Late Cardiac Complications of Sulfur Mustard Poisoning in 38 Iranian Veterans.

It was aimed to investigate possible late cardiac effects of Sulfur mustard (SM) exposure in Iranian veterans. Thirty-eight veterans with late complications of SM exposure were investigated. Clinical history, physical examinations, 12 leads electrocardiography and transthoracic echocardiography were performed. Computed tomography coronary angiography (CTCA) was performed as clinically indicated for angiographic assessment and patients were stratified according to the CTCA findings. Incomplete right bundle branch block and right axis deviation were detected in 3 (7.9%) and 4 (10.5%) cases, respectively. Mean value of left ventricular ejection fraction was 55.7 ± 2.9%. Different degrees of right ventricular dilation was observed in seven (18.4%) patients. All the patients showed mild to moderate degrees of tricuspid regurgitation. Increased pulmonary artery pressure (PAP) was detected in 16 (42.1%) patients. Out of 18 patients who underwent CTCA, non-obstructive and obstructive coronary artery disease (CAD) were observed in three (16.66%) and eight (44.44%) patients, respectively. CAD was stratified to single vessel (5.5%), two vessels (27.8%) and three vessels disease (11.1%). Mean coronary artery calcium score was 50.91 ± 115.58. SM has cardiovascular toxicity, as a delayed complication of this chemical warfare poisoning.

Cabergoline-induced fibrosis of prolactinomas: a neurosurgical perspective.

Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading to valvular insufficiency, necessitating surgical treatment of prolactinoma. Fibrosis of prolactinoma can be induced by prolonged medical treatment with bromocriptine, and this usually occurs after years of treatment. In comparison to bromocriptine, there have been no reports of cabergoline-induced fibrosis of prolactinoma. There is a potential for greater emphasis to be placed on assessing the tumour consistency from preoperative MRI scans, or even preoperative contrast-enhanced 3D Fast Imaging Employing Steady-state Acquisition imaging to allow better planning of the surgery. We report a rare case of fibrosis of prolactinoma after cabergoline treatment resulting in its subsequent difficult surgical removal. This patient had early MRI changes of fibrosis of prolactinoma after a short period of 6 months of cabergoline treatment.

Fetal ductus arteriosus constriction and closure: analysis of the causes and perinatal outcome related to 45 consecutive cases.

OBJECTIVE: The aim of this study was to analyze the causes and perinatal outcome related to fetal ductus arteriosus constriction or closure at a single center over a 26-year period. METHODS: This was a retrospective analysis of 45 consecutive cases of constriction (n = 41) and closure (n = 4) from 1987 through 2013. Patients were divided into Group A (maternal use of non-steroidal anti-inflammatory drugs (NSAID), n = 29), Group B (idiopathic, n = 8), and Group C (other drugs not previously described, n = 8). RESULTS: The median gestational age at diagnosis was 34 weeks (range, 27-38), mean systolic and diastolic velocity in the ductus arteriosus was 2.01 ± 0.66 m/s and 0.71 ± 0.46 m/s, respectively. Among the 29 cases of NSAIDs, 27.5% (8/29) have taken a single day use and 75% multiple days/doses. Right ventricular dilatation was present in 82.2% of the fetuses, tricuspid insufficiency in 86.6%, and heart failure in 22.2%. Neonatal persistent pulmonary hypertension occurred in 17.7% of the patients. Late follow-up showed all 43 survivors alive and healthy with only two deaths from unrelated causes. CONCLUSIONS: The results of this study indicate that clinically significant ductal constriction may follow maternal exposure to single doses of NSAIDs. Unknown causes or other new substances were also described, such as naphazoline, fluoxetine, isoxsuprine, caffeine and pesticides. Echocardiographic diagnosis of ductal constriction led to an active medical approach that resulted in low morbidity of this group of patients.

Impact of selective serotonin reuptake inhibitor therapy on heart valves in patients exposed to benfluorex: a multicentre study.

BACKGROUND: Given the association between valvular heart disease and drugs that alter serotonin metabolism, concerns have been raised about the possibility of an association between selective serotonin reuptake inhibitor (SSRI) use and drug-induced valvular disease. In France, SSRI use has been suggested to be an important confounding factor in the development of heart valve lesions in patients exposed to benfluorex in the context of the 'Médiator scandal'. AIMS: To address the relationship between SSRI use and valve regurgitation and morphology in a large cohort of patients exposed to benfluorex. METHODS: Overall, 832 consecutive patients exposed to benfluorex prospectively referred to 10 centres underwent complete echocardiography examinations according to a standardized protocol. Echocardiograms were independently and blindly read off-line by two experts. RESULTS: Ninety patients had been exposed to SSRIs for 3 months or more. The proportions of patients with no or trivial, mild, moderate or severe mitral regurgitation (MR) or aortic regurgitation (AR) were not different between SSRI patients and non-SSRI patients (P=0.63 and 0.58, respectively). The frequencies of AR ≥ mild (20 [22.2%] vs 145 [19.5%]; P=0.55) and MR ≥ mild (14 [15.6%] vs 118 [15.9%]; P=0.93) were similar in SSRI patients and non-SSRI patients. The frequencies of aortic and mitral valve abnormalities suggestive of drug-induced toxicity were also similar in the two patient groups. Multivariable logistic regression analysis confirmed the absence of any identifiable relationship between AR or MR and morphological abnormalities and SSRI use in the present cohort. CONCLUSION: Exposure to SSRIs was not associated with an increased risk of heart valve regurgitation or morphological abnormalities suggestive of drug-induced toxicity in this large cohort of patients exposed to benfluorex.

Cardiac surgery for ergotamine-induced multivalvular heart disease.

Ergotamine is used to abort or prevent vascular headache. Valvular heart disease as an adverse effect of long-term ergotamine therapy has been rarely reported in the English literature, with only a few cases published. It is hypothesized that ergot-derived agents stimulate serotonergic receptors (5-HT2B), causing proliferation of myofibroblasts, with subsequent thickening of valve leaflets and chords. This case presentation aims at increasing clinicians' awareness of this potential complication.

No evidence of a detrimental effect of cabergoline therapy on cardiac valves in patients with acromegaly.

CONTEXT: The effects of cabergoline on cardiac valves have been extensively studied in Parkinson's disease and hyperprolactinemia but not in acromegaly, a condition at risk of cardiac valve abnormalities. OBJECTIVE: We examined the prevalence and incidence of heart valve disease and regurgitation in a series of patients with acromegaly treated with cabergoline, by comparison with matched patients who had never received this drug. DESIGN AND SETTING: We conducted a cross-sectional and longitudinal study in a single referral center. PATIENTS AND METHODS: Forty-two patients who had received cabergoline at a median cumulative dose of 203 mg for a median of 35 months were compared to 46 patients with acromegaly who had never received cabergoline and who were matched for age, sex, and disease duration. A subgroup of patients receiving cabergoline (n = 26) was evaluated longitudinally before and during cabergoline treatment and compared to a group not receiving cabergoline and followed during the same period (n = 26). Two-dimensional and Doppler echocardiographic findings were reviewed by two cardiologists blinded to treatment. RESULTS: Demographic and clinical features were not significantly different between the groups. Compared to acromegalic controls, patients receiving cabergoline did not have a higher prevalence or incidence of valve abnormalities. A slightly higher prevalence of aortic valve regurgitation and remodeling was found in the controls relative to the cabergoline-treated patients (P < 0.02 and P < 0.03, respectively), but this was related to the presence of aortic dilatation. CONCLUSION: Cabergoline therapy is not associated with an increased risk of cardiac valve regurgitation or remodeling in acromegalic patients at the doses used in this study.

No clinically significant valvular regurgitation in long-term cabergoline treatment for prolactinoma.

BACKGROUND: An association between treatment for Parkinson's disease with certain dopaminergic drugs and development of cardiac valve impairment has been reported. Recent studies in hyperprolactinaemic patients treated with cabergoline (CAB) have shown either no significant findings or mild tricuspid regurgitation. OBJECTIVE: To determine the prevalence of cardiac valve dysfunction in patients with hyperprolactinaemic conditions chronically treated with CAB or bromocriptine (BR). DESIGN: Retrospective, multicentric, cross-sectional study of cases vs controls. PATIENTS: Eighty-three hyperprolactinaemic patients (15 men, 68 women aged 16·7-63 years; 64% microprolactinomas, 28% macroprolactinomas and 8% other etiologies) from three Spanish university hospitals chronically treated with BR (14-562·5 weeks, cumulative dose 5603 ± 7729 mg) or CAB (12-765 weeks, 217·4 ± 306·6 mg). MEASUREMENTS: Transthoracic echocardiographic assessment of valvular regurgitation and thickening, mitral valve tenting area and left-ventricular ejection fraction from 83 patients were compared with results from 58 age- and sex-matched controls and correlated with cumulative doses of dopaminergic drugs. RESULTS: No significant differences in valvular regurgitation, valve thickness or any other echocardiographic parameter were observed between controls and patients, except for 15 patients in the higher quartile of CAB cumulative dose (>180 mg), with increased prevalence of mild tricuspid regurgitation (6/15, 40% vs 8/58, 13·8%, P = 0·024; OR 4·1; 1·1-14·9). High BR cumulative dose was associated with no significant findings. CONCLUSIONS: No increased valvular involvement was found after long-term dopaminergic therapy for hyperprolactinaemia except for a significant increase in mild tricuspid regurgitation associated with high cumulative doses of CAB; BR seems spared from this adverse effect, although the low number of cases limits this analysis. Cumulative dose registry and long-term studies are warranted to definitely clarify this item.

Clinical features of the complete closure of the ductus arteriosus prenatally.

OBJECTIVE: Prenatal constriction of the ductus arteriosus associated with maternal drug ingestion was reported several decades ago. There are fewer reports of the complete closure of the ductus arteriosus; therefore, the clinical features of the latter are poorly understood. The aim of this study is to clarify the clinical features of complete ductal closure and postnatal pulmonary hypertension by performing echocardiography of the fetus. PATIENTS: We diagnosed four fetuses with complete ductal closure by performing fetal echocardiography and reviewed the prenatal and postnatal medical records of the mother and fetus. RESULTS: One mother each had bronchial asthma, ulcerative colitis, and idiopathic thrombocytopenic purpura, and they had received nonsteroidal anti-inflammatory drugs and/or corticosteroids during pregnancy. The fourth mother did not have basal disease and had not ingested any drugs. Fetal diagnosis was performed at 32-38 weeks of gestation. All fetuses had right heart dilatation with tricuspid regurgitation in the absence of any cardiac defects, and Doppler echocardiography indicated that the right ventricular pressure was elevated. Two of the fetuses had fetal hydrops, which suggested severe right heart dysfunction. All fetuses were delivered by emergent cesarean delivery. After birth, all the infants developed persistent pulmonary hypertension and required oxygen inhalation. Of these, three required mechanical ventilation, and two, nitric oxide inhalation. All infants improved within 2 weeks, and they had no neurological and cardiac complications after discharge. CONCLUSION: Right heart dilatation and severe tricuspid regurgitation in the absence of a cardiac defect in the fetus strongly suggested ductal dysfunction. Careful evaluation of ductal patency and right ventricular function can lead to precise early diagnosis and good prognosis.

Severe tricuspid regurgitation in a patient receiving low-dose cabergoline for the treatment of acromegaly.

Cabergoline, an ergot-derived dopamine receptor agonist, is used widely in the treatment of Parkinson's disease (PD) and hyperprolactinemia, but may cause heart valve fibrosis, retraction, and clinically significant regurgitation in PD patients. While cabergoline has been used at much lower doses in patients with hyperprolactinemia, controversy persists as to whether it may cause heart valve disease in this situation. Cabergoline is also used in acromegaly at doses similar to those used in hyperprolactinemia. The case is reported of a female patient with acromegaly who had been taking low-dose (0.5 mg/day) cabergoline for one year, and presented with signs and symptoms of right-sided heart failure. Echocardiography revealed a thickened and retracted tricuspid valve associated with severe tricuspid regurgitation and enlargement of the right-heart chambers. The morphology of the tricuspid valve was typical for cabergoline-related valvulopathy. Cabergoline may not be totally safe even at lower doses, and close echocardiographic monitoring is recommended in patients receiving cabergoline treatment, regardless of the dose level employed.

B-type natriuretic peptide and cardiovalvulopathy in Parkinson disease with dopamine agonist.

OBJECTIVE: To elucidate the usefulness of plasma B-type natriuretic peptide (BNP) values for evaluating adverse effects of pergolide or cabergoline on cardiovalvulopathy in patients with Parkinson disease. METHODS: Twenty-five patients treated with pergolide or cabergoline (ergot group) and 25 patients never treated with ergot derivatives (non-ergot group) were enrolled. Plasma BNP values and detailed echocardiography were evaluated. Thirty age- and gender-matched controls were similarly evaluated. RESULTS: Patients with regurgitation more than grade 3 were more frequent in the ergot group than in the non-ergot group as well as control groups (24%, 0%, 3%, p = 0.001). Both composite regurgitation scores and plasma BNP values were significantly higher in the ergot group than in controls. In the ergot group, the cumulative dose correlated to both tenting area (r = 0.57, p = 0.004) and tenting distance (r = 0.62, p = 0.001). Furthermore, plasma BNP values were higher in patients with severe or multiple regurgitation groups (p < 0.001), and were correlated with composite regurgitation score (r = 0.70, p < 0.001). Multiple regression analyses revealed that BNP values were independently correlated with both composite regurgitation and left ventricular ejection fraction. CONCLUSION: The combination of comprehensive echocardiography and plasma B-type natriuretic peptide levels elucidates the presence of cardiac damage in patients with Parkinson disease using ergot derivative dopamine agonists.

Bromocriptine use and the risk of valvular heart disease.

It has been reported that patients on pergolide and carbergoline have an increased risk of developing valvular heart disease. It is uncertain if bromocriptine, an ergot-derived dopamine agonist (DA) with partial 5-HT(2B) activity, is associated with a similar risk. We assessed the frequency of valvular heart disease in Parkinson's disease (PD) patients on bromocriptine compared to pergolide and a control group of PD patients who had not been treated on any DA. Seventy-two PD patients on bromocriptine, 21 patients on pergolide, and 47 control PD patients were recruited. Transthoracic echocardiographic studies were performed and reviewed by a blinded cardiologist. The risk for the bromocriptine group to develop any abnormal valvular regurgitation was 3.32 (adjusted OR, 95% CI: 1.11-9.92, P = 0.03) compared to controls, whereas the risk for the pergolide group was 3.66 (adjusted OR, 95% CI: 1.22-10.97, P = 0.02). When cumulative dose of bromocriptine was analyzed by quartiles, patients with a greater exposure to bromocriptine had significantly higher risk of developing both mild and moderate-severe regurgitations (P for trend, 0.005 and 0.019, respectively). This study demonstrated that bromocriptine use was associated with an increased risk of developing valvular heart disease, which occurred in a cumulative dose-dependent manner.

Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline.

BACKGROUND: Cabergoline, a dopamine receptor-2 agonist used to treat prolactinomas, was associated with increased risk of cardiac valve disease in Parkinson's disease. OBJECTIVE: Our objective was to evaluate prevalence of cardiac valve regurgitation in cabergoline-treated patients with prolactinomas. DESIGN AND SETTING: An observational, case-control study was conducted at a university hospital. PATIENTS: Fifty treated patients (44 women and six men) and 50 sex- and age-matched control subjects participated; 20 de novo patients were also studied. INTERVENTION: In the treated patients, the last cabergoline dose was 1.3 +/- 1.3 mg/wk (<1 mg/wk in 44%, 1-3 mg/wk in 46%, and >3 mg/wk in 10%). Treatment duration was 12-60 months in 32% and more than 60 months in 68%. The cumulative (milligrams x months of treatment) dose of cabergoline ranged from 32-1938 mg (median 280 mg). MEASUREMENTS: Valve regurgitation was assessed according to the recommendations of the American Society of Echocardiography. RESULTS: In de novo patients, treated patients, and controls, the prevalence of mild regurgitation of mitral (35, 22, and 12%, P = 0.085), aortic (0, 4, and 2%, P = 0.59), tricuspid (55, 30, and 42%, P = 0.13) or pulmonic (20, 12, and 6%, P = 0.22) valves was similar. Conversely, the prevalence of moderate tricuspid regurgitation was higher in the treated patients (54%) than in de novo patients (0%) and controls (18%, P < 0.0001). Moderate tricuspid regurgitation was more frequent in patients receiving a cumulative dose above the median (72%) than in those receiving a lower dose (36%, P = 0.023). A higher systolic (P = 0.03) and diastolic blood pressure (P < 0.0001) was found in patients with than in those without moderate tricuspid regurgitation. CONCLUSION: Moderate tricuspid regurgitation is more frequent in patients taking cabergoline (at higher cumulative doses) than in de novo patients and control subjects, but the clinical significance of this finding has not been established. A complete echocardiographic assessment is indicated in patients treated long term with cabergoline, particularly in those requiring elevated doses.

Aortic valve calcification and mild tricuspid regurgitation but no clinical heart disease after 8 years of dopamine agonist therapy for prolactinoma.

OBJECTIVE: Treatment with ergot-derived dopamine agonists, pergolide, and cabergoline has been associated with an increased frequency of valvular heart disease in Parkinson's disease. The aim of the present study was to assess the prevalence of valvular heart disease in patients treated with dopamine agonists for prolactinomas. DESIGN: This was a cross-sectional study. PATIENTS: We performed two-dimensional and Doppler echocardiography in 78 consecutive patients with prolactinoma (mean age 47 +/- 1.4 yr, 26% male, 31% macroprolactinoma) treated with dopamine agonists for at least 1 yr (mean 8 +/- 0.6 yr) and 78 control subjects. Patients were classified according to treatment: patients treated with cabergoline (group 1: n = 47) and patients not treated with cabergoline (group 2: n = 31). RESULTS: Clinically relevant valvular heart disease was present in 12% of patients (nine of 78) vs. 17% of controls (13 of 78) (P = 0.141) and 17% (eight of 47) of patients treated with cabergoline vs. 3% (one of 31) of patients not treated with cabergoline (P = 0.062). Mild tricuspid regurgitation was present in 41% of patients vs. 26% of controls (P = 0.042), and aortic valve calcification was present in 40% of patients, compared with 18% of controls (P = 0.003). There was no relation between the cumulative dose of cabergoline and the presence of mild, moderate, or severe valve regurgitation. CONCLUSION: Several years of dopamine agonist treatment in patients with prolactinomas is associated with increased prevalence of aortic valve calcification and mild tricuspid regurgitation but not with clinically relevant valvular heart disease. Therefore, additional studies on the adverse cardiac effects of dopaminergic drugs in prolactinoma are warranted, especially in patients with much longer use of these drugs.

Treatment with low doses of cabergoline is not associated with increased prevalence of cardiac valve regurgitation in patients with hyperprolactinaemia.

INTRODUCTION AND AIM: Dopamine agonists have been reported to increase the risk of cardiac valve regurgitation in patients with Parkinson's disease. However, it is unknown whether these drugs might be harmful for patients with hyperprolactinaemia (HyperPRL). The aim of the study was to evaluate whether HyperPRL patients treated with dopamine agonists had a higher prevalence of cardiac valves regurgitation than that of general population. METHODS AND PATIENTS: One hundred consecutive patients (79 women, 21 men, mean age 41 +/- 13 years) with HyperPRL during treatment with cabergoline were enrolled in an observational case-control study and compared with 100 matched normal subjects (controls). Valve regurgitation was assessed by echocardiography according to the American Society of Echocardiography recommendations. RESULTS: Seven HyperPRL patients (7%) and six controls (6%) had moderate (grade 3) regurgitation in any valve (p = 0.980). All were asymptomatic and had no signs of cardiac disease. Mean duration of cabergoline treatment was 67 +/- 39 months (range: 3-199 months). Mean cumulative dose of cabergoline was 279 +/- 301 mg (range: 15-1327 mg). Moderate valve regurgitation was not associated with the duration of treatment (p = 0.359), with cumulative dose of cabergoline (p = 0.173), with age (p = 0.281), with previous treatment with bromocriptine (p = 0.673) or previous adenomectomy (p = 0.497) in patients with HyperPRL. DISCUSSION: In conclusion, treatment with cabergoline was not associated with increased prevalence of cardiac valves regurgitation in patients with HyperPRL. Mean cumulative dose of cabergoline was lower in patients with HyperPRL than that reported to be deleterious for patients with Parkinson's disease: hence, longer follow-up is necessary, particularly in patients receiving weekly doses > 3 mg.

Heart valve regurgitation, pergolide use, and parkinson disease: an observational study and meta-analysis.

OBJECTIVE: To investigate the prevalence and risk factors of heart valve disease in patients having PD treated with pergolide. DESIGN: Prospective observational study. SETTING: Patients were recruited at the Hôpital de la Pitié-Salpêtrière, Paris, France. Patients Ninety-six patients having PD treated with pergolide for longer than 3 months vs 50 control subjects. Intervention Standardized echocardiography performed by an investigator blinded to treatment status. Main Outcome Measure Moderate to severe regurgitation in at least 1 heart valve. RESULTS: One hundred thirty-three echocardiograms (86 in the pergolide-treated group and 47 in the control group) were analyzed in the study. Moderate to severe regurgitation was found in 15 patients treated with pergolide (17.4%) and in 2 control subjects (4.3%) (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.02-22.1; P = .03). Moderate to severe regurgitation was associated with the cumulative dose of pergolide (OR, 1.37; 95% CI, 1.04-1.81 per 10-mg/kg increase; P =.03). Including the present study, the meta-analysis comprised 7 trials (394 patients treated with pergolide and 280 controls). The overall OR for moderate to severe regurgitation was 3.1 (95% CI, 1.7-5.6; P < .001) in the pergolide-treated group. Risk differences were correlated with the mean cumulative dose of pergolide (r = 0.90, P < .001). DATA SOURCES: Using an end point of moderate to severe heart valve regurgitation, we performed a meta-analysis of patients having Parkinson disease (PD) treated with pergolide mesylate vs control subjects by searching PubMed (January 1, 1966, to April 1, 2007) and the Cochrane databases to identify English-language prospective observational studies that reported echocardiographic data. CONCLUSION: Heart valve disease is independently associated with the use of pergolide treatment in patients having PD and correlates with its cumulative dose. Trial Registration clinicaltrials.gov Identifier: NCT00202657.

Assessment of valvulopathy in Parkinson's disease patients on pergolide and/or cabergoline.

OBJECTIVE: To assess the effect of ergot derivatives on cardiac valves in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Echocardiography was performed on 46 PD patients who used either pergolide or cabergoline (MonoPD) or both (MixPD) for a minimum of 1 year and 49 age-matched healthy controls. Valvular regurgitation was graded as mild, moderate and severe. MonoPD and MixPD groups were compared with regard to demographic features, drug profile and valvulopathy. RESULTS: The PD group had a mean age of 63 years, agonist duration of 3.8 years and agonist equivalent dose of 3.5mg/day. Moderate regurgitation in all three valves was significantly more common in the PD group than the controls. Severe valvular regurgitation was not observed in either group, with the exception of one PD patient. The frequency of valvulopathy and doses of agonists did not differ between MixPD and MonoPD groups. CONCLUSION: PD patients on dopamine ergot agonists are prone to moderate valvular regurgitation more than age-matched controls. However, the frequency of valvulopathy was similar in patients who used either one or more agonists.