[Heart valve disesases : How sufficient is the knowledge of the German population?] / Herzklappenerkrankungen : Wie aufgeklärt ist die deutsche Bevölkerung?

To evaluate the awareness and knowledge of the German population regarding diseases in general, a survey of 1446 people aged 60 years or older was conducted in 14 German towns. The focus was on heart valve diseases with special emphasis on aortic valve stenosis (AS). While cancer was the disease that respondents were most concerned about (25.2%), only 3.3% were concerned about heart valve diseases. In this respect, the knowledge was broadly limited: only 7.4% of participants claimed to have some familiarity with heart valve diseases and only 12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the participants could correctly name the number of human heart valves, 71.6% knew at least one therapy option for AS and 30.6% were familiar with transcatheter aortic valve implantation (TAVI). After providing a brief clarification of the prevalence, symptoms and course of AS, 45.6% of respondents were more concerned about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7% even recognized the typical symptoms in themselves. Most of the participants would like to seek more information preferably in discussion with a specialist physician (77.2%), with their general practitioner (43.2%) or using the internet (29.7%). Despite its high prevalence, high morbidity and mortality, the vast majority of the German population were neither concerned nor fully aware of treatment options for AS. There is a strong case for public awareness campaigns that provide better knowledge of AS, and support check-ups that enable timely treatment and the avoidance of unnecessary hospitalization and death.

Temporal trends in transcatheter and surgical aortic valve replacement : An analysis of aortic valve replacements in Germany during 2012-2014.

This analysis of the data of the obligatory quality assurance programme AQUA shows the perioperative risk as well as the procedural outcome evaluated by the observed versus expected in-hospital mortality ratio (O/E ratio) of 62,872 patients undergoing isolated surgical (sAVR), transcatheter transvascular (TV-), or transapical (TA-) aortic valve replacement (TAVI) from 2012 to 2014 in Germany. The number of TAVI procedures increased from 9,352 in 2012 to 13,278 in 2014, whereas the number of sAVR remained constant (2012: 9,949; 2014: 9,953). Between 2012 and 2014, the number of TAVI implanted in patients with a logistic EuroScore I (logESI) of ≤10 % (2012: 21 %; 2014: 26 %) as well as with a logESI <20 % (2012: 57 %; 2014: 64 %) increased. In-hospital mortality in TAVI patients decreased from 5.2 % (TV: 5.0 %; TA: 7.4 %) in 2012 to 4.2 % (TV: 3.8 %; TA: 5.5 %) in 2014, whereas it was stable for sAVR patients (2012: 2.8 %; 2014: 2.6 %). The O/E ratio of TAVI patients decreased from 0.91 (TV: 0.79; TA: 1.2) to 0.73 (TV: 0.69; TA: 0.89), whereas this ratio remained constant for sAVR patients (2012: 0.92; 2014: 0.93). In summary, estimated surgical risk, in-hospital mortality, as well as the O/E ratio for patients undergoing TAVI declined constantly during the last 3 years.

Aortic stenosis in high-risk patients. Surgical therapy.

Conventional aortic valve replacement is the standard approach for treating aortic stenosis, it is performed via a full or partial sternotomy, and is associated with low risks for patients and with excellent long-term outcomes. This also holds true for octogenarians, if they present without relevant comorbidities. After resection of the calcified native leaflets, biological prostheses with good functionality and durability are implanted. Elderly patients with an increasing risk profile, however, should be treated by a heart team using transcatheter approaches including cardiac surgery.

Transcatheter aortic valve implantation in nonagenarians: insights from the German Aortic Valve Registry (GARY).

OBJECTIVE: The aim of this study was to compare the outcome of nonagenarians (≥ 90 years) with that of younger (< 90 years) patients undergoing transcatheter aortic valve implantation (TAVI) in current practice. METHODS: Data are collected from the German Aortic Valve Registry (GARY), which was designed to evaluate current practice in the invasive treatment of patients with aortic valve diseases in Germany. Data were analyzed regarding procedural outcome, 30-day, and 1-year outcomes of nonagenarians in comparison to that of younger patients. RESULTS: Between 2011 and 2015, 2436/33,051 (7.3%) nonagenarians underwent TAVI and were included in GARY. Nonagenarians were significantly more often male (45.2% vs. 40.0%, p < 0.001), frail (38.7% vs. 34.7%, p < 0.001), and had higher EuroSCORE scores than younger patient group (23.2% vs. 17.0%). Nonagenarians were significantly less often treated via transapical access (16.3% vs. 22.3%, p < 0.001). Procedure was performed significantly less often in general anesthesia (58.2% vs. 60.7%, p = 0.02) in nonagenarians, while necessity of pacemaker implantation was significantly higher in nonagenarians (27.2% vs. 24.8%, p > 0.001). The incidence of other typical postprocedural complications such as severe bleeding events and vascular complications were comparable between groups. However, 30-day (5.2% vs. 3.9%) and 1-year (22.7% vs. 17.7%) mortality rates were significantly higher among nonagenarians and age ≥ 90 years could be identified as an isolated risk factor for mortality. CONCLUSION: TAVI is a highly standardized procedure that can be performed safely with high procedural success even in very old patients. Although mortality is significantly higher in these patients-most probably due to the intrinsic higher risk profile of the very old patients-the results are still acceptable. To optimize outcome, especially elderly patients seem to profit from a procedure under local anesthesia or conscious sedation, to minimize the rate of postoperative delirium and the length of stay and to facilitate early mobilization.

Early changes in N-terminal pro-B-type natriuretic peptide levels after transcatheter aortic valve replacement and its impact on long-term mortality.

BACKGROUND: N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality. METHODS AND RESULTS: NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2. CONCLUSIONS: The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.

Effect of psychotropic agents upon the blastogenic response of human t-lymphocytes.

Antischizophrenic agents, phenothiazine and nonphenothiazine, inhibit the transformation of the T-lymphocyte in vitro. This inhibition occurs only in the early event and is neither competitive with dopamine, nor appears to involve Na+/K+ adenosine triphosphatase. RNA synthesis is more sensitive to the inhibitory effect than DNA or protein synthesis. This leads to the conclusion that chlorpromazine may act by inhibiting the synthesis of newly formed RNA, and subsequently, transformation, rather than by alteration of the cell membrane.

Recent advances in transcatheter aortic valve implantation: novel devices and potential shortcomings.

During the past years transcatheter aortic valve implantation (TAVI) has evolved to a standard technique for the treatment of high risk patients suffering from severe aortic stenosis. Worldwide the number of TAVI procedures is increasing exponentially. In this context both the transapical antegrade (TA) and the transfemoral retrograde (TF) approach are predominantly used and can be considered as safe and reproducible access sites for TAVI interventions. As a new technology TAVI is in a constant progress regarding the development of new devices. While in the first years only the Edwards SAPIEN(TM) and the Medtronic CoreValve(TM) prostheses were commercial available, recently additional devices obtained CE-mark approval and others have entered initial clinical trials. In addition to enhance the treatment options in general, the main driving factor to further develop new device iterations is to solve the drawbacks of the current TAVI systems: paravalvular leaks, occurrence of AV-blocks and the lack of full repositionability.

Transcatheter Heart Valves: Specific Characteristics and Potential Shortcomings.

During the past years TAVI has evolved to a standard technique for the treatment of high risk patients suffering from severe aortic stenosis. Worldwide the number of TAVI procedures is increasing exponentially. In this context both the transapical antegrade (TA) and the transfemoral retrograde (TF) approach are predominantly used and can be considered as safe and reproducible access sites for TAVI interventions. As a new technology TAVI is in a constant progress regarding the development of new devices. While in the first years only the Edwards SAPIEN™ and the Medtronic CoreValve™ prostheses were commercial available, recently additional devices obtained CE-mark approval and others have entered initial clinical trials. In addition to enhance the treatment options in general, the main driving factor to further develop new device iterations is to solve the drawbacks of the current TAVI systems: paravalvular leaks, occurrence of AV-blocks and the lack of full repositionability.

Cerebral flow pattern monitoring by transcranial Doppler during cardiopulmonary resuscitation.

We describe the transcranial Doppler pattern during a period of cardiopulmonary resuscitation in a patient undergoing a transcatheter off-pump aortic valve implantation. Transcranial Doppler of the middle cerebral artery flow was measured as a part of a separate ongoing study. The patient developed a cardiac arrest during deployment of the valve prosthesis. The incidental presence of the transcranial Doppler allowed us to assess middle cerebral artery flow during cardiopulmonary resuscitation in real time. An initial lack of a diastolic flow pattern seen with transcranial Doppler at the beginning of cardiopulmonary resuscitation led to volume loading and optimisation of the resuscitation technique. After increasing the depth of external cardiac massage, the cerebral flow pattern improved to produce sufficient diastolic flow. The transcranial Doppler provided additional information during cardiopulmonary resuscitation, which was helpful in clinical management. The use of transcranial Doppler may be helpful for other cardiac procedures where cerebral malperfusion may occur.

Blood replacement in dogs by dextran-hemoglobin.

Exchange transfusions in dogs were performed with a solution of either dextran or a covalent complex between dextran and human hemoglobin. Dogs transfused with dextran alone died when their hematocrit was lowered to 6-10%. Dogs transfused with dextran-hemoglobin complex, however, survived a reduction of their hematocrit to 2% or below. In the latter animals, the dextran-hemoglobin complex disappeared from the circulation with an average half-life of 2.4 days. Correcting for oxidation of the hemoglobin moiety to methemoglobin, the half-life of functional unoxidized dextran-hemoglobin in the circulation was 1.9 days. In compensation for the loss of dextran-hemoglobin, vigorous erythropoiesis was observed at a rate of close to 5% hematocrit per day over the first 2 days following the exchange transfusion. As a result, the total hemoglobin concentration in blood was maintained at 5-6% during this period, and the animals went on to complete recovery in room air without the need for further transfusion with dextran-hemoglobin.

Soluble dextran-hemoglobin complex as a potential blood substitute.

A complex between soluble dextran and human hemoglobin has been synthesized by two different methods. In the alkylation method, hemoglobin was allowed to react with bromoacetyl groups incorporated into the dextran; the yield of the complex was about 80% in terms of the hemoglobin used. In the dialdehyde method, hemoglobin was allowed to react with dialdehyde groups on the dextran generated by periodate oxidation; the yield of the complex was about 60%. Both soluble dextran-hemoglobin complexes could bind and release oxygen reversibly, but the oxygen-binding curves were shifted to the left relative to that of free hemoglobin. In the rabbit, the complex obtained by the alkylation method was excreted by the kidneys and cleared from the circulation much more slowly than free hemoglobin.

Synthetic non-peptide inhibitors of HIV protease.

We have studied the inhibition of HIV protease by the antifungal antibiotic cerulenin, as well as by several related synthetic, structurally simpler analogs. The effect of these compounds on HIV protease was conveniently studied by monitoring the cleavage of an authentic single peptide bond in a synthetic nonapeptide corresponding to a natural cleavage site in HIV-1 gag precursor polyprotein. The relative inhibitory effects of these compounds have afforded an insight into the structural characteristics which impart antiprotease activity.

Regulatory concerns for the chemistry, manufacturing, and controls of oligonucleotide therapeutics for use in clinical studies.

It is important to remember that while a new class of therapeutic agents like oligonucleotides may introduce novel concerns, the basic regulatory issues regarding the chemistry, manufacturing, and controls of drug substances and drug products must be addressed. This article focuses on information that should be included in an Investigational New Drug Application (IND), a request to use an investigational drug in clinical studies. The regulatory challenge presented with oligonucleotide therapeutics is to prove the identity of the oligonucleotide, and demonstrate its quality, purity, and strength/potency using both those characteristics that are the same as all other drugs, as well as those that are unique. Most of the discussion will concern issues that are unique to oligonucleotides, or those topics that deserve more detailed attention than would be needed for more typical small molecule drugs. Regulatory issues will need to be evaluated so that safety concerns are addressed while not imposing undue burden on the sponsors of investigational drugs.