Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

[Constellations of findings and derived treatment interventions in telemedical monitoring of patients with heart failure, cardiac arrhythmia or increased risk for sudden cardiac death : Recommendations of the working group 33 telemonitoring of the German Cardiac Society]. / Befundkonstellation und abgeleitete Behandlungsinterventionen bei telemedizinisch überwachten Patienten mit Herzinsuffizienz, Herzrhythmusstörungen oder erhöhtem Risiko für den plötzlichen Herztod : Empfehlungen der Arbeitsgruppe 33 Telemonitoring der Deutschen Gesellschaft für Kardiologie, Herz- und Kreislaufforschung e. V.

The specification of standard operating procedures (SOPs) is a basic requirement for a successful implementation of telemonitoring with implanted cardiac devices and with external measuring devices in patients with heart failure, cardiac arrhytmia or increased risk of sudden cardiac death. The following article summarizes the possibilities of telemonitoring from a technical and organizational point of view and descibes basic requirements on SOPs. these basic requirements should be further specified and anchored in the organizational structure of the individual telemonitoring concept. Moreover, they should de understood as a basic guideline fpr the actions of telemonitoring center (TMC) employees.

[Position paper telemonitoring : From the Nucleus Members of the AG33 Telemonitoring of the DGK and associated members]. / Positionspapier Telemonitoring : Von den Nukleusmitgliedern der AG33 Telemonitoring in der DGK und assoziierten Mitgliedern.

The position paper of the working group 33/Telemonitoring in the German Society for Cardiology e. V. (DGK) discusses the importance of digital solutions in the German health care system and highlights the application possibilities and potentials of telemonitoring in the treatment of patients with cardiac diseases. In addition to telemonitoring of acute ischaemic diseases, acute coronary syndrome and acute cardiac arrhythmias, telemonitoring of chronic cardiac diseases is discussed. Chronic diseases, such as chronic heart failure, are age-associated and present society with the great challenge of providing high-quality, yet cost-efficient care to an increasing number of patients in the future. Telemonitoring offers an opportunity to meet this challenge. However, the introduction of telemonitoring and the associated changes for patients, doctors and other service providers must be accompanied by measures to ensure the acceptance of telemonitoring and the secure handling of sensitive data as well as the quality of telemonitoring services.

[Basic structural features of a cardiac telemedicine center for patients with heart failure and implanted devices, cardiac arrhythmias, and increased risk of sudden cardiac death : Recommendations of the working group 33 Telemonitoring of the German Cardiac Society]. / Grundlegende Strukturmerkmale eines kardiologischen Telemedizinzentrums für Patienten mit Herzinsuffizienz und implantierten Devices, Herzrhythmusstörungen und erhöhtem Risiko für den plötzlichen Herztod : Empfehlungen der Arbeitsgruppe 33 Telemonitoring in der Deutschen Gesellschaft für Kardiologie, Herz- und Kreislaufforschung e. V.

Heart failure is one of the most common diseases. It is associated with high morbidity and mortality. Since heart failure is age-associated, the number of patients with heart failure is constantly increasing. At the same time, the imbalance between the need for treatment and the provision of care is growing. Telemonitoring/telemedicine offers patients in rural or remote areas access to high-quality health care and enables fast access to specialists. The working group 33 Telemonitoring of the German Cardiac Society describes the characteristics and possible applications of telemonitoring/telemedicine in the treatment of patients with heart failure. Furthermore, quality criteria for cardiological telemedicine centres are defined. In addition to the personnel structure of a telemedicine centre and the competencies of employees, requirements for the technical infrastructure and the management of incoming data and alarms are described.

[The telemedical service centre as an essential element of the conceptual approach for telemonitoring of cardiac patients : Requirements on the service, quality, and technical realization of telemonitoring]. / Das Telemedizinische Zentrum als essenzieller Baustein konzeptioneller Ansätze zum Telemonitoring kardialer Patienten : Anforderungen an Leistungen, Qualität und technische Umsetzung von Telemonitoring.

Telemonitoring as part of a treatment strategy supports and facilitates the monitoring, disease management and education of patients with heart failure and cardiac arrhythmias. Therefore, telemonitoring affects quality and success of the therapy. Thus, meeting the needs of the patients and of the involved health care professionals is important for the success of the telemonitoring service. Moreover, a high quality of the service has to be ensured. The following article describes several configuration options for telemonitoring services considering technical as well as quality- and service-related aspects.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

[Aortic valve stenosis: transcatheter aortic valve implantation (TAVI) ­ transarterial or transapical approach]. / Aortenklappenstenosen: Kathetergestützte Aortenklappenimplantation (TAVI) ­ transarterieller oder transapikaler Zugang.

The calcified aortic stenosis is the dominating valve disease. Patients affected are most common elderly people in the 8 (th) or 9 (th) decade of their life who often show associated comorbidities like reduced left ventricular function, impaired renal function, pulmonary hypertension, and further diseases (Diabetes mellitus, stroke, COPD). In many cases perioperative morbidity and mortality are too high for surgical valve replacement and up to 30 % of patients are rejected. Nevertheless, prognosis of aortic stenosis is worse if the typical symptoms like dyspnea on exertion, syncope, and angina occur. The transcatheter aortic valve implantation is a new method treating this particular group of patients. The aortic valve bioprothesis consists of a balloon-expandable stent or a self-expandable frame, in which a valve of bovine or porcine pericardium is incorporated. The implantation is performed by retrograde access via the femoral or subclavian artery; the balloon-expandable prosthesis can also be implanted by transapical approach. Recently, the PARTNER trial and other studies demonstrate a high implantation success rate and better survival in comparison to standard therapy but exhibit also cerebral vascular and peripheral vascular complications. A further reduction of the available delivery systems and new types of valves which are under experimental tests and clinical evaluation contribute to this development.

[Telemedicine--ready for use in the cardiological field?]. / Telemedizin in der Kardiologie. Welche Anwendungen sind reif für die klinische Praxis?

The changes in the demographic structure, the increasing multi-morbidity in connection with a rise in the number of chronic illnesses and the absence of an effective coordination of the different levels of health care services with its discontinuous processes and redundancies will increase the economic burdens in the health care system. The latest developments and appropriate logistic premises nowadays offer a realistic basis for implementing telemonitoring as a central service and information tool as well as an instrument controlling the information- and data-flow between patient, hospital and medical practitioner.

Randomized comparison of effects of suture-based and collagen-based vascular closure devices on post-procedural leg perfusion.

BACKGROUND: Vascular closure devices (VCD) are well established to facilitate hemostasis after cardiac catheterization procedures. However, impairment of flow due to the reduction of femoral artery diameter remains a major concern. The present study aims to evaluate leg perfusion before and after application of collagen- and suture-based vascular closure devices. METHODS: A total of 366 patients (age: 64.3 years+/-10.7, male: 71.3%) were randomized to receive femoral access site closure with either a collagen-based closure device (group A) (n=214) or a suture-mediated device (group B) (n=152), immediately following coronary catheterization procedures. In all patients, the ankle-brachial-index (ABI) was measured before and the day after closure device application. RESULTS: In group A, mean ABI at baseline was 1.09+/-0.2, in group B 1.11+/-0.2. In both groups, there was a significant, albeit clinically not relevant, reduction in post-procedural ABI (group A: 1.04+/-0.2, p<0.01 vs baseline, group B: 1.06+/-0.2, p<0.01 vs baseline). DeltaABI was not different between both VCD groups (p=0.55). In patients with peripheral vascular disease (PVD), neither the Angioseal device (mean ABI at baseline 0.76+/-0.1) nor the Perclose-device (mean ABI at baseline 0.79+/-0.1) induced a remarkable impairment of leg perfusion (Angioseal: 0.77+/-0.1, p=0.9 vs baseline, Perclose: 0.78+/-0.1, p=1.0 vs baseline). Clinically, no aggravation of claudication was observed in the PVD patient group. CONCLUSION: Both vascular closure devices are not associated with clinically relevant reduction in ABI. There was no difference between the two groups with respect to the level of flow impairment. Both devices may be safely used in patients with reduced ABI.

Prevalence of the metabolic syndrome in German women with polycystic ovary syndrome.

The aim of our study was to evaluate the prevalence of the metabolic syndrome (MBS) according to the current International Diabetes Federation definition in German PCOS women. Four hundred and eleven PCOS patients (age 28+/-6.3 years) and 82 controls (age 28+/-7.5 years) were evaluated for anthropometric and metabolic parameters by physical examination, blood testing and a personal interview including family history. A subgroup analysis of controls with BMI-matched PCOS women (BMI 22.9+/-2.8 kg/m (2)) was performed to detect PCOS specific differences in metabolic variables between the groups. The MBS was found in 33.8% of PCOS women compared to 7.3% in the control group. Parameters of insulin resistance, lipid-and glucose metabolism, mean values of all criteria of the MBS as well as the prevalence of the MBS were significantly different between the entire PCOS cohort and controls, but did not differ between BMI-matched PCOS women and controls. In addition, the prevalence of the MBS increased with age. Moreover, in PCOS women an increase in BMI and insulin resistance was accompanied by a further significant increase in the severity of clinical and biochemical hyperandrogenism. In PCOS women, while one out of three PCOS women had the MBS, the presence of metabolic abnormalities did not appear to be associated with PCOS per se, but rather correlated with age and the degree of obesity.

Predicting mortality and rehospitalization in heart failure patients with home monitoring--the Home CARE pilot study.

The increasing worldwide prevalence of heart failure is associated with numerous and protracted hospital admissions. The multidisciplinary team approach together with telemonitoring aims at reducing the number of rehospitalizations, length of hospital stay, and mortality rates. Novel cardiac resynchronization therapy (CRT) devices have a Home Monitoring capability, offering wireless, everyday transfer of the essential status and therapy data to the attending physician. The transmitted data include potential predictors of death or hospitalization, such as the onset of atrial and ventricular arrhythmias, duration of physical activity, mean heart rates over 24 h and at rest, percentage of CRT delivered, and lead impedances. We present here interim results of the prospective, longitudinal, multicenter Home CARE Phase 0 study, conducted in 123 patients (age: 67+/-9 years, 83% male) with clinical indication for CRT. Twenty-nine patients (24%) received a CRT pacemaker, 52 (42%) a prophylactic implantable cardioverter defibrillator (ICD), and 42 (34%) had other ICD indications. All devices have an integrated Home Monitoring feature. In a mean (interim) follow-up period of 3 months (9194 observational days), 11 unplanned rehospitalizations of cardiovascular etiology and 9 deaths occurred. In 70% of the rehospitalization events, the retrospective analysis of transmitted data via Home Monitoring revealed an increase in mean heart rate at rest and in mean heart rate over 24 h within 7 days preceding hospitalization. A decrease in the percentage of CRT was observed in 43% and a reduction in the patients' daily activity in 30% of rehospitalized patients. These interim findings suggest that Home Monitoring data may predict events leading to hospitalization and encourage further research.

[The Herz Handy--a new telemedical service concept for heart patients]. / Das Herz Handy--in neues telemedizinisches Servicekonzept für Herzpatienten.

Telemedicine is a new milestone for the health care system in the care of patients with heart disease. New technologies and the possibilities of fast data transmission have enabled this step forward. The Cardiophone offers a new telemonitoring Service Concept, which is available 24 hours a day. The patient is by the aid of the Cardiophone connected with the Medical Service Center at just the press of a button, can record and transmit an ECG and can be localized by the incorporated GPS. We report about our experiences with 363 patients over 3 years. Out of 5064 patient contacts associated with 7561 calls, 559 emergency contacts occurred. From the initial main complaints, working diagnoses were established. The final confirmed diagnoses were arrhythmias (27.8%), coronary heart disease (25.9%), psychovegetative syndrome (12.7%), backbone pain (6.2%), gastrointestinal syndrome (3.6%), others (1.8%), and exclusion diagnosis (19.9%). Ten myocardial infarctions were diagnosed, of whom 3 were confirmed; the other 7 were treated as stabile angina pectoris. Overall 823 ECG were transmitted, in average 1.6 ECGs per emergency contact. In 131 ECGs changes of the ST-segment or T-wave could be documented; 26 patients showed a pacemaker ECG. Atrial and ventricular arrhythmias as well as conduction disturbances were seen. The majority of emergency contacts (n=477, 85.3%) were successfully managed by the Service Center. In 38 emergency contacts (6.8%) admission to hospital was recommended; in 4 cases (0.7%) an ambulance was activated via the local dispatcher by the Service Center and in 29 cases (5.2%) the emergency ambulance.

Insulin sensitivity and coronary vasoreactivity: insulin sensitivity relates to adenosine-stimulated coronary flow response in human subjects.

OBJECTIVE: Diabetes is associated with coronary microvasculature abnormalities and impaired coronary flow reserve (CFR). CFR is the ratio of coronary flow under maximal vasodilation to basal flow and is a measure for coronary vasoreactivity. Insulin resistance is the central defect in the development of type 2 diabetes, preceding its onset by 10-20 years. Thus, the relationship between insulin sensitivity and CFR in nondiabetic subjects is particularly interesting. The aim of the study was to investigate this relationship. DESIGN: Cross-sectional study. PATIENTS: The study population consisted of 18 nondiabetic subjects without coronary artery stenosis on coronary angiography. We excluded patients with structural heart disease or with conditions affecting CFR or insulin sensitivity such as low density lipoprotein (LDL)-cholesterol > or = 4.14 mmol/l, smoking, hypertension or obesity with a body mass index (BMI) > 28 kg/m(2). MEASUREMENTS AND RESULTS: CFR was 3.1 +/- 0.8 (range 1.7-4.8), as assessed by intracoronary Doppler measurements in the left anterior descending coronary arteries after adenosine stimulation. Intravascular ultrasound revealed zero to moderate coronary atherosclerotic changes. Whole-body insulin sensitivity (M-value) was 7.5 +/- 2.9 mg/kg/min (range 2.2-12.6), as assessed by the hyperinsulinaemic-euglycaemic clamp test. Subjects with low CFR (< 3.0) had a significantly lower M-value than subjects with normal CFR (> 3.0) (6.0 +/- 2.5 vs. 9.0 +/- 2.5 mg/kg/min, P = 0.021). Univariate linear regression demonstrated a strong correlation between CFR and M-value (r = 0.76, P < 0.001). In multiple regression analysis, the significant association of CFR with M-value was independent of potential confounders (sex, age, BMI, LDL-cholesterol and plaque burden on intravascular ultrasound). Bootstrap analysis corroborated this finding. CONCLUSIONS: Whole-body insulin sensitivity relates to coronary vasoreactivity. Across a wide range of both insulin sensitivity and coronary flow reserve from markedly abnormal to normal values, an increase in insulin sensitivity appears to be associated with an increase in coronary flow reserve. Insulin resistance is therefore associated with coronary microvasculature abnormalities in nondiabetics.

Photoproduction of eta-mesic 3He.

The photoproduction of eta-mesic 3He has been investigated using the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive cross section for the reaction gamma3He-->etaX has been measured for photon energies from threshold to 820 MeV. The total and angular differential coherent eta cross sections have been extracted up to energies of 745 MeV. A resonancelike structure just above the eta production threshold with an isotropic angular distribution suggests the existence of a resonant quasibound state. This is supported by studies of a competing decay channel of such a quasibound eta-mesic nucleus into pi(0)pX. A binding energy of (-4.4+/-4.2) MeV and a width of (25.6+/-6.1) MeV is deduced for the quasibound eta-mesic state in 3He.

In-medium modifications of the pipi interaction in photon-induced reactions.

Differential cross sections of the reactions (gamma,pi(0)pi(0)) and (gamma,pi(0)pi(+/-)) have been measured for several nuclei (1H,12C, and (nat)Pb) at an incident-photon energy of E(gamma)=400-460 MeV at the tagged-photon facility at MAMI-B using the TAPS spectrometer. A significant nuclear-mass dependence of the pipi invariant-mass distribution is found in the pi(0)pi(0) channel. This dependence is not observed in the pi(0)pi(+/-) channel and is consistent with an in-medium modification of the pipi interaction in the I=J=0 channel. The data are compared to pi-induced measurements and to calculations within a chiral-unitary approach.

The reaction gammap-->pi0gamma'p and the magnetic dipole moment of the Delta+ 1232 resonance.

The reaction gammap-->pi(0)gamma'p has been measured with the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI for energies between sqrt[s]=1221-1331 MeV. The cross section's differential in angle and energy have been determined for the photon gamma' in three bins of the excitation energy. This reaction channel provides access to the magnetic dipole moment of the Delta(+)(1232) resonance and, for the first time, a value of mu(Delta(+))=[2.7(+1.0)(-1.3)(stat)+/-1.5(syst)+/-3(theor)]mu(N) has been extracted.

Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances.

OBJECTIVES: We sought to investigate the impact of six months of cardiac resynchronization therapy (CRT) on echocardiographic variables of left ventricular (LV) function. BACKGROUND: Cardiac resynchronization therapy has recently been introduced as a new therapeutic modality in patients with advanced heart failure (HF) and conduction abnormalities. However, most studies have only investigated the early hemodynamic effects of CRT. METHODS: Twenty-five patients (12 women and 13 men; 59.8 +/- 5.1 years old) with advanced HF caused by ischemic (n = 7) or idiopathic dilated cardiomyopathy (n = 18) and a prolonged QRS complex were analyzed. All patients underwent early hemodynamic testing with a randomized testing protocol; echocardiographic measurements were compared before implantation and after six months of CRT. RESULTS: Left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD, respectively) were significantly reduced after six months (LVEDD from 71 +/- 10 to 68 +/- 11 mm, p = 0.027; LVESD from 63 +/- 11 to 58 +/- 11 mm, p = 0.007), as were LV end-diastolic and end-systolic volumes (LVEDV from 253 +/- 83 to 227 +/- 112 ml, p = 0.017; LVESV from 202 +/- 79 to 174 +/- 101 ml, p = 0.009). Ejection fraction was significantly increased (from 22 +/- 7% to 26 +/- 9%, p = 0.03). "Nonresponders," with regard to LV volume reduction, had significantly higher baseline LVEDV, compared with "responders" (351 +/- 52 vs. 234 +/- 74 ml, p = 0.018). Overall, there was only mild mitral regurgitation at baseline, with a minor reduction by semiquantitative analysis. The results of early hemodynamic testing did not predict the volume response. CONCLUSIONS: Cardiac resynchronization therapy may lead to a reduction in LV volumes in patients with advanced HF and conduction disturbances. Volume nonresponders have significantly higher baseline LVEDV.

Stimulation of the left ventricle through the coronary sinus with a newly developed 'over the wire' lead system--early experiences with lead handling and positioning.

AIMS: This report describes the initial clinical results with a newly designed guiding catheter and an 'over the wire' pacing lead based on angiolasty technology to stimulate the left ventricle using the transvenous route via the coronary sinus (OTW-CV lead). METHODS AND RESULTS: In 75% of the 15 patients (6 males, 9 females, mean age of 53 +/- 9 years) with congestive heart failure, access to coronary sinus required less than 2 min; in one patient. the attempt failed. Mean R wave amplitudes plus or minus the standard deviation, measured at apical, mid-ventricular and basal positions the anterior (11.4 +/- 9.2, 10.8 +/- 6.2, 9.3 +/- 6.3 mV) and lateral or posterior veins (10.1 +/- 10.7, 8.6 +/- 6.4, 7.7 +/- 4.3 mV) showed a trend favouring the apex without statistical significance. Pacing impedance, measured at the same sites and vein tributaries, ranged from 670 +/- 191 to 915 +/- 145 ohms. Pacing thresholds measured at apical and mid ventricular sites were significantly lower than at the base in the anterior vein 2.5 +/- 2.8 and 2.8 +/- 1.8 vs 5.6 +/- 2.7 V at 0.5 ms, P<0.001). Thresholds in the lateral/posterior veins showed a similar trend but did not reach statistical significance (3.0 +/- 1.7, 3.6 +/- 1.4 +/- 1.8 V at 0.5 ms). In patients, in whom thresholds were determined in more than one vein, the 'best' mean threshold was 1.6 +/- 0.7 V. CONCLUSION: The new 'over the wire' lead and guiding catheter system allows uncomplicated access to the coronary sinus and the depth of the coronary vein tributaries. Left ventricular sensing and pacing thresholds are acceptable for chronic use in implanted cardiac rhythm management systems.

Testing the reverse transcriptase model of somatic mutation.

Somatic hypermutation of the variable (V) regions of rearranged immunoglobulin genes leads to antibody affinity maturation. Although this process has been extensively studied, the mechanisms responsible for these multiple point mutations are still elusive. One mechanism that was proposed over 10 years ago by Steele and Pollard was that an intrinsic reverse transcriptase (RT) copies the nascent mRNA creating the large number of observed point mutations due to its high error rate. A cDNA copy of the mutated V region would then replace the endogenous DNA through a gene conversion-like event, thus integrating these point mutations into the genome. This model of hypermutation would account for the very high mutation rate, the presence of hotspots, strand bias, the requirement for transcription and localization of mutation within the immunoglobulin V region. Using AZT and ddC to inhibit endogenous RTs, we have assayed for somatic mutation using a murine in vivo model. Somatic mutation occurred at similar frequencies and with the same characteristics with or without treatment of RT inhibitors, suggesting that standard reverse transcription is not required for antibody V region hypermutation in the mouse.