Exercise Dynamics in Secondary Mitral Regurgitation: Pathophysiology and Therapeutic Implications.

Secondary mitral valve regurgitation (MR) remains a challenging problem in the diagnostic workup and treatment of patients with heart failure. Although secondary MR is characteristically dynamic in nature and sensitive to changes in ventricular geometry and loading, current therapy is mainly focused on resting conditions. An exercise-induced increase in secondary MR, however, is associated with impaired exercise capacity and increased mortality. In an era where a multitude of percutaneous solutions are emerging for the treatment of patients with heart failure, it becomes important to address the dynamic component of secondary MR during exercise as well. A critical reappraisal of the underlying disease mechanisms, in particular the dynamic component during exercise, is of timely importance. This review summarizes the pathophysiological mechanisms involved in the dynamic deterioration of secondary MR during exercise, its functional and prognostic impact, and the way current treatment options affect the dynamic lesion and exercise hemodynamics in general.

Shifting Perceptions of Risk and Reward: Use of Anticoagulation in Patients With Acute Brain Ischemia and Atrial Fibrillation: Nine-Year Data From a National Acute Stroke Registry (National Acute Stroke Israeli Survey [NASIS]).

BACKGROUND AND PURPOSE: Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia and atrial fibrillation, vast underuse has been reported. METHODS: Use of anticoagulation for secondary stroke prevention was assessed in the National Acute Stroke Israeli Survey registry (NASIS) of hospitalized patients with atrial fibrillation and acute brain ischemia. Logistic regression analysis was performed to evaluate the effects of clinical covariates on anticoagulation therapy at discharge, and anticoagulation use over time was assessed in subgroups of patients with identified barriers to anticoagulation utilization. RESULTS: There were 1254 survivors of acute brain ischemia with atrial fibrillation (mean age 77.2±10.6 years; 57.7% female). Between 2004 and 2013, the proportion of patients discharged on anticoagulation increased from 55% to 76.2%, and among those without perceived contraindications from 70% to 96% (P<0.0001). Older age, greater stroke severity, earlier registry period, and presence of contraindications were independent predictors of withholding therapy. Increased anticoagulation use over the years was observed even in patients with barriers to anticoagulation use, including patients with potential contraindications (P<0.001). CONCLUSIONS: In survivors of acute brain ischemia with atrial fibrillation, we observed a substantial increase in anticoagulation utilization within less than a decade. This change was mainly driven by greater utilization of anticoagulation in subgroups with traditional clinical barriers to anticoagulation use, indicating a shift in physicians' perceptions of the risk-benefit ratio of anticoagulation.

Dynamic obstruction in hypertrophic cardiomyopathy.

PURPOSE OF REVIEW: The present article reviews the recent advances in the echocardiographic assessment of left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM). In particular, it highlights the role of novel imaging techniques in promoting our understanding of the pathophysiology of obstruction and discusses the prognostic value of information obtained from exercise echocardiography and the emerging role of image-guidance technologies for interventional relief of obstruction. RECENT FINDINGS: The advent of novel echocardiography technologies, such as vector flow mapping, continues to expand our understanding of the exact mechanism of systolic anterior motion leading to dynamic LVOT obstruction by providing new insights into the interaction between pathologic mitral geometry and the left ventricular flow field. New studies provide evidence for the prognostic value of exercise echocardiography in the assessment of patients with HCM. Myocardial contrast perfusion imaging can delineate the anatomy of septal perforator arteries and identify the downstream septal perfusion bed, which is critical for safely guiding the procedure of alcohol septal ablation. SUMMARY: Echocardiography represents a versatile, continuously evolving, and easily repeatable technique, allowing truly dynamic imaging studies, and is therefore most appropriate to evaluate a dynamic disease condition such as LVOT obstruction in HCM. It provides profound insights into the pathophysiology of LVOT obstruction, information on its clinical impact, and guidance for its relief by interventional strategies.

Estimating mortality in survivors of the acute coronary syndrome by the 4-drug score.

OBJECTIVE: Four drug classes, platelet inhibitors, ß-blockers, statins, and angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), have been shown to reduce mortality in clinical trials. We sought to evaluate whether the simple number of secondary prevention drugs at discharge is independently associated with 1-year mortality in acute coronary syndrome (ACS) patients. METHODS: We analyzed a prospective cohort study using data of all 5 Acute Coronary Syndrome Israeli Surveys (ACSIS) conducted between 2002 and 2010 in all Israeli cardiology departments. All 9,107 hospital survivors of ACS participated. RESULTS: A score from 1 to 4 discharge drugs was significantly associated with gradual decreasing rates of 1-year mortality (14.4, 9.0, 5.1, and 3.6%, respectively; p for trend <0.001). Only when the number of discharge drugs increased to 3-4 as a result of the intervention during hospitalization in patients initially admitted with 0-2 drugs, a significant multivariate-adjusted decrease in the hazard ratio (HR), independent of multiple baseline, admission presentation, and in-hospital course characteristics, was measured (HR, 0.66; 95% confidence interval, 0.50-0.87). CONCLUSION: The use of a higher number of secondary prevention drugs at discharge following ACS was associated with significantly lower mortality rates, particularly in patients with mono- or dual-baseline therapy.

Artificial Intelligence Assessment of Biological Age From Transthoracic Echocardiography: Discrepancies with Chronologic Age Predict Significant Excess Mortality.

BACKGROUND: Age and sex can be estimated using artificial intelligence on the basis of various sources. The aims of this study were to test whether convolutional neural networks could be trained to estimate age and predict sex using standard transthoracic echocardiography and to evaluate the prognostic implications. METHODS: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (n = 556). Finally, a prospective cohort of handheld point-of-care ultrasound devices (n = 319; ClinicalTrials.gov identifier NCT05455541) was used to confirm the findings. A multivariate Cox regression model was used to investigate the association between age estimation and chronologic age with overall survival. RESULTS: The mean absolute error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥5 years vs chronologic age was associated with an independent 34% increased risk for death during follow-up (P < .001). CONCLUSIONS: Applying artificial intelligence to standard transthoracic echocardiography allows the prediction of sex and the estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Pseudo-discordance mimicking low-flow low-gradient aortic stenosis in transcatheter aortic valve replacement patients with severe symptomatic aortic stenosis.

BACKGROUND: While the combination of a small aortic valve area (AVA) and low mean gradient is frequently labeled 'low-flow low-gradient aortic stenosis (AS)', there are two potential causes for this finding: underestimation of mean gradient and underestimation of AVA. METHODS: In order to investigate the prevalence and causes of discordant echocardiographic findings in symptomatic patients with AS and normal left ventricular (LV) function, we evaluated 72 symptomatic patients with AS and normal LV function by comparing Doppler, invasive, computed tomography (CT) LV outflow tract (LVOT) area, and calcium score (CaSc). RESULTS: Thirty-six patients had discordant echocardiographic findings (mean gradient < 40 mmHg, AVA ≤ 1 cm²). Of those, 19 had discordant invasive measurements (true discordant [TD]) and 17 concordant (false discordant [FD]): In 12 of the FD the mean gradient was > 30 mmHg; technical pitfalls were found in 10 patients (no reliable right parasternal Doppler in 6). LVOT area by echocardiography or CT could not differentiate between concordants and discordants nor between TD and FD (p = NS). CaSc was similar in concordants and FD (p = 0.3), and it was higher in true concordants than in TD (p = 0.005). CaSc positive predictive value for the correct diagnosis of severe AS was 95% for concordants and 93% for discordants. CONCLUSIONS: Discordant echocardiographic findings are commonly found in patients with symptomatic AS. Underestimation of the true mean gradient due to technical difficulties is an important cause of these discrepant findings. LVOT area by echocardiography or CT cannot differentiate between TD and FD. In the absence of a reliable and compete multi-window Doppler evaluation, patients should undergo CaSc assessment.

Transapical aortic valve implantation with a self-expanding anatomically oriented valve.

AIMS: The Medtronic Engager™ aortic valve bioprosthesis is a self-expanding valve with support arms facilitating anatomically correct positioning and axial fixation. Valve leaflets, made of bovine pericardium, are mounted on a Nitinol frame. Here, we report the first in man study with this new implant (Trial Identifier NCT00677638). METHODS AND RESULTS: Thirty patients (mean age 83.4 ± 3.8 years; 83% female) with tricuspid aortic valve stenosis were included in the study. Mean logistic EuroSCORE was 23.4 ± 11.9. Mean aortic annulus diameter was 21.8 ± 1.4 mm. For this study, the Engager was available in only one size (23 mm), to fit aortic annuli of 19-23 mm. Standard transapical valve implantation was performed using pre-dilation of the aortic valve and rapid ventricular pacing during balloon valvuloplasty and most valve deployments. Accurate valve placement was achieved in 29/30 cases (97%). Post-implant peak-to-peak gradient was 13.3 ± 9.3 mmHg. In 80% of the patients, no more than grade I paravalvular leakage was observed, in 13% grades I-II and in 3% grade II. Three patients (10%) required permanent pacemaker implantation for higher-degree or complete atrioventricular block. Four dissections (13%) occurred during positioning of the valve and were treated surgically in three cases. Thirty-day and in-hospital mortality were 20% and 23%, respectively, and 6-month survival was 56.7%. No structural failure occurred for up to 1 year. CONCLUSION: This series established the feasibility of implanting a novel self-expanding transapical aortic valve prosthesis predictably into an anatomically correct position. Observed complications led to complete redesign of the delivery system for upcoming clinical studies with the goal of establishing safety and performance.

Repair with annuloplasty only of balanced bileaflet mitral valve prolapse with severe regurgitation.

OBJECTIVES: Repair of severe mitral valve and mitral regurgitation (MR) in patients with degenerative bileaflet pathology can be challenging. Initial results with a ring-only repair (ROR) approach have shown promising results, but long-term outcomes in larger series are lacking. We report on outcomes of ROR in severe MR secondary to bileaflet prolapse, including Barlow's disease. METHODS: Eighty patients with degenerative multi-segment bileaflet disease underwent ROR for severe MR with a predominantly central regurgitant jet indicating balanced bileaflet prolapse. The main outcome measure of this study was long-term recurrent MR probability. Secondary outcomes were late mortality, reoperation and in-hospital complications. RESULTS: The mean age was 53 ± 15 years and 54% were males. The mean ejection fraction was 59.2 ± 6.6, 24% and 40% had atrial fibrillation. Barlow's disease was found in 77% of the patients. Minimally invasive surgery was performed in 15 patients (19%). There were no perioperative mortalities or cerebrovascular events in the entire cohort. Post-repair mild outflow tract obstruction (systolic anterior motion) was observed in 4 patients (5%) after ROR. In a mean follow-up of 60 ± 48 months, there was 1 case of death. At follow-up, there was 1 (1%) reoperation due to recurrent MR, and 4 patients who had recurrent moderate or more MR. The 10-year freedom from recurrent MR was 97%. None had severe MR at the latest follow-up. CONCLUSIONS: In patients with severe MR and a central regurgitant jet secondary to balanced multi-segment bileaflet mitral valve prolapse, ROR is a simple and efficient approach providing excellent long-term results without a substantial risk of systolic anterior motion.

Secondary chordal resection with septal myectomy for treatment of symptomatic obstructive hypertrophic cardiomyopathy.

OBJECTIVES: Left ventricular outflow tract obstruction causes symptoms of heart failure in most patients with hypertrophic cardiomyopathy. Resection of the secondary mitral valve (MV) chordae has recently been shown to move the MV apparatus posteriorly, thereby eradicating the outflow gradient. The aim of this study was to evaluate whether secondary chordal resection concomitant to septal myectomy improves outcomes. METHODS: Between 2005 and 2020, a total of 165 patients underwent septal myectomy without MV repair or replacement in our Medical Center. Secondary MV chordal resection was performed in 60 patients, and their outcomes were compared with those of the remaining 105 patients who did not undergo chordal resection (controls). Mean age was 61 ± 13 and 58 ± 16 years, respectively (P = 0.205). RESULTS: There were no in-hospital deaths throughout the entire cohort. Of those patients who underwent secondary chordal resection, New York Heart Association functional class decreased from 3 (interquartile range 2-3) preoperatively to 1 (interquartile range 1-2) postoperatively (P < 0.001), and resting outflow gradient decreased from 91 ± 39 mmHg to 13 ± 8 mmHg (86% change, P < 0.001). Compared with controls, patients who underwent secondary chordal resection had a significant lower resting outflow gradient at follow-up (14 ± 7 mmHg vs 21 ± 15 mmHg, P = 0.002). The rate of moderate or more than moderate mitral regurgitation at 5 years was 2% in the secondary chordal resection group and 5% in the controls (hazard ratio 1.05, confidence interval 0.11-10.32; P = 0.965). CONCLUSIONS: In this observational study, we report that secondary chordal resection concomitant to septal myectomy for left ventricular outflow tract obstruction is safe, relieves heart failure symptoms and reduces left ventricular outflow tract gradient in appropriately selected patients.

Short membranous septum length in bicuspid aortic valve stenosis increases the risk of conduction disturbances.

BACKGROUND: Distinct anatomical features predispose bicuspid AS patients to conduction disturbances after TAVR. This study sought to evaluate whether the incidence of permanent pacemaker implantation (PPMI) and left bundle branch block (LBBB) in patients with bicuspid aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR) is related to an anatomical association between bicuspid AS and short membranous septal (MS) length. METHODS: Sixty-seven consecutive patients with bicuspid AS from a Bicuspid AS TAVR multicenter registry and 67 propensity-matched patients with tricuspid AS underwent computed tomography before TAVR. RESULTS: MS length was significantly shorter in bicuspid AS compared with tricuspid AS (6.2 ± 2.5 mm vs. 8.4 ± 2.7 mm, respectively; p < 0.001). In patients with bicuspid AS, MS length and aortic valve calcification were the most powerful pre-procedural independent predictors of PPMI or LBBB (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.15 to 1.55, p = 0.003 and OR: 1.92, 95% CI: 1.1 to 3.34, p = 0.022, respectively). When taking into account pre- and post-procedural parameters, aortic valve calcification and the difference between MS length and implantation depth were the most powerful independent predictors of PPMI or LBBB in patients with bicuspid AS (OR: 1.82, 95%: 1.1 to 3.1, p = 0.027; OR: 1.25, 95% CI: 1.10 to 1.38, p = 0.003). CONCLUSION: MS length, which was significantly shorter in bicuspid AS compared with tricuspid AS, aortic valve calcification, and device implantation deeper than MS length predict PPMI or LBBB in bicuspid AS after TAVR.

Percutaneous implantation of the self-expandable CoreValve for high risk patients with severe aortic valve stenosis: early Israeli experience.

BACKGROUND: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR has emerged. OBJECTIVES: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel. METHODS: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI in four Israeli centers. RESULTS: Patients' mean age was 81.7 +/- 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 +/- 0.16 cm2. The calculated mean logistic Euroscore was 19.3 +/- 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 +/- 13 to 9 +/- 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 +/- 0.6 at baseline to 1.4 +/- 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients. CONCLUSIONS: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Outcomes of Degenerative Mitral Valve Repair Surgery for Anterior, Posterior, and Bileaflet Pathology.

BACKGROUND: Degenerative mitral valve disease involving anterior leaflet pathology is considered less favorable regarding durability of surgical repair than isolated posterior leaflet disease. We aimed to compare the outcomes of patients undergoing mitral valve repair for anterior, posterior, and bileaflet pathologies, and to investigate predictors for repair failure. METHODS: Of the 760 consecutive patients with degenerative leaflet disease who underwent mitral valve repair, 485 (64%) had posterior, 223 (29%) had bileaflet, and 52 (7%) had anterior leaflet pathology. Mean age was 58 ± 12, 54 ± 14, and 58 ± 17 years, respectively (P = .001). Mean follow-up was 67 ± 47 months. RESULTS: There was no in-hospital or 30-day mortality. Freedom from reoperation was 97%, 95%, and 92%, respectively, and there were 25 (5%), 9 (4%), and 1 (2%) late deaths in the posterior, bileaflet, and anterior groups, respectively (not significant). Late echocardiography revealed that 94%, 97%, and 96% of patients (posterior, bileaflet, and anterior groups respectively) were free from moderate-severe or severe mitral regurgitation (P = .375). Postoperative residual mild mitral regurgitation emerged as the strongest predictor for recurrent mitral regurgitation (grade 3/4) at follow-up (hazard ratio = 2.36; 95% confidence interval, 1.30-4.29; P = .005). Unlike patients with excess mitral tissue, among patients with fibroelastic deficiency or those who underwent major leaflet resection, the use of larger ring annuloplasty was associated with recurrent mitral regurgitation (hazard ratio = 1.31/ring size increment; P < .001). CONCLUSIONS: Mitral valve repair can be achieved with excellent early and intermediate results across all valve pathologies. Further studies are required to determine the potential long-term impact of the underlying pathology on the rate of recurrent mitral regurgitation.

Calcification of the thoracic aorta as detected by spiral computed tomography among stable angina pectoris patients: association with cardiovascular events and death.

BACKGROUND: Calcification of the thoracic aorta is associated with atherosclerotic risk factors, yet its pathogenesis and clinical implications are not yet elucidated. The goal of the present study was to assess whether thoracic aorta calcification is associated with an increased risk of cardiovascular events and death in patients with stable angina pectoris. METHODS AND RESULTS: A prospective cohort of 361 stable angina pectoris patients (307 men, 54 women; age range, 37 to 83 years) underwent chest spiral computed tomography and were evaluated for aortic calcification. We recorded the incidence of cardiovascular events and death during a 4.5- to 6-year follow-up. Aortic calcification was documented in 253 patients (70% of patients; 213 men, 40 women). Patients with aortic calcification were older (mean age, 65+/-7 versus 55+/-9 years; P<0.001), and fewer were classified as smokers (13% versus 26%; P=0.014) compared with patients without aortic calcification. Significant correlation was found between patients with and those without aortic calcification for the presence of aortic valve calcification (28% versus 11%; P<0.001), mitral annulus calcification (29% versus 4%; P<0.001), and coronary calcification as expressed by coronary calcium score. (P<0.001). During 4.5 to 6 years of follow-up, 19 patients died, all of whom were in the aortic calcification group. Age-adjusted hazard ratios for total events and cardiovascular events by aortic calcification were 2.84 (95% CI, 1.52 to 5.30; P=0.001) and 2.70 (95% CI, 1.33 to 5.47; P=0.006), respectively. In multivariable analysis, hazard ratios for total events and cardiovascular events were 2.79 (95% CI, 1.46 to 5.20; P=0.002) and 4.65 (95% CI, 1.19 to 18.26; P=0.028), respectively. CONCLUSIONS: Calcification of the thoracic aorta is age related and associated with coronary calcification and valvular calcification. Thoracic aortic calcification is associated with an increased risk of death and cardiovascular disease.

Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment.

BACKGROUND: The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. RESULTS: During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). CONCLUSION: Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.

Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease?

BACKGROUND: Epidemiologic studies have suggested that hypertriglyceridemia and insulin resistance are related to the development of colon cancer. Nuclear peroxisome proliferator-activated receptors (PPAR), which play a central role in lipid and glucose metabolism, had been hypothesized as being involved in colon cancerogenesis. In animal studies the lipid-lowering PPAR ligand bezafibrate suppressed colonic tumors. However, the effect of bezafibrate on colon cancer development in humans is unknown. Therefore, we proposed to investigate a possible preventive effect of bezafibrate on the development of colon cancer in patients with coronary artery disease during a 6-year follow-up. METHODS: Our population included 3011 patients without any cancer diagnosis who were enrolled in the randomized, double blind Bezafibrate Infarction Prevention (BIP) Study. The patients received either 400 mg of bezafibrate retard (1506 patients) or placebo (1505 patients) once a day. Cancer incidence data were obtained by matching a subject's identification numbers with the National Cancer Registry. Each matched record was checked for correct identification. RESULTS: Development of new cancer (all types) was recorded in 177 patients: in 79 (5.25%) patients from the bezafibrate group vs. 98 (6.51%) from the placebo group. Development of colon cancer was recorded in 25 patients: in 8 (0.53%) patients from the bezafibrate group vs. 17 (1.13%) from the placebo group, (Fisher's exact test: one side p = 0.05; two side p = 0.07). A difference in the incidence of cancer was only detectable after a 4 year lag and progressively increased with continued follow-up. On multivariable analysis the colon cancer risk in patients who received bezafibrate tended to be lower with a hazard ratio of 0.47 and 95% confidence interval 0.2-1.1. CONCLUSION: Our data, derived from patients with coronary artery disease, support the hypothesis regarding a possible preventive effect of bezafibrate on the development of colon cancer.

Improved exercise capacity in patients after minor ischemic stroke undergoing a supervised exercise training program.

BACKGROUND: Regular physical activity is known to have a beneficial impact on multiple cardiovascular risk factors, but there is no routine provision of exercise training programs for patients after ischemic stroke. OBJECTIVES: To assess the tolerability, safety and effect of an outpatient supervised exercise training program in patients after a non-disabling ischemic stroke. METHODS: Patients discharged home following a minor ischemic stroke (modified Rankin scale; mRS < or = 2) were referred to a 3 month outpatient supervised exercise training program, performed twice weekly as prescribed by a physiologist and supervised by physical therapy. Exercise capacity was evaluated by the 6 minute walk test and the modified Bruce exercise test. RESULTS: Of the 52 patients who met the selection criteria, 43 underwent supervised exercise training within 2 months of stroke onset and 9 did not (control group). The baseline characteristics were comparable between the two groups. Following the exercise training program, an improvement in exercise capacity was observed manifested by improvement in the 6 minute walk test (444 +/- 90 to 557 +/- 99 meters in the exercise group vs. 438 +/- 101 to 418 +/- 126 in the control group; P = 0.002 for the score changes) and in the exercise duration achieved in the modified Bruce test and the metabolic equivalents achieved [9.6 +/- 3.7 to 12.4 +/- 3.2 minutes and 6.2 +/- 2.8 to 8.5 +/- 3.4 respectively in the exercise group (n = 41) vs. 9.2 +/- 3.5 to 8.0 +/- 3.4 min and 5.8 +/- 1.8 to 5.8 +/- 2.8 in the control group (n = 7); P = 0.0009 and 0.01 for score changes, respectively]. CONCLUSIONS: An outpatient supervised exercise training program after a minor ischemic stroke is feasible, well tolerated and is associated with improvement in exercise capacity. We strongly recommend that an aerobic exercise program be offered to suitable patients after an ischemic stroke.

[Ischemic preconditioning of the heart].

The phenomenon of "ischemic preconditioning" has been well known for nearly two decades. In this phenomenon, a brief period of ischemia prior to a more prolonged one improves myocardial function and reduces infarction. This phenomenon is described in animals and, in recent years, also in human hearts, in vitro and in vivo. Two types of ischemic preconditioning are known: the classic or early preconditioning and the delayed or late preconditioning. The mechanism of late preconditioning is well described and is different from its early phase. Fully understanding the mechanism of this amazing phenomenon promises to be a novel discovery as for developing preconditioning mimetic agents and, thereby, using preconditioning as a therapeutic tool or as a preventive factor in cardiovascular diseases.

Rationale and design of the EACVI AFib Echo Europe Registry for assessing relationships of echocardiographic parameters with clinical thrombo-embolic and bleeding risk profile in non-valvular atrial fibrillation.

The European Society of Cardiology (ESC) guidelines for management of atrial fibrillation (AF) recommend the use of CHA2DS2VASc risk score for assessment of thromboembolic (TE) risk, whereas the stratification of bleeding risk should be obtained by HAS-Bleed to balance the most appropriate anticoagulation (OAC) therapy. However, men with CHA2DS2VASc score = 1 and women with CHA2DS2VASc = 2, who are at intermediate TE risk, represent a grey zone where guidelines do not provide a definite OAC indication. Accordingly, implementation of risk stratification with echocardiography could be extremely useful. Both prospective and cross-sectional studies on transthoracic echocardiography (TTE) prediction of TE events and studies utilizing transoesophageal echocardiographic parameters as surrogate markers of TE events makes sustainable the hypothesis that echocardiography could improve TE prediction in non-valvular AF. Moreover, considering the close association of AF and stroke, all echo-Doppler parameters that have shown to predict AF onset and recurrence could be useful also to predict TE events in this clinical setting. Accordingly, EACVI AFib Echo Europe Registry has been designed as an observational, cross-sectional study, with the aim of evaluating: (i) left atrial (LA) size and function together with left ventricular geometry, systolic and diastolic functions in paroxysmal, persistent, and permanent AF; (ii) relationships of structural/functional parameters with clinical TE and bleeding risk profile. By the AFib Echo Europe Registry, we expect to collect data on echocardiographic phenotype of patients with AF. The large data set accumulated will be useful to test the level of agreement of different echocardiographic measurements with the available risk scores.