Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

Infective endocarditis in adult patients with congenital heart disease.

BACKGROUND: Congenital Heart Disease (CHD) predisposes to Infective Endocarditis (IE), but data about characterization and prognosis of IE in CHD patients is scarce. METHODS: The ESC-EORP-EURO-ENDO study is a prospective international study in IE patients (n = 3111). In this pre-specified analysis, adult CHD patients (n = 365, 11.7%) are described and compared with patients without CHD (n = 2746) in terms of baseline characteristics and mortality. RESULTS: CHD patients (73% men, age 44.8 ± 16.6 years) were younger and had fewer comorbidities. Of the CHD patients, 14% had a dental procedure before hospitalization versus 7% in non-CHD patients (p < 0.001) and more often had positive blood cultures for Streptococcus viridans (16.4% vs 8.8%, p < 0.001). As in non-CHD patients, IE most often affected the left-sided valves. For CHD patients, in-hospital mortality was 9.0% vs 18.1% in non-CHD patients (p < 0.001), and also, during the entire follow-up of 700 days, survival was more favorable (log-rank p < 0.0001), even after adjustment for age, gender and major comorbidities (Hazard Ratio (HR) 0.68; 95%CI 0.50-0.92). Within the CHD population, multivariable Cox regression revealed the following effects (HR and [95% CI]) on mortality: fistula (HR 6.97 [3.36-14.47]), cerebral embolus (HR 4.64 [2.08-10.35]), renal insufficiency (HR 3.44 [1.48-8.02]), Staphylococcus aureus as causative agent (HR 2.06 [1.11-3.81]) and failure to undertake surgery when indicated (HR 5.93 [3.15-11.18]). CONCLUSIONS: CHD patients with IE have a better outcome in terms of all-cause mortality. The observed high incidence of dental procedures prior to IE warrants further studies about the current use, need and efficacy of antibiotic prophylaxis in CHD patients.

Optimal Timing of a Physical Exercise Intervention to Improve Cardiorespiratory Fitness: During or After Chemotherapy.

Background: Despite the widely acknowledged benefit of exercise for patients with cancer, little evidence on the optimal timing of exercise on adverse effects of cancer treatment is available. Objectives: The aim of this study was to determine whether an exercise intervention initiated during chemotherapy is superior to an intervention initiated after chemotherapy for improving long-term cardiorespiratory fitness (peak oxygen uptake [VO2peak]). Methods: In this prospective, randomized clinical trial, patients scheduled to receive curative chemotherapy were randomized to a 24-week exercise intervention, initiated either during chemotherapy (group A) or afterward (group B). The primary endpoint was VO2peak 1 year postintervention. Secondary endpoints were VO2peak postintervention, muscle strength, health-related quality of life (HRQoL), fatigue, physical activity, and self-efficacy. Between-group differences were calculated using intention-to-treat linear mixed-models analyses. Results: A total of 266 patients with breast (n = 139), testicular (n = 95), and colon cancer (n = 30) as well as lymphoma (n = 2) were included. VO2peak immediately postintervention and 1 year postintervention did not differ between the 2 groups. Immediately postchemotherapy, patients in group A exhibited significantly lower decreases in VO2peak (3.1 mL/kg/min; 95% CI: 2.2-4.0 mL/kg/min), HRQoL, and muscle strength and reported less fatigue and more physical activity than those in group B. Conclusions: Exercise can be safely performed during chemotherapy and prevents fatigue and decreases in VO2peak, muscle strength, and HRQoL, in addition to hastening the return of function after chemotherapy. Also, if exercise cannot be performed during chemotherapy, a program afterward can enable patients to regain the same level of function, measured 1 year after completion of the intervention. (Optimal Timing of Physical Activity in Cancer Treatment [ACT]; NCT01642680).

Right ventricular dysfunction in patients with new-onset heart failure: longitudinal follow-up during guideline-directed medical therapy.

AIMS: Improvement in left ventricular ejection fraction (LVEF) after up-titration of guideline-directed medical therapy (GDMT) has been well described in heart failure (HF) patients. Less is known about the prevalence and clinical course of right ventricular dysfunction (RVD) in patients with new-onset HF. METHODS AND RESULTS: From 2012 to 2018, 625 patients with a recent (<3 months) diagnosis of HF were referred to a specialized nurse-led HF clinic for protocolized up-titration of GDMT. RVD, defined as tricuspid annular plane systolic excursion (TAPSE) <17 mm, was assessed at baseline and at the follow-up visit. Patients were followed for the combined endpoint of all-cause mortality and HF hospitalization for a mean of 3.3 ± 1.9 years. Of the 625 patients, 241 (38.6%) patients had RVD at baseline. Patients with RVD were older, more symptomatic, had a lower LVEF, and more often had a history of cardiothoracic surgery and atrial fibrillation. After a median follow-up of 9 months, right ventricular function normalized in 49% of the patients with baseline RVD. RVD at baseline was associated with a higher risk of the combined endpoint (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.21-2.18). Right ventricular function normalization was associated with a lower risk for the combined endpoint (HR 0.56, 95% CI 0.31-0.99), independent of baseline TAPSE, age, sex, and LVEF. CONCLUSION: More than one-third of patients with new-onset HF have RVD. RVD is associated with a higher risk of all-cause mortality and HF hospitalization. Recovery of RVD regularly occurs during up-titration of GDMT and is associated with improved clinical outcomes.

Reduction of Lung Hyperinflation Improves Cardiac Preload, Contractility, and Output in Emphysema: A Clinical Trial in Patients Who Received Endobronchial Valves.

Rationale: Pulmonary hyperinflation in patients with chronic obstructive pulmonary disease has been related to smaller cardiac chamber sizes and impaired cardiac function. Currently, bronchoscopic lung volume reduction (BLVR) with endobronchial valves is a treatment option to reduce pulmonary hyperinflation in patients with severe emphysema. Objectives: We hypothesized that reduction of hyperinflation would improve cardiac preload in this patient group. In addition, we investigated whether the treatment would result in elevated pulmonary artery pressures because of pulmonary vascular bed reduction. Methods: We included patients with emphysema and severe hyperinflation (defined by a baseline residual volume >175% of predicted) who were eligible for BLVR with endobronchial valves. Cardiac magnetic resonance imaging was obtained one day before treatment and at 8-week follow-up. Primary endpoint was cardiac preload, as measured by the right ventricle end-diastolic volume index. As secondary endpoints, we measured indexed end-diastolic and end-systolic volumes of the right ventricle, left atrium, and left ventricle; pulmonary artery pressures; cardiac output; ejection fraction; and strain. Measurements and Main Results: Twenty-four patients were included. At 8-week follow-up, right ventricle end-diastolic volume index was significantly improved (+7.9 ml/m2; SD, 10.0; P = 0.001). In addition to increased stroke volumes, we found significantly higher ejection fractions and strain measurements. Although cardiac output was significantly increased (+0.9 L/min; SD, 1.5; P = 0.007), there were no changes in pulmonary artery pressures. Conclusions: We found that reduction of hyperinflation using BLVR with endobronchial valves significantly improved cardiac preload, myocardial contractility, and cardiac output, without changes in pulmonary artery pressures. Clinical trial registered with www.clinicaltrials.gov (NCT03474471).

Association between comorbidities and left and right atrial dysfunction in patients with paroxysmal atrial fibrillation: Analysis of AF-RISK.

BACKGROUND: To identify the association between comorbidities and left atrial (LA) and right atrial (RA) function in patients with paroxysmal atrial fibrillation (AF). METHODS: This is a cross-sectional study. Speckle-tracking echocardiography was performed in 344 patients with paroxysmal AF at baseline, and available in 298 patients after 1-year follow-up. The number of comorbidities (hypertension, diabetes mellitus, coronary artery disease, body mass index > 25 kg/m2, age > 65 years, moderate to severe mitral valve regurgitation and kidney dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73 m2)) was determined and the association with atrial strain was tested. RESULTS: Mean age of the patients was 58 (SD 12) years and 137 patients were women (40%). Patients with a higher number of comorbidities had larger LA volumes (p for trend <0.001), and had a decrease in all strain phases from the LA and RA, except for the RA contraction phase (p for trend 0.47). A higher number of comorbidities was associated with LA reservoir and conduit strain decrease independently of LA volume (p < 0.001, p < 0.001 respectively). Patients with 1-2 comorbidities, but not patients with 3 or more comorbidities, showed a further progression of impaired LA and RA function in almost all atrial strain phases at 14 [13-17] months follow-up. CONCLUSIONS: In patients with paroxysmal AF, individual and combined comorbidities are related to lower LA and RA strain. In patients with few comorbidities, impairment in atrial function progresses during one year of follow-up. Whether comorbidity management prevents or reverses decrease in atrial function warrants further study.

Left atrial structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF): systematic review and meta-analysis.

Left atrial (LA) structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF) is only established in small studies. Therefore, we conducted a systematic review of LA structure and function in order to find differences between patients with HFrEF and HFpEF. English literature on LA structure and function using echocardiography was reviewed to calculate pooled prevalence and weighted mean differences (WMD). A total of 61 studies, comprising 8806 patients with HFrEF and 9928 patients with HFpEF, were included. The pooled prevalence of atrial fibrillation (AF) was 34.4% versus 42.8% in the acute inpatient setting, and 20.1% versus 33.1% in the chronic outpatient setting when comparing between HFrEF and HFpEF. LA volume index (LAVi), LA reservoir global longitudinal strain (LAGLSR), and E/e' was 59.7 versus 52.7 ml/m2, 9.0% versus 18.9%, and 18.5 versus 14.0 in the acute inpatient setting, and 48.3 versus 38.2 ml/m2, 12.8% versus 23.4%, and 16.9 versus 13.5 in the chronic outpatient setting when comparing HFrEF versus HFpEF, respectively. The relationship between LAVi and LAGLSR was significant in HFpEF, but not in HFrEF. Also, in those studies that directly compared patients with HFrEF versus HFpEF, those with HFrEF had worse LAGLSR [WMD = 16.3% (22.05,8.61); p < 0.001], and higher E/e' [WMD = -0.40 (-0.56, -0.24); p < 0.05], while LAVi was comparable. When focusing on acute hospitalized patients, E/e' was comparable between patients with HFrEF and HFpEF. Despite the higher burden of AF in HFpEF, patients with HFrEF had worse LA global function. Left atrial myopathy is not specifically related to HFpEF.

Late cardiac toxicity of neo-adjuvant chemoradiation in esophageal cancer survivors: A prospective cross-sectional pilot study.

PURPOSE: Although cure rates in esophageal cancer (EC) have improved since the introduction of neoadjuvant chemoradiation (nCRT), evidence for treatment-related cardiac toxicity is growing, of which the exact mechanisms remain unknown. The primary objective of this study was to identify (subclinical) cardiac dysfunction in EC patients after nCRT followed by surgical resection as compared to surgery alone. MATERIALS AND METHODS: EC survivors followed for 5-15 years after curative resection with (n = 20) or without (n = 20) nCRT were enrolled in this prospective cross-sectional pilot study. All patients underwent several clinical and diagnostic tests in order to objectify (sub)clinical cardiac toxicity including cardiac CT and MRI, echocardiography, ECG, 6-minutes walking test, physical examination and EORTC questionnaires. RESULTS: We found an increased rate of myocardial fibrosis (Linear late gadolinium enhancement (LGE) 4 vs. 1; p = 0.13; mean extracellular volume (ECV) 28.4 vs. 24.0; p < 0.01), atrial fibrillation (AF) (6 vs. 2; p = 0.07) and conduction changes in ECG among patients treated with nCRT as compared to those treated with surgery alone. The results suggested an impact on quality of life in terms of worse role functioning for this patient group (95.0 vs. 88.8; p = 0.03). CONCLUSION: Based on our analyses we hypothesize that in EC patients, radiation-induced myocardial fibrosis plays a central role in cardiac toxicity leading to AF, conduction changes and ultimately to decreased role functioning. The results emphasize the need to verify these findings in larger cohorts of patients.

Radiation-Induced Myocardial Fibrosis in Long-Term Esophageal Cancer Survivors.

PURPOSE: Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there is a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). METHODS AND MATERIALS: Forty patients with EC treated with a transthoracic esophagectomy with (n = 20) or without (n = 20) nCRT (CROSS study regimen) were included. Cardiovascular magnetic resonance imaging (1.5 Tesla) for left ventricular (LV) function, late gadolinium enhancement, and T1 mapping were performed. Extracellular volume (ECV), as a surrogate for collagen burden, was measured for all LV segments separately. The dose-response relationship between ECV and mean radiation dose per LV myocardial segment was evaluated using a mixed-model analysis. RESULTS: Seventeen nCRT and 16 control patients were suitable for analysis. The mean time after treatment was 67.6 ± 8.1 (nCRT) and 122 ± 35 (controls) months (P = .02). In nCRT patients, we found a significantly higher mean global ECV of 28.2% compared with 24.0% in the controls (P < .001). After nCRT, LV myocardial segments with elevated ECV had received significantly higher radiation doses. In addition, a linear dose-effect relation was found with a 0.136% point increase of ECV for each Gy (P < .001). There were no differences in LV function measures and late gadolinium enhancement between both groups. CONCLUSIONS: Myocardial ECV was significantly higher in long-term EC survivors after nCRT compared with surgery only. Moreover, this ECV increase was linear with the radiation dose per LV segment, indicating radiation-induced myocardial fibrosis.

CT-Derived Pulmonary Artery Diameters to Preselect for Echocardiography in COPD Patients Eligible for Bronchoscopic Treatments.

BACKGROUND: Currently, patients with COPD who are evaluated for bronchoscopic treatments are routinely screened for pulmonary hypertension (PH) and systolic left ventricle dysfunction by echocardiography. OBJECTIVES: We evaluated the prevalence of PH and systolic left ventricle dysfunction in this patient group and investigated if the previously proposed CT-derived pulmonary artery to aorta (PA:A) ratio >1 and PA diameter measurements can be used as alternative screening tools for PH. METHODS: Two hundred fifty-five patients were included in this retrospective analysis (FEV1 25%pred, RV 237%pred). All patients received transthoracic echocardiography and chest CT scans on which diameters of the aorta and pulmonary artery were measured at the bifurcation and proximal to the bifurcation. RESULTS: Following echocardiography, 3 patients (1.2%) had PH and 1 (0.4%) had systolic left ventricle dysfunction. Using a PA:A ratio >1, only 10.3% of the patients with a right ventricular systolic pressure (RVSP) ≥35 mm Hg were detected and none of the patients with an RVSP >50 mm Hg were detected. Patients with an RVSP ≥35 mm Hg had significantly higher PA diameters (29.5 vs. 27.5 mm; p = 0.02) but no significantly different PA:A ratios. All patients with an RVSP >50 mm Hg had PA diameters >30 mm. CONCLUSIONS: The prevalence of PH and systolic left ventricle dysfunction is low in this preselected cohort of patients with severe COPD. In this population, a PA:A ratio >1 is not a useful cardiac screening tool for PH. A PA diameter >30 mm could substitute for routinely performed echocardiography in the screening for PH in this patient group.

Sex differences in patients with repaired tetralogy of Fallot support a tailored approach for males and females: a cardiac magnetic resonance study.

Purpose Substantial differences between sexes exist with respect to cardiovascular diseases, including congenital heart disease. Nevertheless, clinical decisions in the long-term follow-up of patients with repaired tetralogy of Fallot (rTOF) are currently based on unisex thresholds for cardiac magnetic resonance (CMR) measurements. This study aimed to assess whether sex differences exist in cardiac adaptation to hemodynamic loading conditions in patients with rTOF. Methods and Results This cross-sectional, two-center, combined pediatric and adult cohort included 320 rTOF patients (163 males, 51%) who underwent routine CMR. Despite similar age (median and interquartile range [m + IQR] 23.4 [15.2-34.4] years), surgical history, and hemodynamic loading, males with rTOF demonstrated higher biventricular CMR-derived volumes and masses, indexed for body surface area, compared to females (e.g. m + IQR right ventricular (RV) end-diastolic volume: males 123 [100-151] mL/m2, females 114 [94-131] mL/m2, P = 0.007). Sex-specific Z-scores of biventricular volumes and masses were similar for males and females. RV volumes and masses correlated with hemodynamic loading, but these relations did not differ between sexes. Biventricular ejection fraction (EF) appeared to be lower in male patients, compared to female patients (e.g. m + IQR RVEF: males 48 [43-54]%, females 52 [46-57]%, P < 0.001). Conclusion Indexed ventricular volumes and masses are higher in males with rTOF, compared to females, similar to the healthy population. RV hypertrophy and dilatation correlated to loading conditions similarly for both sexes. However, under comparable loading conditions, males demonstrated more severe functional impairment. These results indicate that sex-differences should no longer be ignored in treatment strategies, including timing of pulmonary valve replacement.

Pulmonary artery size is associated with functional clinical status in the Fontan circulation.

OBJECTIVE: In the Fontan circulation, non-pulsatile pulmonary blood flow is suggested to negatively affect pulmonary artery growth. The pulmonary vasculature is regarded a key determinant of outcome after Fontan completion. We hypothesised that in Fontan patients pulmonary artery size correlates with follow-up and functional clinical status. METHODS: This is a single-centre, cross-sectional cohort study. Thirty-nine paediatric and adult Fontan patients with a concomitant cardiac magnetic resonance (CMR) scan and a cardiopulmonary exercise test between 2012 and 2013 were included. CMR-derived left and right pulmonary artery cross-sectional areas were expressed as Nakata index. Functional status was defined as peak oxygen consumption (pVO2) indexed for weight, as percentage of predicted (pred) and as New York Heart Association Functional Class (NYHA-FC). RESULTS: Age at CMR was 18±7.2 years. Time since Fontan completion was 11.9±7.4 years. Nakata index was lower versus the reference values (238.6±78.5 vs 330±30 mm2/m2, p<0.001). Nakata index correlated negatively with age at CMR (r=-0.393, p=0.013) and time since Fontan completion (r=-0.341, p=0.034). pVO2 was 27.9±8.9 mL/min/kg and pVO2pred was 58.1%±14.1%. Nakata index correlated positively with pVO2 (r=0.468, p=0.003) and pVO2pred (r=0.353, p=0.028). Nakata index correlated negatively with NYHA-FC (r=-0.450, p=0.004). Nakata index was an independent predictor (ß=0.359, p=0.007) for pVO2 (adjusted R2=0.442, with maximum heart rate and oxygen pulse at peak exercise). CONCLUSIONS: Pulmonary artery size expressed as Nakata index is a novel independent predictor for functional clinical status. Nakata index negatively correlated with follow-up duration, suggesting that chronic abnormal non-pulsatile pulmonary blood flow plays a role in lagging pulmonary arterial growth in the Fontan circulation.

Pulmonary versus aortic pressure behavior of a bovine pericardial valve.

BACKGROUND: The Carpentier Edwards Perimount Magna Ease aortic valvular prosthesis (Edwards Lifesciences, Irvine, Calif) has been among the most frequently and successfully used tissue prosthetic cardiac valves. Furthermore, this prosthesis has been used off-label in the pulmonary position. Until now, there has been a paucity of data regarding the functioning of tissue prosthetic valves under pulmonary conditions. METHODS: Using a pulse duplicator, hydrodynamic characteristics of a 21-mm and 25-mm Magna Ease valve were evaluated. Among parameters evaluated were leakage orifice area, closing time (ie, time required to close), and leakage duration. This procedure was performed under different pulmonic pressure conditions (15/5 mm Hg, 28/11 mm Hg, 73/32 mm Hg) and normal aortic pressure (120/80 mm Hg) as a reference. Moving images were obtained using a Phantom MIRO M320S high-speed camera (Vision Research Inc, Wayne, NJ) at 600 frames per second and used to analyze valve area in closed position. RESULTS: Under normal pulmonic conditions (28/11 mm Hg) the leakage orifice area was 0.020 ± 0.012 mm2 for the 21-mm valve and 0.054 ± 0.041 mm2 for the 25-mm valve (P = .03). Hydrodynamic characteristics of the valves differed between pulmonary and aortic testing condition. Valve closing volumes were significantly lower under pulmonary hypotension and normal pulmonary conditions than under normal aortic conditions (P < .05). CONCLUSIONS: Under normal pulmonary pressure conditions, the hydrodynamic characteristics of Magna Ease valves are significantly different compared with aortic conditions. Further research is needed to determine whether these results are associated with prosthetic valve failure.

A stented bovine pericardial prosthesis in the pulmonary position.

BACKGROUND: Pulmonary valve replacement is very common among patients with congenital heart disease. The Carpentier Edwards Perimount valve (Edwards Lifesciences, Irvine, Calif), which was originally designed for the aortic position is among the most implanted valves. We aim to describe the follow-up of this valve in the pulmonary position. METHODS: Patients with a Perimount valve implanted between 2003 and 2013 in the University Medical Center Groningen were followed for the primary end point reintervention, defined as surgical or transcatheter valve replacement. Secondary end point was the occurrence of valve failure, defined as significant valvular regurgitation or stenosis. Explanted valves were histologically examined. RESULTS: Forty-five patients (median age at operation 27.8 years, 55.6% women) had a mean follow-up duration of 5.8 ± 3.3 years. There were 7 reinterventions (5 surgical and 2 transcatheter). Freedom from reintervention was respectively 95% ± 4% and 83% ± 8% at 5- and 10- years of follow-up. Freedom from valve failure was 75% ± 4% at 2 years, 65% ± 8% at 5 years of follow-up and 57% ± 10% at 10 years of follow-up. Morphology evaluation (n = 4) showed stiffened valves in the open position, with extensive fibrous tissue overgrowth on the leaflets and a variable proliferation of myofibroblasts. CONCLUSIONS: The Perimount valve has adequate function in the pulmonary valve position at 5 years of follow-up, although after 10 years of follow-up valve failure and reinterventions are common. Explanted valves show retraction and stiffening of the leaflets due to a fibrotic layer on both sides of the leaflet.

Concentric vs. eccentric remodelling in heart failure with reduced ejection fraction: clinical characteristics, pathophysiology and response to treatment.

AIMS: Heart failure is traditionally classified by left ventricular ejection fraction (LVEF), rather than by left ventricular (LV) geometry, with guideline-recommended therapies in heart failure with reduced ejection fraction (HFrEF) but not heart failure with preserved ejection fraction (HFpEF). Most patients with HFrEF have eccentric LV hypertrophy, but some have concentric LV hypertrophy. We aimed to compare clinical characteristics, biomarker patterns, and response to treatment of patients with HFrEF and eccentric vs. concentric LV hypertrophy. METHODS AND RESULTS: We performed a retrospective post-hoc analysis including 1015 patients with HFrEF (LVEF <40%) from the multinational observational BIOSTAT-CHF study. LV geometry was classified using two-dimensional echocardiography. Network analysis of 92 biomarkers was used to investigate pathophysiologic pathways. Concentric LV hypertrophy was present in 142 (14%) patients, who were on average older and more likely hypertensive compared to those with eccentric LV hypertrophy. Network analysis revealed that N-terminal pro-B-type natriuretic peptide was an important hub in eccentric hypertrophy, whereas in concentric hypertrophy, tumour necrosis factor receptor 1, urokinase plasminogen activator surface receptor, paraoxonase and P-selectin were central hubs. Up-titration of beta-blockers was associated with a mortality benefit in HFrEF with eccentric but not concentric LV hypertrophy (P-value for interaction ≤0.001). For angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the hazard ratio for mortality was higher in concentric hypertrophy, but the interaction was not significant. CONCLUSION: Patients with HFrEF with concentric hypertrophy have a clinical and biomarker phenotype that is distinctly different from those with eccentric hypertrophy. Patients with concentric hypertrophy may not experience similar benefit from up.-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers compared to patients with eccentric hypertrophy.

The Natural and Unnatural History of Congenital Aortic Arch Abnormalities Evaluated in an Adult Survival Cohort.

BACKGROUND: This study describes the different types of congenital vascular rings according to their anatomy, symptoms, and age at clinical onset and reports the surgical outcomes. METHODS: A retrospective observational database study was conducted, reviewing the medical charts of 69 adult survivors with a history of a vascular ring, identified from the Dutch Congenital Cor vitia database. RESULTS: Median age at presentation was 8.5 years (0-53.0 years). Thirty patients (43.5%) had a "left aortic arch with aberrant right subclavian artery," 21 patients (30.4%) a "double aortic arch," and 16 patients (23.2%) a "right aortic arch with aberrant left subclavian artery." The main symptomatology at presentation comprised respiratory symptoms (82.9%). Almost three-quarters of patients were also diagnosed with asthma/bronchial hyperreactivity. Patients with a double aortic arch had more symptoms than patients with a left aortic arch with aberrant right subclavian artery and right aortic arch with aberrant left subclavian artery (P < 0.001), requiring surgery most often (P < 0.001). In patients with childhood onset of symptoms, preoperative spirometry (ie, peak expiratory flows) was more often abnormal as compared with adult patients (P = 0.007). Surgery was performed in 42.0% of all patients at a median age of 17 years (0-63.0 years). Twenty-four (92.3%) of the operated patients showed improvement or complete relief of symptoms shortly after surgery. Of 26 asymptomatic nonoperated patients, 3 patients (11.5%) eventually developed symptoms. CONCLUSIONS: The low incidence of vascular rings, their anatomic heterogeneity, and a wide range of common symptoms often lead to misdiagnosis. Clinical awareness is warranted as a large subset of patients could benefit from surgery, even at an adult age.

Influence of Transvalvar Pressure Gradient on Hinge Washing in Closed Mechanical Prosthetic Cardiac Valves Under Pulmonary Pressure Conditions: A Comparative In Vitro Study.

OBJECTIVE: Hinge washing is a crucial factor in the prevention of mechanical prosthetic valvar thrombosis, especially in the pulmonary valve position. The aim of this laboratory study was to determine the relationship between pressure difference and the amount of hinge washing in the closed position, using the pressures that are normal for the right ventricle and pulmonary artery. METHODS: In an in vitro setting, four different bileaflet mechanical valves were tested for hinge washing in closed position. Based on similarity in inner diameter (range: 20.5-21.4 mm), the following valves were tested: Abbott SJM Regent size 23, Cryolife On-X size 23, LivaNova Carbomedics-R size 25, Medtronic Open Pivot (M-OP)-A size 25. Tests were carried out in a range between 3 and 100 mm Hg pressure difference, using water as a test fluid. The amount of leakage per minute through the closed valve was measured. RESULTS: All four valves showed an increase in leakage with increasing transvalvar gradient, and the relationship between pressure and leakage behaves in logarithmic fashion. Leakage under normal pulmonary diastolic pressure conditions (10 mm Hg) was between 23.3% and 29.3% of the leakage under aortic diastolic pressure conditions (80 mm Hg). The Cryolife On-X valve showed the highest closed leakage volume under pulmonary conditions (10 mm Hg) 0.254 ± 0.01 (L/min), where the Medtronic M-OP showed the lowest leakage volume with 0.125 ± 0.014 (mL/min). CONCLUSION: Hinge washing is related to transvalvar pressure difference in closed position. Valve brands differed significantly from each other in the amount of hinge washing.

High burden of drug therapy in adult congenital heart disease: polypharmacy as marker of morbidity and mortality.

AIMS: To assess medication use in adult congenital heart disease (ACHD) patients compared to the age- and sex-matched general population, identify patterns of pharmacotherapy, and analyse associations between pharmacotherapy and adverse outcomes in ACHD. METHODS AND RESULTS: Data of 14 138 ACHD patients from the CONCOR registry [35 (24-48) years, 49% male] and age- and sex-matched referents (1:10 ratio) were extracted from the Dutch Dispensed Drug Register for the years 2006-14. Adult congenital heart disease patients had more cardiovascular and non-cardiovascular drugs than referents (median 3 vs. 1, P < 0.001). Polypharmacy, defined as ≥5 dispensed drug types yearly, was present in 30% of ACHD and 15% of referents {odds ratio [OR] = 2.47 [95% confidence interval (CI) 2.39-2.54]}. Polypharmacy was independently associated with female sex [OR = 1.92 (95% CI 1.88-1.96)], older age [for men: OR = 2.3/10 years (95% CI 2.2-2.4) and for women: OR = 1.6/10 years (95% CI 1.5-1.6); Pinteraction < 0.001], and ACHD severity [mild: OR = 2.51 (95% CI 2.40-2.61), moderate: OR = 3.22 (95% CI 3.06-3.40), severe: OR = 4.87 (95% CI 4.41-5.38)]. Cluster analysis identified three subgroups with distinct medication patterns; a low medication use group (8-year cumulative survival: 98%), and a cardiovascular and comorbidity group with lower survival (92% and 95%, respectively). Cox regression revealed a strong association between polypharmacy and mortality [hazard ratio (HR) = 3.94 (95% CI 3.22-4.81)], corrected for age, sex, and defect severity. Polypharmacy also increased the risk of hospitalization for adverse drug events [HR = 4.58 (95% CI 2.04-10.29)]. CONCLUSION: Both cardiovascular and non-cardiovascular medication use is high in ACHD with twice as much polypharmacy compared with the matched general population. Patients with polypharmacy had a four-fold increased risk of mortality and adverse drug events. Recognition of distinct medication patterns can help identify patients at highest risk. Drug regimens need repeating evaluation to assess the appropriateness of all prescriptions. More high-quality studies are needed to improve ACHD care with more evidence-based pharmacotherapy.

Quality of Life Among Patients With Congenital Heart Disease After Valve Replacement.

Most studies concerning valve replacement in congenital heart disease (CHD) focus on surgical morbidity and mortality. However, with the increased life expectancy of these patients, the focus shifts to quality of life (QOL). The aim of this study was to report and compare the QOL of CHD patients after valve replacement with the general population and to find factors associated with QOL. In a multicenter cross-sectional observational study of adults with CHD, QOL was measured with the RAND-36 questionnaire (a health-related QOL questionnaire, with 8 domains scoring from 0 to 100; higher scores indicate a better QOL). Functional status was measured with exercise capacity testing. Uni- and multivariable linear regression was used to find associations with QOL. In total, 324 patients with CHD and a prosthetic valve were included in this study. CHD patients with a valve replacement scored significantly lower than the general population on the general health, vitality, and social functioning domains (P < 0.05). On the bodily pain domain, they scored significantly higher (less pain) (P < 0.001). Higher NYHA class was associated with a lower QOL for all domains, reflecting the importance of functional capacity. Other variables related to aspects of QOL were age, gender, exercise capacity, and employment status. Adult patients with CHD and a prosthetic valve have lower scores on the QOL domains general health, vitality, and social functioning as compared to the general population. NYHA class was negatively associated with all QOL domains. Health care professionals should be aware of these patterns in counseling patients.