Assessing the value of coronary artery computed tomography as the first-line anatomical test for stable patients with indications for invasive angiography due to suspected coronary artery disease. Initial cost analysis in the CAT-CAD randomized trial.

BACKGROUND: Clinical and safety outcomes of the strategy employing coronary computed tomography angiography (CCTA) as the first-choice imaging test have recently been demonstrated in the recently published CAT-CAD randomized, prospective, single-center study. Based on prospectively collected data in this patient population, we aimed to perform an initial cost analysis of this approach. METHODS: 120 participants of the CAT-CAD trial (age:60.6 ±â€¯7.9 years, 35% female) were included in the analysis. We analyzed medical resource use during the diagnostic and therapeutic episode of care. We prospectively estimated the cumulative cost for each strategy by multiplying the number of resources by standardized costs in accordance to medical databases and the 2015 Procedural Reimbursement Payment Guide. RESULTS: The total cost of coronary artery disease (CAD) diagnosis was significantly lower in the CCTA group as compared to the direct invasive coronary angiography (ICA) group ($50,176 vs $137,032) with corresponding per-patient cost of $836 vs $2,284, respectively. Similarly, the entire diagnostic and therapeutic episode of care was significantly less expensive in the CCTA group ($227,622 vs $502,827) with corresponding per-patient cost of $4630 vs $8,380, respectively. Overall, the application of CCTA as a first-line diagnostic test in stable patients with indications to ICA resulted in a 63% reduction of CAD diagnosis costs and a 55% reduction composite of diagnosis and treatment costs during 90-days follow-up. CONCLUSIONS: Application of CCTA as the first-line anatomic test in patients with suspected significant CAD decreased the total costs of diagnosis. This is likely attributable to reduced numbers of invasive tests and hospitalisations. Initial cost analysis of the CAT-CAD randomized trial suggests that this approach may provide significant cost savings for the entire health system.

Long-term follow-up and safety assessment of angiogenic gene therapy trial VIF-CAD: Transcatheter intramyocardial administration of a bicistronic plasmid expressing VEGF-A165/bFGF cDNA for the treatment of refractory coronary artery disease.

There have been a number of angiogenic gene therapy trials, yielding mixed results as to efficacy, but demonstrating uniform short-term treatment safety. Data regarding long-term safety of angiogenic gene therapy are limited. Double-blind VIF-CAD trial (NCT00620217) assessed myocardial perfusion and clinical data in 52 refractory coronary artery disease (CAD) patients randomized into treatment (VIF; n = 33) and Placebo (n = 19) arms. VIF group received electromechanical system NOGA-guided intramyocardial injections of VEGF-A165/bFGF plasmid (VIF) into ischemic regions, while the Placebo group-placebo plasmid injections. Full 1-year follow-up data have been published. This study presents the results of over 10-year (median 133 months, range 95-149) safety follow-up of VIF-CAD patients. Overall, 12 (36.4%) patients died in VIF and 8 (42.1%) in Placebo group (P = .68). Cardiovascular mortality was 12/33 (36.4%) in the VIF group and 6/19 (31.6%) in Placebo group (P = .73). Two Placebo patients died due to malignancies, but no VIF patients (P = .17). The Kaplan-Meier curves of combined endpoint: cardiovascular mortality, myocardial infarction and stroke were similar for both patient groups (P = .71). Odds ratio of Placebo group increasing (reaching a worse) their CCS class versus VIF was non-significant (OR 1.28, 95% CI = 0.66-2.45; P = .47). However, CCS class improved in time irrespectively of treatment-OR of reaching a less favorable CCS class per each year of follow-up was 0.74 (95% CI 0.685-0.792; P < .0001, pooled data). There were no differences in readmission rates. Intramyocardial VEGF-A165/bFGF plasmid administration appears safe, with no evidence of an increase in the incidence of death, malignancy, myocardial infarction or stroke during 10-year follow-up in this limited patient population.

Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies.

PURPOSE: To assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. MATERIALS AND METHODS: Patients scheduled for CRT in NYHA class II-IV, left ventricular ejection fraction <35%, QRS ≥ 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. RESULTS: 52 patients (age 60.3 ± 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p=0.002), the percent of LGE was higher (7.7% [0-13.5%] vs. 19.0% (0-31.9%], p=0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 ± 0.08 vs. 0.34 ± 0.09, p=0.009) and uniformity of radial strain was higher (0.72 ± 0.25 vs. 0.56 ± 0.29, p=0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02-5.02, p=0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non-responders vs. responders (26.3% vs. 15.0% respectively, p=0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77-0.98, p=0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non-ischaemic HF QRS was wider (162 ms vs. 140 ms, p=0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p=0.002) and uniformity of radial strain was lower (0.52 vs. 0.80, p=0.049) in non-responders vs. responders. Univariable logistic regression showed that RVV was a predictor of response to CRT (HR 1.50, 95% CI 1.06-2.13, p=0.022), providing the sensitivity of 94% and specificity of 85% at the cutoff point of 0.31. CONCLUSIONS: CMR derived parameters of dyssynchrony such as RVV may provide an additive value in prediction of response to CRT, especially in patients with non-ischaemic etiology of heart failure. In patients with ischaemic HF the transmurality of LGE is an important predictor of lack of response to CRT.

Right ventricular outflow tract obstruction as a confounding factor in the assessment of the impact of pulmonary regurgitation on the right ventricular size and function in patients after repair of tetralogy of Fallot.

PURPOSE: To compare right ventricular (RV) size and function between patients with combined pulmonary regurgitation (PR) plus RV outflow tract (RVOT) obstruction (RVOTO) and patients with isolated PR. MATERIALS AND METHODS: Consecutive individuals with significant PR (PR fraction ≥ 20%) after tetralogy of Fallot (TOF) repair who underwent cardiovascular magnetic resonance (CMR) were included. Patients with additional hemodynamic abnormalities (residual ventricular septal defect, extracardiac shunt, and/or more than mild regurgitation at a valve other than the pulmonary valve) were excluded. Significant RVOTO was defined as peak gradient across RVOT ≥ 30 mmHg. RESULTS: Significant differences between patients with combined PR+RVOTO (n = 9) and isolated PR (n = 33) were observed in RV end-diastolic volume (138.6 ± 25.1 vs. 167.0 ± 34.6 mL/m(2) , P = 0.02, respectively), RV end-systolic volume (65.0 ± 9.6 vs. 92.7 ± 26.2 mL/m(2) , P = 0.003), and RV ejection fraction (RVEF) (52.8 ± 3.7 vs. 45.0 ± 6.4%, P = 0.001). Both PR and peak RVOT gradient were independent predictors of RV size. CONCLUSION: Patients with combined PR+RVOTO had smaller RV volumes and higher RVEF when compared with patients with isolated PR. The confounding effect of RVOTO on RV size and function needs to be considered in CMR studies evaluating patients after TOF repair.

Mortality implications of primary percutaneous coronary intervention treatment delays: insights from the Assessment of Pexelizumab in Acute Myocardial Infarction trial.

BACKGROUND: Prior studies demonstrate a direct relationship between treatment delays to primary percutaneous intervention and mortality in patients with ST-segment elevation myocardial infarction (STEMI). This analysis compared the relationship of symptom onset-to-balloon time and door-to-balloon time on mortality in patients with STEMI. METHODS AND RESULTS: We analyzed different treatment delays (symptom onset-to-balloon time, door-to-balloon time) and mortality in 5745 STEMI patients. Baseline characteristics, flow grade, 90-day mortality, and clinical outcomes were compared in patients stratified by treatment delay. Multivariable logistic regression modeling was performed to assess the independent and relative effect of each treatment delay on 90-day mortality. Female sex, increased age, and worse thrombolysis in myocardial infarction flow grade were significantly associated with longer symptom onset-to-balloon times and door-to-balloon times. Longer symptom onset-to-balloon time was significantly associated with worse 90-day mortality (3.7%, 4.2%, and 6.5% for time delays <3 hours, 3 to 5 hours, and >5 hours, respectively, P<0.0001). Similarly, longer door-to-balloon times were significantly associated with worse 90-day mortality (3.2%, 4.0%, 4.6%, and 5.3% for delays <60 minutes, 60 to 90 minutes, 90 to 120 minutes, and ≥120 minutes respectively, P<0.0001). In a multivariate model of 90-day mortality, door-to-balloon time (χ(2) 6.0, P<0.014), and symptom onset-to-hospital arrival (χ(2) 9.8, P<0.007) remained independent determinants. CONCLUSIONS: Both symptom onset-to-balloon time and hospital door-to-balloon time are strongly associated with 90-day mortality following STEMI. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00091637.

Assessment of renal artery stenosis using both resting pressures ratio and fractional flow reserve: relationship to angiography and ultrasonography.

BACKGROUND. Clinical benefit from renal artery revascularization remains controversial, probably because of inaccurate stenosis severity assessment. Objective. The aim of the study was to evaluate resting translesional pressures ratio and renal fractional flow reserve (rFFR) in relation to angiography and Doppler duplex ultrasonography in patients with at least moderate renal artery stenosis (RAS). METHODS. 44 hypertensive patients (48% of males, mean age 65 years) with at least moderate RAS were investigated. Translesional systolic pressure gradient (TSPG), resting Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR - after intrarenal administration of papaverine - were evaluated. Quantitative angiographic analysis of stenosis severity was performed including minimal lumen diameter (MLD) and percent diameter stenosis (DS) assessment. Renal/aortic ratio (RAR), resistive index (RI) and deltaRI (side-to side difference) were obtained in Doppler-duplex ultrasonography. The predictive value of selected variables was calculated using receiver-operating characteristics curves. RESULTS. Mean Pd/Pa ratio was 0.86 ± 0.12 and decreased to 0.79 ± 0.13 after papaverine administration. Both Pd/Pa ratio and rFFR strongly correlated with TSPG (r = -0.92, p < 0.0001 and r = -0.88, p < 0.0001, respectively) and moderately with MLD (r = 0.62, p < 0.0001 and r = 0.66, p < 0.0001) and DS (r = -0.63, p < 0.0001 and r = -0.70, p < 0.0001). To identify more than 70% RAS, considered severe, the most predictive cut-off values were 0.93 for Pd/Pa ratio and 0.80 for rFFR. CONCLUSIONS. Mean Pd/Pa ratio and rFFR strongly correlated with angiographic data and in less pronounced manner with ultrasound parameters reflecting intrarenal blood flow. The best accuracy cut-off points for severe RAS predicting were 0.93 and 0.80, respectively.

Quantitative assessment of pulmonary regurgitation in patients with and without right ventricular tract obstruction.

BACKGROUND: There are concerns whether there is a difference in clinical utility of pulmonary regurgitation (PR) fraction (PRF) and PR volume (PRV) in subgroups of patients with isolated PR and individuals with combined PR and right ventricular outflow tract obstruction (RVOTO). The aim of the study was to compare PRF and PRV in patients with or without RVOTO. METHODS AND RESULTS: 82 consecutive patients after repair of tetralogy of Fallot (TOF) who underwent cardiovascular magnetic resonance and echocardiography were studied. There was no difference in PRF between patients with moderate and severe right ventricular (RV) dilatation (32±13% vs. 37±12%; p=0.18). Significant difference in PRV was observed between these groups (23±10 ml/m2 vs. 31±12 ml/m2, respectively; p=0.02). PRV had better ability than PRF in identification of severe RV dilatation, both in group with RVOTO [area under the curve (AUC) 0.82 vs. 0.72, p=0.005] and in patients without RVOTO (AUC 0.83 vs. 0.77, p=0.04). A strong correlation was seen between PRF and PRV both in patients with and without RVOTO [r=0.93, p<0.0001 and r=0.92, p<0.0001, respectively]. In both subgroups high variability of PRF was found in subjects with similar degree of PRV. CONCLUSIONS: PRV shows better ability than PRF in evaluating influence of PR on RV in patients after TOF repair, both in population with and without concomitant RVOTO.

[POL-PAVTI--Polish report on transcatheter pulmonary artery valve implantation of Melody-Medtronic prosthesis in the first 14 patients in Poland]. / Ogólnopolski raport POL-PAVTI z nieoperacyjnego wszczepienia biologicznej zastawki plucnej Melody-Medtronic u pierwszych w Polsce 14 chorych.

AIM: To assess the early results of the pulmonary artery valve transcatheter implantation (PAVTI) in pts included into POL-PAVTI registry. Detailed medical and economic analyses were performed. METHODS: Pulmonary artery valve implantation was performed in 14 pts (9 men), aged 16-31 (mean 24.6 +/- 4.8) years, with pulmonary homograft dysfunction after total repair of tetralogy of Fallot (4 pts), pulmonary atresia (2 pts), pulmonary stenosis (1 pt), common arterial trunk type I (1 pt), Ross procedure (3 pts) and TGA - Rastelli operation (3 pts). Eleven pts underwent in the past 2-5 surgical or/and catheter interventions. Indication for PAVTI was based on clinical evaluation and echocardiographic studies. Assessment of morphological and functional features of the right ventricle (RV) and homograft with the use of cardiac magnetic resonance (CMR) was performed in 10 cases. Pulmonary stenosis (max. pulmonary gradient 32-119, mean 72 +/- 28 mmHg) was observed in 13 pts and/or significant pulmonary regurgitation in 10 pts. The procedure was performed in general anesthesia. The deployment of a valved stent in the pulmonary valve position was preceded by a metal stent implantation. Results were evaluated by echocardiography two days after the procedure and one month later. Four patients were evaluated 6 months after procedure. RESULTS: Time of the procedure varied 60-190 (mean 127 +/- 35) min, time of fluoroscopy ranged 12-31 (mean 21 +/- 11) min. PAVTI was successfully performed in all pts without serious complications. Patients were discharged from the hospital 48-293 (mean 120 +/- 71) h after procedure. Significant reduction of pulmonary gradient after the procedure assessed by echocardiography was observed on the second day (20-60, mean 38 +/- 12 mmHg, p < 0.0001) and one month (19-52, mean 34 +/- 9 mmHg, p < 0.0001). Mild pulmonary regurgitation was observed in 2 pts. In 5 pts evaluated 6 months after procedure haemodynamic parameters were unchanged; no late complications were observed. Average cost of the procedure including a price of the valve (82 000 PLN) was 98 000 PLN. CONCLUSIONS: Pulmonary artery valve transvascular implantation is an effective and safe method of non-surgical treatment for patients with homograft dysfunction. Cost-effectiveness is approvable.

Assessment of the inflammatory process by endomyocardial biopsy in patients with dilated cardiomyopathy based on pathological and immunohistochemical methods.

INTRODUCTION: Myocarditis may lead to dilated cardiomyopathy (DCM) in immunogenetically predisposed individuals. The diagnosis of myocardial inflammation is currently based on histopathological and immunohistochemical methods. Previous studies indicate that inflammatory cardiomyopathy occurs in approximately 50% of patients with DCM. AIM: The goal of the study was to assess the inflammatory process in patients with DCM by endomyocardial biopsy using histopathological and immunohistochemical methods. METHODS: Endomyocardial biopsy specimens was examined using routine histopathological methods and immunochemical staining for T lymphocytes (CD3(+), n=84), major histocompatibility complex I (HLA ABC, n=48) and II (HLA DPQR, n=84) antigens and the adhesion molecules ICAM-1 (n=51) and VCAM-1 (n=48) in 84 patients (69 male, 15 female; mean age 35.0+/-10.5 years) with angiographically-confirmed DCM. Familial disease occurrence was noted in 14 (16.7%) patients. Cardiac samples obtained from 18 patients who died of non-cardiovascular causes were used as a control group. RESULTS: Myocarditis was diagnosed, according to the Dallas criteria, in 8 (9.5%) patients. The frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes per high-power field (hpf) in myocardial biopsy, was 14.3%. When broader criteria were applied (presence of >2.0 CD3(+) lymphocytes/hpf and/or 1.5 CD3(+) lymphocytes/hpf in multiple foci and increased expression of class I/II HLA), inflammatory cardiomyopathy was diagnosed in 32.1% of patients. Inflammatory activation of the endothelium, indicated by increased expression of at least three adhesion molecules (class I and II HLA, ICAM-1, VCAM-1), was present in 22 (45.8%) patients. The expression of HLA DPQR, HLA ABC and ICAM-1 was observed on the endothelium of capillaries and larger vessels, interstitial cells, and the surface of activated lymphocytes; immunohistochemical reactions were diffuse. In patients with markedly elevated expression of the aforementioned adhesion molecules, the expression was also present on cardiomyocyte cell membranes. VCAM-1 was restricted to the endothelium of individual small veins. The control group did not demonstrate any signs of myocarditis, inflammatory cardiomyopathy or inflammatory endothelial activation. CONCLUSIONS: The application of immunohistochemical methods to myocardial biopsy in order to identify the inflammatory cell phenotype and the presence of adhesion molecules permits the diagnosis of inflammatory cardiomyopathy in 14% or 32% of patients, depending on the criteria used, while conventional pathology allows for this diagnosis in 9% of patients. The observed frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes/hpf in the myocardium, was lower (14%) than in previous studies, while the frequency of inflammatory endothelial activation was similar (45%).

[Echocardiographic assessment of left atrial volume and emptying in hypertrophic cardiomyopathy]. / Echokardiograficzna ocena objetosci i oprózniania lewego przedsionka w kardiomiopatii przerostowej.

UNLABELLED: Left ventricular diastolic dysfunction plays an important role in the pathogenesis of symptoms in patients with hypertrophic cardiomyopathy (HCM). Theoretically abnormal LV filling should lead to left atrium (LA) enlargement and abnormal emptying. Our study was performed in 27 pts with hypertrophic cardiomyopathy (mean ventricular septum thickness 2.4 +/- 0.73 cm, mean posterior wall thickness 1.23 +/- 0.42 cm and mean LV wall thickness measured at 10 segments 1.93 +/- 0.37 cm) and 38 healthy volunteers. Transmitral Doppler flow parameters (Emax, Amax, t decE, Emax/Amax) did not differ in both groups. We used 2D echocardiographic automatic borderline detection method to assess the following LA volumes during its emptying: maximal volume (LAVmax), volumes at the end of rapid emptying (LAV-RE), before atrial contraction--P wave on ECG (LAV-P) and minimal LA volume after atrial contraction (LAVmin). We also calculated total LA emptying fraction (%LAEF), absolute volume changes during LA early emptying (delta LAV-RE) and atrial contraction (delta LAV-AC) and their ratio (delta LAV-RE/delta LAV-AC). 11 pts had mitral regurgitation. The mitral regurgitation fraction was calculated as the ratio of the area of mitral regurgitation to LA area. RESULTS: Significantly larger LAVmax (75.8 +/- 28.0 vs 60.7 +/- 18.1 ml, p<0.01), LAV-RE (50.4 +/- 21.4 vs 35.3 +/- 13.8 ml, p<0.005), LAV-P (50.7 +/- 20.5 vs 38.4 +/- 13.8 ml, p<0.01) and LAVmin (33.0 +/- 15.1 vs 26.3 +/- 11.7 ml, p<0.05) were found in HCM compared to C. The total LA emptying fraction %LAEF (58.0 +/- 11.4 vs 57.4 +/- 12.1%, NS), DLAV-RE (27.3 +/- 12.6 vs 25.3 +/- 11.0 ml, NS), and ratio delta LAV-RE/DLAV-AC (1.94 +/- 1.22 vs 2.38 +/- 1.10, NS) were similar both groups and active emptying delta LAV-AC (17.6 +/- 9.7 vs 12.1 +/- 5.3 ml, p<0.005) was significantly larger in HCM. The regurgitation fraction observed in HCM was 2.7-31.1%. Statistically significant correlation between LA total emptying fraction (%LAEF) and mitral regurgitation fraction (r=-0.47, p<0.05) and no relations between LA size and function parameters and LV hypertrophy parameters were found in HCM. CONCLUSION: LV hypertrophy in hypertrophic cardiomyopathy leads to LA enlargement and changes in its emptying. We found larger the following LA volumes: maximal volume, volume after early emptying, before atrial contraction and minimal volume and greater LA volume change during active emptying. Total LA emptying fraction, volume change during early/passive emptying and passive/active emptying volumes ratio were similar in both groups. No correlation existed between the degree of LV hypertrophy and LA volume and emptying parameters. We observed negative relation between mitral regurgitation fraction and LA total emptying fraction, but because of small group of pts with mitral regurgitation, further studies are needed.