Incidence of heart valve disease in women treated with the ergot-derived dopamine agonist bromocriptine

Abstract Background Ergot-derived dopamine agonists are thought to induce fibrotic changes in cardiac valve leaflets. We sought to determine the incidence of heart valve disease in women treated with bromocriptine compared with age and sex matched controls from the background population. Methods In nationwide Danish registries we identified female patients treated with bromocriptine in the period 1995–2018. Patients were included at date of second redeemed prescription and were matched 1:5 with controls from the background population based on age, sex and year of inclusion by use of incidence density sampling. The outcomes were hospital admission for or outpatient diagnosis of heart valve disease, and death as competing risk. Incidence rates, cumulative incidence curves, and adjusted cox-proportional hazard models adjusted for cardiovascular risk factors were used to assess outcomes in bromocriptine users versus controls. Results A total of 3035 female bromocriptine users and 15,175 matched controls were included. Median age at inclusion was 32 years (Q1–Q3, 28–37 years). Both bromocriptine users and controls had few comorbidities and low use of concomitant pharmacotherapy. Within 10 years of follow-up, 11 patients (0.34%, 95% CI 0.13–0.55%) and 44 controls (0.29%, 95% CI 0.20–0.37) met the primary endpoint of heart valve disease, p = 0.63. The adjusted cox regression analysis yielded a hazard ratio of 0.96 (95% confidence interval (CI) 0.55–1.69, p = 0.89). Conclusions Treatment initiation with ergot-derived dopamine agonist bromocriptine in younger women with few comorbidities, was associated with a low absolute long-term risk of heart valve disease, not significantly different from the risk in age and sex matched population controls. Thus, indicating a low clinical yield of pre-treatment echocardiographic screening in this patient population in accordance with current guidelines.

Download Full-text

Incidence of heart valve disease in women treated with the ergot-derived dopamine agonist bromocriptine

10.21203/rs.3.rs-184426/v1 ◽

2021 ◽

Author(s):

Marianne F. Clausen ◽

Rasmus Rørth ◽

Christian Torp-Pedersen ◽

Lucas Malta Westergaard ◽

Peter E. Weeke ◽

...

Keyword(s):

Dopamine Agonist ◽

Heart Valve ◽

Cox Regression ◽

Incidence Rates ◽

Valve Disease ◽

Heart Valve Disease ◽

Incidence Density ◽

Cox Regression Analysis ◽

Background Population ◽

Age And Sex

Abstract Background Ergot-derived dopamine agonists are thought to induce fibrotic changes in cardiac valve leaflets. We sought to determine the incidence of heart valve disease in women treated with bromocriptine compared with age and sex matched controls from the background population. Methods In nationwide Danish registries we identified female patients treated with bromocriptine in the period 1995–2018. Patients were included at date of second redeemed prescription and were matched 1:5 with controls from the background population based on age, sex and year of inclusion by use of incidence density sampling. The outcomes were hospital admission for or outpatient diagnosis of heart valve disease, and death as competing risk. Incidence rates, cumulative incidence curves, and adjusted cox-proportional hazard models adjusted for cardiovascular risk factors were used to assess outcomes in bromocriptine users vs. controls. Results A total of 3035 female bromocriptine users and 15175 matched controls were included. Median age at inclusion was 32 years (Q1-Q3, 28–37 years). Both bromocriptine users and controls had few comorbidities and low use of concomitant pharmacotherapy. Within 10 years of follow-up, 11 patients (0.34%, 95 % CI 0.13%-0.55%) and 44 controls (0.29%, 95 % CI 0.20–0.37) met the primary endpoint of heart valve disease, p = 0.63. The adjusted cox regression analysis yielded a hazard ratio of 0.96 (95% confidence interval (CI) 0.55–1.69, p = 0.89). Conclusions Treatment initiation with ergot-derived dopamine agonist bromocriptine in younger women with few comorbidities, was associated with a low absolute long-term risk of heart valve disease, not significantly different from the risk in age and sex matched population controls. Thus, indicating a low clinical yield of pre-treatment echocardiographic screening in this patient population in accordance with current guidelines.

Download Full-text

P4668Risk of valvular heart disease in bromocriptine-treated women with hyperprolactinaemic disorders

European Heart Journal ◽

10.1093/eurheartj/ehz745.1050 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Clausen ◽

R Roerth ◽

C Torp-Pedersen ◽

G H Gislason ◽

L Koeber ◽

...

Keyword(s):

Heart Disease ◽

Valvular Heart Disease ◽

Cumulative Incidence ◽

Disease Incidence ◽

Incidence Rates ◽

Cardiac Valve ◽

Valve Disease ◽

Incidence Density ◽

Cardiac Valve Disease ◽

Age And Sex

Abstract Background Systematic echocardiographic screening is currently recommended for patients with hyperprolactinemic disorders treated with dopamine agonists, due to a perceived risk of cardiac valve regurgitation as observed in patients with Parkinson's disease. The dopamine agonist bromocriptine is used frequently in hyperprolactinemia patients, but its relation to cardiac valve disease remain uncertain. Purpose To determine the incidence of valvular heart disease in bromocriptine-treated women with hyperprolactinaemic disorders compared with matched controls from background population. Methods In nationwide Danish registries, we identified patients with hyperprolactinaemic disorders treated with bromocriptine between 1995–2017. Patients were matched 1:5 with population controls based on age and sex using incidence density sampling. We estimated the risk of valvular heart disease defined as admission and/or outpatient clinic visits. Incidence rates, cumulative incidence curve and adjusted cox-proportional hazard models were used to assess outcomes. Results A total of 23883 female bromocriptine users and 119415 controls were included. Median age was 29.9 years (Q1-Q3 26.4–33.8). Both groups had few comorbidities, 218 (0.9%) patients and 787 (0.7%) controls with hypertension, 160 (0.7%) patients and 629 (0.5%) controls with diabetes, 408 (1.7%) patients and 1305 (1.1%) controls were beta-blocker users. During a mean follow-up of 19 years 106 (0.44%) patients and 416 (0.35%) controls were diagnosed with valvular heart disease. Incidence rates were 0.254 per 1000 patient years (PY) in bromocriptine users (95% CI 0.21–0.31) and 0.198 per 1000 PY in the control cohort (95% CI 0.18–0.22). Overall, the cumulative incidence of valvular heart disease was 0.6% (95% CI 0.48–0.73) among patients and 0.5% (95% CI 0.4–0.51) among controls; P=0.03 (figure 1a). In adjusted analysis bromocriptine users still had a significant higher risk of valvular heart disease (hazard ratio=1.32, 95% CI 1.06–1.64, P=0.01). Incidence of valvular heart disease Conclusion The use of bromocriptine in younger and otherwise healthy women with hyperprolactinaemic disorders, were associated with a low absolute risk of cardiac valve disease. Still risk was approximately 30% higher compared with age- and sex matched controls. Our study suggests a low clinical yield of echocardiographic screening in this patient population. Acknowledgement/Funding Internal grant, Copenhagen University Hospital Rigshospitalet

Download Full-text

Diabetes mellitus was not associated with lower amputation-free survival after open revascularization for chronic limb-threatening ischemia – A nationwide propensity score adjusted analysis

Vascular Medicine ◽

10.1177/1358863x211008249 ◽

2021 ◽

pp. 1358863X2110082

Author(s):

Erika Lilja ◽

Anders Gottsäter ◽

Mervete Miftaraj ◽

Jan Ekelund ◽

Björn Eliasson ◽

...

Keyword(s):

Diabetes Mellitus ◽

Propensity Score ◽

Vascular Surgery ◽

Incidence Rate ◽

Cox Regression ◽

Major Amputation ◽

Incidence Rates ◽

Major Adverse Cardiovascular Events ◽

Cox Regression Analysis ◽

Number Of Patients

The risk of major amputation is higher after urgently planned endovascular therapy for chronic limb-threatening ischemia (CLTI) in patients with diabetes mellitus (DM). The aim of this nationwide cohort study was to compare outcomes between patients with and without DM following urgently planned open revascularization for CLTI from 2010 to 2014. Out of 1537 individuals registered in the Swedish Vascular Registry, 569 were registered in the National Diabetes Register. A propensity score adjusted Cox regression analysis was conducted to compare outcome between the groups with and without DM. Median follow-up was 4.3 years and 4.5 years for patients with and without DM, respectively. Patients with DM more often had foot ulcers ( p = 0.034) and had undergone more previous amputations ( p = 0.001) at baseline. No differences in mortality, cardiovascular death, major adverse cardiovascular events (MACE), or major amputation were observed between groups. The incidence rate of stroke was 70% higher (95% CI: 1.11–2.59; p = 0.0137) and the incidence rate of acute myocardial infarction (AMI) 39% higher (95% CI: 1.00–1.92; p = 0.0472) among patients with DM in comparison to those without. Open vascular surgery remains a first-line option for a substantial number of patients with CLTI, especially for limb salvage in patients with DM. The higher incidence rates of stroke and AMI among patients with DM following open vascular surgery for infrainguinal CLTI require specific consideration preoperatively with the aim of optimizing medical treatment to improve cardiovascular outcome postoperatively.

Download Full-text

Heart valve disease, left ventricular hypertrophy, and heart failure: a lifelong relationship and continuing clinical responsibility

European Journal of Heart Failure ◽

10.1002/ejhf.2373 ◽

2021 ◽

Author(s):

Alan G Fraser ◽

Piotr Szymański

Keyword(s):

Heart Failure ◽

Left Ventricular Hypertrophy ◽

Heart Valve ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Valve Disease ◽

Heart Valve Disease ◽

Clinical Responsibility

Download Full-text

Evaluation of Patients with Heart Valve Disease

Heart Valve Disease ◽

10.1007/978-3-030-23104-0_2 ◽

2019 ◽

pp. 9-19

Author(s):

Jose Zamorano ◽

Ciro Santoro ◽

Álvaro Marco del Castillo

Keyword(s):

Heart Valve ◽

Valve Disease ◽

Heart Valve Disease

Download Full-text

Inflammatory Regulation of Valvular Remodeling: The Good(?), the Bad, and the Ugly

International Journal of Inflammation ◽

10.4061/2011/721419 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 15

Author(s):

Gretchen J. Mahler ◽

Jonathan T. Butcher

Keyword(s):

Heart Valve ◽

Cell Biology ◽

Heart Valves ◽

Valve Disease ◽

Heart Valve Disease ◽

Inflammatory Signaling ◽

Current State ◽

Valve Remodeling ◽

Inflammatory Regulation ◽

Key Questions

Heart valve disease is unique in that it affects both the very young and very old, and does not discriminate by financial affluence, social stratus, or global location. Research over the past decade has transformed our understanding of heart valve cell biology, yet still more remains unclear regarding how these cells respond and adapt to their local microenvironment. Recent studies have identified inflammatory signaling at nearly every point in the life cycle of heart valves, yet its role at each stage is unclear. While the vast majority of evidence points to inflammation as mediating pathological valve remodeling and eventual destruction, some studies suggest inflammation may provide key signals guiding transient adaptive remodeling. Though the mechanisms are far from clear, inflammatory signaling may be a previously unrecognized ally in the quest for controlled rapid tissue remodeling, a key requirement for regenerative medicine approaches for heart valve disease. This paper summarizes the current state of knowledge regarding inflammatory mediation of heart valve remodeling and suggests key questions moving forward.

Download Full-text

Role of Disease Modifying Treatment in the Risk of Alloimmunization in Transfused Patients with Myelodysplastic Syndromes: A Population-Based Study

Blood ◽

10.1182/blood-2019-123357 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4253-4253

Author(s):

Hanne Rozema ◽

Robby Kibbelaar ◽

Nic Veeger ◽

Mels Hoogendoorn ◽

Eric van Roon

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Cox Regression ◽

Population Based ◽

Incidence Rates ◽

Blood Products ◽

Cox Regression Analysis ◽

In The Beginning ◽

Observation Period

The majority of patients with myelodysplastic syndromes (MDS) require regular red blood cell (RBC) transfusions. Alloimmunization (AI) against blood products is an adverse event, causing time-consuming RBC compatibility testing. The reported incidence of AI in MDS patients varies greatly. Even though different studies on AI in MDS patients have been performed, there are still knowledge gaps. Current literature has not yet fully identified the risk factors and dynamics of AI in individual patients, nor has the influence of disease modifying treatment (DMT) been explored. Therefore, we performed this study to evaluate the effect of DMT on AI. An observational, population-based study, using the HemoBase registry, was performed including all newly diagnosed MDS patients between 2005 and 2017 in Friesland, a province of the Netherlands. All available information about treatment and transfusions, including transfusion dates, types, and treatment regimens, was collected from the electronic health records and laboratory systems. Follow-up occurred through March 2019. For our patient cohort, blood products were matched for AB0 and RhD, and transfused per the 'type and screen' policy (i.e. electronic matching of blood group phenotype between patient and donor). After a positive antibody screening, antibody identification and Rh/K phenotyping was performed and subsequent blood products were (cross)matched accordingly. The observation period was counted from first transfusion until last transfusion or first AI event. Univariate analyses and cumulative frequency distributions were performed to study possible risk factors and dynamics of AI. DMT was defined as hypomethylating agents, lenalidomide, chemotherapy and monoclonal antibodies. The effect of DMT as a temporary risk period on the risk of AI was estimated with incidence rates, relative risks (RR) and hazard ratios (HR) using a cox regression analysis. Follow-up was limited to 24 months for the cox regression analysis to avoid possible bias by survival differences. Statistical analyses were performed using IBM SPSS 24 and SAS 9.4. Out of 292 MDS patients, 236 patients received transfusions and were included in this study, covering 463 years of follow-up. AI occurred in 24 patients (10%). AI occurred mostly in the beginning of the observation period: Eighteen patients (75%) were alloimmunized after receiving 20 units of RBCs, whereas 22 patients (92%) showed AI after 45 units of RBCs (Figure 1). We found no significant risk factors for AI in MDS patients at baseline. DMT was given to 67 patients (28%) during the observation period. Patients on DMT received more RBC transfusions than patients that did not receive DMT (median of 33 (range: 3-154) and 11 (range: 0-322) RBC units respectively, p<0,001). Four AI events (6%) occurred in patients on DMT and 20 AI events (12%) occurred in patients not on DMT. Cox regression analysis of the first 24 months of follow-up showed an HR of 0.30 (95% CI: 0.07-1.31; p=0.11). The incidence rates per 100 person-years were 3.19 and 5.92 respectively. The corresponding RR was 0.54 (95% CI: 0.16-1.48; p=0.26). Based on our results, we conclude that the incidence of AI in an unselected, real world MDS population receiving RBC transfusions is 10% and predominantly occurred in the beginning of follow-up. Risk factors for AI at baseline could not be identified. Our data showed that patients on DMT received significantly more RBC transfusions but were less susceptible to AI. Therefore, extensive matching of blood products may not be necessary for patients on DMT. Larger studies are needed to confirm the protective effect of DMT on AI. Disclosures Rozema: Celgene: Other: Financial support for visiting MDS Foundation conference.

Download Full-text

Perioperative Management of Sectio Caesarea Surgery in Patient With Heart Valve Disorders

Solo Journal of Anesthesi, Pain and Critical Care (SOJA) ◽

10.20961/soja.v1i1.49474 ◽

2021 ◽

Vol 1 (1) ◽

pp. 1

Author(s):

Purwoko Purwoko ◽

Zidni Afrokhul Athir

Keyword(s):

Mitral Regurgitation ◽

Cesarean Section ◽

Maternal Mortality ◽

Pulmonary Edema ◽

Heart Valve ◽

Mitral Stenosis ◽

Valve Disease ◽

Heart Valve Disease ◽

Normal Limits ◽

In Pregnancy

<div class="WordSection1">Cardiovascular disease in pregnancy is common range from 1% to 3 and contributes to 10-15% of maternal mortality. Valvular heart disease accounts for about 25% of cases of cardiac complications in pregnancy and important cause of maternal mortality, some of which are mitral stenosis and mitral regurgitation. Cesarean delivery remains the preferred choice, as it reduces the hemodynamic changes that can occur in normal delivery and allows for better monitoring and hemodynamic management. Our paper provide in-depth information regarding the pathophysiology of heart valve disease in pregnant women and an appropriate perianesthesia approach to obtain a good prognosis. We report a case of a 26-year-old pregnant woman, with obstetric status G1P0A0, 36 weeks’ gestation, body weight 61 kg accompanied by severe mitral regurgitation and moderate mitral stenosis. This patient was planned to undergo elective cesarean section. The patient's condition in the perioperative examination was: GCS E4V5M6, other vital signs within normal limits, SpO2 98-99% in supine position. Other physical and laboratory examinations were also within normal limits. The goal of anesthesia during surgery in patients with heart valve disease undergoing cesarean section maintain pulmonary capillary pressure to prevent acute pulmonary edema. In this case, regional anesthesia of epidural anesthesia was chosen because it can reduce systemic vascular resistance and provide better post-cesarean section pain. The patient's hemodynamics perianesthesia tended to be stable without any complications such as pulmonary edema. </div>

Download Full-text