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Despite the high prevalence and adverse clinical outcomes of severe tricuspid regurgitation (TR), conventional treatment options, surgical or pharmacological, are limited. Surgery is associated with a high peri-operative risk and medical treatment has not clearly resulted in clinical improvements. Therefore, there is a high unmet need to reduce morbidity and mortality in patients with severe TR. During recent years, several transcatheter solutions have been studied. This review focuses on the transcatheter edge-to-edge repair of TR (TTVR) with respect to patient selection, the procedure, pre- and peri-procedural echocardiographic assessments and clinical outcomes. Furthermore, we highlight the current status of TTVR in the Netherlands and provide data from our initial experience at the University Medical Centre Groningen. [ABSTRACT FROM AUTHOR]

Aims: A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We therefore analysed the association between abdominal fat, measured via waist-to-hip ratio (WHR), BMI and all-cause mortality in patients with HF.Methods and Results: For this analysis, 1738 patients from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. In total, 1479 patients were included, of which 33% were female and mean age was 75 ±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher New York Heart Association functional class. There was a significant interaction between sex and WHR on its association with mortality (P <0.001). In women, a higher WHR was associated with a higher mortality risk [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37-3.63; P =0.001], whereas no significant association was found in men (HR 0.87, 95% CI 0.63-1.20; P = 0.409). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while these associations were less profound in men.Conclusions: A higher WHR was associated with a higher risk of death in female but not in male HF patients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF. [ABSTRACT FROM AUTHOR]

Aims: Patients hospitalized for heart failure (HF) are at high risk for 30-day readmission. This study sought to examine the timings and causes of readmission within 30 days of an HF hospitalization.Methods and Results: Timing and cause of readmission in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure) trial were assessed. Early and late readmissions were defined as admissions occurring within 0-7 days and 8-30 days post-discharge, respectively. Patients who died in hospital or remained hospitalized at day 30 post-randomization were excluded. Patients were compared by timing and cause of readmission. Logistic and Cox proportional hazards regression analyses were used to identify independent risk factors for early vs. late readmission and associations with 180-day outcomes. Of the 6584 patients (92%) in the ASCEND-HF population included in this analysis, 751 patients (11%) were readmitted within 30 days for any cause. Overall, 54% of readmissions were for non-HF causes. The median time to rehospitalization was 11 days (interquartile range: 6-18 days) and 33% of rehospitalizations occurred by day 7. Rehospitalization within 30 days was independently associated with increased risk for 180-day all-cause death [hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.93-2.94; P < 0.001]. Risk for 180-day all-cause death did not differ according to early vs. late readmission (HR 0.99, 95% CI 0.67-1.45; P = 0.94).Conclusions: In this hospitalized HF trial population, a significant majority of 30-day readmissions were for non-HF causes and one-third of readmissions occurred in the first 7 days. Early and late readmissions within the 30-day timeframe were associated with similarly increased risk for death. Continued efforts to optimize multidisciplinary transitional care are warranted to improve rates of early readmission. [ABSTRACT FROM AUTHOR]

Aims: To investigate the prevalence of iron deficiency (ID) in heart failure (HF) patients with normal vs. abnormal red cell indices (RCI), the associations between iron parameters and RCI, and prognostic consequences of ID independently of RCI.Methods and Results: We analysed clinical data of 1821 patients with HF [mean age 66 ± 13 years; 71% men; New York Heart Association class I/II/III/IV (11%/39%/44%/6%); left ventricular ejection fraction >45%: 19%]. Iron deficiency (ferritin <100 µg/L or ferritin 100-299 µg/L with transferrin saturation <20%) was common irrespective of the presence of anaemia (haemoglobin <12 g/dL in women and <13 g/dL in men) or low RCI, from 75% in anaemic subjects with low mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and MCH concentration (MCHC), to 36% in non-anaemic subjects with MCV, MCH, and MCHC above the lower limit of normal. After adjustment for clinical variables, iron parameters remained independently associated with haemoglobin, MCV, MCH, MCHC, mean reticulocyte haemoglobin content (CHR), and red cell distribution width (RDW). In multivariable Cox proportional hazard regression models there was a trend towards higher mortality in patients with vs. without ID when adjusted for relevant HF prognosticators and MCH or MCHC (but not haemoglobin, CHR or RDW).Conclusions: Patients with HF should be routinely screened for ID irrespective of the presence of anaemia or abnormal RCI. The detrimental impact of ID on long-term survival in HF is partially independent of RCI. [ABSTRACT FROM AUTHOR]

Objective: The blood urea nitrogen-to-creatinine (BUN/creatinine) ratio has been proposed as a useful parameter in acute heart failure (AHF), but data on the normal range and the added value of the ratio compared with its separate components in patients with AHF are lacking. The aim of this study is to define the normal range of BUN/creatinine ratio and to investigate its clinical significance in patients with AHF.Methods: In 4484 subjects from the general population without cardiovascular comorbidities, we calculated age-specific and sex-specific normal values of the BUN/creatinine ratio, deriving a higher and lower than normal range of BUN/creatinine ratio (exceeding the 95% prediction intervals). Association of abnormal range to prognosis was tested in 2033 patients with AHF for the outcome of all-cause death through 180 days, death or cardiovascular or renal rehospitalisation through 60 days and heart failure (HF) rehospitalisation within 60 days.Results: In a cohort of patients with AHF, 482 (24.6%) and 28 (1.4%) patients with HF were classified into higher and lower than normal range groups, respectively. In Cox regression analysis, higher than normal range of BUN/creatinine ratio group was an independent predictor for all-cause death (HR: 1.86, 95% CI 1.29 to 2.66) and death or cardiovascular or renal rehospitalisation (HR: 1.37, 95% CI 1.03 to 1.82), but not for HF rehospitalisation (HR: 1.23, 95% CI 0.81 to 1.86) after adjustment for other prognostic factors including both creatinine and BUN.Conclusions: In patients with AHF, BUN/creatinine higher than age-specific and sex-specific normal range is associated with worse prognosis independently from both creatinine and BUN. CLINICAL TRIALS: gov identifier NCT00328692 and NCT00354458. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) is a common manifestation of patients with primary and secondary causes of iron overload, whereas in patients with established HF iron deficiency impairs outcome. Whether iron stores, either depleted or in overload, amplify the risk for new-onset HF among healthy individuals is unknown. The present study aimed to assess whether markers of iron status or the iron-regulatory hormone hepcidin are associated with new-onset HF or cardiovascular (CV) events in the general population.Methods and Results: In 6386 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) trial, a prospective, community-based, cohort study, markers of iron status and the iron-regulatory hormone hepcidin were measured. Mean age was 53.1 ± 12.0 years, and 50.7% of the cohort was female. During a median follow-up of 8.3 (interquartile range 7.8-8.9) years, 199 subjects (3.1%) were newly diagnosed with HF, 456 (7.1%) experienced a CV event, and 356 (5.6%) died from all causes. A higher annual HF incidence per ferritin quartile was observed in women (P < 0.001), but not in men (P for interaction 0.032). Multivariable analyses demonstrated ferritin levels to remain independently predictive for new-onset HF in women only (P = 0.024). This association persisted within strata defined by markers of the metabolic syndrome, markers of inflammation, or other markers of iron homeostasis, including hepcidin. No association between ferritin or hepcidin and incident CV events or all-cause mortality was observed in either sex.Conclusions: Increased serum ferritin levels independently amplify the risk for new-onset HF in women in the community. [ABSTRACT FROM AUTHOR]

Aims: In patients with heart failure (HF), serum erythropoietin (EPO) levels are elevated and associated with disease severity and outcome. Whether endogenous EPO levels are prospectively associated with the development of HF or cardiovascular events in the general population is unknown.Methods and Results: Serum EPO levels were measured at baseline in 6686 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Mean age (±SD) was 53 ± 12 years, 49.8% were male, and the median (interquartile range) EPO level was 7.7 (5.9-10.2) IU/L. During a median follow-up of 8.3 (7.7-8.8) years, 209 (3.1%) subjects were newly diagnosed with HF, 97 (1.5%) died of a cardiovascular cause, and 386 (6.0%) subjects had a non-fatal cardiovascular event (277 cardiac events and 93 strokes). Each doubling of EPO level was multivariably associated with new-onset HF [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.03-1.69, P = 0.031]. EPO levels showed interaction with urinary albumin excretion (P = 0.006) and were only associated with HF in subjects with albuminuria (HR 1.51, 95% CI 1.13-2.03, P = 0.005). There was an independent association of EPO levels with stroke in women (HR 1.82, 95% CI 1.24-2.65, P = 0.002), but not in men. No association was observed for EPO levels with other cardiovascular events or cardiovascular mortality.Conclusion: High serum EPO levels are independently associated with an increased risk of new-onset HF in subjects with albuminuria. More research into the pathophysiological mechanisms linking EPO levels to HF is needed to understand this association. [ABSTRACT FROM AUTHOR]

Objectives: To report the prevalence of aortic valve prosthesis-patient mismatch (PPM) in an adult population with congenital heart disease (CHD) and its impact on exercise capacity. Adults with congenital heart disease (ACHD) with a history of aortic valve replacement may outgrow their prosthesis later in life. However, the prevalence and clinical consequences of aortic PPM in ACHD are presently unknown.Methods: From the national Dutch Congenital Corvitia (CONCOR) registry, we identified 207 ACHD with an aortic valve prosthesis for this cross-sectional cohort study. Severe PPM was defined as an indexed effective orifice area ≤0.65 cm2/m2 and moderate PPM as an indexed orifice area ≤0.85 cm2/m2 measured using echocardiography. Exercise capacity was reported as percentage of predicted exercise capacity (PPEC).Results: Of the 207 patients, 68% was male, 71% had a mechanical prosthesis and mean age at inclusion was 43.9 years ±11.4. The prevalence of PPM was 42%, comprising 23% severe PPM and 19% moderate PPM. Prevalence of PPM was higher in patients with mechanical prostheses (p<0.001). PPM was associated with poorer exercise capacity (mean PPEC 84% vs. 92%; p=0.048, mean difference =-8.3%, p=0.047). Mean follow-up was 2.6±1.1 years during which New York Heart Association (NYHA) class remained stable in most patients. PPM showed no significant effect on death or hospitalisation during follow-up (p=0.218).Conclusions: In this study we report a high prevalence (42%) of PPM in ACHD with an aortic valve prosthesis and an independent association of PPM with diminished exercise capacity. [ABSTRACT FROM AUTHOR]

Background: Information on the outcome of pregnancy in patients with pulmonary valvar stenosis is scarce, mostly limited to cardiac complications observed during pregnancy. Objectives: To investigate the magnitude and determinants of non-cardiac and fetal risks during pregnancy of women with isolated pulmonary valvar stenosis. Methods: Using the nationwide registry (CONgenital CORvitia), 106 women with (un-)corrected pulmonary valvar stenosis receiving care in six tertiary medical centres in The Netherlands were included. A total of 51 women had 108 pregnancies, including 21(19%) miscarriages and 6 elective abortions. Results: In the 81 completed (>20 weeks of gestation) pregnancies, we observed a high number of hypertension-related disorders (n = 12, 15%, including pre-eclampsia (n = 4) and eclampsia (n = 2)), premature deliveries (n = 14, 17%, including one twin) and thromboembolic events (n = 3, 3.7%). Furthermore, recurrence of congenital heart defects in the offspring was detected in three children (3.7%, pulmonary valvar stenosis (n =2) and complete transposition of the great arteries in combination with anencephaly). In addition to the intrauterine fetal demise of the transposition child, three other children died shortly after birth owing to immaturity, hydrocephalus combined with prematurity and meningitis (overall offspring mortality, 4.8%). Conclusion: In this largest report on pregnancy in women with (un-) corrected isolated pulmonary valvar stenosis, an excessive number of (serious) non-cardiac complications and mortality were observed in the offspring. [ABSTRACT FROM AUTHOR]

Background: Obese subjects have lower natriuretic peptide levels, but males and females have different anthropometric characteristics and fat distribution. Whether obesity-associated lowering of natriuretic peptides differs among males and females is unknown. Therefore, we investigated sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels among adults in the general population.Methods and Results: Using 8260 participants (50.1% females) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, we evaluated the relationship of NT-proBNP levels with obesity-associated parameters, i.e. waist circumference (WC), body mass index (BMI) and body weight in the overall population, and in males and females separately. NT-proBNP levels were higher in females (median, interquartile range: 50.5, 28.2-87.0 ng/L) than in males (24.3, 10.1-54.6 ng/L; P < 0.001). In the overall population, NT-proBNP levels were significantly lower in heavier individuals and displayed a 'U-shaped' relationship with increasing WC, but were not associated with BMI. After sex stratification, there was no significant association between NT-proBNP concentrations and anthropometric measures in females. However, in males increasing WC and BMI were associated with higher NT-proBNP levels (P < 0.05) while increasing body weight was associated with slightly lower NT-proBNP levels (P < 0.05). Age strongly confounded the association of NT-proBNP levels with obesity, and age-associated increases in NT-proBNP were significantly higher in males than in females (P < 0.001). In multivariable adjusted analyses, the inverse association of obesity and NT-proBNP levels was also significantly modified by sex: NT-proBNP levels were lower with increasing WC, BMI and body weight among females compared with males (Pinteraction  < 0.05). After also accounting for BMI, abdominal obesity was associated with lower NT-proBNP levels in females, but not in males (Pinteraction  < 0.001).Conclusions: Natriuretic peptide deficiency in obesity mostly pertains to females with abdominal obesity, whereas the relationship between obesity and natriuretic peptides appears to be more complex in males. [ABSTRACT FROM AUTHOR]

Aim: Improved prediction of early post-discharge death or rehospitalization after admission for acute heart failure is a major unmet need. We evaluated the value of biomarkers to predict either low or high risk for early post-discharge events.Methods and Results: A total of 1653 patients enrolled in the PROTECT trial who were discharged alive and with available blood samples were included. Forty-seven biomarkers were serially evaluated in these patients. Measurement closest to discharge was used to evaluate the predictive value of biomarkers for low and high post-discharge risk. Patients were classified as 'low risk' if post-discharge 30-day risk of death or heart failure rehospitalization was <5% while risk >20% was used to define 'high risk'. Cut-off values that yielded a 95% negative predictive value and a 20% positive predictive value were identified for each biomarker. Partial area under the receiver operating characteristic curve (pAUC) in the high-sensitivity and high-specificity regions was calculated to compare low-risk and high-risk predictive values. Of patients analysed, 193 (11.7%) patients reached the 30-day death or heart failure rehospitalization outcome. We found marked differences between low-risk and high-risk predictors. Cardiac-specific troponin I was the strongest biomarker for low-risk prediction (pAUC = 0.552, 95% confidence interval 0.52-0.58) while endothelin-1 showed better performance for high-risk prediction (pAUC = 0.560, 95% confidence interval 0.53-0.59). Several biomarkers (individually and in combination) provided added predictive value, on top of a clinical model, in both low-risk and high-risk regions.Conclusion: Different biomarkers predicted low risk vs. high risk of early post-discharge death or heart failure readmission in patients hospitalized for acute heart failure. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate the relationship between increased central venous pressure (CVP), renal function, and mortality in a broad spectrum of cardiovascular patients. Background: The pathophysiology of impaired renal function in cardiovascular disease is multifactorial. The relative importance of increased CVP has not been addressed previously. Methods: A total of 2,557 patients who underwent right heart catheterization in the University Medical Center Groningen, the Netherlands, between January 1, 1989, and December 31, 2006, were identified, and their data were extracted from electronic databases. Estimated glomerular filtration rate (eGFR) was assessed with the simplified modification of diet in renal disease formula. Results: Mean age was 59 ± 15 years, and 57% were men. Mean eGFR was 65 ± 24 ml/min/1.73 m2, with a cardiac index of 2.9 ± 0.8 l/min/m2 and CVP of 5.9 ± 4.3 mm Hg. We found that CVP was associated with cardiac index (r = −0.259, p < 0.0001) and eGFR (r = −0.147, p < 0.0001). Also, cardiac index was associated with eGFR (r = 0.123, p < 0.0001). In multivariate analysis CVP remained associated with eGFR (r = −0.108, p < 0.0001). In a median follow-up time of 10.7 years, 741 (29%) patients died. We found that CVP was an independent predictor of reduced survival (hazard ratio: 1.03 per mm Hg increase, 95% confidence interval: 1.01 to 1.05, p = 0.0032). Conclusions: Increased CVP is associated with impaired renal function and independently related to all-cause mortality in a broad spectrum of patients with cardiovascular disease. [Copyright &y& Elsevier]

Objective: We investigated the clinical outcome of venous coronary artery bypass graft surgery., Methods: A study group consisting of 428 consecutive patients-operated on between 1 April 1976 and 1 April 1977-was followed prospectively. Single or sequential saphenous vein grafts were performed with a mean of 3.2 coronary anastomoses per patient. A left ventricular aneurysmectomy was performed in 25 patients., Results: Complete revascularisation was achieved in 78% of the patients. Follow-up was 99.8% complete and averaged 15.4 years for the survivors. Actuarial survival after 5, 10, and 15 years was 91.4%, 79.9%, and 61.1%, respectively. The cumulative probabilities of event-free survival at 10 years were as follows: cardiac death, 87.3%; acute myocardial infarction, 84.1%; reoperation, 88.6%; coronary artery balloon angioplasty, 94.1%; angina pectoris, 48.7%; and any event, 40.8%., Conclusions: The results are comparable with those of the few other long-term studies that have been published. With isolated venous bypass grafting, satisfactory results can be obtained until approximately 7 years after operation. Thereafter mortality increases, as does the rate of myocardial infarction, reoperation, and balloon angioplasty.