Speckle tracking echocardiography and ß-thalassemia major. A systematic review.

Heart disease is among the primary causes of morbidity and mortality in ß-thalassemia major (ß-TM). Conventional echocardiography has failed to identify myocardial dysfunction at an early stage among these patients, thus speckle tracking echocardiography (STE) has been lately used. The objectives of this review were to 1) identify all published studies having evaluated myocardial strain among ß-TM patients, 2) gather their results, 3) compare their findings and 4) propose recommendations based on these data. Literature search was conducted in PubMed, SCOPUS and Cohrane Library. Data regarding left ventricular global longitudinal (LV-GLS), circumferential (LV-GCS) and radial strain (LV-GRS), right ventricular longitudinal strain (RV-GLS), left and right atrial strain were extracted. Thirty-five studies (34 original articles and 1 meta-analysis) have met the inclusion criteria. LV-GLS has been reported being worse in patients compared to controls in 13 of 21 studies, LV-GCS in 7 of 11 studies, LV-GRS in 6 of 7 studies, RV-GLS in 2 of 3 studies and left atrial strain in all case-control studies. Myocardial iron overload (MIO) patient subgroups had worse LV-GLS in 6 of 15 studies, LV-GCS in 2 of 7 studies and LV-GRS in none of 7 studies. A small number of studies suggest left atrial strain correlation with electrical atrial ectopy and atrial fibrillation. It is suggested that STE should be applied supplementary to conventional echocardiography for early identification of myocardial dysfunction among ß-TM patients. Potential myocardial strain utilities could be screening for myocardial iron overload, left ventricular diastolic dysfunction and atrial fibrillation.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

Overview of salt restriction in the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet for blood pressure reduction.

Despite considerable advances in pharmacological treatments, hypertension remains a major cause of premature morbidity and mortality worldwide since elevated blood pressure (BP) adversely influences cardiovascular and renal outcomes. Accordingly, the current hypertension guidelines recommend the adoption of dietary modifications in all subjects with suboptimal BP levels. These modifications include salt intake reduction and a healthy diet, such as the Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean diet (MedDiet), independently of the underlying antihypertensive drug treatment. However, dietary modifications for BP reduction in adults with prehypertension or hypertension are usually examined as stand-alone interventions and, to a lesser extent, in combination with other dietary changes. The purpose of the present review was to summarize the evidence regarding the BP effect of salt restriction in the context of the DASH diet and the MedDiet. We also summarize the literature regarding the effects of these dietary modifications when they are applied as the only intervention for BP reduction in adults with and without hypertension and the potent physiological mechanisms underlying their beneficial effects on BP levels. Available data of randomized controlled trials (RCTs) provided evidence about the significant BP-lowering effect of each one of these dietary strategies, especially among subjects with hypertension since they modulate various physiological mechanisms controlling BP. Salt reduction by 2.3 g per day in the DASH diet produces less than half of the effect on systolic blood pressure (SBP)/diastolic blood pressure (DBP) (-3.0/-1.6 mmHg) as it does without the DASH diet (-6.7/-3.5 mmHg). Although their combined effect is not fully additive, low sodium intake and the DASH diet produce higher SBP/DBP reduction (-8.9/-4.5 mmHg) than each of these dietary regimens alone. It is yet unsettled whether this finding is also true for salt reduction in the MedDiet.

Meat consumption, depressive symptomatology and cardiovascular disease incidence in apparently healthy men and women: highlights from the ATTICA cohort study (2002-2012).

Objectives: To evaluate the association of meat consumption with prevalent depressive symptomatology and cardiovascular disease (CVD) incidence in apparently healthy individuals.Methods: ATTICA study was conducted during 2001-2012 including n = 1514 men and n = 1528 women (aged >18 years old) from the greater Athens area, Greece. At baseline, depressive symptomatology through Zung Self-Rating Depression Scale (range 20-80) and meat consumption (total meat, red, white and processed meat) through validated semi-quantitative food frequency questionnaire were assessed. Follow-up (2011-2012) was achieved in n = 2020 participants (n = 317 cases); n = 845 participants with complete psychological metrics were used for the primary analysis.Results: Ranking from 1st to 3rd total meat consumption (low to high) tertiles, participants assigned in 2nd tertile had the lowest depressive-symptomatology scoring (p<0.001). This trend was retained in multiadjusted logistic regression analysis; participants reporting moderate total and red meat consumption had ∼20% lower likelihood to be depressed (i.e. Zung scale<45) compared with their 1st tertile counterparts (Odds Ratio (OR)total meat 0.82, 95% Confidence Interval (95%CI) (0.60, 0.97) and ORred meat 0.79 95%CI (0.45, 0.96)). Non-linear associations were revealed; 2-3 serving/week total meat and 1-2 servings/week red meat presented the lowest odds of depressive symptomatology (all ps<0.05). These U-shape trends seemed to attenuate the aggravating effect of depressive symptomatology on CVD hard endpoints. All aforementioned associations were more evident in women (all ps for sex-related interaction<0.05).Discussion: The present findings generate the hypothesis that moderate total meat consumption and notably, red meat may be more beneficial to prevent depressed mood and in turn hard CVD endpoints.

Association of non-invasive electrocardiographic risk factors with left ventricular systolic function in post-myocardial infarction patients with mildly reduced or preserved ejection fraction: Insights from the PRESERVE-EF study.

BACKGROUND: Electrocardiographic non-invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post-myocardial infarction (post-MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE-EF trial. METHODS: We studied 575 post-MI ischemia-free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non-sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T-wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence. RESULTS: There was a statistically significant relationship between LPs (Chi-squared = 4.975; p < .05), nsVT (Chi-squared = 5.749, p < .05), PVCs (r= -.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02-3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18-5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%-49% versus the preserved LVEF: ≥50%. CONCLUSION: Late potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post-MI patients with mildly reduced or preserved LVEF.

Noninvasive risk factors for the prediction of inducibility on programmed ventricular stimulation in post-myocardial infarction patients with an ejection fraction ≥40% at risk for sudden cardiac arrest: Insights from the PRESERVE-EF study.

BACKGROUND: In the PRESERVE-EF study, a two-step sudden cardiac death (SCD) risk stratification approach to detect post-myocardial infarction (MI) patients with left ventricle ejection fraction (LVEF) ≥40% at risk for major arrhythmic events (MAEs) was used. Seven noninvasive risk factors (NIRFs) were extracted from a 24-h ambulatory electrocardiography (AECG) and a 45-min resting recording. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS) and inducible patients received an Implantable Cardioverter - Defibrillator (ICD). METHODS: In the present study, we evaluated the performance of the NIRFs, as they were described in the PRESERVE-EF study protocol, in predicting a positive PVS. In the PRESERVE-EF study, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analyzed. RESULTS: Among the NIRFs examined, the presence of signal averaged ECG-late potentials (SAECG-LPs) ≥ 2/3 and non-sustained ventricular tachycardia (NSVT) ≥1 eposode/24 h cutoff points were important predictors of a positive PVS study, demonstrating in the logistic regression analysis odds ratios 2.285 (p = .027) and 2.867 (p = .006), respectively. A simple risk score based on the above cutoff points in combination with LVEF < 50% presented high sensitivity but low specificity for a positive PVS. CONCLUSION: Cutoff points of NSVT ≥ 1 episode/24 h and SAECG-LPs ≥ 2/3 in combination with a LVEF < 50% were important predictors of inducibility. However, the final decision for an ICD implantation should be based on a positive PVS, which is irreplaceable in risk stratification.

Transvenous extraction of permanent pacemaker and defibrillator leads: Reduced procedural complexity and higher procedural success rates in patients with infective versus noninfective indications.

INTRODUCTION: Transvenous lead extraction (TLE) is critical in the long-term management of patients with cardiac implanted electronic devices (CIEDs). The aim of the study is to evaluate the outcomes of TLE and to investigate the impact of infection. METHODS AND RESULTS: Data of patients undergoing extraction of permanent pacemaker and defibrillator leads during October 2014-September 2019 were prospectively analyzed. Overall, 242 consecutive patients (aged 71.0 ± 14.0 years, 31.4% female), underwent an equal number of TLE operations for the removal of 516 leads. Infection was the commonest indication (n = 201, 83.1%). Mean implant-to-extraction duration was 7.6 ± 5.4 years. Complete procedural success was recorded in 96.1%, and clinical procedural success was achieved in 97.1% of attempted lead extractions. Major complications occurred in two (0.8%) and minor complications in seven (2.9%) patients. Leads were removed exclusively by using locking stylets in 65.7% of the cases. In the subgroup of noninfective patients, advanced extraction tools were more frequently required compared to patients with CIED infections, to extract leads (success only with locking stylet: 55.8% vs. 67.8%, p = .032). In addition, patients without infection demonstrated lower complete procedural success rates (90.7% vs. 97.2%, p = .004), higher major complication rates (2.4% vs. 0.5%, p = .31) and longer procedural times (136 ± 13 vs. 111 ± 15 min, p = .001). CONCLUSIONS: Our data demonstrate high procedural efficacy and safety and indicate that in patients with noninfective indications, the procedure is more demanding, thus supporting the hypothesis that leads infection dissolves and/or prohibits the formation of fibrotic adherences.

Syncope associated with supraventricular tachycardia: Diagnostic role of implantable loop recorders.

Syncope represents a relatively uncommon symptom of supraventricular tachycardia (SVT). It is likely that an impaired autonomic vasomotor response to the hemodynamic stress of tachycardia is the determinant of hemodynamic changes leading to cerebral hypoperfusion and syncope. In this regard, tilt-table test may detect abnormalities in the autonomic nervous function and predict the occurrence of syncope during SVT. Electrophysiology studies may reproduce the SVT, distinguish it from other life-threatening ventricular tachyarrhythmias, and exclude other causes of syncope. Not infrequently mixed syncope mechanisms are revealed during the above diagnostic workup raising doubts about the operating mechanism in the clinical setting. In such cases of uncertainty, an implantable loop recorder, providing long-term cardiac monitoring, may play a pivotal role in the establishment of the diagnosis, confirming the association of an arrhythmic event with the symptom. Herein, we present four such cases with recurrent unexplained syncope finally attributed to paroxysmal SVT guiding them to a potentially radical treatment through radiofrequency catheter ablation.

Comparison of the Mediterranean diet and the Dietary Approach Stop Hypertension in reducing the risk of 10-year fatal and non-fatal CVD events in healthy adults: the ATTICA Study (2002-2012).

OBJECTIVE: To compare the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets in deterring 10-year CVD. DESIGN: Prospective cohort (n 2020) with a 10-year follow-up period for the occurrence of combined (fatal or non-fatal) CVD incidence (International Classification of Diseases (ICD)-10). Baseline adherence to the Mediterranean and DASH diets was assessed via a semi-quantitative FFQ according to the MedDietScore and DASH scores, respectively. SETTING: Attica, Greece. PARTICIPANTS: Two thousand twenty individuals (mean age at baseline 45·2 (sd 14·0) years). RESULTS: One-third of individuals in the lowest quartile of Mediterranean diet consumption, as compared with 3·1 % of those in the highest quartile, developed 10-year CVD (P < 0·0001). In contrast, individuals in the lowest and highest DASH diet quartiles exhibited similar 10-year CVD rates (n (%) of 10-year CVD in DASH diet quartiles 1 v. 4: 79 (14·7 %) v. 75 (15·3 %); P = 0·842). Following adjustment for demographic, lifestyle and clinical confounding factors, those in the highest Mediterranean diet quartile had a 4-fold reduced 10-year CVD risk (adjusted hazard ratio (HR) 4·52, 95 % CI 1·76, 11·63). However, individuals with highest DASH diet quartile scores did not differ from their lowest quartile counterparts in developing such events (adjusted HR 1·05, 95 % CI 0·69, 1·60). CONCLUSIONS: High adherence to the Mediterranean diet, and not to the DASH diet, was associated with a lower risk of 10-year fatal and non-fatal CVD. Therefore, public health interventions aimed at enhancing adherence to the Mediterranean diet, rather than the DASH diet, may most effectively deter long-term CVD outcomes particularly in Mediterranean populations.

Prognostic role of diastolic dysfunction in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: Prior studies have shown that left ventricular diastolic dysfunction (DD) is associated with increased mortality after surgical aortic valve replacement but studies on transcatheter aortic valve replacement (TAVR) are limited and have not taken into account mitral annular calcification (MAC), which limits the use of mitral valve annular tissue Doppler imaging. We performed a single-center retrospective analysis to better evaluate the role of baseline DD on outcomes after TAVR. METHODS: After excluding patients with atrial fibrillation, mitral valve prostheses and significant mitral stenosis, 359 consecutive TAVR patients were included in the study. Moderate-to-severe MAC was present in 58% of the patients. We classified patients into severe versus nonsevere DD based on the evaluation of elevated left ventricular filling pressure. The outcome measure was all-cause mortality or heart failure hospitalization. RESULTS: Over a mean follow-up time of 13 months, severe DD was associated with an increased risk for the outcome measure (HR 2.02 [1.23-3.30], p = .005). However, this association was lost in a propensity-matched cohort. In multivariate analysis, STS score was the only independent predictor of all cause mortality of heart failure hospitalization (HR 1.1 [1.05-1.15], p < .001). CONCLUSIONS: We evaluated the role of baseline DD on outcomes after TAVR by taking into account the presence of MAC. Severe DD was associated with increased all-cause mortality or heart failure hospitalization but not independently of other structural parameters and known predictors of the outcome measure.

Functional assessment of bioprosthetic mitral valves by cardiovascular magnetic resonance: An in vitro validation and comparison to Doppler echocardiography.

BACKGROUND: A comprehensive non-invasive evaluation of bioprosthetic mitral valve (BMV) function can be challenging. We describe a novel method to assess BMV effective orifice area (EOA) based on phase contrast (PC) cardiovascular magnetic resonance (CMR) data. We compare the performance of this new method to Doppler and in vitro reference standards. METHODS: Four sizes of normal BMVs (27, 29, 31, 33 mm) and 4 stenotic BMVs (27 mm and 29 mm, with mild or severe leaflet obstruction) were evaluated using a CMR- compatible flow loop. BMVs were evaluated with PC-CMR and Doppler methods under flow conditions of; 70 mL, 90 mL and 110 mL/beat (n = 24). PC-EOA was calculated as PC-CMR flow volume divided by the PC- time velocity integral (TVI). RESULTS: PC-CMR measurements of the diastolic peak velocity and TVI correlated strongly with Doppler values (r = 0.99, P < 0.001 and r = 0.99, P < 0.001, respectively). Across all conditions tested, the Doppler and PC-CMR measurement of EOA (1.4 ± 0.5 vs 1.5 ± 0.7 cm2, respectively) correlated highly (r = 0.99, P < 0.001), with a minimum bias of 0.13 cm2, and narrow limits of agreement (- 0.2 to 0.5 cm2). CONCLUSION: We describe a novel method to assess BMV function based on PC measures of transvalvular flow volume and velocity integration. PC-CMR methods can be used to accurately measure EOA for both normal and stenotic BMV's and may provide an important new parameter of BMV function when Doppler methods are unobtainable or unreliable.

Endothelial dysfunction and impaired arterial wall properties in patients with retinal vein occlusion.

Retinal vein occlusion (RVO) is a common retinal vascular lesion, and a leading cause of visual impairment. Patients with RVO have an increased risk for cardiovascular disease and share multiple common risk factors. In this study, we investigated the endothelial function and arterial stiffness of patients with RVO compared to healthy-control (CL) subjects. We enrolled 40 consecutive patients with RVO and 40 CL subjects. RVO was diagnosed by an ophthalmologist, endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery, and carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) of the radial artery were measured to evaluate arterial stiffness and reflected waves, respectively. No significant differences were detected between the studied groups in sex, age, presence of hypertension or dyslipidemia, body mass index, systolic and diastolic blood pressure levels, total cholesterol levels, and smoking habits (p > 0.05 for all). However, patients with RVO had impaired FMD (p = 0.002) and increased PWV (p = 0.004), even after adjustment for several confounders. Both FMD and PWV were also significantly and independently associated with the development of RVO. Furthermore, a significant and positive correlation between PWV and systolic blood pressure existed only in the CL group. Therefore, we have shown that RVO is associated with significant endothelial dysfunction and increased arterial stiffness. Our results strengthen the vascular theory, according to which, systemic endothelial dysfunction and arteriosclerosis play a significant role in the pathogenesis of RVO.

Dairy products, surrogate markers, and cardiovascular disease; a sex-specific analysis from the ATTICA prospective study.

BACKGROUND AND AIMS: Dairy products are a very diverse food group with multiple effects on the cardiac health of men and women. The aim of this work was to evaluate the sex-specific association between dairy products (total and subtypes) and 10-year first fatal/nonfatal cardiovascular disease (CVD) incidence. METHODS AND RESULTS: In 2001-2002, n = 1514 men and n = 1528 women (>18 years old) from greater Athens area, Greece, were enrolled. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Dairy product consumption was examined in relation to 10-year CVD incidence. Follow-up (2011-2012) was achieved in n = 2020 participants (n = 317 CVD cases). Ranking from lowest (<1 serving/day) to highest (>2 servings/day) total dairy intake, CVD incidence in men was 17.8%, 15.0%, and 10.9% (p = 0.41), while in women it was 14%, 6.0%, and 5.7% (p = 0.02). Multiadjusted analysis revealed that total dairy intake protected against CVD only in women [Hazard Ratio (HR) = 0.48 and 95% Confidence Interval (95% CI) (0.23, 0.90)], irrespective of the fat content. Further analysis revealed that only fermented products (yogurt and cheese), protected against CVD. For per 200 g/day yogurt consumption, CVD risk was 20%-30% lower with this claim being more evident in women, while for per 30 g/day cheese intake, about 5% lower risk was observed particularly in men. As for butter, nonsignificant associations were highlighted. These associations were mainly retained in the case of hepatic steatosis, insulin resistance, and systemic inflammation. CONCLUSIONS: This work provides incentives for researchers to elucidate the diversity of ingredients and mechanisms through which dairy products exert their effect on cardiac health separately for men and women.

Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort. METHODS AND RESULTS: In 2001-2002, a random sample of 1514 males (18-87 years old) and 1528 females (18-89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011-2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p < 0.05), but not in carriers of the GA polymorphism (all, p > 0.05). CONCLUSION: ApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.

Prognostic value of exercise tolerance test for predicting cardiovascular disease in asymptomatic individuals with heterozygous familiar hypercholesterolemia.

Heterozygous familiar hypercholesterolemia (hFH) is an autosomal dominant inherited dyslipidemia, associated with premature cardiovascular disease (CVD). Aim of the study was to define prognostic factors for cardiovascular events (CVE) in asymptomatic individuals with hFH. All participants with recent diagnosis of hFH were recruited from the outpatient lipid clinic from 1987 to 2016, without any previous clinical evidence of CVD. A detailed clinical evaluation and laboratory investigation was obtained. Exercise tolerance test (ETT) was performed until maximum exercise capacity was achieved, without evidence of ischemia. Primary endpoint of the study was the first CVE. Four hundred fifty one participants were followed up for 10 ± 8 years, with 68 recorded cases of CVD (15%). Cumulative incidence of CVD was 15%, 24% and 32% for the 3 decades, respectively. In univariate analysis, male gender (p = 0.016), progression of age (p < 0.001), menopause (p = 0.030), waist-hip ratio (p = 0.043) and increased levels of Lp(α) (p = 0.014) were significantly associated with increased CVD incidence; whereas, exercise capacity (p = 0.025), low variation of heart rate (HR) during all stages of ETT compared to resting state (p = 0.020), maximum systolic (p = 0.014) and diastolic (p < 0.001) blood pressure were inversely associated with CVD. In multi-adjusted analysis, male gender (p < 0.001), duration of ETT (p = 0.023), estimated HR (p = 0.029), variation of HR during ETT compared to resting state (p < 0.05) and maximum diastolic pressure (p = 0.044) were significantly associated with CVD. Parameters of ETT in asymptomatic individuals with hFH, without any evidence of ischemia, may predict CVD in these high-risk patients after decades of observation.

Temporal changes of noninvasive electrocardiographic risk factors for sudden cardiac death in post-myocardial infarction patients with preserved ejection fraction: Insights from the PRESERVE-EF study.

BACKGROUND: Several noninvasive risk factors (NIRFs) have been proposed for sudden cardiac death risk stratification in post-myocardial infarction (post-MI) patients with preserved ejection fraction (EF). However, it remains unclear if these factors change over time. METHODS: We evaluated seven electrocardiographic NIRFs as they were described in the PRESERVE-EF trial in 80 post-MI patients with EF ≥ 40%, at least 40 days after revascularization and 1 year later. RESULTS: Mean patient age was 56 ± 10 years, and 88% were men. Mean EF was 50 ± 5%. The prevalence of (a) positive late potentials (27.5% vs. 28.8%, p = .860), (b) >30 premature ventricular complexes/hour (8.8% vs. 11.3%, p = .598), (c) nonsustained ventricular tachycardia (8.8% vs. 5%, p = .349), (d) standard deviation of normal RR intervals <75 ms (3.8% vs. 3.8%, p = 1.000), (e) QTc derived from 24-hr electrocardiography >440 ms (men) or >450 ms (women) (17.5% vs. 17.5%, p = 1.000), (f) deceleration capacity ≤4.5 ms and heart rate turbulence onset ≥0% and slope ≤2.5 ms (2.5% vs. 3.8%. p = 1.000), and (g) ambulatory T-wave alternans ≥65 µV in two Holter channels (6.3% vs. 6.3%, p = 1.000) were similar between the two measurements. However, five patients (6.3%) without any NIRFs during the first assessment had at least one positive NIRF at the second assessment and six patients (7.5%) with at least one NIRF at baseline had no positive NIRFs at 1 year. CONCLUSIONS: While the prevalence of the examined electrocardiographic NIRFs between the two examinations was similar on a population basis, some patients without NIRFs at baseline developed NIRFs at 1 year and vice versa, highlighting the need for risk factor reassessment during follow-up.

Arrhythmic risk stratification in post-myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study.

AIMS: Sudden cardiac death (SCD) annual incidence is 0.6-1% in post-myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)≥40%. No recommendations for implantable cardioverter-defibrillator (ICD) use exist in this population. METHODS AND RESULTS: We introduced a combined non-invasive/invasive risk stratification approach in post-MI ischaemia-free patients, with LVEF ≥ 40%, in a multicentre, prospective, observational cohort study. Patients with at least one positive electrocardiographic non-invasive risk factor (NIRF): premature ventricular complexes, non-sustained ventricular tachycardia, late potentials, prolonged QTc, increased T-wave alternans, reduced heart rate variability, abnormal deceleration capacity with abnormal turbulence, were referred for programmed ventricular stimulation (PVS), with ICDs offered to those inducible. The primary endpoint was the occurrence of a major arrhythmic event (MAE), namely sustained ventricular tachycardia/fibrillation, appropriate ICD activation or SCD. We screened and included 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive NIRF. Forty-one of 152 patients undergoing PVS (27-7.1% of total sample) were inducible. Thirty-seven (90.2%) of them received an ICD. Mean follow-up was 32 months and no SCDs were observed, while 9 ICDs (1.57% of total screened population) were appropriately activated. None patient without NIRFs or with NIRFs but negative PVS met the primary endpoint. The algorithm yielded the following: sensitivity 100%, specificity 93.8%, positive predictive value 22%, and negative predictive value 100%. CONCLUSION: The two-step approach of the PRESERVE EF study detects a subpopulation of post-MI patients with preserved LVEF at risk for MAEs that can be effectively addressed with an ICD. CLINICALTRIALS.GOV IDENTIFIER: NCT02124018.

Sex-Related Differences of the Effect of Lipoproteins and Apolipoproteins on 10-Year Cardiovascular Disease Risk; Insights from the ATTICA Study (2002-2012).

The sex-specific effect of lipid-related biomarkers on 10-year first fatal/non fatal cardiovascular disease (CVD) incidence was evaluated. ATTICA study was conducted during 2001-2012. n = 1514 men and n = 1528 women (>18 years) from greater Athens area, Greece were recruited. Follow-up (2011-2012) was achieved in n = 2020 participants. Baseline lipid profile was measured. Overall CVD event was 15.5% (n = 317) (19.7% in men and 11.7% in women, p < 0.001). High density lipoprotein cholesterol (HDL-C) and triglycerides (TAG) were independently associated with CVD in women; per 10 mg/dL HDL-C increase, hazard ratio (HR) = 0.73, 95% confidence interval (95% CI) (0.53, 1.00); and per 10 mg/dL TAG increase, HR = 1.10, 95% CI (1.00, 1.21). Apolipoprotein A1 (ApoA1) (per 10 mg/dL increase, HR = 0.90, 95% CI (0.81, 0.99)) was inversely associated with CVD in women, while a positive association with apolipoprotein B100 (ApoB100) was observed only in men (per 10 mg/dL increase, HR = 1.10, 95% CI (1.00, 1.21)). Non-HDL-C was associated with CVD in the total sample (HR = 1.10, 95% CI (1.00, 1.21)) and in women (HR = 1.10, 95% CI (1.00, 1.21)); a steep increase in HR was observed for values >185 mg/dL in the total sample and in men, while in women, a raise in CVD risk was observed from lower values (>145 mg/dL). As for non-HDL-C/HDL-C and TC/HDL-C ratios, similar trends were observed. Beyond the common cholesterol-adjusted risk scores, reclassifying total CVD risk according to other lipid markers may contribute to early CVD prevention. Biomarkers such as HDL-C, non-HDL-C, and TAG should be more closely monitored in women.

Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial.

BACKGROUND: Previous catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing. METHODS: In this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20-80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher; a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening; and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with ClinicalTrials.gov, number NCT02439775, and follow-up is ongoing. FINDINGS: Between July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure -7·0 mm Hg, 95% CI -12·0 to -2·1; p=0·0059, 24 h diastolic blood pressure -4·3 mm Hg, -7·8 to -0·8; p=0.0174, office systolic blood pressure -6·6 mm Hg, -12·4 to -0·9; p=0·0250, and office diastolic blood pressure -4·2 mm Hg, -7·7 to -0·7; p=0·0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference -6·8 mm Hg, 95% CI -12·5 to -1·1; p=0·0205), 24 h systolic blood pressure (difference -7·4 mm Hg, -12·5 to -2·3; p=0·0051), office diastolic blood pressure (difference -3·5 mm Hg, -7·0 to -0·0; p=0·0478), and 24 h diastolic blood pressure (difference -4·1 mm Hg, -7·8 to -0·4; p=0·0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group. INTERPRETATION: Renal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common. FUNDING: Medtronic.

Percutaneous lead extraction and repositioning: An effective and safe therapeutic strategy for early ventricular lead perforation with dislocation both inside and outside the pericardial sac following a cardiac device implantation.

INTRODUCTION: Cardiac perforation of the right ventricle associated with pacemaker or implantable cardioverter defibrillator (ICD) leads' implantation is uncommon, albeit potentially life-threatening, complication. The aim of this study is to further identify the optimal therapeutic strategy, especially when lead dislocation has occurred outside the pericardial sac. METHODS AND RESULTS: The study population included 10 consecutive patients (six female, mean age: 66.5 years old) diagnosed with early ventricular lead perforation following a pacemaker or ICD implantation, with significant protrusion inside the pericardial sac (n = 2) or migration of the lead at the pleural space ( n = 3), the diaphragm ( n = 1), or the abdominal cavity ( n = 4), during the period 2013-2017. All patients were symptomatic; however, individuals presenting with hemodynamic instability were excluded. The outcome of the percutaneous therapeutic approach was retrospectively assessed. All patients underwent a successful removal of the perforating lead percutaneously at the electrophysiology lab, by direct traction, and repositioning in another location of the right ventricle. The operation was performed by a multidisciplinary team, under continuous hemodynamic and transesophageal echocardiographic monitoring and cardiac surgical backup. The periprocedural period was uneventful. Subjects were followed up for at least 1 year. Interestingly, all patients developed a type of postcardiac injury syndrome, successfully treated with a 3-month regimen of ibuprofen and colchicine. CONCLUSION: Percutaneous traction and repositioning of the perforating ventricular lead are effective, safe, and less invasive compared with the thoracotomy method in hemodynamically stable patients when dislocation has occurred outside the pericardial sac provided that there is no visceral organs injury.