Percutaneous mitral annuloplasty with the Carillon device: Outcomes in proportionate and disproportionate functional mitral regurgitation.

BACKGROUND: It has been suggested that the disparity of outcomes between the studies of transcutaneous edge-to-edge repair (TEER) for functional mitral regurgitation (FMR) in heart failure with reduced ejection fraction (HFrEF) could be due to systematic differences in the populations studied. One proposal is that there are 2 broad groups: those with proportional FMR who respond less favorably, and those in whom the FMR is greater than expected (disproportionate) FMR where edge-to-edge TEER seems to be more effective. Whether this grouping is relevant for other percutaneous interventions for FMR is unknown. OBJECTIVES: We sought to compare clinical and echocardiographic outcomes of patients with HFrEF and proportionate and disproportionate FMR treated with indirect annuloplasty using the Carillon device. METHODS: This is a pooled analysis from 3 trials of patients with FMR. Key patient eligibility in these trials specified persistent grade 2+ to 4+ FMR with >5.5 cm left ventricular (LV) end-diastolic diameter (LVEDD) and reduced ejection fraction. Patients with an effective regurgitant orifice area/LV end-diastolic volume (EROA/LVEDV) ratio under 0.15 were assigned to the proportionate FMR group (n = 74;65%) and those with a ratio above 0.15 were classed as having disproportionate FMR (n = 39;35%). RESULTS: At 12 months following treatment, both groups showed improvements in all MR variables including regurgitation volume, EROA and vena contracta. Moreover, in patients with proportionate MR there were clinically relevant and statistically significant improvements in LV volumes and diameters. There was no independent relationship between the degree of proportionality as a continuous variable and the remodeling response to Carillon therapy (change in LVEDV r = 0.17; change in LVESV r = 0.14). CONCLUSION: Percutaneous mitral annuloplasty with the Carillon device reduces MR in patients with both proportionate and disproportionate FMR, and also results in LV reverse remodeling in those with proportionate FMR. The effect on remodeling remains to be verified in a large-scale trial.

Electrocardiographic criteria for anterior STEMI - Does the cut-off point affect treatment delay?

BACKGROUND: Diagnostic criteria for anterior STEMI differ between the European Society of Cardiology (ESC) and the European Resuscitation Council (ERC). A greater degree of ST-segment elevation is required to meet ERC criteria compared to ESC criteria. This may potentially lead to discrepancies in management between emergency teams and cardiologists, subsequent delay in reperfusion therapy and worse prognosis. METHODS: We performed an observational study in patients with anterior STEMI routinely treated with primary PCI and assessed whether differing electrocardiographic diagnostic criteria could impact treatment and short-term prognosis. All patients in the study had anterior STEMI confirmed by electrocardiographic ESC criteria and subsequent coronary angiography. Patients were divided into two groups. Those who did not meet ERC criteria in the index ECG were assigned to the "non-ERC" group and were compared with those who met them - the "ERC" group. RESULTS: Out of 60 patients with anterior STEMI based on ESC criteria (mean age 66.9 ± 13.6 years, 70% males), 26 patients (44%) did not meet ERC criteria ("non-ERC" group) for STEMI. There were no significant differences in age, gender distribution or clinical characteristics between "ERC" and "non-ERC" patients. Total-Ischemic-Time, Patient-Delay, and System-Delay times were significantly longer in "non-ERC" group (433.1 ± 389.9 min vs. 264.2 ± 229.6 min, p = 0.03; 290.8 ± 337.6 min vs. 129.5 ± 144.9 min; p < 0.05 and 158.8 ± 158 vs 134.6 ± 191 min, p < 0.02 respectively). There were no differences in In-Hospital-Delay, procedure duration, and success rate of PCI. Proximal LAD occlusion (64.7%) and TIMI = 0 flow (73.5%) tended to be more frequently observed in "ERC" than in the "non-ERC" group (53.8% and 65.4%, respectively). Hospitalization time and LVEF (44.4 ± 8.7 vs 42.8 ± 9.5%, p = 0.53) were similar between groups. CONCLUSIONS: Differences in electrocardiographic criteria for anterior STEMI leave a significant proportion of patients undiagnosed. Patients with STEMI who failed to meet less strict ERC criteria had more distal LAD disease with better TIMI flow but received reperfusion therapy later. Thus, character of the disease may compensate for treatment delay but this needs to be further evaluated. Finally, lowering the cut-off point with stricter criteria compromises specificity and is expected to increase the false positive rate, however there were no false positives in this study as all patients were angiographically confirmed to have acute coronary obstruction.

Emergency treatment of iatrogenic coronary perforation by transcatheter embolization with gelatin sponge particles-Description of technique.

Coronary artery perforation (CAP) is a rare but potentially life-threatening complication of percutaneous coronary intervention (PCI) that requires prompt diagnosis and effective treatment. Importantly, dynamic advances in interventional cardiology reflected by the increasing percentage of more challenging PCIs performed in more complex lesions have resulted in significant changes in CAPs pattern. Herein, we describe a technique and present a case report of CAP that occurred during percutaneous recanalization of the occluded restenotic right coronary artery (RCA) successfully treated with transcatheter embolization using gelatin sponge particles prepared on-site. The patient underwent coronary angiography with a subsequent attempt to open chronically occluded RCA. During the procedure, a guidewire was inadvertently positioned outside the arterial bed resulting in type III CAP. After unsuccessful prolonged balloon inflations as well as an anticoagulation reversal, embolization of the RCA with gelatin sponge particles as an ultima ratio treatment was performed. Sponge particles were prepared on-site by the operator, by cutting gelatin sponge used for wound healing. The procedure resulted in a total occlusion of the RCA and significant clinical improvement. The patient did not require pericardiocentesis and was discharged from the hospital after 10 days of an uneventful postprocedural course. The described technique is an easy and effective method of guidewire-related CAPs treatment in whom stent grafts cannot be implanted. Noteworthy, the technique can be applied in most cath labs as it utilizes a widely available gelatin sponge and does not require any specific expertise.

A randomized double-blind trial of an interventional device treatment of functional mitral regurgitation in patients with symptomatic congestive heart failure-Trial design of the REDUCE FMR study.

The Carillon Mitral Contour System has been studied in 3 nonrandomized trials in patients with symptomatic congestive heart failure and functional mitral regurgitation. The REDUCE FMR study is a uniquely designed, double-blind trial evaluating the impact of the Carillon device on reducing regurgitant volume, as well as assessing the safety and clinical efficacy of this device. Carillon is a coronary sinus-based indirect annuloplasty device. Eligible patients undergo an invasive venogram to assess coronary sinus vein suitability for the Carillon device. If the venous dimensions are suitable, they are randomized on a 3:1 basis to receive a device or not. Patients and assessors are blinded to the treatment assignment. The primary end point is the difference in regurgitant volume at 1 year between the implanted and nonimplanted groups. Other comparisons include clinical parameters such as heart failure hospitalizations, 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and other echocardiographic parameters. An exercise echo substudy will also be included.

Percutaneous Trans-Coronary Venous Mitral Annuloplasty in Patients With Functional Mitral Regurgitation: Analysis of Poznan Carillon Registry Data.

OBJECTIVES: The purpose of our study is to verify, whether percutaneous mitral annuloplasty results in reverse remodeling in patients with functional mitral regurgitation (FMR) and impaired ejection fraction (EF) and to investigate which echo parameters may help in prediction of the efficacy of the procedure. BACKGROUND: FMR exacerbates left ventricular (LV) dilatation and contributes to both LV remodeling and heart failure. METHODS: We analyzed baseline and 1 month follow-up data in 22 consecutive patients with FMR, who underwent successful percutaneous trans-coronary venous mitral annuloplasty with the Carillon device. RESULTS: Significant reduction of FMR echo parameters, including vena contracta (VC), effective regurgitant orifice area (EROA), and regurgitant volume (RV) were observed and maintained throughout 1 month follow up and did not correlate with baseline annular, LV or with the left atrial diameters. Baseline mitral tenting area correlated negatively with the relative improvement (% difference) of EROA (r = -0.5898) and RV (r = -0.4363), but not with VC (r = 0.1341). In addition, increased EF as well as a significant reduction in left ventricular diameters were noted. The increase in EF negatively correlated with the change in EROA (r = -0.50058), PISA (r = -0.5327), and RV (r = -0.5457). Baseline mitral tenting area significantly correlated with the 1 month change in EF (r = 0.5946) and stroke volume (r = 0.6913). CONCLUSIONS: The improvement of FMR after treatment with the Carillon device is associated with LV reverse remodeling and an increase in systolic performance, that correlates with the reduction in mitral regurgitation, being not dependent on baseline heart diameters. Mitral tenting area seems to be an important parameter in prediction of benefit from percutaneous mitral annuloplasty.

Comparison of Baseline Heart Rate Variability in Stable Ischemic Heart Disease Patients with and without Stroke in Long-Term Observation.

GOAL: Decreased heart rate variability (HRV) has predictive value in postinfarction as well as in ischemic stroke patients. However, it is unknown if ischemic heart disease (IHD) patients who are at high risk of stroke have different HRV profile. The goal of this study was to compare baseline HRV (traditional and novel indices) in stable IHD patients with and without stroke in long-term observation. METHODS: A total of 139 consecutive patients with stable IHD scheduled for coronary angiography were enrolled. Five-minute electrocardiogram readings were taken. Traditional and novel HRV measures were calculated. After 70.06 ± 4.297 months of follow-up, baseline HRV indices in patients who had had a stroke were compared with indices in patients without the aforementioned cerebrovascular event. RESULTS: During follow-up, 6 patients developed stroke. Compared to patients without such a cerebrovascular event, these patients with stroke had lower values for the following HRV indices: de Hann long-term irregularity (30,521 ± 32,767 versus 46,678 ± 25,328; P < .05), Yeh interval index (.0207 ± .0208 versus .0326 ± .0157; P < .05), Organ BAND (3.0563 ± 3.328 versus 4.515 ± 2.276; P < .05), Dalton standard deviation (SD) (17,887 ± 17,636 versus 29,859 ± 16,478; P < .05), Zugaib short-term variability (.004 ± .00416 versus .00622 ± .00418; P < .05), Zugaib long-term variability (.0161 ± .0151 versus .0247 ± .0115; P < .05), standard deviation of all NN intervals (8,954 ± 8,812 versus 16,724 ± 11,594; P < .05), total power (2,616 ± 4,855 versus 4,678 ± 4,653; P < .05), w2 (.71 ± .338 versus 1.719 ± 1.08; P < .05), w3 (1.399 ± .924 versus 2.552 ± 1.609; P < .05), and w4 (1.367 ± 1.705 versus 2.824 ± 2.027; P < .05). No significant differences in other analyzed indices were observed. CONCLUSIONS: Patients with IHD and stroke in long-term observation have different baseline profiles of HRV indices. Further investigations are needed to assess the usefulness of HRV analysis in stroke risk assessment.

Transseptal puncture from the jugular vein and balloon cryoablation for atrial fibrillation in a patient with azygos continuation of an interrupted inferior vena cava.

AIMS: Inferior vena cava (IVC) interruption is a rare anatomic variant where the azygos vein (AV) drains the blood from the IVC to the upper part of the right atrium via the superior vena cava. Here, we report balloon cryoablation of the pulmonary veins (PVs) via superior access in a patient with atrial fibrillation. METHODS AND RESULTS: After the first failed ablation attempt due to IVC interruption, balloon cryoablation with a 28-mm Arctic Front Advance cryoballoon (Medtronic CryoCath LP, Quebec, Canada) via superior access was performed; it requires only a single transseptal puncture (TP), and the patient had optimal PV anatomy. Deflectable electrodes were inserted into the right ventricle and coronary sinus from the right femoral vein. The right internal jugular vein was accessed using an SL0 transseptal sheath and BRK needle. The TP was performed under transoesophageal echocardiographic guidance with a Safe Sept wire because the septum was stiff. All PVs were engaged: the left using an ablation catheter before balloon insertion and the inferior following a 'push-up' technique because of a leak above the veins. Cryothermal energy was delivered after checking for occlusion. The procedure lasted 210 min, fluoroscopy time was 78 min, and air-kerma dose was 194 mGy. During the 6-month follow-up, no episodes of atrial fibrillation were detected on several Holter recordings. CONCLUSIONS: Successful PV isolation in patients with AV continuation of an interrupted IVC can be safely performed using superior access with balloon cryoablation, after several modifications of standard equipment.

Cost-utility analysis of percutaneous mitral valve repair in inoperable patients with functional mitral regurgitation in German settings.

BACKGROUND: To determine the cost-effectiveness of the percutaneous mitral valve repair (PMVR) using Carillon® Mitral Contour System® (Cardiac Dimensions Inc., Kirkland, WA, USA) in patients with congestive heart failure accompanied by moderate to severe functional mitral regurgitation (FMR) compared to the prolongation of optimal medical treatment (OMT). METHODS: Cost-utility analysis using a combination of a decision tree and Markov process was performed. The clinical effectiveness was determined based on the results of the Transcatheter Implantation of Carillon Mitral Annuloplasty Device (TITAN) trial. The mean age of the target population was 62 years, 77% of the patients were males, 64% of the patients had severe FMR and all patients had New York Heart Association functional class III. The epidemiological, cost and utility data were derived from the literature. The analysis was performed from the German statutory health insurance perspective over 10-year time horizon. RESULTS: Over 10 years, the total cost was €36,785 in the PMVR arm and €18,944 in the OMT arm. However, PMVR provided additional benefits to patients with an 1.15 incremental quality-adjusted life years (QALY) and an 1.41 incremental life years. The percutaneous procedure was cost-effective in comparison to OMT with an incremental cost-effectiveness ratio of €15,533/QALY. Results were robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analysis with a willingness-to-pay threshold of €35,000/QALY, PMVR had a 84 % probability of being cost-effective. CONCLUSIONS: Percutaneous mitral valve repair may be cost-effective in inoperable patients with FMR due to heart failure.

Transcatheter treatment of functional mitral valve regurgitation.

Functional mitral regurgitation is a clinical entity with increasing prevalence and significant impact on morbidity and mortality. Because of the unsatisfactory results of medical therapy and high perioperative risk resulting in low referral/high denial rates for surgical treatment, benefits of which still remain controversial, novel minimally invasive transcatheter techniques are under development. Herein, in the present review, we discuss the recent progress in the emerging field of catheter-based techniques for functional mitral regurgitation.

Treating symptoms and reversing remodelling: clinical and echocardiographic 1-year outcomes with percutaneous mitral annuloplasty for mild to moderate secondary mitral regurgitation.

AIMS: To determine the effects of percutaneous mitral annuloplasty on symptoms, walk distance and left ventricular (LV) structure and function in patients with mild or moderate secondary mitral regurgitation (SMR). METHODS AND RESULTS: This was a pooled analysis of patients (n = 68) who, despite guideline-directed medical therapy had symptomatic heart failure (HF) with mild (n = 25) or moderate (n = 43) SMR treated with percutaneous mitral annuloplasty as part of the TITAN, TITAN II, or REDUCE-FMR trials. Primary outcomes were changes in symptoms, 6-min walk distance, and quality of life assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) after 1 year. Secondary analyses included changes in LV structure and function. At 1 year, New York Heart Association class status was maintained (48%) or improved (46%) in most patients, mean KCCQ scores increased from baseline by 10 units [95% confidence interval (CI) 3 to17; P < 0.01] and mean 6-min walk test distance increased by 34 m (95% CI 12 to 57; P < 0.01). SMR grade improved in 25% of patients and was maintained in 58% of patients with changes in mean regurgitant volume of -7 mL (95% CI -11 to -3; P < 0.001), vena contracta -0.11 cm (95% CI -0.20 to -0.02; P < 0.05), and effective regurgitant orifice area -0.03 cm2 (95% CI -0.06 to -0.01; P < 0.05). There were non-significant improvements in LV ejection fraction and volumes. Survival over 1 year was 89% with no difference between mild (96%) and moderate (86%) SMR (log-rank P = 0.22). Progression-free survival was 70% (82% in mild vs. 63% in moderate SMR; P = 0.16). Freedom from HF hospitalization was 73% (87% in mild SMR vs. 66% in moderate SMR; P = 0.07). CONCLUSION: Among patients with symptomatic HF and mild or moderate SMR on guideline-directed medical therapy, percutaneous mitral annuloplasty was associated with improvements in symptoms, SMR, a stabilization of LV structure and function, and high survival rates.

Percutaneous mitral annuloplasty for functional mitral regurgitation: results of the CARILLON Mitral Annuloplasty Device European Union Study.

BACKGROUND: Functional mitral regurgitation (FMR), a well-recognized component of left ventricular remodeling, is associated with increased morbidity and mortality in heart failure patients. Percutaneous mitral annuloplasty has the potential to serve as a therapeutic adjunct to standard medical care. METHODS AND RESULTS: Patients with dilated cardiomyopathy, moderate to severe FMR, an ejection fraction <40%, and a 6-minute walk distance between 150 and 450 m were enrolled in the CARILLON Mitral Annuloplasty Device European Union Study (AMADEUS). Percutaneous mitral annuloplasty was achieved through the coronary sinus with the CARILLON Mitral Contour System. Echocardiographic FMR grade, exercise tolerance, New York Heart Association class, and quality of life were assessed at baseline and 1 and 6 months. Of the 48 patients enrolled in the trial, 30 received the CARILLON device. Eighteen patients did not receive a device because of access issues, insufficient acute FMR reduction, or coronary artery compromise. The major adverse event rate was 13% at 30 days. At 6 months, the degree of FMR reduction among 5 different quantitative echocardiographic measures ranged from 22% to 32%. Six-minute walk distance improved from 307+/-87 m at baseline to 403+/-137 m at 6 months (P<0.001). Quality of life, measured by the Kansas City Cardiomyopathy Questionnaire, improved from 47+/-16 points at baseline to 69+/-15 points at 6 months (P<0.001). CONCLUSIONS: Percutaneous reduction in FMR with a novel coronary sinus-based mitral annuloplasty device is feasible in patients with heart failure, is associated with a low rate of major adverse events, and is associated with improvement in quality of life and exercise tolerance.

Echocardiographic evaluation of percutaneous valve repair in patients with mitral regurgitation using the CARILLON system.

BACKGROUND: Dilated cardiomyopathy is characterised by significant enlargement of cardiac chambers, which can lead to functional mitral regurgitation. Surgery is a widely accepted treatment of secondary mitral regurgitation. Conventional cardiac surgery has a high procedural risk and therefore new techniques for percutaneous repair of mitral valve are being developed. The CARILLON system is one of devices that is implanted into the coronary venous system, which enables tension of the mitral ring in order to improve coaptation of the leaflets. AIM: Echocardiographic analysis of the CARILLON system implantation efficacy evaluated directly and one month after implantation. METHODS: The study in included 9 patients, aged 58.56 +/- 6 years, with severe functional mitral regurgitation, who fulfilled the following echocardiographic criteria: large central jet l 4 cm(2) or l 20% of the left atrium area or wall-impinging eccentric jet reaching the pulmonary veins, vena contracta (VC) l 0.30 cm, effective regurgitant orifice area (ERO) l 0.2 cm(2), regurgitant volume (RV) l 30 ml or regurgitant fraction (RF) > 30%. Exclusion criteria were: concomitant severe tricuspid valve insufficiency, significant organic mitral valve pathology, chronic atrial fibrillation, foreign body in the coronary sinus, or thrombus in the left atrial appendage. The prerequsite for implanting the device was a significant reduction in the mitral regurgitation jet observed by transesophageal echo-cadiography (TEE), seen during the procedure. After one month, a transthoracic echocardiography (TTE) was performed to evaluate mitral regurgitation by analysing the same parameters assessed before implanting CARILLON to the coronary sinus. RESULTS: A significant improvement of VC after the procedure, in comparison to the value before the procedure (0.43 +/- 0.12 vs. 0.66 +/- 0.14 cm, p < 0.05), was observed. This improvement was lower one month after the implantation of the device (0.35 +/- 0.1 cm, p < 0.005). The ratio of the jet area to the left atrial area was reduced from 54.96 +/- 11.18% to 38.57 +/- 9.79% (p < 0.005) and sustained after a month at 36.33 +/- 10.15% (p < 0.005). Other echocardiographic parameters of evaluation of mitral regurgitation tended to improve, however the differences did not reach statistical significance. The ERO in subsequent studies was: 0.25 +/- 0.09 cm(2), 0.23 +/- 0.07 cm(2), and 0.24 +/- 0.07 cm(2), and RV decreased from 33.06 +/- 11.81 ml before the procedure, to 32.33 +/- 7.84 ml one month after the procedure. CONCLUSIONS: The CARILLON system implantation to the coronary venous system in patients with secondary mitral regurgitation can lead to the improvement of selected echocardiographic indices of mitral regurgitation.

Long-term prognosis of patients treated by coronary sinus-based percutaneous annuloplasty: single centre experience.

AIMS: This study aims to report long-term mortality, echocardiographic, and clinical outcomes of patients receiving treatment for functional mitral regurgitation (FMR) with the Carillon device. METHODS AND RESULTS: This was a single centre analysis of prospectively collected data from patients treated with the Carillon Mitral Contour System for symptomatic congestive heart failure despite guideline-directed medical therapy, who were included from a single centre from the TITAN II study. All patients presented with New York Heart Association (NYHA) class 2 or greater symptoms, grade 2+ to 4+ FMR, left ventricular enlargement, and reduced ejection fraction. Surviving patients were evaluated for long-term follow-up post-procedure, averaging 6.9 years. Fifteen (15) patients (mean age 72 years, 60% male, 100% NYHA class III or IV, 50% MR grade 3+ or 4+) were treated with the Carillon device. The Kaplan-Meier mortality rate was 40% at 6 years of follow-up. Long-term survival through 6 years was associated with echocardiographic improvement in mitral regurgitation (change in effective regurgitant orifice area in survivors versus non-survivors from baseline to 1 year follow-up, -9.0 ± 5.6 vs. -1.7 ± 1.5, P = 0.02) and clinical status at 12 months (difference in NYHA at 1 year follow-up between survivors versus non-survivors, P = 0. 05) which was sustained throughout follow-up. All patients at 6 year follow-up had ≤2+ MR, with 6 of 7 having 0-1+ MR. Left ventricular end-diastolic volume was reduced from 154.0 ± 65.7 mL at baseline to 104.5 ± 59.2 mL at 6 year follow-up, P = 0.03 in survivors with both measurements. CONCLUSIONS: Among patients with congestive heart failure treated with the Carillon device, long-term survival is associated with favourable 1 year and sustained improvements in mitral regurgitation, left ventricular volume, ejection fraction, and clinical status.

Long-Term Survival Following Transcatheter Mitral Valve Repair: Pooled Analysis of Prospective Trials with the Carillon Device.

PURPOSE: To report long-term survival and to identify potential determinants of survival among patients receiving treatment for functional mitral regurgitation (FMR) with the Carillon device. METHODS: This was a post hoc analysis in which we pooled prospectively collected data from three studies of the Carillon device with available long-term vital status data. Patient eligibility in these trials specified symptomatic congestive heart failure despite guideline-directed medical therapy, grade 2 to 4 FMR, left ventricular enlargement, and reduced ejection fraction. Echocardiographic parameters were available through the 12-month visit and vital status was available through 5 years. The association of patient characteristics and changes in echocardiographic parameters at 6 and 12 months with long-term survival was analyzed using Cox proportional hazards regression. RESULTS: A total of 74 patients (mean age 67 years, 72% male, 59% MR grade 3 or 4) were treated with the Carillon device. Over 1 year of follow-up, the New York Heart Association (NYHA) class decreased in 64% of patients, distance on the 6-minute walk test increased, and echocardiographic measures indicated significant decreases in MR grade and favorable left ventricular remodeling. The Kaplan-Meier survival rate was 83.6% at 1 year, 73.1% at 2 years, 67.9% at 3 years, and 56.2% at 4 and 5 years of follow-up. Primary determinants of long-term survival were a decrease in NYHA class, an increase in 6-minute walk test distance, and a decrease in regurgitant volume during the first year of follow-up. CONCLUSIONS: Among patients with congestive heart failure and grade 2 to 4 FMR who were symptomatic despite guideline-directed medical therapy, transcatheter mitral valve repair with the Carillon device resulted in a favorable 5-year survival rate. The survival benefit was greatest among patients with improvement in clinical and hemodynamic parameters during the first year of follow-up.

Presence of irregularity in region between -1115 and -784 nt in P1 promoter of insulin-like growth factor-1 gene may indicate beneficial effect on coronary arteries in a group of patients with stable angina: preliminary data.

Insulin-like growth factor-1 (IGF-1) plays an important role in arterial homeostasis. Its properties seem to depend on circulating IGF-1 level changes. The various IGF-1 levels are caused by varied expression of IGF-1 gene, due to the polymorphic structure of IGF-1 gene or its regulatory sequences. We examined the P1 promoter, being responsible for most IGF-1 transcripts, in patients with stable angina, to evaluate its sequence changes and to assess its influence on protein synthesis as well as on the degree of arteriosclerosis. For that purpose we evaluated the DNA isolated from blood cells. The DNA was amplified by using polymerase chain reaction (PCR), then analyzed using the SSCP (single-strand conformation polymorphism) technique. Products of every stage were verified by electrophoresis on agarose gel. In addition, every patient had coronary angiography performed and IGF-1, IGFBP3, and lipid levels measured. The SSCP in the region between -1115 and -784 nt was less commonly observed among subjects with positive MI (myocardial infarction) familial history (P = 0.0008) and with MI history (P = 0.012) than in patients without these conditions. Subjects with this irregularity tended towards higher circulating IGF-1 levels. In addition high Gensini scores - over 95th percentile, 105 points in our study - were more frequent in SSCP patients (P = 0.03). We presume that presence of SSCP in the P1 region between -1115 and -784 nt may positively affect coronary arteries by increasing circulating IGF-1 levels, but its clinical importance requires molecular verification and further studies.

Changes in heart rate variability caused by coronary angioplasty depend on the localisation of coronary lesions.

BACKGROUND: Coronary angioplasty (PTCA) is a common treatment method in patients with coronary heart disease, but its effects on heart rate variability (HRV) have not been well established. AIM: To verify whether the localisation of coronary lesion undergoing PTCA affects HRV parameters. METHODS: Ninety six consecutive individuals underwent elective coronary angiography with subsequent ad hoc successful PTCA. Two five-minute ECG were recorded, one before PTCA and the second 24-hour after PTCA. The HRV indices were determined by means of classical and 'new' mathematical models. RESULTS: The PTCA-induced changes in HRV variables depended on the localisation of dilated lesion. PTCA of the circumflex artery revealed the most significant HRV changes--a decrease in value of domain indices: Yeh DI (0.033+/-0.031 vs. 0.011+/-0.006 un/unitless, p=0.005), Yeh II (0.053+/-0.039 vs. 0.032+/-0.013 un, p=0.017), Organ BAND (9.101+/-9.245 vs. 4.62+/-2.205 bpm/beat per minute, p=0.031), Huey STV (208.821+/-262.248 vs. 76.444+/-35.281 bpm, p=0.013), Dalton MABB (15.733+/-16.575 vs. 7.57+/-4.89 ms, p=0.015), Dalton SD (48.741+/-37.468 vs. 27.759+/-10.533 ms, p=0.015), Zugaib STV (0.0129+/-0.0132 vs. 0.005+/-0.003 un, p=0.005), SDNN (27.204+/-18.592 vs. 21.329+/-32.784 ms, p=0.044), rMSSD (56.239+/-19.751 vs. 51.496+/-43.889 ms, p=0.025) and increased LF/HF (2.384+/-2.072 vs. 5.632+/-5.379 un, p=0.044). Angioplasty of the right coronary artery resulted in decreased AR TP (18.273+/-2.296 vs. 17.085+/-2.256 ms(2), p=0.017) and alteration of the sympathovagal balance of the autonomic nervous system towards predominance of sympathetic activity: AR LF (0.264+/-0.029 vs. 0.284+/-0.040 un, p=0.007), LF/HF (4.310+/-4.457 vs. 6.958+/-7.013 un, p=0.018), HF (0.199+/-0.165 vs. 0.141+/-0.157 un, p=0.031), AR HF (0.647+/-0.043 vs. 0.621+/-0.054 un, p=0.014). PTCA of the left anterior descending artery caused no change. CONCLUSION: Changes in heart rate variability caused by coronary angioplasty depend on the localisation of coronary lesions.

The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation.

OBJECTIVES: This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. BACKGROUND: Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. METHODS: In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. RESULTS: Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: -11.7 to -2.5] vs. an increase of 3.3 ml/beat [95% CI: -6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: -18.5 to -2.4] vs. an increase of 6.5 ml [95% CI: -5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: -12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: -1.42 to 13.6]; p = 0.04). CONCLUSIONS: The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy. (Carillon Mitral Contour System for Reducing Functional Mitral Regurgitation [REDUCE FMR]; NCT02325830).

The effect of atorvastatin treatment on lipid profile and adhesion molecule levels in hypercholesterolemic patients: relation to low-density lipoprotein receptor gene polymorphism.

Inflammation has been indicated to play a major role in the development of atherosclerosis. The beneficial effect of statins has been suggested to be related to their anti-inflammatory properties. We have studied plasma levels of soluble adhesion molecules in patients with hypercholesterolemia before and after 3 months of treatment with atorvastatin and evaluated possible relations to the mutations in low-density lipoprotein receptor (LDLR) gene. In patients with no LDLR gene polymorphism (group A), lower baseline levels of total cholesterol and LDL cholesterol were found than in patients with LDLR gene polymorphism (group B). The soluble adhesion molecules sICAM-1, sE-selectin and sP-selectin, but not sVCAM-1 and sL-selectin, were higher in group B than in group A. sICAM-1 levels decreased in group A by 7% (p = 0.007) and in group B by 21% (p = 0.039), whereas levels of sVCAM-1 decreased in group A by 12% (p = 0.001) and in group B patients by 19% (p = 0.039). Atorvastatin did not change sE-selectin nor sP-selectin levels in group A. However, in group B, the treatment reduced E-selectin and sP-selectin levels by 39% (p = 0.007) and 24% (p = 0.007), respectively. Atorvastatin attenuates the inflammatory reaction in hypercholesterolemic patients, but in patients with LDLR gene polymorphism, this effect is more profound.

Impact of previous percutaneous coronary interventions on the course and clinical outcomes of coronary artery bypass grafting.

BACKGROUND: Despite the increasing number of patients after percutaneous coronary intervention (PCI) requiring coronary artery bypass grafting (CABG), studies on the impact of these procedures on surgical revascularisation outcomes are sparse. Furthermore, advances in cardiology require reassessment of their potential prognostic significance. AIM: We sought to assess the influence of previous PCI on CABG outcomes. METHODS: A total of 211 consecutive patients scheduled for CABG were enrolled into this prospective study. Patients after PCI (group 1, n = 99) were compared with subjects with no history of PCI (group 2, n = 112) in terms of preoperative, operative, and postoperative data. All the patients were followed-up for the incidence of in-hospital (cardiogenic shock, myocardial infarction, stroke, acute renal failure, reoperation, death) and long-term (overall mortality, occlusion of at least one graft in 64-row computed tomography) clinical endpoints. RESULTS: Group 1 had more advanced heart failure and coronary artery disease as reflected by New York Heart Association (2.43 ± 0.57 vs. 2.17 ± 0.68; p < 0.001) and Canadian Cardiovascular Society (2.44 ± 0.59 vs. 2.03 ± 0.65; p < 0.001) scales, respectively. Compared with group 2, longer aortic cross-clamp (33.5 ± 9.9 vs. 29.5 ± 8.4; p < 0.05) and cardiopul-monary bypass (67.5 ± 28.2 vs. 56.5 ± 17.9; p < 0.001) times were observed as well as a higher number of implanted grafts (3.0 ± 0.7 vs. 2.8 ± 0.70; p < 0.05). No significant differences were observed in terms of in-hospital clinical endpoints. During 12 ± 3.41 months of follow-up group 1 had higher mortality (5.05% vs. 0%; p < 0.05) but similar graft patency. CONCLUSIONS: "Stent-loaded" patients undergo more time-consuming CABG with a higher number of grafts. Furthermore, they have higher long-term mortality but similar graft patency and in-hospital mortality/morbidity.

Percutaneous valve repair for mitral regurgitation using the Carillon Mitral Contour System. Description of the method and case report.

Mitral regurgitation may result from left ventricular dilatation and cause progression of heart failure. Percutaneous techniques for mitral valve repair are under development. Techniques utilizing a trans-coronary venous approach exploit the anatomical relationship between the mitral annulus and the venous system of the heart. The coronary sinus, great cardiac vein and the origin of the anterior interventricular vein surround the posterior mitral annulus. This enables percutaneous approaches to annuloplasty for mitral regurgitation. Devices can be implanted into the coronary veins that modify the shape and size of the mitral annulus. We present a case of ischaemic mitral regurgitation successfully treated by use of a percutaneous approach, the Carillon Mitral Contour System. Significant reduction of the mitral regurgitation jet was observed. The patient was discharged 4 days after the procedure. During the follow-up visits, the patient showed an improved general condition and increased exercise capacity. Procedural steps are shown in detail and the current status of the coronary sinus based technique is discussed. Percutaneous techniques for mitral valve repair may be an attractive alternative to cardiac surgery in heart failure patients with secondary mitral regurgitation. The Carillon Mitral Contour System is under ongoing clinical evaluation in the AMADEUS trial.