments and bivalves collected from 280 sites since 1986. Using the 1997 sediment data, Pearson correlation (r=0.44, p<0.0001) suggested that Cd distributions in sediment can, be to some extent, explained by the proximity of sites to population centers. The 2003 tissue data indicated that "high" Cd concentrations (greater than 5.6 microg/g dry weights [dw] for mussel and 5.4 microg/g dw for oysters) were related to salinity along the East and Gulf coasts. Along the West coast, however, these "high" sites appeared to be related to upwelling phenomenon. Additionally, sedimentary diagenesis was found to be the most likely explanation of why sediment and mollusk Cd content were not well correlated.

Modeling arsenic in the Patuxent Estuary.

A water quality model was developed to track the fate and transport of four arsenic species in the Patuxent Estuary: arsenate (As(V)), arsenite (As(III)), methylarsonate (MMA), and dimethylarsinate (DMA). Processes simulated include mass transport, solid-liquid partitioning with suspended solids, uptake and transformation of As(V) by phytoplankton, oxidation of As(III), demethylation of MMA and DMA, and settling/deposition/ resuspension of particulate arsenic in the water column. A sediment module was also developed and linked with the water column to generate fluxes of inorganic arsenic from the sediment bed. The arsenic model was calibrated using water quality data from the Patuxent Estuary over a period ranging from May 24, 1995 to October 29, 1997. Model results indicated that transformation of arsenic by phytoplankton is not a significant source of DMA to the lower Patuxent. Instead, results suggested that the primary source of methylated arsenic (DMA and MMA) to the lower estuary is beyond the downstream boundary (Chesapeake Bay). However, model results supported the hypothesis that flux of arsenic from the sediment is a significant source of inorganic arsenic to the lower estuary.

Differences in the bioaccumulation of arsenic by oysters from Southeast coastal US and Chesapeake Bay: environmental versus genetic control.

The potential sources of relatively great concentrations of arsenic (As) in oysters from the Southeastern United States coast was examined in a study conducted from August 1998 through October 1999. A transplant experiment was conducted to determine whether genetic or environmental differences accounted for the observed difference between Southeastern oysters, and oysters elsewhere on the east coast. Oysters originating in South Carolina (a region where As in oysters is usually greater) and Maryland (a region where arsenic is oysters is less) were reciprocally transplanted to determine whether site of growth or site of origin would determine the accumulation of As. To examine the potential role of various potential sources of As exposure on the concentrations of As in oysters, samples of native oysters, water, pore water and suspended particles were collected and analyzed for As monthly, while the sediments were examined four times during the year. Concentrations of As in transplanted oysters matched the concentrations of As in oysters native to the area in which they were grown, rather than that of oysters from their site of origin. Oysters from South Carolina had average concentrations of As approximately 3.2 times that of oysters from Maryland. This enrichment was similar to enrichments of water (3.4 times), sediment (2.5 times), suspended particles (1.7 times), and pore water (3.1 times) from South Carolina compared to Maryland. This supports the hypothesis that the cause of the apparent As enrichments in the Southeastern oysters is environmental, but leaves the question of the primary source for arsenic incorporation by oysters open.

The role of the trehalose system in regulating the maltose regulon of Escherichia coli.

The maltose regulon consists of 10 genes encoding an ABC transporter for maltose and maltodextrins as well as enzymes necessary for their degradation. MalK, the energy-transducing subunit of the transport system, acts phenotypically as a repressor of MalT, the transcriptional activator of the mal genes. Using MacConkey maltose indicator plates we isolated an insertion mutation that strongly reduced the repressing effect of overproduced MalK. The insertion had occurred in treR encoding the repressor of the trehalose system. The loss of TreR function led to derepression of treB encoding an enzymeIITre of the PTS for trehalose and of treC encoding TreC, the cytoplasmic trehalose-6-phosphate hydrolase. Further analysis revealed that maltose can enter the cell by facilitated diffusion through enzymeIITre, thus causing induction of the maltose system. In addition, derepression of TreC by itself caused induction of the maltose system, and a mutant lacking TreC was reduced in the uninduced level of mal gene expression indicating synthesis of endogenous inducer by TreC. Extracts containing TreC transformed [14C]-maltose into another 14C-labelled compound (preliminarily identified as maltose 1-phosphate) that is likely to be an alternative inducer of the maltose system.