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.

Heart transplantation in a low-organ-donation environment: a single center experience.

OBJECTIVE: Heart transplantation is the "gold standard" for treating patients in end-stage heart failure who satisfy strict selection criteria. However, infrequent transplant performance, eg, less than nine per year, may be associated with suboptimal results. METHODS: We reviewed our 13-year clinical experience (1996-2008) with 73 orthotopic heart transplants performed under strict selection criteria and followed closely thereafter at the only accredited center in Greece, a country with an annual rate of only seven donors per million population. RESULTS: Low perioperative (5.47%) and long-term (7.5%) mortality rates were responsible for a 94% survival rate in the first year, 92% at five years, and 70% at ten years-similar to those reported worldwide-along with excellent functional recovery. CONCLUSION: Strict recipient and donor selection criteria, combined with a rigorous multidisciplinary follow-up, yield excellent results despite the existing shortage of available grafts.

Long-term oral bosentan treatment in patients with pulmonary arterial hypertension related to congenital heart disease: a 2-year study.

OBJECTIVE: To evaluate the long-term clinical and exercise effect of chronic oral administration of the non-selective endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). DESIGN: Extension of a preceding prospective non-randomised open clinical study on bosentan treatment in PAH related to CHD. SETTING: A tertiary referral centre for cardiology. PATIENTS: 19 of the original 21 patients of mean (standard deviation (SD)) age 22 (3) years (13 with Eisenmenger syndrome) in World Health Organization (WHO) class II-IV and having a mean (SD) oxygen saturation of 87 (2) %. INTERVENTION: Patients received bosentan treatment for 2.4 (0.1) years and underwent clinical and exercise evaluation at baseline, 16 weeks and 2 years of treatment, with haemodynamic assessment at baseline and 16 weeks. RESULTS: All patients remained stable with sustained subjective clinical and WHO class improvement (p<0.01) at 16 weeks and 2 years of treatment without significant side effects or changes in oxygen saturation. After the initial 16-week improvement (p<0.05) in peak oxygen consumption and exercise duration at treadmill test, and walking distance and Borg dyspnoea index at 6-min walk test, all exercise parameters appeared to return to their baseline values at 2 years of follow-up. CONCLUSIONS: Long-term bosentan treatment in patients with PAH related to CHD is safe and induces clinical stability and improvement, but the objective exercise values appear to slowly return to baseline. Larger studies on long-term endothelin receptor antagonism including quality of life assessment are needed to evaluate the therapeutic role of bosentan in this population.

Cardiac repair--fact or fancy?

Patients with ischemic cardiomyopathy have a poor prognosis despite all pharmacological, interventional and surgical treatment modalities currently applied. Heart transplantation remains the ideal treatment for this group of patients but the scarcity of donors hinders its widespread application. The autologous transplantation of stem cells (SCs) for cardiac repair is emerging as a new therapy for patients with myocardial dysfunction early after an acute infarction or ischemic cardiomyopathy. The rationale of this novel method is the enhancement of the repair mechanisms achieved by tissue-specific and circulating stem/progenitor cells. SCs assist naturally occurring myocardial repair by contributing to increased myocardial perfusion and contractile performance especially in the setting of acute myocardial infarction (AMI), but also in patients with chronic ischemic heart failure and advanced, diffuse coronary artery disease. The exact mechanism of their action has not been fully elucidated. Few studies continue to suggest a formation of few new contractile tissue. The majority if investigators believe that these cells do not persist long in the myocardium but that they secrete vascular growth and other cardioprotective factors.

Iloprost for prevention of contrast-mediated nephropathy in high-risk patients undergoing a coronary procedure. Results of a randomized pilot study.

OBJECTIVE: The prevention of contrast-mediated nephropathy (CMN), which accounts for considerable morbidity and mortality, remains a vexing problem. Contrast induced renal vasoconstriction is believed to play a pivotal role in the CMN mechanism. The aim of this pilot study was to examine the safety and efficacy of two doses of the prostacyclin analogue iloprost in preventing CMN in high-risk patients undergoing a coronary procedure. METHODS: Forty-five patients undergoing coronary angiography and/or intervention who had a serum creatinine concentration >or=1.4 mg/dL were randomized to receive iloprost at 1 or 2 ng/kg/min or placebo, beginning 30-90 minutes before and terminating 4 hours after the procedure. CMN was defined by an absolute increase of serum creatinine >or=0.5 mg/dL or a relative increase of >or=25% measured 2 to 5 days after the procedure. Study drug infusion was discontinued in 2 patients in the low-dose iloprost group due to flush/nausea and in 5 patients in the high-dose group due to severe hypotension. RESULTS: The mean creatinine concentration change in the placebo group (0.02 mg/dL) was unfavorable compared to that in the low-dose iloprost group (-0.11 mg/dL; p=0.08) and high-dose iloprost group (-0.23 mg/dL; p=0.048). The difference between the absolute changes in creatinine clearance was favorable compared to placebo for both the low (mean difference 6.1 mL/min, 95%CI -0.5 to 12.8 mL/min, p=0.07) and the high-dose iloprost group (11.8 mL/min, 95%CI 4.7 to 18.8 mL/min, p=0.002). Three cases of CMN were recorded; all in the placebo group (p=0.032). CONCLUSIONS: The results of this pilot study suggest that prophylactic administration of iloprost may effectively prevent CMN, but higher dosages are connected with substantial tolerability issues.

Effect of the oral endothelin antagonist bosentan on the clinical, exercise, and haemodynamic status of patients with pulmonary arterial hypertension related to congenital heart disease.

OBJECTIVE: To evaluate the clinical, exercise, and haemodynamic effects of chronic oral administration of the non-selective endothelin receptor antagonist bosentan on patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). DESIGN: Prospective non-randomised open clinical study. SETTING: Cardiology tertiary referral centre. PATIENTS: 21 patients with a mean (SEM) age of 22 (3) years with chronic PAH related to CHD (15 with Eisenmenger's syndrome). Patients were in World Health Organization (WHO) class II to IV with oxygen saturation 87 (2)%. INTERVENTION: Patients underwent clinical, exercise, and haemodynamic evaluations at baseline and after 16 weeks of treatment. RESULTS: Bosentan improved (p < 0.01) WHO class, peak oxygen consumption from 16.8 (1.4) to 18.3 (1.4) ml/kg/min, exercise duration from 9.0 (0.8) to 10.7 (0.6) minutes during the treadmill test, walking distance from 416 (23) to 459 (22) m, and Borg dyspnoea index from 2.8 (0.2) to 2.0 (0.1) during the six minute walk test. Bosentan treatment improved (p < 0.05) mean pulmonary artery pressure from 87 (4) to 81 (4) mm Hg, pulmonary blood flow index from 3.2 (0.4) to 3.7 (0.5) l/min/m2, pulmonary to systemic blood flow ratio from 1.2 (0.2) to 1.4 (0.2), and pulmonary vascular resistance index from 2232 (283) to 1768 (248) dyn.s.cm(-5). Two patients died, presumably of arrhythmic causes, who were in WHO class IV at baseline and who had improved during treatment. CONCLUSIONS: Bosentan induces short and mid term clinical, exercise, and haemodynamic improvements in patients with PAH related to CHD. Larger studies with long term endothelin receptor antagonism are needed to assess the safety and possible treatment role of bosentan in this population.

Image quality criteria in cardiology.

Image quality evaluation plays a key role in the process of optimisation in radiological procedures. Image quality criteria for cardiac cine-angiography were recently agreed as part of a European Research Project, and a scoring system based on these criteria has been developed to allow an 'objective' measurement of the quality of cardiac angiograms. Two studies aimed at the evaluation of the methodology have been completed, demonstrating that the method can be applied to cardiac images and translated into a scoring system that yields reproducible data. Based on the results of these studies, quality criteria have been further reviewed by DIMOND III panel and the updated version is presented in this paper.

A study to validate the method based on DIMOND quality criteria for cardiac angiographic images.

A method based on image quality criteria (QC) for cine-angiography was developed to measure the quality of cine-angiograms (CA). A series of 30 CA for left ventriculography (LV) and left and right coronary angiography (LCA, RCA) have been scored and 172 readings were obtained. Standard deviation of quality scores indicated the reproducibility of the method. Each part of CA was examined separately, giving scores for LV, LCA and RCA and a total score (TS), with clinical (C) and technical (T) criteria defined and examined separately. In 83% of the studies TS was >0.8 and with standard deviation from 0.02 to 0.21. In general, LV had a lower score and greater disagreement compared with RCA and LCA. Disagreement was greater in T, compared with C. In conclusion, these results indicate that QC, translated into a scoring system, yields reproducible data on the quality of cardiac images.

TNF-alpha, TGF-beta1, IL-10, IL-6, gene polymorphisms in latent autoimmune diabetes of adults (LADA) and type 2 diabetes mellitus.

Abundant evidence suggests that cytokines involve in the pathogenesis of latent autoimmune diabetes of adults (LADA). This is a slowly progressive form of type 1 diabetes, which is initially diagnosed as type 2 diabetes. In this study, healthy individuals LADA and type 2 diabetic patients were genotyped for IL-6-174G/C, TNF-alpha-308A/G, TGF-beta1-codon10T/C, TGF-beta1-codon25G/C, IL-10-1082A/G, IL-10-819T/C, IL-10-592A/C gene polymorphisms, by sequence-specific-primer polymerase chain reaction methodology. A significant difference in the frequencies of -1082A/G IL-10 alleles was observed, with the -1082*A allele (known to be associated with low IL-10 production), predominating in LADA diabetics than type 2 diabetics (p=0.036). No significant differences of genotypes, phenotypes, or haplotype frequencies in the remaining cytokine polymorphisms were observed. Analysis of allele combinations revealed a significant involvement of the low and high in vitro production IL-10 alleles in the development of LADA and type 2 diabetes, respectively. These results suggest that the G/A mutation at position -1082 of IL-10 promoter gene region might be one of the factors participating to the pathogenesis of LADA diabetes and that identification of cytokine gene polymorphisms might contribute to the characterization of the different types of diabetes mellitus.

Coronary flow: clinical considerations.

In the measurement of coronary blood flow to determine the success of percutaneous coronary intervention, invasive techniques, coupled with plaque characterisation and other intracoronary imaging modalities, may prove invaluable.

Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine.

BACKGROUND: Statins are widely used to decrease cholesterol and improve morbidity and mortality associated with coronary artery disease. Myopathy constitutes a rare but potentially life-threatening adverse reaction, which is related to plasma HMG-CoA reductase inhibitory activity. Therefore, the incidence of rhabdomyolysis increases dramatically when statins are co-administered with drugs that inhibit their hepatic transformation, such as cyclosporine or azoles. METHODS AND RESULTS: We present a case of severe rhabdomyolysis and acute renal failure induced by itraconazole in a heart transplant recipient chronically treated with cyclosporine and simvastatin. The literature with regard to the pathogenetic mechanisms and the clinical implications are reviewed. CONCLUSIONS: To avoid severe myopathy, cyclosporine levels should be monitored sooner than weekly intervals and statins should be discontinued or their dosage should be reduced, as long as azoles need to be prescribed in transplant recipients. Rhabdomyolysis and acute renal insufficiency should be promptly recognized and aggressively treated.

Quality criteria for cardiac images in diagnostic and interventional cardiology.

The quality of cardiac imaging plays a pivotal role in clinical decision-making and depends mainly on the technical performance of the imaging system and on angiographic technique. The Italian Society of Invasive Cardiology and The Italian Society of Physics in Medicine have set quality criteria giving precise guidelines regarding how an angiogram should appear provided that good equipment and correct angiographic technique are used. The criteria have been reviewed by the European Concerted Action DIMOND Cardiology group and are reported here to provide a reference standard for images for the most common procedures in daily practice.

Intracoronary irradiation and stent placement in a chronic total coronary occlusion: long-term clinical, angiographic, and intracoronary ultrasound follow-up.

Intracoronary irradiation emerges as a promising method in a variety of restenosis prone coronary lesions. We report the acute and long-term clinical, angiographic, and ICUS follow-up of a patient who underwent a successful angioplasty with stent placement in a chronic coronary occlusion with adjuvant gamma-intracoronary radiation.

Prediction of restenosis after coronary angioplasty by use of a new index: TIMI frame count/minimal luminal diameter ratio.

BACKGROUND: It has been shown recently that postangioplasty coronary flow reserve and the degree of residual stenosis have a modest predictive value for short- and long-term clinical outcomes after coronary angioplasty. Corrected TIMI frame count (CTFC) is a simple quantitative index of coronary blood flow. Its relationship with Doppler coronary flow velocity and clinical outcome after coronary angioplasty has not been fully clarified. The aim of this study was to identify clinical, angiographic, and functional predictors of clinical and angiographic restenosis after conventional coronary angioplasty. METHODS AND RESULTS: We studied 70 consecutive patients in whom intracoronary Doppler flow-velocity measurements were performed before and after angioplasty. Patients were evaluated for restenosis by clinical follow-up, exercise stress test/(201)Tl scintigraphy, and follow-up angiography, which was performed at 10. 5+/-10.3 months in 63 patients. According to the results of univariate analysis, a new index, postangioplasty CTFC/minimal luminal diameter (MLD) ratio, was created. Multivariate analysis revealed that CTFC/MLD ratio was the only independent predictor of angiographic (OR 2.02; 95% CI 1.37 to 2.97; P<0.0004) and clinical (OR 1.60; 95% CI 1.15 to 2.21; P<0.005) restenosis. The receiver operating characteristic curve area of this index was 79% for angiographic and 73% for clinical restenosis. The optimal CTFC/MLD ratio cutoff values were 7.88 for angiographic and 7.94 for clinical restenosis, respectively. CONCLUSIONS: Our data indicate that postangioplasty CTFC/MLD ratio, which incorporates both the angiographic and functional features of coronary lesions, is a reliable, objective, and inexpensive index for prediction of angiographic and clinical restenosis after conventional coronary angioplasty.

Intracoronary flow velocity measurements in adjacent stenotic and normal coronary arteries during incremental intravenous dobutamine stress and intracoronary adenosine injection.

To investigate the concomitant coronary flow and hemodynamic changes induced by dobutamine and adenosine in the catheterization laboratory, we studied stenotic and adjacent normal coronary arteries in 20 patients using paired Doppler Flowires. Coronary flow velocity and hemodynamics were measured sequentially after intracoronary (ic) adenosine, during incremental iv dobutamine infusion, and after the addition of ic adenosine during sustained peak dobutamine stress (adenosine on dobutamine). Distal to stenotic arteries, average peak velocity (APV) increased significantly (from 11 +/- 5 to 16 +/- 7 cm/sec, P < 0.001) at an intermediate dose of dobutamine (20 microg/kg/min, Dobutamine20) but did not change further thereafter to peak dobutamine stress (17 +/- 7 cm/sec), despite the significant further increase in rate-pressure product (RPP). Peak stress APV did not change with adenosine on dobutamine (to 18 +/- 7 cm/sec). In normal arteries, APV increased at Dobutamine20 (from 20 +/- 7.5 to 30 +/- 12 cm/sec, P < 0.01) and further at peak dobutamine stress (to 42 +/- 10 cm/sec, P < 0.0001) always exceeding the concomitant significant increases in RPP. Peak stress APV increased further with adenosine on dobutamine (to 53 +/- 13 cm/sec, P < 0.001). Our data demonstrate that at peak dobutamine stress there is supply/demand mismatch only in stenotic arteries where coronary flow reserve is exhausted at an intermediate dobutamine dose. Furthermore, adenosine on dobutamine potentiates coronary flow heterogeneity between stenotic and normal adjacent arteries. Cathet. Cardiovasc. Intervent. 48:1-9, 1999.

Estimation of coronary flow reserve using the Thrombolysis In Myocardial Infarction (TIMI) frame count method.

A simple and readily available method of estimating coronary flow velocity reserve may have significant clinical value. With use of intracoronary adenosine we documented a very good correlation between coronary flow reserve values obtained with the Thrombolysis In Myocardial Infarction trial frame count method and the invasive Doppler wire (Flowire) technique.

Usefulness of flow reserve in the left internal mammary artery to determine graft patency to the left anterior descending coronary artery.

Two-dimensional Doppler echocardiography (DE) and intravascular Doppler-tipped guidewire (flowire) have been used to measure flow in aortocoronary conduits at rest and during hyperemia, but they have not been compared. We investigated which flow velocity parameters obtained with these 2 different techniques can predict left internal mammary artery (LIMA) graft patency. Twenty-nine patients with previous coronary artery bypass grafting referred for evaluation of symptoms of coronary artery disease were studied after cardiac catheterization using the flowire and DE. Proximal LIMA graft flow velocity was measured at rest and during hyperemia produced by 140 microg/kg/min of intravenous adenosine infusion over 6 minutes with both methods. Normal LIMA grafts and left anterior descending artery (LAD) distal to the anastomosis were present in 16 patients, whereas 13 had >70% graft or native vessel stenosis. The coronary flow velocity reserve (r = 0.79) and the diastolic-to-systolic velocity ratio during hyperemia (r = 0.73) correlated very well between the 2 techniques. Among the variables obtained with the 2 techniques, the intragraft coronary flow velocity reserve measured by both methods was the only independent predictor of graft/recipient LAD patency. This variable had a sensitivity and specificity of 86% at a cutoff point of 2.07 with the flowire method and 83% at a cutoff point of 1.54 with DE. The areas below the receiver-operating characteristic curves were 0.91 and 0.93, respectively. Coronary flow velocity reserve measurements obtained with DE appears a reliable noninvasive method for assessing LIMA graft and/or LAD distal to the anastomosis patency in patients after bypass surgery and correlate very well with those directly obtained by intravascular Doppler.