Dobutamine stress echocardiography for detection and assessment of coronary artery disease.

Stress echocardiography with dobutamine infusion for detection of coronary artery disease is a potential alternative to exercise stress testing with some theoretic advantages. Fifty patients who were not receiving cardioactive medication were prospectively studied with two-dimensional echocardiography and 12-lead electrocardiography (ECG) during incremental dobutamine infusion (5, 10, 15 and 20 micrograms/kg body weight per min, each dose for 8 min). Images were analyzed by using an 11-segment left ventricular model. All patients underwent correlative exercise ECG and coronary angiography, which revealed normal coronary arteries in 14 and significant disease (greater than or equal to 70% diameter stenosis) in 36. Peak rate-pressure product during dobutamine infusion was 18,845 +/- 4,156 versus 23,740 +/- 6,158 mm Hg/min on exercise (p less than 0.01). Interobserver concordance for wall motion analysis was good (kappa coefficient = 0.77). The use of baseline (n = 14) or reversible (n = 24) regional asynergy to define an abnormal dobutamine echocardiogram resulted in a sensitivity for detecting coronary artery disease of 78% and a specificity of 93%. Corresponding data for the dobutamine ECG were 47% and 71% and for the exercise ECG were 72% and 71%, respectively. The development of new mitral regurgitation on Doppler color flow imaging (n = 4) improved sensitivity to 81% without loss of specificity. Inducible asynergy or new mitral regurgitation was observed in 6 (50%) of 12 patients with single-, 6 (60%) of 10 with double- and 12 (86%) of 14 with triple-vessel disease. The site of transient asynergy provided additional localizing information. Exercise duration and time to diagnostic ST segment shift were shorter in patients with coronary artery disease with versus those without echocardiographic evidence of ischemia (both p less than 0.05). Side effects during dobutamine infusion were mild and short-lived. Dobutamine stress echocardiography is well tolerated, is useful for detection and assessment of coronary artery disease and is applicable to patients unable to exercise.     

Relation of left ventricular function and prognosis in hypertrophic cardiomyopathy: an angiographic study

Left ventricular cineangiograms performed at the time of diagnosis in 88 patients with hypertrophic cardiomyopathy were digitized to evaluate the relation of left ventricular function and prognosis in hypertrophic cardiomyopathy. Eleven patients died suddenly after a mean follow-up period of 7.5 +/- 7 years, 10 patients died of congestive heart failure or after cardiac surgery and 67 were alive after a mean follow-up period of 8.6 +/- 4 years. Measurements of left ventricular volume, ejection fraction, peak rate of ejection and filling and time to peak rate of ejection and filling were derived from curves of ventricular volume and its rate of change during the cardiac cycle. Patients who died suddenly had a lower peak rate of ventricular ejection (stroke volume-normalized peak ejection rate 5.41 +/- 0.69 versus 6.24 +/- 1.33 s-1; p = 0.006) and lower peak rate of ventricular filling (end-diastolic volume-normalized peak filling rate 4.02 +/- 0.94 versus 4.88 +/- 1.53 s-1; p = 0.02) and stroke volume-normalized peak filling rate (4.75 +/- 1.08 versus 5.82 +/- 1.70 s-1; p = 0.01) compared with survivors. Stepwise regression analysis revealed that sudden death was best predicted by the combination of increased end-diastolic volume, small end-systolic volume and low peak filling rate (predictive accuracy 32%, false negative 18% and false positive 28%). The addition of clinical features and hemodynamic measurements to the analysis improved predictive accuracy to 43% (false negative 18% and false positive 18%). Ambulatory electrocardiographic monitoring performed in 57 of the 88 patients 1 month to 17 years (median 8 years) after diagnosis revealed ventricular tachycardia in 14 (25%). Of these, 10 who survived had hyperkinetic systolic function at diagnosis, whereas the 4 who died suddenly had impaired systolic function (end-diastolic volume-normalized peak ejection rate 5.93 +/- 1.2 versus 4.01 +/- 1.2 s-1, respectively; p = 0.04). In hypertrophic cardiomyopathy, ventricular tachycardia is a sensitive but nonspecific marker of adults who are at risk of sudden death. Impaired systolic function may be an important determinant of which patients with ventricular tachycardia die suddenly. This study shows that indexes of ventricular function contribute to the identification of patients at particular risk of sudden death. However, the predictive power of the clinical features and hemodynamic and angiographic measurements that could be assessed was poor.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pregnancy in patients after valve replacement.

This report is based on information obtained from a questionnaire sent to major cardiac centres in the United Kingdom. This produced details of 39 pregnancies in 34 patients after valve replacement. The 39 pregnancies gave rise to 30 healthy babies. The small size of the series probably reflects both the increasing rarity of young women with rheumatic heart disease in this country and the cautious attitude of their cardiologists. This makes it likely that these women represented the best end of the spectrum of cardiac function after valve replacement. Twenty-four pregnancies in 20 women who were not given anticoagulants producted 23 healthy babies and 1 spontaneous abortion. This group comprised 6 patients with free aortic homografts, 1 patient with a fascia lata mitral valve, 1 with a Beall tricuspid prosthesis, 1 with a combined mitral homograft and Starr Edwards aortic prosthesis, and 1 with mitral and aortic frame-mounted fascia lata valves. There were no maternal deaths or thromboembolic complications in this group which included 5 patients who were in atrial fibrillation. Fifteen pregnancies in 14 women who received anticoagulants gave rise to 7 healthy babies. The fetal losses were one stillbirth, one intrauterine death at 34 weeks, and 3 spontaneous abortions; one surviving child has hydrocephalus as a result of blood clot and there were 2 maternal deaths. This group included 13 patients with Starr Edwards valves, 11 mitral and 2 aortic. A patient with a Hammersmith mitral valve was the only one to have been treated with heparin and her valve thrombosed. One patient with a mounted mitral homograft had a cerebral embolus. Nine of these patients were in atrial fibrillation. In 3 additional patients the valve replacement was carried out during pregnancy. Two of the patients survived operation. In one of these who was treated with warfarin the pregnancy well, but there is an increased fetal wastage in patients pregnancy gave rise to a congenitally malformed baby who died in the neonatal period. The baby born to the mother who did not receive anticoagulants has a hare-lip and talipes. Women with artificial valves can tolerate the haemodynamic load of pregnancy well, but there is an increased fetal wastage in patients taking oral anticoagulants. This is probably largely attributable to fetal haemorrhage but there is also a risk of malformation caused by a teratogenic effect of warfarin. Experience gained in non-pregnant patients suggests that withholding anticoagulatns in pregnant patients with prosthetic valves would usually be undersirable but warfarin should be avoided. The advantages of biological valves were apparent in this series.     

Outcome of pregnancy in women with valve prostheses.

OBJECTIVE--To study the outcome of pregnancy in women with artificial heart valves treated in major European centres, and to compare the safety and efficacy of different anticoagulant regimens and of mechanical and bioprosthetic valves. DESIGN--Retrospective study. METHOD--The information was obtained by questionnaire sent to all major cardiac centres in Europe sending one cardiologist from each centre a covering letter suggesting that the questionnaire be handed on where appropriate to the most relevant colleague. RESULTS--214 pregnancies were reported in 182 women; 151 pregnancies in 133 women with mechanical valves, and 63 pregnancies in 45 women with bioprostheses. Most women were in New York Heart Association class I or II and in sinus rhythm. 150 women with mechanical valves and 11 (17%) with bioprostheses received anticoagulants during pregnancy. One patient with an aortic valve prosthesis refused to take anticoagulants. Including the spontaneous abortions reported as well as the therapeutic abortions 83% of the pregnancies in women with bioprostheses and 73% in those with mechanical valves resulted in a healthy baby, full term or premature, who did well (NS). The incidence of stillbirths (3% and 6%) and of reported spontaneous abortions are excluded (because they are unlikely to have been fully reported), the success rate was 91% for women with bioprosthetic valves and 84% for women with mechanical valves (NS). 114 (53%) of the women had taken warfarin for some part of the pregnancy (46 (40%) of these during the first trimester) but there were no embryopathies. There were 13 valve thromboses (four fatal), eight embolic events (two fatal), and seven bleeds in women with mechanical valves. Most of these complications occurred with heparin but fatal aortic valve thrombosis occurred in the one woman who refused anticoagulant treatment out of the 151 women with mechanical valves. There were no maternal deaths in the bioprosthesis group but in 17/49 (35%) of these valves functional deterioration led to urgent replacement during pregnancy (two) or soon after. CONCLUSIONS--The outcome of pregnancy was similar for women with mechanical valves or bioprostheses. Warfarin treatment was safe and effective and was not associated with embryopathy. Heparin treatment was associated with more thromboembolic complications and more bleeding complications. Bioprostheses deteriorate rapidly during pregnancy.     

Genesis of arrhythmias in the failing heart and therapeutic implications

Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life.     

A comparison of parathyroid hormone‐related protein (1‐36) and parathyroid hormone (1‐34) on markers of bone turnover and bone density in postmenopausal women: The PrOP study

Parathyroid hormone‐related protein (PTHrP)(1‐36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1‐34). We performed a 3‐month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1‐36) to PTH(1‐34). Thirty‐five women were randomized to each of three groups: PTHrP(1‐36) 400 µg/day; PTHrP(1‐36) 600 µg/day; and PTH(1‐34) 20 µg/day. The primary outcome measures were changes in amino‐terminal telopeptides of procollagen 1 (PINP) and carboxy‐terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)₂ vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1‐34) (92%) (p < 0.005) was greater than for PTHrP(1‐36) (30%) (p < 0.05). PTH(1‐34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1‐36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1‐36) (p < 0.05) at the TH and for PTHrP(1‐36) 400 (p < 0.05) at the FN. PTHrP(1‐36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1‐36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1‐34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)₂D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1‐36) and PTH(1‐34) cause similar increases in LS BMD. PTHrP(1‐36) also increased hip BMD. PTH(1‐34) induced greater changes in bone turnover than PTHrP(1‐36). PTHrP(1‐36) was associated with mild transient hypercalcemia. Longer‐term studies using lower doses of PTHrP(1‐36) are needed to define both the optimal dose and full clinical benefits of PTHrP. © 2013 American Society for Bone and Mineral Research. © 2013 American Society for Bone and Mineral Research.     

The endangered clinical teacher-scholar: a promising update from one dental school

Clinical dental faculty members' lack of scholarly activity not only impacts their ability to be promoted and retained in their institutions but limits the contributions they could make to clinical discovery. Contributing factors to this situation include the lack of purposeful mentoring and the widespread faculty shortages, which increase faculty workloads. One way to address this challenge is to develop and implement formal mentoring programs, endorsed by the dental school's administration, that use reward structures in which novice clinical faculty members are teamed with faculty members experienced in scholarly activity. The Clinical Research Scholars Program at the University of Pittsburgh School of Dental Medicine has been in existence since 2008. Preliminary data from this program suggest that this has been a successful plan for increasing the scholarly activity of the clinical teacher-scholar. Although not without limitations, this program may serve as a model for other schools to consider as they encourage their own clinical faculty members to undertake research initiatives. Similar programs at dental schools across the country can enhance discovery, research, and treatment by expanding the number of researchers who are addressing the public's oral and systemic health needs.     

Venous thromboembolism in women undergoing pelvic reconstructive surgery with mechanical prophylaxis alone

Introduction and hypothesis

The objective of this study was determine the frequency of symptomatic perioperative venous thromboembolism (VTE) and risk factor(s) associated with VTE occurrence in women undergoing elective pelvic reconstructive surgery using only intermittent pneumatic compression (IPC) for VTE prophylaxis.

Methods

A multi-center case–cohort retrospective review was conducted at six clinical sites over a 66-month period. All sites utilize IPC as standard VTE prophylaxis for urogynecological surgery. VTE cases occurring during the same hospitalization and up to 6 weeks postoperatively were identified by ICD9 code query. Four controls were temporally matched to each case. Information collected included demographics, medical history, route of surgery, operative time, and intraoperative characteristics. Univariate and multivariate backward stepwise logistic regression analyses were performed to identify potential risk factors for VTE.

Results

Symptomatic perioperative VTE was diagnosed in 27 subjects from a cohort of 10,627 women who underwent elective urogynecological surgery (0.25 %). Univariate analysis identified surgical route (laparotomy vs others), type of surgery (“major” vs “minor”), history of gynecological cancer, surgery time, and patient age as risk factors for VTE (P?<?0.05). Multivariate analysis identified increased frequency of VTE with laparotomy, age?≥?70, and surgery duration?≥?5 h.

Conclusions

In our study cohort, the frequency of symptomatic perioperative VTE was low. Laparotomy, age?≥?70 years, and surgery duration?≥?5 h were associated with VTE occurrence.     

A Biomechanical Comparison of Three Different Posterior Fixation Constructs Used for C6–C7 Cervical Spine Immobilization: A Finite Element Study

The intralaminar screw construct has been recently introduced in C6–C7 fixation. The aim of the study is to compare the stability afforded by three different C7 posterior fixation techniques using a three-dimensional finite element model of a C6–C7 cervical spine motion segment. Finite element models representing three different cervical anchor types (C7 intralaminar screw, C7 lateral mass screw, and C7 pedicle screw) were developed. Range of motion (ROM) and maximum von Mises stresses in the vertebra for the three screw techniques were compared under pure moments in flexion, extension, lateral bending, and axial rotation. ROM for pedicle screw construct was less than the lateral mass screw construct and intralaminar screw construct in the three principal directions. The maximum von Misses stress was observed in the C7 vertebra around the pedicle in all the three screw constructs. Maximum von Mises stress in pedicle screw construct was less than the lateral mass screw construct and intralaminar screw construct in all loading modes. This study demonstrated that the pedicle screw fixation is the strongest instrumentation method for C6–C7 fixation. Pedicle screw fixation resulted in least stresses around the C7 pedicle-vertebral body complex. However, if pedicle fixation is not favorable, the laminar screw can be a better option compared to the lateral mass screw because the stress around the pedicle-vertebral body complex and ROM predicted for laminar screw construct was smaller than those of lateral mass screw construct.