Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism

Background

Plasma levels of brain natriuretic peptide (BNP) are increased in patients with left heart failure. In patients with severe pulmonary embolism (PE), primary right ventricular (RV) dysfunction is frequent. Little is known about BNP secretion in acute RV failure.

Methods

We prospectively studied 50 consecutive patients with confirmed PE (age range, 57 ± 19 years; 36 men). PE was confirmed with pulmonary angiography, spiral computed tomography, or echocardiography and subsidiary analyses. On admission, echocardiography and BNP measurements were performed in all patients.

Results

Patients without RV dysfunction had significantly lower BNP levels than patients with RV dysfunction (55 ± 69 pg/mL vs 340 ± 362 pg/mL, P <.001). There was a significant correlation between RV end-diastolic diameter and BNP (r = 0.43, P <.05). BNP discriminated patients with or without RV dysfunction (area under the receiver operating characteristic curve, 0.78; 95% CI, 0.64-0.92). A BNP >90 pg/mL was associated with a risk ratio of 28.4 (95% CI, 3.22-251.12) for the diagnosis of RV dysfunction. All patients without LV systolic dysfunction who had syncope necessitating cardiopulmonary resuscitation had normal BNP levels. Patients with RV dysfunction had significantly more in-hospital complications (cardiogenic shock, inotropic therapy, mechanical ventilation). However, BNP levels were not predictive of mortality or in-hospital complications.

Conclusions

BNP levels are frequently increased in patients with PE who have RV dysfunction, whereas patients without RV dysfunction show reference range BNP levels in the absence of left ventricular dysfunction. In acute PE, BNP elevation is highly predictive of RV dysfunction, but not of in-hospital complications and mortality.     

Coagulation changes and edema formation during long-distance bus travel.

Long-distance travel in a cramped position by aircraft or by bus and car has been suggested to be associated with an increased risk for thromboembolic events. Recently, we demonstrated moderate activation of coagulation after a long-haul flight. At present the single contributing factors (i.e. hypoxia and low humidity on board an aircraft and prolonged sitting in an aircraft, car or bus inducing venous stasis) have not yet been investigated. Therefore we measured markers of coagulation and fibrinolysis as well as functional parameters of coagulation using activated thrombelastography in 19 healthy volunteers before, during and after a real 10-h bus journey. In addition, changes in leg volume were measured. Thrombelastography revealed moderate activation of coagulation in all travelers, which was accompanied by a significant increase in prothrombin fragment F1 + 2. Thrombin-antithrombin III complexes and D-dimer remained unchanged, and tissue-type plasminogen activator and plasminogen-activator inhibitor 1 decreased after travel. After the travel we found a significant increase in leg volume that was exclusively distributed in the calf. We conclude that beside long-haul flights also long-distance bus travel induces a certain activation of the coagulation system. Thus, it is questionable whether hypoxia is the crucial risk factor for thromboembolic events after long-haul flights.     

ATX-101 for reduction of submental fat

Introduction: Facial esthetics are important for self-esteem. Undesired submental fat (SMF) deposits lead to an unappealing submental profile associated with aging and overweight. Compound ATX-101 is a proprietary formulation of purified synthetic deoxycholic acid for pharmacological submental contouring.

Review areas covered: This reviews covers anatomy of SMF, biochemistry of deoxycholic acid related to adipose tissue and tissue response to injection of ATX-101. Data from clinical trials were analyzed for efficacy and safety.

Methodology: Published studies using PubMed^© database 2000 – 2014 have been analyzed. The terms ‘deoxycholate’, ‘deoxycholic acid’, ‘ATX-101’ and ‘injection lipolysis’ were used.

Results: Deoxycholic acid causes adipocyte breakdown and an inflammatory tissue reaction leading to fat cell reduction and limited fibrosis. Four large clinical Phase III trials demonstrated efficacy of ATX-101 in reduction of SMF measured by validated scales and objective measurements. Patients reported improved psychological features and feeling. Adverse effects were mild and temporary.

Expert opinion: Adipocytolysis of SMF by ATX-101 is an important step forward to the development of approved drugs for reduction of localized fat pads. This could become a growing market.     

Increased Ca 2+-sensitivity of myofibrillar tension in heart failure and its functional implication

In human failing myocardium, an increased Ca ²⁺-sensitivity of myofilament tension development has been described in Triton X skinned cardiac myocytes compared to cardiomyocytes obtained from non-failing human donor hearts. The present study aimed to investigate whether there are functional implications of the increased Ca ²⁺-sensitivity in heart failure and whether alterations of myofilament function are already obvious at earlier stages of heart failure, such as in cardiac hypertrophy or whether alterations of the intracellular Ca ²⁺-homeostasis are able to induce alterations in myofilament function. Ca ²⁺-activated tension development was measured in Triton X-skinned fibers from human failing and non-failing myocardium. Ca ²⁺-sensitivity of myofilament tension development was significantly shifted to the left in human failing myocardium. Plots of diastolic free Ca ²⁺ versus diastolic tension development showed that in a range of similar diastolic Ca ²⁺-concentrations, diastolic tension was significantly enhanced in the failing hearts. The Ca ²⁺/tension relationship was shifted to the right in Triton X-skinned fiber preparations from transgenic renin overexpressing rats (TG(mREN2)27), shown to have concentric hypertrophy. In addition, the Ca ²⁺/tension relationship was unchanged in phospholamban knock-out mice with an increased systolic Ca ²⁺ (and enhanced diastolic Ca ²⁺-load). It is concluded that the increased Ca ²⁺-sensitivity of myofilament tension observed in single cardiomyocytes from failing human myocardium may be a phenomenon also present in multicellular preparations and may contribute to the diastolic dysfunction observed in human heart failure. Alterations of myofilament function occur at very early stages of heart failure and may be species dependent, or dependent on intracellular free Ca ²⁺-levels.