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.

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.

Coronary flow velocity changes after intravenous dipyridamole infusion: measurements using intravascular Doppler guide wire. A documentation of flow inhomogeneity.

OBJECTIVES: This study assessed changes in coronary flow velocity measured distal to a significant stenosis of the left anterior descending coronary artery and at the adjacent normal left circumflex coronary artery, produced by intravenous administration of dipyridamole, in patients undergoing coronary angioplasty with a documented perfusion defect on dipyridamole-thallium-201 scintigraphy. BACKGROUND: Significant flow inhomogeneity is believed to develop during coronary vasodilation induced by dipyridamole, causing a defect in the thallium-201 scintigram. The recently developed intracoronary Doppler guide wire permits assessment of flow velocity variables in normal and stenotic arteries. METHODS: In 17 patients with stable angina we studied changes in time-averaged peak velocity and the diastolic/systolic velocity ratio simultaneously using two 0.014-in. (0.36-mm) Doppler guide wires at baseline and after 4 min of dipyridamole infusion (0.56 mg/kg body weight). Coronary flow velocity reserve and relative flow reserve were correlated with the degree of stenosis on coronary angiography and quantitative analysis of thallium-201 images. RESULTS: No changes in distal flow velocity was observed in the stenotic vessel (5.5 +/- 33.7% [mean +/- SD]), in contrast to a significant increase observed in the adjacent normal vessel (162.4 +/- 39.8%). Poststenotic coronary flow velocity reserve correlated with percent lumen diameter stenosis (r = -0.66, p < 0.05). A correlation was also observed between the relative flow reserve/thallium-201 relative perfusion ratio (r = 0.90, p < 0.001). CONCLUSIONS: To our knowledge, these findings represent the first direct proof of dipyridamole-induced flow inhomogeneity producing a perfusion defect on thallium-201 imaging. The degree of inhomogeneity is related to the extent of the perfusion defect.

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.

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.

Effect of plaque burden on coronary vasoreactivity in early atherosclerosis.

Coronary atherosclerosis, during its initial stages of development, may result in abnormal endothelium-dependent vasomotor responses. The relation between the degree of vasoreactivity and the amount of atheromatous plaque load has not been decisively determined. The aim of the present study was to investigate the effects of segmental plaque burden on endothelium-dependent and independent coronary stimulation. We studied 37 individual coronary segments along the course of coronary arteries that had angiographically either nonvisible or nonobstructive atheromatous lesions. Endothelium-dependent and independent stimulation of each segment from 10 patients with known significant coronary artery disease was examined with intracoronary administrations of normal saline, acetylcholine 10(-6) M and 10(-5) M, and nitroglycerin, respectively, using quantitative coronary angiography. Simultaneous vasomotor effects on the microcirculation were evaluated by a Doppler guidewire (Flowire). Subsequently, intracoronary ultrasound was used at each segment for detailed morphometric and composition analysis. By quantitative coronary angiography, when compared with normal saline, acetylcholine produced a reduction in minimal lumen diameter of 15.2 +/- 25.6%, and nitroglycerin produced an increase of 18.0 +/- 22.5%. The degree of vasoconstriction induced by acetylcholine correlated inversely (r = 0.51, p = 0.001) to the amount of segmental maximal plaque thickness. No relation between the response to nitroglycerin and the parameters obtained by intracoronary ultrasound was documented. Fibrous coronary plaques showed less vasomotor changes than plaques with mixed echogenicity, probably due to a significantly larger plaque burden. Acetylcholine produced overall a differential vasomotor response in the epicardial segments (vasoconstriction) compared with the microcirculation (vasodilation). These results indicate that in early atheromatous coronary lesions, the degree of endothelium-dependent vasoconstrictive response is inversely related to the amount of segmental plaque burden.

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.

Prognostic significance of echocardiographically estimated right ventricular shortening in advanced heart failure.

Little is known about the association of echocardiographic estimates of right ventricular (RV) function with survival, in relation to hemodynamic and exercise-derived predictors of outcome in congestive heart failure. We prospectively studied 40 patients (age 55+/-10 years, in New York Heart Association functional class III [70%] and IV [30%]), with left ventricular (LV) ejection fraction <30%. At enrollment, all patients underwent echocardiographic evaluation of LV dimensions and function. RV shortening was measured as the difference of the end-diastolic distance - the end-systolic distance between the tricuspid annulus and the RV apex. Thirty-five patients (88%) were able to perform a maximal symptom-limited exercise test. Peak oxygen consumption (peak VO2) and percent peak age- and gender-adjusted predicted oxygen consumption (%peak VO2) were calculated. Of 40 patients, 10 died during a mean follow-up period of 14+/-10 months. On univariate analysis, nonsurvivors had lower RV shortening (p=0.0001), higher pulmonary artery wedge pressure (p=0.009), higher pulmonary vascular resistance (p=0.02), and lower mean aortic pressure (p=0.05). Cox proportional-hazards model revealed that the only independent associate of survival was RV shortening (p=0.0005), with a trend toward significance for mean aortic pressure (p=0.08). The best cutoff point of RV shortening identified by the receiver-operating curve was 1.25 cm. This value had a sensitivity of 90%, specificity of 80%, and overall predictive accuracy of 83% to distinguish survivors from nonsurvivors. In patients with advanced heart failure, preserved RV function as indicated by an echocardiographically derived RV shortening > 1.25 cm is a strong predictor of survival.

Superior vena caval thrombosis detected by transesophageal echocardiography.

Three patients with clinical suspicion of bacterial endocarditis, induced by either pacemaker or indwelling catheter, underwent transesophageal echocardiography. High short-axis cuts through the great vessels, however, revealed the presence of superior vena caval thrombus in all three patients. Transesophageal echocardiography is more sensitive in establishing the diagnosis of superior vena caval thrombus than surface echocardiography. Comparison of transesophageal echocardiography with other diagnostic modalities is needed in assessing its overall sensitivity and specificity.

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.

Directional coronary atherectomy in women compared with men.

The influence of gender on the procedural outcome of directional coronary atherectomy (DCA) is controversial. This study of 373 consecutive patients (418 lesions) undergoing DCA demonstrates that the procedural success rate of DCA is significantly lower in women compared with men (72.7 vs. 82.9%, p = 0.011). Women have significantly smaller coronary arteries than men (2.5 mm vs. 2.7 mm, p = 0.028) and were older than men (66 vs. 61 years, p = 0.0001). Multivariate analysis identifies small coronary vessel size rather than female gender per se as an independent predictor of poor procedural outcome. Procedural success rates in women with coronary vessel size > or = 2.5 mm is significantly higher (92.2%) than in women with coronary vessel size < 2.5 mm (73.1%), and parallels that in men with vessel size > or = 2.5 mm (89.3%). Inability to engage the ostium of the coronary artery adequately with the guiding catheter and to cross the lesion with the atherectomy device is significantly more common in women compared with men. Major ischemic complication rates are similar in women and men (8.5 vs. 8.7%). Groin complications are significantly more common in women compared with men (13.5 vs. 2.9%). We conclude that procedural success rates in women may be improved by careful patient selection, with particular attention to small vessel size. DCA is best performed in vessels > 2.5 mm in diameter.

Intracoronary Palmaz-Schatz stent placement after complicated angioplasty: medium term follow-up.

Acute or impending coronary artery occlusion during percutaneous coronary balloon angioplasty represents a serious and potentially life-threatening complication. We studied the clinical and angiographic outcome in 21 patients who underwent emergent intracoronary Palmaz-Schatz stent implantation (11 due to persistent residual stenosis and 10 due to flow-limiting dissection) during complicated balloon angioplasty and who were followed for a mean period of 7.9 +/- 5.7 months. Excluding one patient lost to follow-up, the event-free survival rate was 70%. Six (30%) patients developed adverse clinical events. One died and 3 required elective revascularization procedures. One subacute stent thrombosis was documented. Acute Q-wave myocardial infarction occurred in 2 patients. Among 9 patients studied angiographically 5.6 +/- 2.5 months after stent placement, 2 had developed restenosis (> 50% luminal narrowing). Eleven have remained essentially symptom free. For selected patients, emergent deployment of a Palmaz-Schatz coronary stent, following complicated balloon angioplasty, offers satisfactory long-term results, thus obviating the need for a high risk emergency bypass surgery.

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.