Local electromechanical alterations determine the left ventricle rotational dynamics in CRT-eligible heart failure patients.

Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system (NOGA XP, Biosense Webster). The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients' grouping into two categories: wringing rotation (Group A, n = 6) and RBT rotation (Group B, n = 24). All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.Clinical trial registration: SUM No. KNW/0022/KB1/17/15.

Incident heart failure in outpatients with chronic coronary syndrome: results from the international prospective CLARIFY registry.

AIM: The contemporary incidence of heart failure (HF) in patients with chronic coronary syndrome is unclear. We aimed to study the incidence and predictors of cardiovascular (CV) death, HF hospitalization or new-onset HF not requiring hospitalization, in patients included in the CLARIFY registry. METHODS AND RESULTS: CLARIFY is a contemporary, international registry of ambulatory patients with chronic coronary artery disease, conducted in 45 countries. At baseline, data on demographics, ethnicity, CV risk factors, medical history, cardiac parameters and medication were collected. Patients were followed up yearly up to 5 years. In this analysis, 26 769 patients with no HF history were included. At 5-year follow-up, 4393 patients (16.4%) reached the primary endpoint comprising CV death, HF hospitalization, or new-onset HF. Only 16.7% of them (n = 732) required hospitalization for HF. All-cause death occurred in 6.6% of patients (61.4% were CV). Age over 70 years, left ventricular ejection fraction <50%, Canadian Cardiovascular Society class ≥2 angina, atrial fibrillation or paced rhythm on the ECG, body mass index <20 kg/m2 , and a history of stroke, were the most robust predictors of the primary outcome. Age <50 years, Asian ethnicity, and percutaneous revascularization were negative predictors of the outcome. CONCLUSION: A sizeable proportion of patients with chronic coronary syndrome develop HF, which only infrequently requires hospitalization. Early identification of patients with HF may lead to early treatment, and help to further decrease mortality and morbidity. This concept needs confirmation in future studies.

Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry.

AIMS: Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary syndrome in the contemporary era, as well as outcomes and their determinants. METHODS AND RESULTS: Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome [cardiovascular death or non-fatal myocardial infarction (MI)] 5-year rate was 8.0% [95% confidence interval (CI) 7.7-8.3] overall [male 8.1% (7.8-8.5); female 7.6% (7.0-8.3)]. A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate [11.8% (95% CI 10.9-12.9) vs. 8.2% (95% CI 7.8-8.7) in patients with no angina, P < 0.001], whereas among patients without prior MI, event rates were similar for patients with [6.3% (95% CI 5.4-7.3)] or without angina [6.4% (95% CI 5.9-7.0)], P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high. CONCLUSION: This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment. CLINICAL REGISTRY: ISRCTN43070564.

Management strategies and 5-year outcomes in Polish patients with stable coronary artery disease versus other European countries: data from the CLARIFY registry.

INTRODUCTION An international registry of ambulatory patients with stable coronary artery disease (CLARIFY) allows a comparison of management and outcomes in real­life setting. OBJECTIVES We aimed to compare the management strategies and 5­year outcomes in patients from Poland and from other European countries. PATIENTS AND METHODS Stable coronary artery disease was defined as previous myocardial infarction (MI) or revascularization, coronary stenosis greater than 50%, or documented symptomatic myocardial ischemia. Patients were followed on an annual basis for 5 years. RESULTS Among the total of 32 703 patients, 1000 were enrolled in Poland, and 17 326 in other European countries. Polish patients were younger, with a higher proportion of women, smokers, and patients with previous MI, dyslipidemia, and hypertension. Patients in both cohorts received adequate medical treatment, with more Polish patients receiving ß­blockers. Blood pressure and lipid control to target was similar and remained low in both cohorts. Diabetes control and successful smoking cessation rates were lower in Poland than in other European countries. Polish patients more often underwent percutaneous coronary intervention. All­cause (8.5% vs 7.9%; P = 0.81) and cardiovascular death rates (5.3% vs 4.9%; P = 0.82) did not differ between the groups, but fatal or nonfatal MI occurred more often in the Polish cohort (5% vs 3.1%; P = 0.006). Angina control was better in Poland than in other European countries (Canadian Cardiovascular Society class II-IV, 11.5% vs 15.8% of patients; P <0.001). CONCLUSIONS Risk factor control was insufficient both in patients from Poland and in those from other European countries. The more frequent use of revascularization in Polish patients was not linked to improved outcomes, but, together with more extensive prescription of ß­blockers, might have contributed to better angina control.

Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial.

BACKGROUND: The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina. METHODS: Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment. RESULTS: The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period. CONCLUSIONS: Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

Secular trends in first-time hospitalization for heart failure with following one-year readmission and mortality rates in the 3.8 million adult population of Silesia, Poland between 2010 and 2016. The SILCARD database.

BACKGROUND: Heart failure (HF) continues to be an important medical and social problem, with high morbidity and mortality. Data on the trends in hospitalizations, hospital readmissions and mortality is of great importance both from the epidemiological and clinical points of view. METHODS AND RESULTS: We analyzed the secular trends in first-time hospital admissions for heart failure between 2010 and 2016, derived from SILCARD database, covering a population of 3.8 million adults. Patient characteristics as well as data on in-hospital and 12-month outcomes were recorded for each year. The total number of first-time hospitalizations for HF as the primary diagnosis showed a downward trend during the study period (reduction by 12%, p = 0.07), with a constant patient age (mean 74.3 ±â€¯11.3 years). The length of hospital stay shortened from 10.9 to 9.6 days (p = 0.003). Crude in-hospital mortality remained constant at around 14% (p = 0.55), but after adjustment for sex and age, mortality rates tended to decrease from 17.2% in 2010 to 11.5% in 2016 (p = 0.007). All-cause hospital readmission rates in 12-month follow-up increased which was due to non-CV hospitalizations, since both CV- and HF-related readmissions were constant throughout the years. Crude 12-month mortality was constant, but after adjustment for age and sex absolute reduction by about 10% was found (p = 0.02). CONCLUSIONS: Despite the decreasing duration of hospital stay, significant improvement in both in-hospital and long-term survival was observed, with constant rates of hospital readmissions related to HF.

Transcatheter paravalvular leak closure and hemolysis - a prospective registry.

INTRODUCTION: Paravalvular leak (PVL) related to a surgical prosthetic valve may be associated with clinically significant hemolysis. The influence of transcatheter PVL closure (TPVLC) on hemolysis remains uncertain. MATERIAL AND METHODS: The prospective registry included patients undergoing TPVLC due to PVL-related heart failure and/or hemolysis. Procedural data, laboratory markers of hemolysis and heart failure status were recorded at baseline, discharge and at 1- and 6-month follow-up. RESULTS: Of 116 patients from all those qualified for TPVLC, 79 fulfilled the inclusion/exclusion criteria. Hemolysis was significantly more frequent in patients with mitral location of PVL and with calcifications in its channel. After TPVLC prompt reduction of lactate dehydrogenase activity (617.0 (342.0-899.0) vs. 397 (310.0-480.5) IU/l, p < 0.05) and gradual resolution of anemia (hemoglobin (HGB) 11.7 (10.4-13.8) vs. 13.4 (12.9-13.8) g%, p < 0.05) over 6 months were noted. Effective closure of PVL (> 90% reduction of PVL cross-sectional area) resulted in a more prominent increase of red blood cell count and HGB than in patients with residual regurgitation. The TPVLC-related exacerbation of hemolysis was recorded in 14 patients. Its risk was aggravated by presence of significant hemolysis at baseline or residual flow either by a partially uncovered channel or across the occluder. Reduction of hemolysis after successful TPVLC was sustained in 6-month follow-up. CONCLUSIONS: Risk factors for PVL-related hemolysis were the presence of calcifications in the defect and mitral location of PVL. The TPVLC effectively reduced hemolysis if at least 90% reduction of PVL cross sectional area was achieved. The effect was sustained in 6-month follow-up. Incomplete closure of PVL may increase the magnitude of hemolysis after TPVLC, but it occurred rarely.

Differences in outcomes in patients with stable coronary artery disease managed by cardiologists versus noncardiologists. Results from the international prospective CLARIFY registry.

INTRODUCTION    Clinical outcomes of patients with stable coronary artery disease (CAD) may differ between those primarily managed by cardiologists versus noncardiologists. OBJECTIVES    Our main objective was to analyze the clinical outcomes of outpatients with stable CAD in relation to the specialty of the managing physicians. PATIENTS AND METHODS    We studied 32 468 outpatients with stable CAD included in the CLARIFY registry, with up to 4 years of follow­up data. Cardiologists provided medical care in 84.1% and noncardiologists in 15.9% of the patients. Primary outcome was the composite of cardiovascular death, nonfatal myocardial infarction (MI), or stroke. RESULTS    Important differences in management as well as demographic and clinical characteristics were observed between the groups at baseline. Patients treated by cardiologists were younger and more of them had dyslipidemia, hypertension, and diabetes. The use of ß­blockers and thienopyridines, as well as history of percutaneous coronary intervention were more frequent in this group. More patients treated by noncardiologists had a history of MI as well as concomitant peripheral artery disease and asthma or chronic obstructive pulmonary disease. They also had lower left ventricular ejection fraction and more often received lipid­lowering drugs. After adjustment for baseline differences, patients treated by cardiologists had a lower risk of the primary outcome (adjusted hazard ratio, 0.80; 95% confidence interval, 0.68­0.94; P = 0.0067) and of most secondary outcomes, but greater risk of bleeding. CONCLUSIONS Outpatients with stable CAD managed by cardiologists had a lower rate of cardiovascular outcomes than those managed by noncardiologists. We did not find clear evidence that cardiologists provided superior guideline­based treatment, so the differences in outcome were most likely due to unquantifiable differences in patient characteristics.

Effects of Transendocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

RATIONALE: New therapies for refractory angina are needed. OBJECTIVE: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. METHODS AND RESULTS: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], P=0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. CONCLUSION: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

Prognostic value of coronary artery calcium score in patients with symptoms suggestive of coronary artery disease. Results from the Silesian Calcium Score (SILICAS) study.

INTRODUCTION    The prognostic value of coronary artery calcium score (CACS) in symptomatic patients with a suspicion of coronary artery disease (CAD) has been poorly defined. OBJECTIVES    The aim of the study was to assess the predictive value of the CACS in the incidence of major adverse coronary events (MACEs) in patients with an intermediate probability of CAD and establish its usefulness as the first-line risk assessment tool. PATIENTS AND METHODS    This single-center, observational, prospective study enrolled consecutive symptomatic patients without a previous diagnosis of CAD, referred to our center for CACS assessment with non-contrast-enhanced cardiac computed tomography (CT). CACS measurements were performed using an electrocardiogram-gated 64-row CT scanner. The CACS measurement was treated as the first­line noninvasive test. Patients with positive CACS values were divided into 4 subgroups: <100 Agatston units (AU), 100 to 399 AU; 400 to 999 AU; and ≥1000 AU. The incidence of MACEs was analyzed in 2 ways: negative versus positive CACS and by the CACS subgroups. RESULTS    We included 588 patients (mean age, 61.1 ±9.7 years; women, 64%). The median follow-up period was 707 days. There were 239 patients (49.3%) with no coronary calcium. In these patients, no MACEs were observed, while in those with positive CACS values, they occurred in 108 patients (30.9%) (P <0.001). The incidence of MACEs was dependent on the CACS values, reaching 91% in those with a CACS of 1000 or higher AU. CONCLUSIONS    In selected symptomatic patients with an intermediate probability of CAD, the CACS measurement may be used as the first-line test to assess the risk of MACEs.

Traditional risk factors and coronary artery calcium in young adults.

BACKGROUND AND METHODS: 362 symptomatic subjects of 45 years of age or younger were selected from a large database of around 4100 persons who underwent coronary artery calcium (CAC) scoring by means of a 64-multidetector computed tomography (MDCT). Amongst them, a group with the CAC > 0 Agatston units (n = 65) and a group with no detectable calcium (CAC = 0, n = 297) were compared in terms of risk factors presence. Risk factors considered were gender, body mass index, smoking habits, blood pressure level, blood lipids, presence of diabetes mellitus, family history of cardiovascular disease, and physical activity. RESULTS: The vast majority of subjects with a positive CAC were males (54, 83.1%) compared to those with a negative CAC (147, 49.5%, p < 0.001, χ2). More frequent results of CAC < 0 were observed in obese subjects (38.5% vs. 24.2%, p < 0.05), among smokers (41.5% vs. 27.6%, p < 0.05). Presence of arterial hypertension coexisted with a more frequent CAC > 0 (76.9% vs. 60.6%, p < 0.05). Also, the frequency of a positive CAC was significantly higher in patients with diabetes mellitus (10.8%), compared to those without diabetes mellitus (4.0%, p < 0.05). Effects of high lipids, family history, and physical activity were not observed. Accumulation of at least 4 risk factors was associated with more frequent positive CAC (26.0 vs. 15.9%, p < 0.05). Multivariate regression analysis showed that only male gender and presence of diabetes mellitus were independent predictors of a positive CAC in younger subjects (F = 5.06, p < 0.001, multiple R = 0.321). CONCLUSIONS: Traditional risk factors, apart from gender and diabetes mellitus, do not seem to allow for distinguishing young persons with a premature coronary atherosclerosis. Therefore, CAC scoring might be considered justified in symptomatic young men with diabetes mellitus.

Mobilization of CD34+CXCR4+ stem/progenitor cells and the parameters of left ventricular function and remodeling in 1-year follow-up of patients with acute myocardial infarction.

Mobilization of stem cells in acute MI might signify the reparatory response. Aim of the Study. Prospective evaluation of correlation between CD34+CXCR4+ cell mobilization and improvement of LVEF and remodeling in patients with acute MI in 1-year followup. Methods. 50 patients with MI, 28 with stable angina (SAP), and 20 individuals with no CAD (CTRL). CD34+CXCR4+ cells, SDF-1, G-CSF, troponin I (TnI) and NT-proBNP were measured on admission and 1 year after MI. Echocardiography and ergospirometry were carried out after 1 year. Results. Number of CD34+CXCR4+ cells in acute MI was significantly higher in comparison with SAP and CTRL, but lower in patients with decreased LVEF ≤40%. In patients who had significant LVEF increase ≥5% in 1 year FU the number of cells in acute MI was significantly higher versus patients with no LVEF improvement. Number of cells was positively correlated (r = 0,41, P = 0,031) with absolute LVEF change and inversely with absolute change of ESD and EDD in 1-year FU. Mobilization of CD34+CXCR4+ cells in acute MI was negatively correlated with maximum TnI and NT-proBNP levels. Conclusion. Mobilization of CD34+CXCR4+ cells in acute MI shows significant positive correlation with improvement of LVEF after 1 year.

The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina.

BACKGROUND: Anti-ischaemic effect of A1 adenosine receptor agonists was shown in animal and preclinical studies. The present proof-of-concept study aimed at evaluation of the efficacy and safety of a new adenosine A1 receptor agonist capadenoson in patients with stable angina. METHODS: This was a randomized, double-blind, placebo-controlled, single dose-escalating, multicenter trial comparing the effect of capadenoson at 1, 2.5, 5, 10, and 20 mg versus placebo. For each dose step patients were randomized to receive single doses of either capadenoson or matching placebo in a 5:1 ratio. The primary efficacy variable was the absolute difference in heart rate (HR) at maximum comparable level of workload between baseline and post dose exercise tolerance test at maximum concentration of capadenoson. Capadenoson effect on total exercise time and time to 1-mm ST-segment depression were also measured. RESULTS: Sixty-two male patients with stable angina were enrolled in the study. There was a consistent trend for HR reduction at comparable maximum work load in active treatment groups, with significant differences against placebo for 10 and 20 mg (HR reduction by 12.2 and 6.8 beats per min, p = 0.0002 and p = 0.032, respectively). A statistically significant trend (p = 0.0003) for a reduction in HR with increasing doses of capadenoson was shown. Increases in total exercise time and time to 1-mm ST-segment depression were also observed. CONCLUSIONS: In patients with stable angina capadenoson lowers exercise HR at comparable maximum workload, which is associated with improved total exercise time and prolongation of time to ischaemia.

ARISTOTLE RE-LYs on the ROCKET. What's new in stroke prevention in patients with atrial fibrillation?

Warfarin has long been considered the gold standard for stroke prevention in patients with atrial fibrillation (AF). Recently, three major trials comparing the efficacy and safety of new drugs: a thrombin inhibitor dabigatran and two inhibitors of factor Xa - rivaroxaban and apixaban, with that of warfarin, have been published. The aim of this paper is to present the main results of the RE-LY, ROCKET AF and ARISTOTLE trials, compare study populations and outcomes, and discuss clinical implications of their results for the long-term anticoagulation in patients with nonvalvular AF.