Fertility clinics have a duty of care towards patients who do not have children with treatment.

In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients' hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize 'success' and 'failure' in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop 'plan(s) B', to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.

Human in vitro spermatogenesis from pluripotent stem cells: in need of a stepwise differentiation protocol?

Recently, complete in vitro generation of male gametes starting from pluripotent stem cells was obtained in a mouse model with live offspring as a result. This breakthrough was probably due to the use of a stepwise differentiation protocol taking the tightly regulated in vivo situation into account. As shown previously, factors of the TGFß superfamily, metabolites of vitamin A, growth hormones, sex steroids and, most importantly, somatic cell support are major regulators of the development, survival, proliferation and differentiation of male gametes. However, up till now, all differentiation protocols starting from human pluripotent stem cells only focused on one or two of these substantive factors, not taking any timeframe into account, leading to promising but unsatisfying results with low efficiency. Therefore, progress might be achieved by including a stepwise differentiation protocol, including all proven contributing regulators, and therefore mimicking more closely human in vivo spermatogenesis and its temporo-spatial organization. In this review, the indispensable regulators of in vivo spermatogenesis and the outcomes of related human in vitro studies are discussed with the aim of unravelling the most successful combinations of medium factors to be used in future differentiation protocols.

The role of the reprogramming method and pluripotency state in gamete differentiation from patient-specific human pluripotent stem cells.

The derivation of gametes from patient-specific pluripotent stem cells may provide new perspectives for genetic parenthood for patients currently facing sterility. We use current data to assess the gamete differentiation potential of patient-specific pluripotent stem cells and to determine which reprogramming strategy holds the greatest promise for future clinical applications. First, we compare the two best established somatic cell reprogramming strategies: the production of induced pluripotent stem cells (iPSC) and somatic cell nuclear transfer followed by embryonic stem cell derivation (SCNT-ESC). Recent reports have indicated that these stem cells, though displaying a similar pluripotency potential, show important differences at the epigenomic level, which may have repercussions on their applicability. By comparing data on the genetic and epigenetic stability of these cell types during derivation and in-vitro culture, we assess the reprogramming efficiency of both technologies and possible effects on the subsequent differentiation potential of these cells. Moreover, we discuss possible implications of mitochondrial heteroplasmy. We also address the ethical aspects of both cell types, as well as the safety considerations associated with clinical applications using these cells, e.g. the known genomic instability of human PSCs during long-term culture. Secondly, we discuss the role of the stem cell pluripotency state in germ cell differentiation. In mice, success in germ cell development from pluripotent stem cells could only be achieved when starting from a naive state of pluripotency. It remains to be investigated if the naive state is also crucial for germ cell differentiation in human cells and to what extent human naive pluripotency resembles the naive state in mouse.

First Robinsoniella peoriensis aortic cross homograft mycotic pseudoaneurysm: A case report and review of the literature.

Mycotic aortic aneurysm is a rare and challenging complication of aortic homografts caused by an infection and is associated with high morbidity and mortality. We report the first case of an aortic cross homograft mycotic pseudoaneurysm caused by Robinsoniella peoriensis in a 70-year-old man. Our patient underwent surgery for a recurrence of aortic cross mycotic pseudoaneurysm at the level of the aortic homograft he had had 7 years before. A clot-removal of the pseudoaneurysm was surgically carried out and the homograft was completely removed. Anaerobic culture from tissue samples yielded pure growth of a spore-forming Gram-positive rod, identified later as Robinsoniella peoriensis by 16S rRNA gene sequencing. The patient was then discharged with oral clindamycin according to the in vitro susceptibility testing. Identification of R. peoriensis might be challenging in clinical laboratories with no access to molecular methods.

Stimulating fertility awareness: the importance of getting the language right.

While education about fertility is not intrinsically controversial, finding the right language to communicate the topic can be challenging, as there are several risks of unintended negative effects such as dissonance, anxiety, culpability, and stigma due to social norming. In this article, we share some of our learnings from promoting fertility awareness in the hope that they will inspire further debate and research on this topic. Starting from the ethical principles of respect for reproductive autonomy, avoiding harm (in terms of stigma or anxiety) and inclusivity, we have formulated five recommendations: (i) frame fertility awareness messages with (reproductive) autonomy in mind and aim to be inclusive of those who do not represent the traditional nuclear family; (ii) be empathetic and steer clear of blame; (iii) avoid scaremongering and offer a positive angle; (iv) give due consideration to both women and men in fertility health messaging; and (v) tailor the messages to particular contexts and audiences and develop resources in close collaboration with the target groups.

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Recent developments in genetics and medically-assisted reproduction: from research to clinical applications†‡.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

The quantitative determination of metabolites of 6-mercaptopurine in biological materials. VII. Chemical synthesis by phosphorylation of 6-thioguanosine 5'-monophosphate, 5'-diphosphate and 5'-triphosphate, and their purification and identification by reversed-phase/ion-pair high-performance liquid chromatography and by various enzymatic assays.

A fast and reliable two-step method has been established for the chemical synthesis of 6-thioguanosine 5'-monophosphate, 6-thioguanosine 5'-diphosphate and 6-thioguanosine 5'-triphosphate starting from the ribonucleoside. In the first step, 6-thioguanosine dissolved in triethyl phosphate, at high yield reacts with phosphorus oxide trichloride to 6-thioguanosine 5'-monophosphate which is purified by anion-exchange chromatography on DEAE-Sephadex using a step gradient of hydrochloric acid. In the second step, 6-thioguanosine 5'-monophosphate dissolved in water, reacts with phosphoric acid in the presence of pyridine/dicyclohexyl carbodiimide and is converted to 6-thioguanosine 5'-diphosphate and 6-thioguanosine 5'-triphosphate which are separated from each other and from the 6-thioguanosine 5'-monophosphate by anion-exchange chromatography on DEAE-Sephadex using a gradient of ammonium bicarbonate. Material from each step of the preparation procedure is separated by reversed-phase HPLC chromatography and analyzed for its free ribonucleoside content, 5'-monophosphate, 5'-diphosphate, 5'-triphosphate and small amounts of unidentified phosphorylated compounds. The purity of the final preparations and the identity of each 6-thioguanosine 5'-phosphate are proven by highly specific enzymatic peak-shifting/HPLC analyses using alkaline phosphatase, 5'-nucleotidase, pyruvate kinase, nucleoside diphosphate kinase and combined hexokinase/glucose 6-phosphate dehydrogenase.

Assessment of hibernating myocardium by dobutamine stimulation in a canine model.

OBJECTIVES: The purpose of this study was to 1) develop an animal model of hibernating myocardium, and 2) evaluate the ability of dobutamine stimulation to detect hibernating myocardium using both qualitative and quantitative assessment of regional myocardial function. BACKGROUND: Left ventricular dysfunction may be due to chronic ischemia with or without myocardial infarction and may improve after coronary blood flow is enhanced by revascularization procedures. This condition has been coined "hibernating myocardium" and variably defined in recent years. The results of recent clinical studies suggest that dobutamine echocardiography may be useful for detecting viable myocardium in patients with left ventricular dysfunction. METHODS: Twenty-one dogs underwent initial operation. Sonomicrometer crystals were implanted, and baseline measurements of segment shortening and wall thickening (by echocardiography) were made. A coronary artery was ligated; the chest was closed; and measurements were repeated. Dobutamine was incrementally infused with determination of wall thickening and segment shortening at baseline and on days 3 and 7 and weeks 2 and 4 after coronary artery occlusion. Finally, the chest was reopened; the ligated vessel was bypassed; and measurements were repeated. RESULTS: Of the 10 dogs that completed the entire protocol, 7 had varying degrees of nontransmural myocardial infarction (group 1), and 3 had complete transmural myocardial infarction (group 2). In group 1, baseline function was significantly impaired compared with preligation function but increased during dobutamine infusion. When reperfused after 4 weeks, both wall thickening and segment shortening increased significantly. In group 2, significant changes were not seen during the dobutamine studies or after reperfusion. Myocardial perfusion during dobutamine infusion increased in group 1 but did not change in group 2. CONCLUSIONS: We demonstrated improvement in chronically dysfunctional myocardium after restoration of previously interrupted myocardial blood flow in dogs after nontransmural myocardial infarction, thus validating a canine model of hibernating myocardium. As assessed by two independent methods, dobutamine infusion identified hibernating myocardium in an animal model.

Exercise echocardiography for the evaluation of patients after nonsurgical coronary artery revascularization.

OBJECTIVES: The purpose of this study was to demonstrate the accuracy of stress echocardiography for detecting the progression of coronary artery disease after nonsurgical revascularization. BACKGROUND: The expanding role of nonsurgical coronary revascularization procedures mandates the development of sensitive noninvasive techniques for the detection of recurrent ischemia. METHODS: Bicycle stress echocardiography was performed in a series of 86 patients 6.5 +/- 1.3 months after a revascularization procedure. Seven patients were excluded from analysis because of poor echocardiographic image quality. RESULTS: Digital analysis achieved a sensitivity of 83% for the entire group and a specificity of 85% for stress echocardiographic detection of significant coronary artery disease. Sensitivity was greater in patients with (88%) than in those without (75%) prior myocardial infarction, but this difference did not reach statistical significance. Additional analysis using an increase in end-systolic volume index or a decrease in ejection fraction during stress as an additional marker for ischemia tended to enhance sensitivity (90% for the entire group and 93% for the subgroup with prior myocardial infarction). CONCLUSIONS: Stress echocardiography is a useful and sensitive method for the follow-up of patients undergoing nonsurgical revascularization procedures. The addition of volume determination to routine wall motion analysis may be helpful in patients with prior infarction who have scar tissue that may be difficult to distinguish from an adjacent exercise-induced wall motion abnormality.

Local versus systemic adjunctive antibiotic therapy in 28 patients with generalized aggressive periodontitis.

BACKGROUND: Although the use of systemic antibiotics has been studied in patients with generalized aggressive periodontitis (formerly rapidly progressive periodontitis), the use of adjunctive tetracycline fibers in these patients has not been reported. The purpose of the present study was to compare the clinical response of local versus systemic antibiotic treatment as adjuncts to scaling and root planing in patients with GAgP. METHODS: After initial therapy and full-mouth scaling and root planing (SRP), 30 patients were randomly assigned to 1 of 2 antibiotic treatment groups. Probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded with an automated probe prior to SRP at baseline (BL) and 15, 30, 41, and 54 weeks later. Three months after SRP, the patients were treated with amoxicillin/clavulanic acid (500 mg tid; SRP + AUG group) or with local tetracycline fiber in pockets with PD > or =5 mm (SRP + TCF group). RESULTS: In both treatment groups, PD decreased significantly from BL to week 54 (6.2+/-1.5 mm to 4.7+/-1.4 mm for SRP + TCF and 6.5+/-1.4 mm to 4.2+/-0.6 mm for SRP + AUG). However, there was no statistically significant difference between the 2 groups in pocket reduction. Similarly, in both treatment groups, there were small but significant gains in CAL from BL to week 54 (12.0+/-1.8 mm to 11.3+/-1.8 mm for SRP + TCF and 12.3+/-1.5 mm to 11.2+/-1.2 mm for SRP + AUG). The difference in CAL gain between the 2 groups was not statistically significant. At the final examination, both groups showed significant PD reduction and CAL gain (P <0.001) compared to BL. The frequency and percentage of bleeding sites decreased significantly in both groups. At week 54, this decrease was significantly greater in the SRP + AUG group (31.67% for SRP + TCF versus 3.85% for SRP + AUG). CONCLUSIONS: These results indicate that the local delivery of tetracycline by a fiber or the systemic administration of amoxicillin/clavulanic acid given 3 months after scaling and root planing produced similar clinical outcomes over the 9-month observation period.

The portrayal of healthy women requesting oocyte cryo-preservation.

The possibility to cryopreserve oocytes to be used in IVF treatment later in life has not only enlarged the reproductive options of cancer patients who are faced with gonadotoxic treatments, but also holds the promise of enlarging the reproductive options of healthy women whose personal circumstances (most often the absence of a partner) do not allow them to reproduce in their most fertile years. Opinions for and against this application of the cryopreservation technology are often based on different portrayals of the women who might use it. Three different portrayals can be discerned in the debate about the ethics of so-called 'social egg freezing' or 'non medical egg freezing'. First, these women have been portrayed as selfish career-pursuing women. Second, healthy women who might benefit from oocyte cryopreservation have been portrayed as victims of a male-oriented society that makes it difficult for women to combine motherhood with a good education or professional responsibilities. Third, healthy women -opting to cryopreserve oocytes have been portrayed as wise, proactive women who will not have to depend on -oocyte donors should they suffer from age-related infertility by the time they are ready to reproduce. Each of these three portrayals has its own shortcomings that one should be wary of, as they lead to an oversimplification of the ethical debate.

Oocyte donation for stem cell research.

The future success of stem cell research by means of somatic cell nuclear transfer (SCNT) depends on a sufficient supply of human oocytes. However, oocyte donation presents certain risks for the donor, and concerns for women's welfare are rightly vocalized. At the same time, these risks are comparable with the risks faced by other healthy research subjects. Thus, research donation can withstand ethical scrutiny if it fulfils the same conditions as other research involving healthy human subjects. Specifically, this means that the benefits of the research project need to outweigh the harms, that risks must be minimized, that informed consent has to be guaranteed by averting undue inducement and the recruitment of vulnerable women and that donors can and should be reimbursed for their research participation.

[Reference values of global and regional myocardial function for stress echocardiography]. / Normalwerte der globalen und regionalen Myokardfunktion für die Belastungsechokardiographie.

Two-dimensional echocardiography has become a sensitive method to differentiate between normal and pathological myocardial function during exercise. Examining 50 healthy volunteers we determined normal values for global and regional left-ventricular function during bicycle exercise. Ejection fraction increased from 59 +/- 10% at rest to 85 +/- 7% at 210 watts workload, endsystolic volume decreased from 22.1 ml/m2 at rest to 7.1 ml/m2 at 210 watts. Enddiastolic volume showed a tendency to decrease from 55 +/- 21 ml/m2 at rest to 45 +/- 23 ml/m2 at 210 watts. Quantitative analysis showed an extended distribution both for Centerline- and Radiant-Method, during exercise Centerline-Method was superior. Two-dimensional echocardiography is useful for assessment of global and regional myocardial function during exercise. Decrease of ejection fraction or increase of endsystolic volume seems to be a pathological marker. Enddiastolic volume is a less useful parameter for evaluating left-ventricular function during stress. Quantitative analysis of left ventricular wall motion can be applied with restrictions.

[Resuscitation of a near-drowning patient by the use of a portable extracorporeal circulation device]. / Reanimation eines Beinah-Ertrunkenen mittels einer portablen extrakorporalen Zirkulation.

We report on a 21-year old patient who nearly drowned in cold water under inexplicable circumstances. About 1/2 hour later he was found with cardiac arrest. Immediate cardiopulmonary resuscitation remained unsuccessfully but was continued. After transportation to the nearest hospital a core temperature of 26.1 degrees C was recorded. A team of our hospital arrived 2 1/2 hours after start of cardiopulmonary resuscitation. After introducing a femo-femoral bypass the patient was rapidly rewarmed and oxygenated using a portable extracorporeal circulation and membrane oxygenation. Defibrillation succeeded at a core temperature of 34.4 degrees C. A severe ARDS developed the same day which was successfully treated by membrane oxygenation. 41 days later the patient left the hospital fully recovered.

[Stress echocardiography: a sensitive method in diagnosis of coronary heart disease]. / Belastungsechokardiographie: eine sensitive Methode in der Diagnostik der koronaren Herzkrankheit.

Prevalence of coronary artery disease requires sensitive diagnostic methods for screening and follow-up. The sensitivity of stress-ECG is low, 201-thallium scintigraphy is more sensitive but has the disadvantages of radiation and costs. Improved echocardiographic resolution with better identification of endocardial border as well as digital imaging technique have increased the interest in stress echocardiography as a diagnostic tool in coronary artery disease since a decade ago the clinical usefulness of stress echocardiography has been demonstrated. For stress echocardiography a semisupine bicycle position for continuous recording of echocardiographic images from the apical position in the two-chamber- and RAO-view was developed. Echocardiographic images were digitized with a frame rate of 30/s and stored on optical discs with a storage capacity of 1 Gbyte. Rest and exercise images were analysed simultaneously for newly-occurring wall motion abnormalities or deterioration of already present hypokinesia or extension of existing wall motion abnormalities. Segmental wall motion was scored according to the scheme in Figure 2. In addition end-diastolic, end-systolic volume, and ejection fraction were calculated. In a patient population of 150, 30 female and 120 male, age 56.6 +/- 8.3 years, we could confirm the results reported by other working groups and demonstrate a high sensitivity in the diagnosis of single vessel disease. Our technique with the patient cycling in semi-supine position allows continuous echocardiographic registration during exercise and offers adequate image quality. The mean workload at peak stress was 127 +/- 30 watts, the maximal heart rate 137 +/- 18 bpm. Digital cine-loop imaging allowed evaluation of the examinations in about 90% of the cases. The sensitivity in the whole study group was 87%, the specificity 80%. Under full antianginal medication, 43% of the patients developed angina pectoris during exercise and 58% had a positive stress-ECG. The sensitivity in single-vessel coronary artery disease was 93% for the left anterior descending, 80% for the left circumflex, and 83% for the right coronary artery. These results in single-vessel disease were superior compared to findings of other authors using different techniques of stress echocardiography. In addition to the qualitative analysis, quantitative measurement of end-systolic volume and ejection fraction seems to be important. We found a significantly more pronounced decrease of ejection fraction at peak exercise in patients with multivessel disease compared to those with single-vessel disease. In single-vessel disease ejection fraction was 61 +/- 12% at rest and 57 +/- 17% during exercise, this difference was not significant.(ABSTRACT TRUNCATED AT 400 WORDS)

[Left ventricular inflow behavior in dual chamber stimulation with differential atrioventricular conduction: an echocardiography study]. / Linksventrikuläres Einstromverhalten unter Zweikammerstimulation mit unterschiedlicher AV-Uberleitung: Eine echokardiographische Untersuchung.

The influence of the AV interval on early passive (E) and late active diastolic filling (A) during transmitral flow was analyzed in patients with AV sequential pacing. In 16 patients with dual-chamber pacemakers at the age of 25 to 76 years CW- and color Doppler echocardiography was used to determine inflow time (t), flow velocity (Vmax), the E/A ratio, the time-velocity integral (TVI), and the inflow jet at constant AV sequential pacing (80 bpm) with various AV interval settings (50-100-150-200-250 ms). The inflow pattern was compared to findings in 16 normals (age 26 +/- 7 years). The prolongation of the AV interval from 50 to 250 ms resulted in the following changes: 1) Decrease of tE: 220 +/- 30 ms to 170 +/- 40 ms (p less than 0.05), of VmaxE: 78 +/- 12 to 68 +/- 14 cm/s) (ns) and of TVI-E: 8.5 +/- 2.1 to 5.6 +/- 1.7 cm (p less than 0.001); 2) Increase of tA: 140 +/- 30 to 270 +/- 60 ms (p less than 0.001), of VmaxA: 48 +/- 18 to 73 +/- 24 cm/s (p less than 0.001) and of TVI-A: 2.4 +/- 1.1 to 6.1 +/- 2.9 cm (p less than 0.001); 3) Decrease of the E/A ratio from 1.6 +/- 05 to 0.85 +/- 02. Longer AV intervals shortened the total diastolic filling period and produced more diastolic aliasing without change of the relative diastolic inflow jet. The AV interval of 150 ms was associated with an abnormal high atrial component of transmitral inflow, as found with abnormal diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ultra-high dosage streptokinase lysis in dysfunction of a St. Jude aortic prosthesis]. / Ultrahochdosierte Streptokinase-Lyse bei Dysfunktion einer St.-Jude-Aortenprothese.

HISTORY AND CLINICAL FINDINGS: A 64-year-old man was hospitalised because of progressively worsening dyspnoea over the preceding few months. Three years previously he had undergone aortic valve replacement (St. Jude Medical bileaflet valve) for severe aortic stenosis and some regurgitation. He was much improved postoperatively and one year after the operation echocardiography demonstrated a well functioning prosthetic valve and a transvalvar pressure gradient (by Doppler echocardiography) of 28 mm Hg. On admission the patient reported to have stopped phenprocoumon 9 months before admission. The patient was in cardiac failure, grade III (NYHA classification). On auscultation there was a 4/6 crescendo-decrescendo systolic murmur and a 2/6 early diastolic decrescendo murmur maximal over the second right ICS. INVESTIGATIONS: Echocardiography confirmed the suspected diagnosis of dysfunction of the prosthetic valve, one leaflet being immobile, with severe outflow obstruction (peak transvalvar pressure gradient 101 mm Hg) combined with severe regurgitation. At fluoroscopy one leaflet moved normally, the other one being fixed between opening and closing positions. TREATMENT AND COURSE: As thrombosis was the most likely cause of the prosthetic valve dysfunction, thrombolysis treatment was started. After administration of 9 mill. IU streptokinase both leaflets showed normal movement. The peak transvalvar gradient (by echocardiography) was now 40 mm Hg and there was only slight regurgitation. No complications were noted. After oral anticoagulation for 6 months the prosthetic valve was functioning normally with unchanged movement pattern of both leaflets. CONCLUSION: Thrombolysis may be successful in thrombotic dysfunction of a prosthetic valve. If there are no contraindications, this form of treatment should be tried before reoperation is undertaken.

Dynamic stress echocardiography for evaluating anti-ischemic drug profiles in post-MI patients.

Exercise ECG is an established method of evaluating the anti-ischemic properties of drugs. However, there are considerable methodologic limitations to this procedure and its use is restricted to patients with exercise-provoked ECG alterations which can be interpreted as ischemia. The principal, earlier onset of wall motion abnormalities according to the ischemic cascade can be detected by stress echocardiography and might be utilized as a pharmacological stress testing modality. Sixteen consecutive patients (15 men, one woman; 53 +/- 9 years old) with angiographically proven coronary artery disease (8 with one-, 5 with two-, and 3 with three-vessel disease) and exercise-induced wall motion abnormalities were examined by dynamic stress echocardiography (50 watt followed by 20-watt increases/min). Anti-ischemic drugs were withdrawn prior to and on day 1; on the following day 2, 0.2 microgram/kg/min nisoldipine was infused intravenously during the test after a 3 micrograms/kg bolus was given. At maximum comparable workload 15/16 patients showed an improved wall motion score on treatment (day 1: 22.9 +/- 4.9 vs day 2: 20.0 +/- 3.9; normal score: 12; one-sided binomial test: p = 0.0003). Eight of 16 patients demonstrated ST-segment deviations on day 1 and day 2. The double product did not differ at any workload stage until the maximum of 130 watt (day 1: 14,101 +/- 3140 vs day 2: 13,365 +/- 2865; n.s.). Dynamic stress echocardiography seems to be a valuable tool in pharmacologic stress testing and in terms of accuracy is supposed to be superior to conventional exercise ECG. Nisoldipine reduces exercise-induced wall motion abnormalities in patients with and without exercise-induced ECG alterations. The data result from a controlled pilot study, and further studies are required to confirm these promising methodological and therapeutic findings.

Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients.

BACKGROUND: The use of dobutamine stress echocardiography for the evaluation of coronary artery disease is rapidly expanding. New applications of the technique are being investigated in a wide variety of patients including those with advanced coronary artery disease. Despite its widespread use, the safety of dobutamine stress echocardiography has not been sufficiently documented. METHODS AND RESULTS: A consecutive series of 1118 patients undergoing dobutamine stress echocardiography for evaluation of known or suspected coronary artery disease form the basis of this report. Dobutamine stress testing was performed for evaluation of chest pain, risk assessment before noncardiac surgery, after recent myocardial infarction, or as a part of ongoing research protocols. Over the study period, the maximal dose of dobutamine used was increased from 30 to 50 micrograms/kg per minute, and atropine was used in 420 (37%) patients. There were no occurrences of death, myocardial infarction, or episodes of sustained ventricular tachycardia as a result of dobutamine stress testing. The major reasons for test termination were achievement of target heart rate in 583 patients (52.1%), maximum dose in 255 (22.8%), and angina pectoris in 142 (13%). The test was terminated in 36 (3%) patients because of noncardiac side effects including nausea, anxiety, headache, tremor, and urgency. Angina pectoris occurred in 216 (19.3%) patients. Sublingual nitroglycerin, a short-acting beta-blocker, or both types of medication were administered in 80 of these patients for relief of angina pectoris. None required intravenous nitroglycerin. A total of 736 (65%) patients had stable sinus rhythm throughout the test. The most common arrhythmias were frequent premature ventricular complexes (six or more per minute) in 172 patients (15%), and frequent premature atrial complexes in 86 (8%). There were 40 patients with nonsustained ventricular tachycardia. None had symptoms associated with the tachycardia, and only one received specific pharmacological treatment to prevent recurrence of the arrhythmia after the test was terminated. The patients who were evaluated after recent myocardial infarction and those who received atropine did not have a higher frequency of ventricular tachycardia compared with those without recent infarction and those not receiving atropine. CONCLUSIONS: Dobutamine stress echocardiography was safely performed using supplemental atropine and an aggressive dosing protocol. Noncardiac side effects were usually minor. Arrhythmias were well tolerated and rarely required treatment. In this study, serious complications from myocardial ischemia did not occur. Symptomatic ischemia was effectively treated with test termination, sublingual nitroglycerin, or short-acting beta-blockers.