"Too many cooks spoil the broth": the more antigens present, the easier, the quicker, and the more severe the anaphylaxis

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Adult congenital heart disease in Greece: Preliminary data from the CHALLENGE registry.

BACKGROUND: The majority of patients with congenital heart disease (CHD), nowadays, survives into adulthood and is faced with long-term complications. We aimed to study the basic demographic and clinical characteristics of adult patients with congenital heart disease (ACHD) in Greece. METHODS: A registry named CHALLENGE (Adult Congenital Heart Disease Registry. A registry from Hellenic Cardiology Society) was initiated in January 2012. Patients with structural CHD older than 16years old were enrolled by 16 specialized centers nationwide. RESULTS: Out of a population of 2115 patients with ACHD, who have been registered, (mean age 38years (SD 16), 52% women), 47% were classified as suffering from mild, 37% from moderate and 15% from severe ACHD. Atrial septal defect (ASD) was the most prevalent diagnosis (33%). The vast majority of ACHD patients (92%) was asymptomatic or mildly symptomatic (NYHA class I/II). The most symptomatic patients were suffering from an ASD, most often the elderly or those under targeted therapy for pulmonary arterial hypertension. Elderly patients (>60years old) accounted for 12% of the ACHD population. Half of patients had undergone at least one open-heart surgery, while 39% were under cardiac medications (15% under antiarrhythmic drugs, 16% under anticoagulants, 16% under medications for heart failure and 4% under targeted therapy for pulmonary arterial hypertension). CONCLUSIONS: ACHD patients are an emerging patient population and national prospective registries such as CHALLENGE are of unique importance in order to identify the ongoing needs of these patients and match them with the appropriate resource allocation.

Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry.

BACKGROUND/INTRODUCTION: The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. METHODS: In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m2; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. RESULTS: Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 and -29/-12 mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9 mmHg, respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10-mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24-h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. CONCLUSIONS: In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.

Contemporary antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: 1-year outcomes from the GReek AntiPlatElet (GRAPE) Registry.

UNLABELLED: Essentials The comparative efficacy and safety of antiplatelet agents in 'real life' is not clear. We recruited acute coronary syndrome patients receiving percutaneous coronary intervention. At 1-year follow-up, prasugrel offers better anti-ischemic protection than clopidogrel. Prasugrel and ticagrelor are accompanied by more frequent bleeding events. SUMMARY: Background The comparative efficacy and safety of antiplatelet treatment outside randomized trials is not clear. Objectives To investigate long-term efficacy and safety in 'real-life' acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with contemporary use of clopidogrel, prasugrel and ticagrelor. Methods In a prospective, observational, multicenter cohort study, 2047 patients were recruited into the GReek AntiPlatElet (GRAPE) Registry and were followed-up for 1 year for major adverse cardiovascular events (MACE, a composite of death, non-fatal myocardial infarction, urgent revascularization and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). Results Exposure to clopidogrel, prasugrel and ticagrelor by PCI occurred in 959, 363 and 717 patients, respectively. After adjustment, the rate of MACE (primary outcome endpoint) was lower in prasugrel-treated patients (4.4%) than in clopidogrel-treated patients (10.1%) (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.30-0.91), although not significantly different between ticagrelor (6.8%) and clopidogrel groups (HR, 0.78; 95% CI, 0.54-1.12). Any type of BARC-classified bleeding (secondary outcome endpoint) was more frequent in prasugrel-treated patients (51.2%) than in clopidogrel-treated patients (37.6%) (HR, 1.61; 95% CI, 1.33-1.95) and more frequent in ticagrelor-treated patients (56.9%) than in clopidogrel-treated patients (HR, 1.81; 95% CI, 1.55-2.10). An adjusted comparison between prasugrel and ticagrelor-treated groups did not reveal differences in any outcome measure. After adjustment, the death rate was more reduced by novel agents in comparison with clopidogrel (2.9% vs. 6.2%). Conclusions In ACS/PCI patients, prasugrel offered better anti-ischemic protection than clopidogrel, whereas use of both novel agents is accompanied by more frequent bleeding events.

Prasugrel versus high dose clopidogrel to overcome early high on clopidogrel platelet reactivity in patients with ST elevation myocardial infarction.

OBJECTIVE: There is a paucity of data regarding the early effectiveness of the proposed 600 mg clopidogrel loading dose (LD) on platelet reactivity (PR) in ST elevation myocardial infarction (STEMI) patients. If high on-treatment platelet reactivity (HTPR) is present, prasugrel reloading and subsequent maintenance dose (MD), might offer faster and stronger platelet inhibition than high clopidogrel MD. METHODS: In 93 STEMI patients treated by primary percutaneous coronary intervention we assessed PR using the VerifyNow P2Y12 platelet function test, 2 h following 600 mg LD of clopidogrel. All the 60 (64.5 %) patients exhibiting HTPR (defined as PR ≥ 235 P2Y12 reaction units), were randomized to 1 of 2 therapeutic strategies: reloading with prasugrel 60 mg/10 mg MD or high (150 mg) clopidogrel MD. RESULTS: The primary endpoint of PR at 24 h post randomization was lower in the prasugrel compared to the clopidogrel group (51.3, 25.7-77.0 versus 242.4, 215.8-268.9 P2Y12 reaction units, least square estimates, 95 % confidence intervals, p < 0.001). PR at 2 h and 5 days post randomization was lower in the prasugrel compared to the clopidogrel group (117.2, 70.9-163.4 and 101.6, 70.1-133.2 least square mean difference, 95 % confidence intervals, p < 0.001 for both). At all the time points of PR assessment, HTPR rates were lower in prasugrel than in clopidogrel group. CONCLUSIONS: HTPR is commonly observed early post 600 mg clopidogrel LD in STEMI patients. In this case, prasugrel 60 mg LD/10 mg MD provides faster and stronger platelet inhibition than a high clopidogrel MD regimen.

Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity.

BACKGROUND: High on-treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel. OBJECTIVES: The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR. PATIENTS/METHODS: We performed a prospective, single-center, single-blind, investigator-initiated, randomized, crossover study to compare platelet inhibition by prasugrel 10 mg day(-1) with that by high-dose 150 mg day(-1) clopidogrel in 21 patients on chronic HD with HTPR. Platelet function was assessed with the VerifyNow assay, and genotyping was performed for CYP2C19*2 carriage. RESULTS: The primary endpoint of platelet reactivity (PR, measured in P2Y12 reaction units [PRU]) was lower in patients receiving prasugrel (least squares [LS] estimate 156.6, 95% confidence interval [CI] 132.2-181.1) than in those receiving high-dose clopidogrel (LS 279.9, 95% CI 255.4-304.3), P < 0.001). The LS mean differences between the two treatments were - 113.4 PRU (95% CI - 152.9 to - 73.8, P < 0.001) and - 163.8 PRU (95% CI - 218.1 to - 109.2, P < 0.001) in non-carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%, P < 0.001) and in non-carriers (25.7% vs. 80%, P = 0.003). All carriers continued to show HTPR while receiving high-dose clopidogrel, but none showed it while receiving prasugrel. CONCLUSIONS: In HD patients exhibiting HTPR following standard clopidogrel treatment, prasugrel 10 mg day(-1) is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect seems to be influenced by carriage of the loss-of-function CYP2C19*2 allele.

Fever with multiple organ failure: not always sepsis.

We present the case of a 52-year-old female admitted with fever and multiple organ failure, initially treated for presumed sepsis. However the combination of multiple organ failure, hyperthermia and vascular instability raised the suspicion of a phaeochromocytoma multisystem crisis. An emergency abdominal ultrasound in the intensive care unit disclosed a large tumour of the right adrenal. Despite specific medical treatment for the presumed adrenal emergency and multiple organ failure, the patient succumbed. Postmortem examination verified the diagnosis of phaeochromocytoma.

Prednisolone and azathioprine in membranous nephropathy: a 10-year follow-up study.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Although its clinical course is usually benign, some patients develop chronic renal failure. Combination of corticosteroids with cytotoxic drugs and cyclosporin have been used in the treatment of the disease. Conflicting results are reported with the use ofprednisolone and azathioprine. In this study, the effect of treatment with prednisolone and azathioprine and the parameters related to a poor outcome over a follow-up period of 10 years is estimated. METHODS: 50 patients were included in this study; 33 were treated with prednisolone (initially 60 mg/day) and azathioprine (initially 2 mg/kg body weight/day) in gradually reduced doses for 26 +/- 9 months, whereas 17 patients received no immunosuppressive drugs. The clinical course was estimated using the end-points of doubling of baseline serum creatinine and/or end-stage renal failure (ESRF). The contribution of clinical and histological parameters in the clinical outcome was examined by univariate and multivariate analyses. RESULTS: Doubling of baseline serum creatinine was observed in 20 of 50 patients (40%), 14 from treated and 6 from the untreated group (42% vs. 35%, p=NS). ESRF developed in 10 of 50 patients (20%), 7 from treated and 3 from the untreated group (21% vs. 18%, p=NS). Most patients from both groups who reached the end-points had impaired renal function at presentation and persistent nephrotic syndrome during the follow-up period. Both parameters were identified as independent risk factors related to an unfavorable clinical outcome. No difference in the remission rate of nephrotic syndrome was observed between treated and untreated patients (51% vs. 58%, p=NS). CONCLUSION: Treatment with prednisolone and azathioprine seems to be of no long-term benefit in ameliorating the clinical course of nephrotic patients with membranous nephropathy. Thus, other therapeutic regimens including cyclophosphamide, chlorambucil or cyclosporin should be used in nephrotic IMN patients with poor prognostic features.

The right ventricle in congenital heart disease.

In patients with congenital heart disease the right ventricle (RV) may support the pulmonary (subpulmonary RV) or the systemic circulation (systemic RV). During the last 50 years evidence is accumulating that RV dysfunction develops in many of these patients and leads to considerable morbidity and mortality. Therefore RV function in certain groups of congenital heart disease patients needs close surveillance and timely and appropriate intervention to optimise outcomes. Despite major progress being made, assessing the RV either in the subpulmonary or the systemic circulation remains challenging, often requiring a multi-imaging approach and expertise (echocardiography, magnetic resonance imaging, nuclear and occasionally invasive assessment with angiography). This review discusses the implications of volume and pressure loading of the RV in the context of congenital heart disease and describes the most relevant imaging modalities for monitoring RV function.

Intrinsic histological abnormalities of aortic root and ascending aorta in tetralogy of Fallot: evidence of causative mechanism for aortic dilatation and aortopathy.

BACKGROUND: Dilatation of the aortic root is a known feature in tetralogy of Fallot (TOF) patients with pulmonary stenosis (PS) or pulmonary atresia (PA). We hypothesized that intrinsic histological abnormalities of the aortic wall present since infancy are an important causative factor leading to aortic root dilatation. METHODS AND RESULTS: We examined the aortic histology of 17 cases with TOF and PS/PA from our cardiac morphology archive and compared them with a control group of normal aortas. Measured circumference of the aortic root at the sinotubular junction and at the ascending aorta was indexed to the left ventricle. Aortic walls were studied by light microscopy with the use of various stains. Seventeen TOF cases (7 with PS, 10 with PA) including 7 infants, 2 children, and 8 adults were compared with 11 hearts with normal aorta. Aortic root circumference to left ventricular index and ascending aortic circumference to left ventricular index were 1.24+/-0.25 and 1.37+/-0.24, respectively, in the TOF group versus 0.89+/-0.10 and 0.88+/-0.11, respectively, in the control group (P<0.001). Histological changes of grade 2 or 3 were present in 29% (medionecrosis), 82% (fibrosis), 35% (cystic medial necrosis), and 59% (elastic fragmentation) in the ascending aorta of the TOF group. Histology grading scores were significantly higher in the TOF group (median score, 7; range, 1 to 12) compared with normal controls (median score, 2; range, 0 to 6) and correlated with the ascending aortic circumference to left ventricular index (r=0.525, P=0.03). CONCLUSIONS: There are marked histological abnormalities in the aortic root and ascending aortic wall of patients with TOF present from infancy, suggesting a causative mechanism for subsequent aortic root dilatation.

Intravenous magnesium sulfate versus diltiazem in paroxysmal atrial fibrillation.

BACKGROUND: Drugs currently available for the acute treatment of paroxysmal atrial fibrillation have significant limitations. We assessed the safety and effectiveness of intravenous magnesium sulfate versus diltiazem therapy in patients with prolonged episodes of paroxysmal atrial fibrillation. METHODS: In a prospective randomized trial, 46 symptomatic patients presenting with paroxysmal atrial fibrillation were given intravenous magnesium sulfate (n=23) or diltiazem (n=23) therapy. Primary outcome measures were effects on ventricular rate control and proportion of patients restored to sinus rhythm at 6 h after initiation of treatment. RESULTS: There were no differences in baseline characteristics between the two groups. Both forms of treatment were well tolerated, with no adverse clinical events. Both drugs had similar efficacy in reducing the ventricular rate at the first hour of treatment (P<0.05) with a tendency toward a further decrease during infusion times of 2 (P<0.01), 3, 4, 5 and 6 h, respectively (P<0.001). However, at the end of the 6-h treatment period, restoration of sinus rhythm was observed in a significantly higher proportion of patients in the magnesium group compared with the diltiazem group [13 of 23 patients, (57%), versus five of 23 patients, (22%), P=0.03]. CONCLUSIONS: Magnesium sulfate favorably affects rate control and seems to promote the conversion of long lasting episodes of paroxysmal atrial fibrillation to sinus rhythm, representing a safe, reliable and cost-effective alternative treatment strategy to diltiazem.

In-vivo testing of digital cellular telephones in patients with implantable cardioverter-defibrillators.

AIMS: To investigate the susceptibility of implantable cardioverter defibrillators to electromagnetic interference generated by digital cellular telephones, functioning in both international transmission technologies: the Global System for Mobile Communication (GSM) and the Digital Cellular System (DCS 1800). METHODS AND RESULTS: In 36 patients with transvenous implantable cardioverter defibrillators from two manufacturers (Medtronic and Guidant/CPI), cellular telephones with different levels of minimal and maximal power output were tested in the transmitting and receiving mode. Evaluation was performed in activated implantable defibrillators during spontaneous cardiac activity and continuous VVI or DDD pacing to assess possible electromagnetic interference. In two patients, appropriateness of ventricular fibrillation detection and therapy was judged during telephone testing. There was no damage, reprogramming, inappropriate shock therapy or pacing inhibition during the tests. In seven pre-pectoral Medtronic implantable defibrillators, transient electromagnetic interference caused 19 erroneous sensing events, when the operating phone was held in close vicinity to the programmer head. These 'pseudo-oversensing' events, which did not result in logging of arrhythmia episodes in the device counter, were interpreted as an adverse interaction between the telephone and the programming device. CONCLUSION: Digital cellular telephones do not represent a risk to Medtronic and Guidant/CPI recipients of the specific implantable defibrillator models herein tested.

Diagnostic superiority of continuous-loop electrocardiographic recording over other testing in a patient with recurrent syncope and underlying coronary artery disease with severe left ventricular dysfunction.

Dysrhythmic causes of syncope may elude diagnosis in postinfarction patients despite elaborate testing, including electrophysiologic study. For a correct diagnosis, capture of cardiac rhythm during patient's typical symptoms is crucial. This report describes a patient with coronary artery disease and decreased left ventricular ejection fraction who experienced recurrent syncopal episodes without obvious precipitating factors. The 12-lead electrocardiogram showed left bundle-branch block indicating a possible conduction abnormality as the underlying cause of syncope. Twenty-four-h Holter monitoring exhibited no sinus rhythm or conduction disturbances but revealed a nonsustained run of ventricular tachycardia. Findings at electrophysiologic testing led to a presumptive diagnosis of tachyarrhythmic cause of syncope; however, the correct diagnosis was only made with use of a loop monitor which documented a 15-s sinus pause during a syncopal episode.

Significance of R-on-T phenomenon in early ventricular tachyarrhythmia susceptibility after acute myocardial infarction in the thrombolytic era.

We investigated the clinical significance and mechanism of the R-on-T phenomenon in the current thrombolytic era as potential precipitant of R-on-T-induced early ventricular tachyarrhythmias in patients with a thrombolysed acute myocardial infarction. We also examined the role of QT dispersion on ventricular vulnerability and its association with R-on-T-initiated ventricular tachyarrhythmias. A total of 93 patients underwent 24-hour Holter monitoring starting at hospital admission before thrombolysis. Patients were classified into 2 groups: those with (n = 76) and those without (n = 17) reperfusion according to electrocardiographic criteria. All R-on-T ventricular premature complexes (VPCs) and R-on-T-initiated arrhythmic events (ventricular tachycardia [VT], ventricular fibrillation) were counted to estimate arrhythmia density and severity in 2 time periods during and after completion of thrombolysis. Measurements of QT and QTc intervals and dispersion parameters were obtained on the 12-lead electrocardiogram before thrombolysis and at 24 hours in patients with and without R-on-T VTs. Overall, R-on-T VPCs were rarely observed (1.8% of total VPCs over 24 hours), occurring more frequently during than after thrombolysis (at a rate of 8 vs 0.6 VPCs/hour, p = NS) and at a higher rate during thrombolysis in nonreperfused than in perfused patients (15 vs 8/hour, p = NS). Three VF episodes were observed in 1 reperfused patient, and all were R-on-T initiated. Episodes of nonsustained R-on-T VTs (3.3% of total VTs over 24 hours) appeared more frequent during than after thrombolysis (at a rate of 0.8 vs 0.05 VPCs/ hour, p = NS), and compared with non-R-on-T VTs they were significantly faster (374 +/- 56 ms vs 411 +/- 69 ms; p < 0.05), with a trend toward longer duration. Our findings indicate that R-on-T VPCs and R-on-T VTs are early rare features in acute myocardial infarction, and do not serve as triggers of severe ventricular tachyarrhythmia. The study of ventricular repolarization did not elicit an identifiable risk factor of R-on-T VT susceptibility.