Transcatheter Aortic Valve Implantation and Conduction Disturbances: Focus on Clinical Implications.

Transcatheter aortic valve implantation (TAVI) is an established alternative to surgery in patients with symptomatic severe aortic stenosis and has expanded its indications to even low-surgical-risk patients. Conduction abnormalities (CA) and permanent pacemaker (PPM) implantations remain a relatively common finding post TAVI due to the close proximity of the conduction system to the aortic root. New onset left bundle branch block (LBBB) and high-grade atrioventricular block are the most commonly reported CA post TAVI. The overall rate of PPM implantation post TAVI varies and is related to pre- and intra-procedural factors. Therefore, when screening patients for TAVI, Heart Teams should take under consideration the various anatomical, pathophysiological and procedural conditions that predispose to CA and PPM requirement after the procedure. This is particularly important as TAVI is being offered to younger patients with longer life-expectancy. Herein, we highlight the incidence, predictors, impact and management of CA in patients undergoing TAVI.

Floppy mitral valve/mitral valve prolapse and sudden cardiac death.

It is well appreciated today that sudden cardiac death (SCD) occurs in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP) without significant mitral regurgitation . Data from studies most likely represent a heterogeneous population and probably underestimate the true incidence of SCD in this group of patients. SCD in patients with FMV/MVP occurs mostly in young individuals without comorbidities. Over the last decade, the phenotypic expression of patients with FMV/MVP at risk for SCD (bileaflet prolapse, redundant mitral leaflets, symptomatic young women) have been defined, possible pathophysiologic mechanisms leading to SCD have been proposed, and appropriate steps to prevent the catastrophic event, though in evolution, have been suggested. In this review, state-of-the-art knowledge related to SCD in patients with FMV/MVP is summarized.

Effectiveness and safety of a time to isolation strategy of cryoballoon ablation of atrial fibrillation: A systematic review and meta-analysis.

AIM: We conducted a systematic review and meta-analysis of randomized and observational studies with a control group to evaluate the effectiveness and safety of a time to isolation (TTI)-based strategy of cryoballoon ablation (CBA) in the treatment of atrial fibrillation (AF). METHODS: Three electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Embase) without language restrictions were searched. The intervention assessed was a TTI-based strategy of CBA in the treatment of AF. TTI was defined as the time from the start of freezing to the last recorded pulmonary veins' potential. The comparison of interest was intended conventional protocol of CBA. The primary endpoint was freedom from atrial arrhythmia. RESULTS: Nine studies were deemed eligible (N = 2289 patients). Eight studies reported freedom from atrial arrhythmia and pooled results showed a marginally similar success rate between the two protocols (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 0.98-1.56). A prespecified subgroup analysis verified that a high dose TTI strategy (with >120 s duration of cryotherapy post-TTI) compared to the conventional protocol could significantly increase the patients without atrial arrhythmia during follow-up (OR: 1.39; 95% CI: 1.05-1.83). TTI strategy could also significantly decrease total procedure time (SMD: -26.24 min; 95% CI: -36.90 to -15.57) and phrenic nerve palsy incidence (OR: 0.49; 95% CI: 0.29-0.84). CONCLUSION: Moderate confidence evidence suggests that an individualized CBA dosing strategy based on TTI and extended (>2 min post-TTI) duration of CBA is accompanied by fewer recurrences post-AF ablation.

The Association of Healthy Aging with Multimorbidity: IKARIA Study.

The aim of this study was to evaluate several sociodemographic, lifestyle, and clinical characteristics of the IKARIA study participants and to find healthy aging trajectories of multimorbidity of Ikarian islanders. During 2009, 1410 people (aged 30+) from Ikaria Island, Greece, were voluntarily enrolled in the IKARIA study. Multimorbidity was defined as the combination of at least two of the following chronic diseases: hypertension; hypercholesterolemia; diabetes; obesity; cancer; CVD; osteoporosis; thyroid, renal, and chronic obstructive pulmonary disease. A healthy aging index (HAI) ranging from 0 to 100 was constructed using 4 attributes, i.e., depression symptomatology, cognitive function, mobility, and socializing. The prevalence of multimorbidity was 51% among men and 65.5% among women, while the average number of comorbidities was 1.7 ± 1.4 for men and 2.2 ± 1.4 for women. The most prevalent chronic diseases among men with multimorbidity were hypertension, hypercholesterolemia, and obesity while among women they were hypertension, hypercholesterolemia, and thyroid disease. Multimorbidity was correlated with HAI (Spearman's rho = -0.127, p < 0.001) and for every 10-unit increase in HAI, participants had 20% lower odds of being multimorbid. Multimorbidity in relation to HAI revealed a different trend across aging among men and women, coinciding only in the seventh decade of life. Aging is usually accompanied by chronic diseases, but multimorbidity seems to also be common among younger adults. However, healthy aging is a lifelong process that may lead to limited co-morbidities across the lifespan.

Triglycerides are related to left ventricular mass in hypertensive patients independently of other cardiometabolic risk factors: the effect of gender.

Given the inconsistent results on the prognostic significance of triglycerides (TGs), the purpose of the present study was to investigate the association of plasma TGs with left ventricular mass (LVM) in hypertensive patients. We studied 760 never treated, non diabetic, hypertensive patients. Τransthoracic echocardiography was performed and LVMI was calculated according to the Devereux formula, adjusted to body surface area. Triglycerides were associated with LVMI after adjustment for age, gender, systolic blood pressure (SBP), smoking and fasting glucose (b = 0.08, p = 0.009). This relationship remained significant even after adjustment for BMI, LDL-C and ApoB/ApoA1 ratio (b = 0.07, p = 0.04). Gender-stratified analysis indicated that TGs were related to LVMI in men (p = 0.001) but not in women (p = NS). In addition, TGs were related with LV hypertrophy (LVH) in men, increasing the odds by 7% to present LVMI over 115 g/m2 (OR = 1.07 per 10 mg/dl increase in TGs, p = 0.01). In conclusion, TGs are associated with LVMI in hypertensive patients, independently of other risk factors, including LDL-C. Given the prognostic significance of LVH, it might be suggested that TGs may serve as a useful marker for indentifying hypertensive patients at high risk. The gender discrepancy may suggest a possible gender-specific modulatory effect of TGs on LV structure.

The Predictive Role for ST2 in Patients with Acute Coronary Syndromes and Heart Failure.

Intensive research has shed light on the utilization of novel biomarkers which facilitate the diagnosis and prognosis of patients with different medical problems. One of the most important biomarkers especially in the spectrum of heart failure is soluble ST2 (sST2: soluble Suppression of Tumorigenicity 2), which is involved in inflammation, fibrosis and cardiac stress. In the revised 2017 ACC/AHA/HFSA, "Focused Update Guidelines for the Management of Heart Failure" ST2 was given a class-IIa recommendation for the optimal risk assessment in patients with heart failure. Many studies indicate that not only baseline but also serial measurements of ST2 can accurately predict future cardiovascular events in patients with Acute Coronary Syndromes and heart failure. Therefore, in this review, we are going to discuss the studies about the prognostic significance of ST2 in patients with Acute Coronary Syndromes, acute and chronic heart failure.

Α systematic review and meta-analysis of the efficacy of aortic anastomotic devices.

OBJECTIVE: One of the factors contributing to complications related to open repair of the aorta is the construction of a hand-sewn anastomosis. Aortic anastomotic devices (AADs), such as the intraluminal ringed graft (IRG), and the anastomotic stenting technique have been developed to perform a sutureless and less complicated anastomosis. This study performed a systematic review and meta-analysis of the literature reporting clinical use of AADs and aimed to assess, primarily, the effect of each device on 30-day overall and operation-related mortality and aortic cross-clamping time and, secondarily, the rate of successful two-sided application of the IRG device and the operation-related morbidity for each device. METHODS: An electronic search was performed using MEDLINE, Scopus, ScienceDirect, and Cochrane Library by two independent authors. Our exclusion criteria included studies incorporating fewer than three patients and studies reporting results solely from animals or in vitro testing, results solely from end-to-side anastomosis, and results solely from endarterectomy procedures. The last search date was February 1, 2018. RESULTS: A total of 41 studies were identified that reported outcomes for the use of three different device types: IRG, anastomotic stenting technique, and surgical staplers. The last two types were classified together as the non-IRG group. The meta-analysis included 27 studies with 50 cohorts incorporating 1260 patients. The median age of the incorporated patients was 61.4 years (range, 51-73 years), and 68.9% were male. The operations were performed for the treatment of acute aortic dissection in 82.3%. The pooled overall 30-day mortality rate varied by device type; IRG devices had a mean rate of all-cause mortality of 9.71%, whereas non-IRG devices were associated with a significantly (I2 = 15.78%; P for Cochrane Q test < .19) lower rate of death (1.47%). The pooled mean aortic cross-clamping time was 35.83 minutes. Metaregression showed that the performance of two-sided anastomosis with the IRG device significantly decreased the aortic cross-clamping time. However, a successful two-sided ringed anastomosis was performed in approximately half of the cases. CONCLUSIONS: Taking into account that the majority of operations were performed for the treatment of acute aortic dissection, AADs had a relatively low rate of 30-day mortality. Despite the observed heterogeneity in study protocols and the small sample size in the non-IRG group, the non-IRG group presented with the lowest 30-day mortality rate. Specific device-related complications between the different device types need further investigation.

Metastatic malignancies and the effect on arterial stiffness and blood pressure levels: the possible role of chemotherapy.

BACKGROUND: The aim of the prospective study was to evaluate blood pressure (BP) and the arterial stiffness before and after chemotherapy in three subgroups of patients with metastatic colorectal, renal cell, and gastrointestinal carcinoma and exploit, if possible, the effect of chemotherapy and biological agents in the event of cardiotoxicity. METHODS: A total of 171 patients were included in the study: 60 with kidney cancer, 18 with gastrointestinal stromal tumors (GISTs), and 93 with metastatic colorectal cancer. All patients were subjected to full clinical and laboratory evaluation before and after chemotherapy. Arterial-stiffness indices were assessed before the initiation and after the completion of chemotherapy by means of pulse wave velocity (PWV; Complior) and augmentation index (AIx; SphygmoCor). RESULTS: Patients in all three cancer cohorts exhibited significantly (P<0.001) higher levels of carotid-radial PWV, carotid-femoral PWV, and AIx postchemotherapy, which remained significant after adjustment for BP and body-mass index. AIx exhibited greater change in the bowel-cancer cohort compared to the kidney and GIST cohorts (median 3.6, 1.75, and 1.4, respectively; P<0.001), which remained significant after adjustment for BP and body-mass index. Multiple regression analysis showed that patients with higher baseline systolic BP, diastolic BP, ejection fraction, and carotid-femoral PWV exhibited smaller differences postchemotherapy, while AIx75 baseline levels showed no difference postchemotherapy. CONCLUSION: There is a clear burden in arterial stiffness in patients under chemotherapy for kidney, GIST, and metastatic colorectal cancer, irrespective of BP and other confounders.

Prognostic significance of arterial stiffness and osteoprotegerin in patients with stable coronary artery disease.

BACKGROUND: Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question. MATERIALS AND METHODS: We randomly enrolled 262 patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave velocity (PWV) was measured as a well-established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52 months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes. RESULTS: During the follow-up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45 ± 2.19 m/s vs 8.73 ± 2.07 m/s, P = .04) and OPG levels (4.21 ± 2.19 pmol/L vs 3.18 ± 1.74 pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1 m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%. CONCLUSIONS: These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI.

J-shaped relationship between habitual coffee consumption and 10-year (2002-2012) cardiovascular disease incidence: the ATTICA study.

PURPOSE: The purpose of this work was to evaluate the association between coffee consumption and 10-year cardiovascular disease (CVD) incidence in the ATTICA study, and whether this is modified by the presence or absence of metabolic syndrome (MetS) at baseline. METHODS: During 2001-2002, 3042 healthy adults (1514 men and 1528 women) living in the greater area of Athens were voluntarily recruited to the ATTICA study. In 2011-2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Coffee consumption was assessed by a validated food-frequency questionnaire at baseline (abstention, low, moderate, heavy). Incidence of fatal or non-fatal CVD event was recorded using WHO-ICD-10 criteria and MetS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised) criteria. RESULTS: Overall, after controlling for potential CVD risk factors, the multivariate analysis revealed a J-shaped association between daily coffee drinking and the risk for a first CVD event in a 10-year period. Particularly, the odds ratio for low (<150 ml/day), moderate (150-250 ml/day) and heavy coffee consumption (>250 ml/day), compared to abstention, were 0.44 (95% CI 0.29-0.68), 0.49 (95% CI 0.27-0.92) and 2.48 (95% CI 1.56-1.93), respectively. This inverse association was also verified among participants without MetS at baseline, but not among participants with the MetS. CONCLUSIONS: These data support the protective effect of drinking moderate quantities of coffee (equivalent to approximately 1-2 cups daily) against CVD incidents. This protective effect was only significant for participants without MetS at baseline.

Single and combined effects of inflammatory markers on 10 year diabetes incidence: The mediating role of adiposity-Results from the ATTICA cohort study.

BACKGROUND: The role of inflammation in diabetes development is not fully elucidated. The aim of this work was to investigate the independent effect of individual inflammatory markers and combinations of them on diabetes incidence and the potential mediating role of obesity. METHODS: In 2001 to 2002, a random sample of 1514 men (18-87 years old) and 1528 women (18-89 years old) was selected to participate in the ATTICA study, where Athens is a major metropolis. Interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-alpha, serum amyloid alpha, fibrinogen, and homocysteine were measured. Covariates included various clinical, demographic, and lifestyle characteristics, assessed with standard procedures. In 2012, the 10 year follow-up was performed. Diabetes diagnosis was defined according to American Diabetes Association criteria among n = 1485 participants. RESULTS: One hundred ninety-one incident cases of diabetes were documented, yielding an incidence of 12.9% (13.4% in men and 12.4% in women). After adjustments, only elevated IL-6 increased by 2.2 times the 10 year diabetes risk (third vs first tertile, 95% CI: 1.13, 4.28). After investigating combinations of inflammatory markers, combined elevated levels of CRP and IL-6 or CRP and fibrinogen (both markers ≥75th percentile vs <75th percentile) increased the risk by 1.93 times (95% CI: 1.20, 3.08) and 2.37 times (95% CI: 1.37, 4.16), respectively. Body mass index was found to significantly mediate the aggravating effect of inflammation. CONCLUSIONS: The reported results underline the significant role of individual IL-6 or combinations of CRP-IL-6 and CRP-fibrinogen in diabetes prediction. Adiposity seems to be primarily responsible for an increase in inflammatory markers, leading through this mechanism to insulin resistance and increasing diabetes risk.

Adiponectin circulating levels and 10-year (2002-2012) cardiovascular disease incidence: the ATTICA Study.

PURPOSE: Adiponectin is an adipokine with anti-inflammatory and cardiovascular-protective properties. Existing epidemiological evidence is conflicting on the exact relationship between adiponectin and long-term cardiovascular disease (CVD) risk. Our aim was to prospectively assess whether circulating adiponectin is associated with long-term incident CVD. METHODS: A population-based, prospective study in adults (>18 years) without previous CVD history (ATTICA study). Circulating total adiponectin levels were measured at baseline (2001-2002) in a sub-sample (n = 531; women/men: 222/309; age: 40 ± 11 years) of the ATTICA cohort and complete 10-year follow-up data were available in 366 of these participants (women/men: 154/212; age: 40 ± 12 years). RESULTS: After adjusting for multiple factors, including age, sex, body mass index, waist circumference, smoking, physical activity, Mediterranean diet adherence, hypertension, diabetes, and hypercholesterolemia, our logistic regression analysis indicates that an increase in circulating total adiponectin levels by 1 unit was associated with 36% lower CVD risk (relative risk [RR]: 0.64, 95% confidence interval [CI] 0.42-0.96; p = 0.03). Further adjusting for interleukin-6 plasma levels had no significant impact (RR: 0.60, 95% CI 0.38-0.94; p = 0.03), while additional adjustment for circulating C-reactive protein (CRP) modestly attenuated this association (RR: 0.63, 95% CI 0.40-0.99; p = 0.046). CONCLUSIONS: In our study, elevated circulating total adiponectin levels were associated with lower 10-year CVD risk in adults without previous CVD, independently of other established CVD risk factors. This association appeared to be modestly attenuated by CRP, yet was not mediated by interleukin-6 which is the main endocrine/circulating pro-inflammatory cytokine.

Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance.

OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. RESULTS: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. CONCLUSIONS: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.

Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer.

INTRODUCTION: The effect of systemic administration of bevacizumab in cancer patients over a 5-year period after the beginning of chemotherapy treatment and comparison with a control group. METHODS: The study population consists of adult patients with metastatic breast or colorectal cancer who had not previously received antineoplasmatic treatment. Patients were stratified into two groups according to treatment: one group was treated with conventional chemotherapy plus bevacizumab and the other group was treated with conventional chemotherapy alone. The two groups did not differ in their cardiovascular history or demographic characteristics. RESULTS: Fatal outcomes were more frequent in the bevacizumab group in total as well as in different periods of follow up. However, a statistically significant difference was noted at 12 months (P-value 0.007) for new deaths and at 24 (p-value 0.001) and 60 months (p-value 0.004) for all deaths. Moreover, patients who experienced a cardiovascular or thromboembolic event belonged exclusively to the bevacizumab group. At the 5-year follow-up, five patients in the bevacizumab group developed coronary artery disease (19.23%), four experienced an acute myocardial infarction (14.81%) and five patients suffered from a thromboembolic event (17.86%). CONCLUSIONS: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

Impact of physical activity category on incidence of cardiovascular disease: Results from the 10-year follow-up of the ATTICA Study (2002-2012).

The aim of the study was to examine the effects of physical activity (PA) level on 10-year cardiovascular disease (CVD) incidence, taking into consideration several clinical and lifestyle risk factors along with the potential moderating role of gender. An analysis was undertaken on data from the ATTICA prospective cohort study (10-year follow-up, 2002-2012), which followed a Greek adult population (aged 18-89years). A total n=317 of fatal and nonfatal CVD events occurred among the 2020 participants. After adjusting for the lifestyle and clinical risk factors as potential confounders, odds ratio (ORs) of CVD risk of individuals who reported being sufficiently active and highly active were decreased by 58% (95% CI: 0.30, 0.58) and 70% (95% CI: 0.15, 0.56), when compared to those who were inactive/insufficiently active, respectively. Men had nearly two-fold increase in risk of CVD (95% CI: 1.62, 2.18) versus women. Stratified analysis by gender, revealed that sufficiently active men, had 52% (95% CI: 0.24, 0.97) reduced risk of CVD incidence when compared to inactive males, while, for women, the role of PA lost significance following adjusting for lifestyle factors. The current data suggests a beneficial effect of even moderate physical activity levels on 10-year incidence of CVD, reinforcing the importance of physically activity, especially for men.

The impact of dietary flavonoid supplementation on smoking-induced inflammatory process and fibrinolytic impairment.

BACKGROUND AND AIMS: Smoking is associated with increased inflammatory process and impairment of fibrinolytic status. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. We aimed to evaluate the impact of CGJ on smoking-induced impairment of inflammatory and fibrinolytic status in healthy smokers. METHODS: We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on three occasions (day 0: baseline, day 7 and day 14) in a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm) and 20 min after (Sm20) cigarette smoking. Serum levels of intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor 1 (PAI-1) were measured as markers of inflammatory and fibrinolytic status, respectively. RESULTS: Treatment with CGJ reduced pSm sICAM-1 levels (p < 0.001), while placebo had no impact on ICAM-1 levels (p = 0.31). Moreover, treatment with CGJ decreased pSm values of PAI-1 (p < 0.001) while placebo had no impact on PAI-1 levels (p = 0.89). Smoking induced an elevation in PAI-1 levels after smoking compared to pro-smoking levels in all study days and in both arms (CGJ and placebo) of the study (p < 0.001 for all). Interestingly, CGJ compared to placebo, attenuated the acute smoking increase in sICAM-1 and PAI-1 levels (p < 0.001 and p = 0.005 respectively). CONCLUSIONS: CGJ consumption improved inflammatory and fibrinolytic status in healthy smokers and attenuated acute smoking induced increase in ICAM-1 and PAI-1 levels. These findings shed further light on the favorable effects of flavonoids in cardiovascular health.