Biomarker GDF-15 in cardiology.

GDF-15 (Growth differentiation factor 15) is a protein synthesised in some tissues including liver, kidney, heart, or lung. GDF-15 a stress-responsive cytokine. GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. GDF-15 is linked to the incidence and prognosis of heart failure. In acute coronary syndromes GDF-15 identifies risk of complications including bleeding, reinfarction, development of heart failure or mortality. In patients with atrial fibrillation, GDF-15 is a potent marker of bleeding adverse events in anticoagulated patients and a predictor of overall mortality. Role of GDF-15 in cardiology is not definitively constituted.

Role of gamma knife radiosurgery in the treatment of prolactinomas.

PURPOSE: Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS. METHODS: Twenty-eight patients were followed-up after GKRS for 26-195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients). RESULTS: After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient. CONCLUSIONS: GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.

Normative reference ranges for echocardiographic chamber dimensions in a healthy Central European population: results from the Czech post-MONICA survey.

BACKGROUND: Normative reference values for echocardiographic chamber quantification are of great importance; however, this can be challenging. Our aim was to derive these values including degrees of abnormality from a random Central European population sample with a homogeneous subset of healthy subjects. METHODS: We analysed echocardiograms obtained in a randomly selected population sample during the Czech post-MONICA survey in 2007/2008. Overall, 1850 out of 2273 persons of the whole sample of three districts had adequate echocardiograms (81.4%). A healthy subgroup defined by the absence of known cardiovascular disease was used to define normal reference range limits (n = 575, median age 42 years [IQR 34-52], 57% females). The whole population sample with predefined percentile cut-offs was used to define degrees of abnormality. RESULTS: Left ventricular (LV) size tended to decrease with age, while LV mass increased with age in both males and females and in both the healthy and general populations. LV dimensions were larger in males, except for body surface area-indexed LV diameter. M-mode derived LV measurements were larger and LV mass higher compared to 2D measurements. Right ventricle basal dimension was larger in males. CONCLUSIONS: Our study provides reference ranges for echocardiographic measurements obtained in a healthy subgroup derived from an epidemiological study of a Central European population. Where feasible, degrees of abnormality are provided based on the whole population sample including patients with disease. Our data show that age, gender and measurement method significantly affect cardiac dimensions and function and should be always taken into account.

3D electroanatomical mapping is less sensitive to atrial remodeling in estimation of true left atrial volume than echocardiography.

BACKGROUND: Left atrial (LA) enlargement has been identified as a predictor of worse clinical outcome after catheter ablation for atrial fibrillation (AF). We investigated the correspondence of LA size parameters assessed by echocardiography, CT and 3D electroanatomical mapping in patients with AF treated by catheter ablation. METHODS: We analyzed echocardiographic LA volume measurements by disc summation method (LAVDISC), computed tomography (LAVCT) and 3D electroanatomical mapping (LAVCARTO) in 100 pts. (71% males; aged 63 ± 8 years; paroxysmal AF in 55% of patients). RESULTS: Mean LAVDISC was 83 ± 25 ml (median: 115; IQR: 98-140 ml), mean LAVCT was 120 ± 34 ml (median: 115; IQR: 98-140 ml) and mean LAVCARTO was 123 ± 36 ml (median: 118; IQR: 99-132 ml). Pearson's correlation coefficient between LAVDISC a LAVCT was 0.6 (p < 0.0001) and between LAVCARTO and LAVCT was 0.79 (p < 0.0001). There was a significant difference between the two correlation coefficients (p < 0.004). The absolute difference between LAVCARTO and LAVCT (3.5 (95% CI -42 - 43) ml) was significantly lower (p < 0.0001) as compared to LAVDISC and LAVCT (- 39 (95% CI -102 - 24) ml). In opposite to LAVDISC, the bias between LAV obtained by CT and CARTO did not differentiate according to presence of spherical remodeling (1.7 ± 28 vs. vs. 5.1 ± 31 ml). Only presence of sinus rhythm was significant and independent covariate of the difference between CARTO and CT-derived LAVs by multivariate regression analysis. CONCLUSIONS: Even though LA volumes evaluated by 3D-electroanatomical mapping have quite good accuracy, the precision is low. For volumes estimated by echocardiography, both precision and accuracy are low.

Simplified apical four-chamber view evaluation of relative apical sparing of longitudinal strain in diagnosing AL amyloid cardiomyopathy.

AIM OF THE STUDY: To assess the diagnostic utility of a simplified approach to relative apical sparing of longitudinal strain (RAS LS) using only an apical four-chamber view (A4C) in patients with AL amyloid cardiomyopathy (ALAC). METHODS: We retrospectively evaluated echocardiographic recordings of 20 patients with ALAC, 20 patients with Fabry disease-related cardiomyopathy (FD), and 20 patients with concentric hypertensive left ventricular hypertrophy (HLVH) matched for mean LV mean thickness. Peak segmental LS values of the interventricular septum and lateral LV wall were measured in the A4C using two-dimensional speckle-tracking echocardiography. RAS LS was calculated as average apical LS/(average basal LS + average midventricular LS). RESULTS: Relative apical sparing of longitudinal strain values in patients with ALAC (1.23 ± 0.64) were significantly higher than those in FD patients (0.75 ± 0.19, P < 0.05) as well as in individuals with HLVH (0.75 ± 0.23, P < 0.05), but with a significant overlap. The optimal RAS LS value differentiating ALAC from FD and HLVH with 70% sensitivity and 75% specificity was 0.88 (AUC 0.79). In multivariate modeling, RAS LS was significantly additive to traditional predictors of ALAC (low QRS voltage and pseudoinfarct ECG patterns, pericardial effusion, E/e' ratio, E-wave deceleration time; P < 0.05 for all models). CONCLUSIONS: Simplified RAS LS evaluation represents an attractive approach for diagnostics of ALAC. However, because of considerable overlap with other disorders with hypertrophic phenotype, the analysis of RAS LS in the A4C should be combined with other traditional echocardiographic and ECG predictors in differentiating ALAC from other forms of concentric LV wall thickening.

Comparison of echocardiographic parameters in Fabry cardiomyopathy and light-chain cardiac amyloidosis.

BACKGROUND: Fabry cardiomyopathy (FC) and light-chain amyloid cardiomyopathy (AL) present with concentric left ventricular (LV) hypertrophy/remodeling and diastolic rather than systolic dysfunction. Direct comparisons are difficult due to rarity and confounded by variability of LV thickness. AIMS: To compare LV diastolic and systolic properties between patients with FC and AL in a cohort matched for interventricular septal thickness (IVS). METHODS: A two-center echocardiographic analysis was performed, comprising 118 patients with IVS ≥12 mm (FC and AL 59 patients each) matched by IVS. RESULTS: Fabry cardiomyopathy patients had larger LV end-diastolic diameter (47.7 [44.0-50.9] vs 45.0 [41.5-49.0] mm, P = 0.002), better LV ejection fraction (EF 68.7 [63.4-74.0] vs 63.0 [54.0-70.0]%, P = 0.001) and midwall fractional shortening (midFS 14.8 [13.0-16.1] vs 12.1 [8.9-15.0]%, P = 0.006). LV EF <40% was rare in both (2% vs 7%, P = 0.17). AL patients expressed higher LV diastolic dysfunction grade (III in 26% vs 4%, II in 21% vs 12% and I in 54% vs 84%, P = 0.004), with higher E/e' ratio (13.6 [10.2-18.8] vs 9.8 [7.5-12.3], P < 0.0001). Average E/e' ratio and midFS were significantly associated with NYHA severity in both groups (P < 0.05 for all). CONCLUSIONS: Matched AL patients had worse LV diastolic function than FC, driven by E/e'. Significant LV systolic dysfunction was rare overall. MidFS and E/e' were associated with heart failure severity in both groups.

The effect of renal denervation in an experimental model of chronic renal insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study).

BACKGROUND: Renal denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD) due to ischemia with increased activity of the renin-angiotensin-aldosterone system (RAAS), renal denervation can have protective effects by slowing or blocking the progression of renal injury. METHODS: An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model). 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. RESULTS: Viable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of kidney, also did not show significant difference between groups. CONCLUSIONS: In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.

[Treatment of pituitary adenomas]. / Lécba hypofyzárních adenomu.

Pituitary adenomas are the most common tumours of the sellar region. A combination of neurosurgery, radiation and pharmacological approaches are applied for the treatment of pituitary adenomas. In certain cases, patient observation is another option. Neurosurgery is the first-choice treatment for acromegaly, Cushing´s disease and TSH secreting adenomas. Leksell gamma knife irradiation is used in the treatment of tumour residues. Until the effect of the irradiation is evident, pharmacological treatment must be administered. Large and/or growing non-functioning pituitary adenomas are operated. Irradiation is possible if there is sufficient distance between the margin of the adenoma and the optic pathway. The primary therapy for prolactinomas is pharmacological treatment with dopamine agonists. Multidisciplinary collaboration among endocrinologists, neurosurgeons and radiosurgeons is necessary in the treatment of pituitary adenomas.

[TSH secreting adenomas]. / TSH produkující adenomy.

Adenomas which secrete thyrotropic hormone (thyrotropinomas) are rare and constitute less than 3 % of pituitary adenomas. In laboratory studies there is a typical elevation of thyroid hormones with nonsupressible TSH. In differential diagnostics it is necessary to distinguish above all the syndrome of resistance to thyroid hormones. Clinical symptoms are usually mild and correspond to symptoms of hyperthyroidism. Goiter is a common finding. In 80 % of cases thyrotropinomas are diagnosed in a stage of invasively growing macroadenoma. The primary treatment is neurosurgical removal adenoma which results in cure in 40 % of patients. Other treatment options include radiation therapy and medical treatment (treatment with somatostatin analogues). With regard to the risk of adenoma recurrence, the long-term follow-up is similar to that of cases of other pituitary adenomas necessary.Key words: resistance to thyroid hormone - TSH secreting adenoma - thyreotropin.

Gamma knife radiosurgery for Cushing's disease and Nelson's syndrome.

PURPOSE: This paper presents our 18 years of experience in treating ACTH secreting adenomas (Cushing's disease and Nelson's syndrome) using the Leksell gamma knife (LGK) irradiation. METHODS: Twenty-six patients with Cushing's disease were followed-up after LGK irradiation for 48-216 months (median 78 months). Seventeen patients had undergone previous surgery, in nine patients LGK irradiation was the primary therapy. Furthermore, 14 patients with Nelson's syndrome were followed-up for 30-204 months (median 144 months). RESULTS: LGK treatment resulted in hormonal normalization in 80.7 % of patients with Cushing's disease. Time to normalization was 6-54 months (median 30 months). The volume of the adenoma decreased in 92.3% (in 30.7% disappeared completely). There was no recurrence of the disease. In all 14 patients with Nelson's syndrome ACTH levels decreased (in two patients fully normalized) their ACTH levels. When checked up 5-10 years after irradiation regrowth of the adenoma was only detected in one patient (9.1%), in 27.3% adenoma volume remained unchanged, in 45.4% adenoma volume decreased and in 18.2% adenoma completely disappeared. Hypopituitarism did not develop in any patient where the critical dose to the pituitary and distal infundibulum was respected. CONCLUSION: LGK radiation represents an effective and well-tolerated option for the treatment of patients with Cushing's disease after unsuccessful surgery and may be valuable even as a primary treatment in patients who are not suitable for, or refuse, surgery. In the case of Nelson's syndrome it is possible to impede tumorous growth and control the size of the adenoma in almost all patients.

[Contemporary options and perspectives in the treatment of acromegaly]. / Soucasné moznosti a perspektivy lécby akromegalie.

Acromegaly, if untreated, leads to numerous complications and premature death of patients. In recent years, significant changes in the treatment of acromegaly were achieved. The surgical approach was innovated, what allows completely selective removal of most microadenomas without any damage of the pituitary and safe debulking of the tumor mass in macroadenomas. Radiosurgery took the first place among irradiation methods, in our conditions it is the irradiation by the Leksell gamma knife. It allows selective irradiation of an adenoma without damaging the surrounding tissue. However, its effect on the secretory activity of the adenoma remains to be long lasting. Before this effect is attained, it is necessary to suppress the secretory activity pharmacologically. The infrequently effective, but economically advantageous and comfortable for patients is cabergoline, which is administered in tablet form. If cabergolin is not efficient, depot injections of somatostatin analogues - octreotide LAR and lanreotide autogel or their combination with cabergoline are used. The most efficient but financially costly is pegvisomant, blocking the receptors for growth hormone. In our conditions it is reserved for patients unresponsive to other treatments. With sufficient dosage it is possible to normalize hormonal activity of acromegly in 95 % of patients. New forms of the drugs as octreotide implants, oral octreotide octreolin or a new blocker of growth hormone receptors ATL-1103 are in the development.

Long-term outcomes and reverse remodelling in recently diagnosed unexplained left ventricular systolic dysfunction.

AIMS: In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. METHODS AND RESULTS: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m2. LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P < 0.05 for all). CONCLUSIONS: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.

Feature tracking measurement of dyssynchrony from cardiovascular magnetic resonance cine acquisitions: comparison with echocardiographic speckle tracking.

BACKGROUND: Analysis of left ventricular (LV) mechanical dyssynchrony may provide incremental prognostic information regarding cardiac resynchronization therapy (CRT) response in addition to QRS width alone. Our objective was to quantify LV dyssynchrony using feature tracking post processing of routine cardiovascular magnetic resonance (CMR) cine acquisitions (FT-CMR) in comparison to speckle tracking echocardiography. METHODS: We studied 72 consecutive patients who had both steady-state free precession CMR and echocardiography. Mid-LV short axis CMR cines were analyzed using FT-CMR software and compared with echocardiographic speckle tracking radial dyssynchrony (time difference between the anteroseptal and posterior wall peak strain). RESULTS: Radial dyssynchrony analysis was possible by FT-CMR in all patients, and in 67 (93%) by echocardiography. Dyssynchrony by FT-CMR and speckle tracking showed limits of agreement of strain delays of ± 84 ms. These were large (up to 100% or more) relative to the small mean delays measured in more synchronous patients, but acceptable (mainly <25%) in those with mean delays of >200 ms. Radial dyssynchrony was significantly greater in wide QRS patients than narrow QRS patients by both FT-CMR (radial strain delay 230 ± 94 vs. 77 ± 92* ms) and speckle tracking (radial strain delay 242 ± 101 vs. 75 ± 88* ms, all *p < 0.001). CONCLUSIONS: FT-CMR delivered measurements of radial dyssynchrony from CMR cine acquisitions which, at least for the patients with more marked dyssynchrony, showed reasonable agreement with those from speckle tracking echocardiography. The clinical usefulness of the method, for example in predicting prognosis in CRT patients, remains to be investigated.

Three-dimensional echocardiographic left ventricular strain analysis in Fabry disease: correlation with heart failure severity, myocardial scar, and impact on long-term prognosis.

AIMS: Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis. METHODS AND RESULTS: 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = -0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = -0.38, P < 0.001) or 3D LVEF (r = -0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75-0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324). CONCLUSION: 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.

Does Secondary Antibiotic Prophylaxis Improve Clinical Outcomes in Adult Rheumatic Heart Disease Patients Post-Valve Replacement?

BACKGROUND: Secondary prevention of recurrent rheumatic fever in individuals with rheumatic heart disease (RHD) requires continuous antibiotic prophylaxis. However, the impact of antibiotic prophylaxis on the outcome of patients with severe RHD who underwent heart valve replacement is unknown. The objective of the study was to assess the relationship between the use of antibiotics as secondary prophylaxis in RHD patients who underwent valve replacement and clinical outcomes including mortality, reoperation, and valve-related hospitalization. METHODS: We retrospectively compared outcomes of adult patients who underwent heart valve replacement for RHD at our institution from 1990 through 2014 and who received secondary antibiotic prophylaxis (prophylaxis group) with those who did not receive prophylaxis (nonprophylaxis group) using propensity score matching analysis. RESULTS: A total of 1094 patients (56% females, median age 40 years, range 31-53 years) were included with a median follow-up of 9.6 years (range 2.9-12.6 years). Antibiotic prophylaxis was prescribed in 201 patients (18%). Propensity score matching analysis demonstrated no significant difference in overall survival (95% [92%-98%] vs 97% [95%-99%], respectively; P = .7), valve-related hospitalization-independent survival (72% [range 65%-78%] vs 81% [range 76%-88%]; P = .25), and redo valve surgery-independent survival [76% [range 70%-83%] vs 75% [range 72%-79%]; P = .41) at 10-year follow-up in the nonantibiotic prophylaxis versus the antibiotic prophylaxis group. CONCLUSION: Secondary antibiotic prophylaxis among adult RHD patients following valve replacement is not associated with improved clinical outcomes.

Dopamine 2 receptor expression in various pathological types of clinically non-functioning pituitary adenomas.

Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors (D2R). The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation. With the use of the reverse transcriptase PCR technique, D2R mRNA was expressed in all adenomas with very heterogeneous quantity. The expression was very low in corticotroph adenomas (relative median quantity after normalization to housekeeping gene 0.01) and lower in plurihormonal tumors (median 0.4) than in gonadotroph (median 1.3) and null-cell adenomas (median 1.9). The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins. We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity.

Heart failure in Fabry disease revisited: application of current heart failure guidelines and recommendations.

AIMS: Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain. METHODS AND RESULTS: We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow-up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58 ± 11 years, 62% male). HF with preserved ejection fraction (HF-pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e' > 9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) <16% (sensitivity 54% and specificity 88%). Log N-terminal pro-brain natriuretic peptide correlated significantly with LVMi (r = 0.60), E/e' (r = 0.54), and GLS (r = 0.52) (all Ps < 0.001) but not with left ventricular ejection fraction (r = -0.034, P = 0.72). During follow-up (mean 1208 ± 444 days), patients diagnosed with HF had a higher rate of all-cause mortality and worsening HF (33% vs. 1.5%, P < 0.001). Abnormal LVMi, E/e' > 9, and GLS < 16% were all associated with higher all-cause mortality and worsening HF. CONCLUSIONS: This study found a high prevalence of symptomatic HF in FD patients. HF-pEF was the dominant phenotype. LVMi, E/e', and GLS yielded the highest diagnostic utility for HF diagnosis and were significantly correlated with natriuretic peptides levels. Echocardiographic criteria proposed by current ESC HF guidelines apply to Fabry patients and predict cardiovascular events. At follow-up, Fabry patients with HF diagnosis had high event rates and significantly worse prognosis than patients without HF.

Usefulness of Alcohol Septal Ablation in the Left Ventricular Outflow Tract Obstruction in Fabry Disease Cardiomyopathy.

Fabry disease (FD) is an X-linked linked genetic disorder caused by α-galactosidase A deficiency. The typical clinical manifestation is left ventricular hypertrophy, often mimicking hypertrophic cardiomyopathy (HC). In contrast to sarcomeric HC, left ventricular outflow tract obstruction (LVOTO) is less frequent. We describe 6 male patients with genetically confirmed FD and symptomatic LVOTO. All of them underwent a transcatheter alcohol septal ablation with an immediate effect on the obstruction in all cases and without any serious complications. The median LVOT maximal pressure gradient was 85 (60 to 170) mm Hg. The hemodynamic effect persisted during subsequent follow-up (ranging from 6 months to 16 years). Five patients reported substantial symptomatic improvement. Four patients were receiving specific FD therapy before the interventional procedure. In conclusion, alcohol septal ablation appears to be effective in the treatment of LVOTO in patients with FD and appears to be comparable to the limited published experience with surgical septal myectomy. Despite some important differences between FD HC and sarcomeric HC, the recommendation for treating LVOTO should be similar.

Diagnostic Accuracy of Dobutamine Stress Echocardiography for Detection of Cardiac Allograft Vasculopathy in Orthotopic Heart Transplant Patients.

OBJECTIVE: Cardiac allograft vasculopathy is one of the leading causes of late graft failure and subsequent death in orthotopic heart transplant. Although invasive coronary angiography is the gold standard modality for detection of cardiac allograft vasculopathy, dobutamine stress echocardiography has been recently frequently used as an alternative. Our aim was to evaluate the diagnostic performance of dobutamine stress echocardiography for detection of cardiac allograft vasculopathy in transplant patients. METHODS: A retrospective analysis was conducted using a total of 150 dobutamine stress echocardiographic exams that were performed on 99 patients in our institution, with paired coronary angiogram and no acute rejection, within a median of 538 [interquartile range 371-816] days. Sensitivity and specificity of dobutamine echocardiography to detect allograft vasculopathy was evaluated. Allograft vasculopathy was defined as Grade 1 or higher based on ISHLT criteria. A positive dobutamine stress echo result was defined by new or worsening wall motion abnormality. RESULTS: Median age of the population at transplant was 34 [interquartile range 22-46] years; 76 (77%) patients were male. Allograft vasculopathy was present in 31 (20.6%) out of 150 coronary angiograms. Only 7 (4.6%) of that number were positive on dobutamine stress echocardiography. Sensitivity and specificity for allograft vasculopathy detection was 3% and 94%, respectively. Out of 7 false positive dobutamine stress echocardiograms, two were in patients with myocardial bridging. Two patients with mild acute rejection had both negative dobutamine stress echo. CONCLUSIONS: Overall, positivity of dobutamine stress echocardiography in patients after heart transplant is low. It has high specificity, but very low sensitivity for detection of cardiac allograft vasculopathy. Dobutamine stress echocardiography should only be cautiously used as an alternative to coronary angiography.

Combined valve replacement and aortocoronary bypass in an adult mucopolysaccharidosis type VII patient.

Mucopolysaccharidosis type VII (MPS VII) is a rare autosomal recessive lysosomal storage disorder. MPS VII is caused by mutations in the GUSB gene that encodes ß-glucuronidase. Adult MPS VII patients present with musculoskeletal abnormalities, coarse features, and corneal clouding. Cardiac and valvular impairment are common; however, severe valvular disease necessitating surgery has not yet been reported. We present a 32-year-old male MPS VII patient admitted to our hospital with decompensated heart failure. We identified aortic valve disease with severe stenosis (valve area 0.69 cm2) and moderate regurgitation. Severe mitral valve stenosis (valve area 1 cm2) with moderate to severe regurgitation was also found in the patient. In addition, an occlusion of the right coronary artery (RCA) was documented. The patient underwent surgical replacement of the mitral and aortic valves with mechanical prostheses and implantation of a venous bypass graft to his RCA. The surgery led to a significant improvement of his clinical symptoms. Six months after the procedure, both mechanical valves function normally. Histopathological assessment identified chronic inflammatory infiltrates, fibrosis and calcifications in both resected valves. Foamy cytoplasmic transformation was most evident in the valvular interstitial cells. The ultrastructural vacuolar abnormality seen in these cells corresponded to storage changes observed in other MPSs. In conclusion, we describe clinical findings and valvular pathology in an MPS VII patient with the first-reported successful combined surgical valve replacement and myocardial revascularization. The histological and ultrastructural analyses revealed that the lysosomal storage predominantly affected the valvular interstitial cells.