Heinrich Körtke

Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data

BACKGROUND Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. METHODS We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. FINDINGS Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. INTERPRETATION Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up. FUNDING UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.

International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous?

BACKGROUND Severe thromboembolic and hemorrhagic complications after mechanical heart valve replacement essentially depend on the intensity of oral anticoagulation and the fluctuation of individual international normalized ratio (INR) values. METHODS After heart valve replacement with Medtronic Hall, St. Jude Medical, and CarboMedics implants, patients were randomly divided into two groups, one controlling INR values at home, the other being monitored by family practitioners. RESULTS Almost 80% of the INR values recorded by patients at home were within the stipulated therapeutic range, INR 2.5 to 4.5, compared with just 62% of INR values recorded by family practitioners. The overall complication rate (hemorrhages and thromboembolic events) of the self-management group was significantly (p < 0.05) decreased compared with the conventional group. CONCLUSIONS Through INR self-management, an improvement in the quality of ongoing oral anticoagulation could be shown. Starting this form of therapeutic control early after mechanical heart valve replacement appears to effect a further reduction in anticoagulant-induced complications.

Mechanical circulatory support: The Bad Oeynhausen experience

From September 1987 to February 1994, we treated 147 patients ranging between 11 and 82 years old with different mechanical circulatory support systems. The applied devices were the Bio-Medicus centrifugal pump in 61 patients, the Abiomed BVS System 5000 in 49 patients, the Thoratec ventricular assist device in 42 patients, and the Novacor left ventricular assist device in 7 patients. On the basis of indication for mechanical circulatory support, the patients were divided into three groups: group 1 consisted of 72 patients with postcardiotomy cardiogenic shock; group 2, 50 patients in whom mechanical support was used as a bridge to cardiac transplantation; and group 3 (miscellaneous), 25 patients in cardiogenic shock resulting from acute myocardial infarction (n = 14), acute fulminant myocarditis (n = 3), primary graft failure (n = 2), right heart failure after heart transplantation (n = 3), and acute rejection (n = 3). Time of support ranged from 1 hour to 97 days (mean duration, 10.8 days). Seventy-five patients (51%) were discharged from the hospital. The best survival rate was achieved in group 2 with 72%, followed by group 1 with 44% and then group 3 with 28%. The most frequent complications in group 1 were bleeding (44%), multiple-organ failure (24%), neurologic disorders (18%), and acute renal failure (15%). In group 2, the major complications were bleeding (34%) and cerebrovascular disorders (22%) and in group 3, multiple-organ failure and sepsis (60%) and bleeding (32%).

Survival Comparison of the Ross Procedure and Mechanical Valve Replacement With Optimal Self-Management Anticoagulation Therapy Propensity-Matched Cohort Study

Background— It is suggested that in young adults the Ross procedure results in better late patient survival compared with mechanical prosthesis implantation. We performed a propensity score-matched study that assessed late survival in young adult patients after a Ross procedure versus that after mechanical aortic valve replacement with optimal self-management anticoagulation therapy. Methods and Results— We selected 918 Ross patients and 406 mechanical valve patients 18 to 60 years of age without dissection, aneurysm, or mitral valve replacement who survived an elective procedure (1994 to 2008). With the use of propensity score matching, late survival was compared between the 2 groups. Two hundred fifty-three patients with a mechanical valve (mean follow-up, 6.3 years) could be propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the mechanical valve group (P=0.17); the ratio of male to female patients was 3.2 in the Ross procedure group and 2.7 in the mechanical valve group (P=0.46). Linearized all-cause mortality rate was 0.53% per patient-year in the Ross procedure group compared with 0.30% per patient-year in the mechanical valve group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91; P=0.32). Late survival was comparable to that of the general German population. Conclusions— In comparable patients, there is no late survival difference in the first postoperative decade between the Ross procedure and mechanical aortic valve implantation with optimal anticoagulation self-management. Survival in these selected young adult patients closely resembles that of the general population, possibly as a result of highly specialized anticoagulation self-management, better timing of surgery, and improved patient selection in recent years.

A randomized controlled trial on the efficacy of carbohydrate-reduced or fat-reduced diets in patients attending a telemedically guided weight loss program

BackgroundWe investigated whether macronutrient composition of energy-restricted diets influences the efficacy of a telemedically guided weight loss program.MethodsTwo hundred overweight subjects were randomly assigned to a conventional low-fat diet and a low-carbohydrate diet group (target carbohydrate content: >55% energy and <40% energy, respectively). Both groups attended a weekly nutrition education program and dietary counselling by telephone, and had to transfer actual body weight data to our clinic weekly with added Bluetooth® technology by mobile phone. Various fatness and fat distribution parameters, energy and macronutrient intake, and various biochemical risk markers were measured at baseline and after 6, and 12 months.ResultsIn both groups, energy intake decreased by 400 kcal/d compared to baseline values within the first 6 months and slightly increased again within the second 6 months. Macronutrient composition differed significantly between the groups from the beginning to month 12. At study termination, weight loss was 5.8 kg (SD: 6.1 kg) in the low-carbohydrate group and 4.3 kg (SD: 5.1 kg) in the low-fat group (p = 0.065). In the low-carbohydrate group, triglyceride and HDL-cholesterol levels were lower at month 6 and waist circumference and systolic blood pressure were lower at month 12 compared with the low-fat group (P = 0.005–0.037). Other risk markers improved to a similar extent in both groups.ConclusionDespite favourable effects of both diets on weight loss, the carbohydrate-reduced diet was more beneficial with respect to cardiovascular risk factors compared to the fat-reduced diet. Nevertheless, compliance with a weight loss program appears to be even a more important factor for success in prevention and treatment of obesity than the composition of the diet.Trial registrationClinicaltrials.gov as NCT00868387

[INR self-management after mechanical heart valve replacement: ESCAT (Early Self-Controlled Anticoagulation Trial)].

Severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement essentially occur due to intense oral anticoagulation and fluctuating individual INR values around the target range. INR self-management can help to minimize these fluctuations. Beginning this therapeutic control immediately after mechanical heart valve replacement further reduces anticoagulant-induced complications. Included in the study were 1200 patients. The quality of oral anticoagulation also improved through INR self-management. Over an observation period of two years, nearly 80 % of INR values recorded by the patients themselves were within the target therapeutic range of 2.5–4.5. This corresponds to a high significance of p < = 0.001 in favor of INR self-management. Only 64.9 % of INR values monitored by family practitioners were within the desired range. The results differed slightly in quality between patient groups with different levels of training (comprehensive, secondary modern, grammar with or without university). Of patients trained in INR self-management following mechanical heart valve replacement, 91.7 % maintained their competence in this technique throughout the entire follow-up period. Only 8.3 % of those trained immediately after surgery were unable to continue with INR self-management. Grundproblematik und Methodik Das Auftreten von schwerwiegenden, thrombembolischen und hämorrhagischen Komplikationen nach mechanischem Herzklappenersatz ist im Wesentlichen abhängig von der Intensität der oralen Antikoagulation und der Schwankung der einzelnen INR-Messwerte um den Zielbereich. Das INR-Selbstmanagement ist in der Lage, diese Schwankungen zu minimieren. Insbesondere durch den frühen postoperativen Beginn dieser Therapiekontrolle wird eine weitere Reduktion von antikoagulanzieninduzierten Komplikationen bewirkt. Mit dieser Arbeit soll geklärt werden, inwieweit ein unmittelbar postoperativ eingeführtes INR-Selbstmanagement nach mechanischem Herzklappenersatz zu einer verbesserten Therapiecompliance und hieraus resultierend zu einer Reduktion der thrombembolischen Komplikationsrate führt. Patienten und Methodik Insgesamt wurden 1200 Patienten in die ESCAT-Studie eingeschlossen, hiervon konnten 45 Patienten bei der Auswertung nicht berücksichtigt werden, da in 29 Fällen biologische Herzklappen implantiert wurden und 16 Patienten (1,3 %) nicht in der Lage waren, das Studienprotokoll zu erfüllen, somit ergab sich eine Grundpopulation von 1155 Patienten. Entsprechend der Randomisierung entfielen 576 Patienten (49,9 %) in die konventionelle Gruppe, in welcher die Antikoagulationstherapie vom Hausarzt durchgeführt wurde. Auf die Gruppe der Patienten, welche das INR-Selbstmanagement durchführten, entfielen 579 Patienten (50,1 %). Die INR-Werte und Komplikationsereignisse wurden in monatlichen Intervallen mittels Patientenprotokollbogen an das Studienzentrum geschickt. Ergebnisse Die INR-Selbstmanagementgruppe hatte signifikant weniger schwerwiegende Thrombembolien (p = 0,026). Das INR-Selbstmanagement bewirkt eine hohe Qualitatsverbesserung der laufenden oralen Antikoagulation. Annahernd 80 % der von den Patienten ermittelten INR-Werte lagen im vorgegebenen Therapiekorridor von INR 2,5–4,5. Hieraus resultiert eine hochst signifikante Differenz mit p ≤ 0,001 zugunsten des INR-Selbstmanagements. Nur 64,9 % der INR-Werte der konventionell kontrollierten Patienten lagen im gewunschen Therapiebereich. Die thrombembolische Komplikationsrate konnte von 2,8 % pro Patientenjahr auf 1,5 % pro Patientenjahr reduziert werden, unabhangig von der gewahlten Klappenposition, allein durch einen fruhen Beginn des INR-Selbstmanagements unmittelbar nach einem mechanischem Herzklappenersatz. Folgerung 91,7% der Patienten mit Einfuhrung ins INR-Selbstmanagement nach mechanischem Herzklappenersatz zeigten uber die gesamte Follow-up-Zeit ihre Kompetenz hinsichtlich des INR-Selbstmanagements. Nur 8,3 % der Patienten gaben ihren INR-Gerinnungsmonitor zuruck. Sie fuhlten sich nicht in der Lage, das INR-Selbstmanagement durchzufuhren. Insgesamt konnte eine signifikante thrombembolische Komplikationsreduktion nachgewiesen werden.

Microanalysis and distribution of cardiac troponin I phospho species in heart areas.

Sequential phosphorylation and dephosphorylation of cTnI by the cAMP dependent protein kinase and by protein phosphatase 2A, respectively, produce the non-, mono- and bisphosphorylated species (Jaquet et al., 1995, Eur. J. Biochem. 231, 486-490). The aim of this study was to determine these forms even in small tissue samples, e.g. in biopsy probes of approximately 30 mg which would allow to define the phosphorylation state of cTnI in heart areas. In order to do so a micro isolation procedure for cTnI had to be established. cTnI is extracted from small bovine, rabbit and human heart tissue samples (30-100 mg) under special conditions avoiding dephosphorylation and is isolated by affinity chromatography on cTnC Sepharose. All three species, the bis-, mono- and dephospho cTnI, are precipitated quantitatively by acetone, then they are separated by non-equilibrium isoelectric focusing and quantified by scanning densitometry. The method presented here allows to quantify the three cTnI species reproducibly. No other phosphorylated species are detected. Truncated cTnI forms of each phospho species are found in human biopsy samples due to removal of a approximately 36 amino acid peptide from the C-terminus. In bovine, human and rabbit heart the pattern of the three cTnI phospho species is characteristic for left and right atrium, left and right ventricle and septum.

INR-Selbstmanagement nach mechanischem Herzklappenersatz: ESCAT (Early Self-Controlled Anticoagulation Trial)

Severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement essentially occur due to intense oral anticoagulation and fluctuating individual INR values around the target range. INR self-management can help to minimize these fluctuations. Beginning this therapeutic control immediately after mechanical heart valve replacement further reduces anticoagulant-induced complications. Included in the study were 1200 patients. The quality of oral anticoagulation also improved through INR self-management. Over an observation period of two years, nearly 80 % of INR values recorded by the patients themselves were within the target therapeutic range of 2.5–4.5. This corresponds to a high significance of p < = 0.001 in favor of INR self-management. Only 64.9 % of INR values monitored by family practitioners were within the desired range. The results differed slightly in quality between patient groups with different levels of training (comprehensive, secondary modern, grammar with or without university). Of patients trained in INR self-management following mechanical heart valve replacement, 91.7 % maintained their competence in this technique throughout the entire follow-up period. Only 8.3 % of those trained immediately after surgery were unable to continue with INR self-management. Grundproblematik und Methodik Das Auftreten von schwerwiegenden, thrombembolischen und hämorrhagischen Komplikationen nach mechanischem Herzklappenersatz ist im Wesentlichen abhängig von der Intensität der oralen Antikoagulation und der Schwankung der einzelnen INR-Messwerte um den Zielbereich. Das INR-Selbstmanagement ist in der Lage, diese Schwankungen zu minimieren. Insbesondere durch den frühen postoperativen Beginn dieser Therapiekontrolle wird eine weitere Reduktion von antikoagulanzieninduzierten Komplikationen bewirkt. Mit dieser Arbeit soll geklärt werden, inwieweit ein unmittelbar postoperativ eingeführtes INR-Selbstmanagement nach mechanischem Herzklappenersatz zu einer verbesserten Therapiecompliance und hieraus resultierend zu einer Reduktion der thrombembolischen Komplikationsrate führt. Patienten und Methodik Insgesamt wurden 1200 Patienten in die ESCAT-Studie eingeschlossen, hiervon konnten 45 Patienten bei der Auswertung nicht berücksichtigt werden, da in 29 Fällen biologische Herzklappen implantiert wurden und 16 Patienten (1,3 %) nicht in der Lage waren, das Studienprotokoll zu erfüllen, somit ergab sich eine Grundpopulation von 1155 Patienten. Entsprechend der Randomisierung entfielen 576 Patienten (49,9 %) in die konventionelle Gruppe, in welcher die Antikoagulationstherapie vom Hausarzt durchgeführt wurde. Auf die Gruppe der Patienten, welche das INR-Selbstmanagement durchführten, entfielen 579 Patienten (50,1 %). Die INR-Werte und Komplikationsereignisse wurden in monatlichen Intervallen mittels Patientenprotokollbogen an das Studienzentrum geschickt. Ergebnisse Die INR-Selbstmanagementgruppe hatte signifikant weniger schwerwiegende Thrombembolien (p = 0,026). Das INR-Selbstmanagement bewirkt eine hohe Qualitatsverbesserung der laufenden oralen Antikoagulation. Annahernd 80 % der von den Patienten ermittelten INR-Werte lagen im vorgegebenen Therapiekorridor von INR 2,5–4,5. Hieraus resultiert eine hochst signifikante Differenz mit p ≤ 0,001 zugunsten des INR-Selbstmanagements. Nur 64,9 % der INR-Werte der konventionell kontrollierten Patienten lagen im gewunschen Therapiebereich. Die thrombembolische Komplikationsrate konnte von 2,8 % pro Patientenjahr auf 1,5 % pro Patientenjahr reduziert werden, unabhangig von der gewahlten Klappenposition, allein durch einen fruhen Beginn des INR-Selbstmanagements unmittelbar nach einem mechanischem Herzklappenersatz. Folgerung 91,7% der Patienten mit Einfuhrung ins INR-Selbstmanagement nach mechanischem Herzklappenersatz zeigten uber die gesamte Follow-up-Zeit ihre Kompetenz hinsichtlich des INR-Selbstmanagements. Nur 8,3 % der Patienten gaben ihren INR-Gerinnungsmonitor zuruck. Sie fuhlten sich nicht in der Lage, das INR-Selbstmanagement durchzufuhren. Insgesamt konnte eine signifikante thrombembolische Komplikationsreduktion nachgewiesen werden.

Thrombosis of the LVAD inflow cannula detected by transthoracic echocardiography: 2D and 3D thrombus visualization.

(Echocardiography 2011;28:E194‐E195)

Aktuelle Diagnostik und Therapie von Herzklappenerkrankungen

We present a survey of the current standard in diagnosis and therapy of the most frequent heart valve lesions. During the last 50 years there has been a dramatic shift concerning the etiology of valve lesions with a rise of the agedependent degenerative towards rheumatic valve diseases. The aim of the diagnostic evaluation of valve lesions is primarily the clinical and hemodynamic grading of the severity of the valve disease, the recognition of relevant coexisting cardiac and extracardiac diseases and furthermore, an optimal timing of surgery in close correlation with the cardiac surgeons.We present a survey of the current standard in diagnosis and therapy of the most frequent heart valve lesions. During the last 50 years there has been a dramatic shift concerning the etiology of valve lesions with a rise of the agedependent degenerative towards rheumatic valve diseases. The aim of the diagnostic evaluation of valve lesions is primarily the clinical and hemodynamic grading of the severity of the valve disease, the recognition of relevant coexisting cardiac and extracardiac diseases and furthermore, an optimal timing of surgery in close correlation with the cardiac surgeons. Die vorliegende Arbeit soll einen Überblick über den aktuellen Standard der Diagnostik und der Therapie der häufigsten Herzklappenvitien geben. In den letzten 50 Jahren kam es zu einem beträchtlichen Umschwung bezüglich der Ätiologie der Klappenvitien mit einem signifikanten Anstieg der altersabhängigen degenerativen Klappenerkrankung bei gleichzeitiger Abnahme der Häufigkeit rheumatischer Klappenfehler. Ziel der Diagnostik von Herzklappenerkrankungen sind v.a. die Erfassung des klinischen und hämodynamischen Schweregrads sowie das Erkennen relevanter kardialer und extrakardialer Komorbiditäten, um ein möglichst optimales Timing des Operationszeitpunkts bei niedrigen peri- und postoperativen Risiken zu entwickeln. Alle diese Schritte sind letztendlich nur in enger Kooperation mit den Kardiochirurgen denkbar.