Coronary artery disease in renal transplant recipients: an angiographic study.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in renal transplant recipients (RT). Coronary artery disease (CAD) in such patients is poorly studied. METHODS: During 2012-2017, 50 patients with a renal graft (functioning for a minimum of 6 months) were subjected to coronary angiography in our institution. They were matched (for age, gender, diabetes, and indication for angiography) with 50 patients with end-stage renal disease (ESRD) undergoing chronic dialysis and 50 patients with normal renal function who were subjected to coronary angiography during the same period. The extent and severity of CAD were assessed by using the SYNTAX score. RESULTS: RT had a significantly longer duration of ESRD than patients on dialysis (17.5±7.1 vs. 8.5±8.7 years, p<0.01). Mean SYNTAX score was 13.3±12.0 in RT, 20.6±17.5 in patients on dialysis, and 9.4±9.2 in control patients (p<0.01). At least one significantly calcified lesion was present in 75.7% of RT recipients, 92.1% of patients on dialysis, and 15.8% of control patients (p<0.01). Percutaneous coronary intervention (PCI) was successful in 93.8% of the attempted cases in RT, 75% of patients on chronic dialysis, and 100% of control patients (p=0.04). In the RT group, SYNTAX score significantly correlated with smoking (p=0.02) and the total vintage of ESRD (p=0.04). CONCLUSIONS: In this angiographic study, CAD was less severe in RT than in patients on long-term dialysis despite a longer duration of ESRD. Coronary artery calcification was highly prevalent after renal transplantation. PCI in RT had a high rate of angiographic success.

The impact of financial crisis on coronary artery disease burden in Greece.

BACKGROUND: Economic crisis poses an immense threat to public health worldwide and has been linked to cardiovascular morbidity and mortality. Greece is facing a distinctive recession over the recent years. However, the exact impact on coronary artery disease (CAD) burden has not been adequately addressed. METHODS: Demographic, clinical, and angiographic data of 3895 hospitalized patients were retrospectively studied. Patients were classified into two groups: those before crisis (2006-2007, n = 1228) and those during crisis (2011-2015, n = 2667). RESULTS: All data before and during crisis were compared. During crisis, patients presented with less acute coronary syndrome (ACS - 45.5% vs. 39.9%, p < 0.001). Subsequently, there were more patients without CAD (23.7% vs. 35.1%, p < 0.001) or one-vessel disease (20.5% vs. 23%, p < 0.001). The prevalence of traditional risk factors decreased significantly or remained stable except obesity (26.3% vs. 31.4%, p = 0.002). A significant increase in the examined females (23.6% vs. 26.7%, p = 0.04) was also observed. CONCLUSIONS: The burden of CAD in Greece was partially affected during the financial crisis. Even though the incidence of ACS was decreased, more women and more patients with no- or single-vessel disease were referred for cardiac catheterization. In addition, the prevalence of traditional risk factors for CAD did not increase except obesity confirming the "obesity paradox." It seems that the impact of traditional risk factors for CAD is not an immediate process and is somewhat related to living conditions or other exogenous and social factors.

White coat hypertension and haemostatic/fibrinolytic balance disorders.

White coat hypertension (WCH) or isolated clinic hypertension is generally accepted to be a benign condition, although some reports have suggested that it may be associated with an increased cardiovascular event rate or other cardiovascular alterations. It has been previously shown that essential hypertension (EH) is associated with abnormalities in haemostatic/fibrinolytic balance and endothelial function. The aim of our study was to assess the impact of WCH on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), fibrinogen, and thrombomodulin. These markers were determined in 71 patients with EH, 26 with WCH and 87 normotensive healthy control subjects. The three groups were not different with respect to age, gender, smoking habits, BMI and blood lipids. Subjects with WCH were found to have increased plasma levels of PAI-1, tPA, fibrinogen and thrombomodulin compared to controls, but less compared to hypertensive ones. Our results suggest that WCH may be associated with decreased fibrinolytic potential and endothelial dysfunction, indicating that WCH may not be a completely harmless trait.

Trimetazidine protects isolated rat hearts against ischemia-reperfusion injury in an experimental timing-dependent manner.

The present study investigated the tolerance of the isolated rat heart to ischemia-reperfusion after administration of trimetazidine (TMZ) at different experimental phases, as well as the possible involvement of p38 MAPK and JNKs in this response. Isolated rat hearts were perfused in Langendorff mode. Untreated hearts after stabilization (S) were subjected to 20 min of zero-flow global ischemia (I) and 45 min of reperfusion (R), (NORM), n = 9. TMZ (10(-5) M) was administered (in the perfusate): a) only at S phase, (TMZ-STAB), n = 8, b) only at R, (TMZ-REP), n = 8 and c) during both S and R, (TMZ-STAB+REP), n = 8. Recovery of left ventricular developed pressure at 45 min of R (Rec) was significantly higher in TMZ-STAB and TMZ-STAB+REP and LDH release was lower in TMZ-STAB+REP and TMZ-STAB than NORM, [1153.2 (121.0) and 1152.1 (86.8) vs 1573.5 (138.2), P < 0.05]. TMZ induced cardioprotection did not involve p38 MAPK and JNKs. Phospho-p38 MAPK and JNKs levels after I/R were not changed with TMZ treatment. In TMZ-REP, Rec and LDH release were similar to NORM, but the rate of functional recovery (ratio of Rec at 10 min of R to Rec) was 86.7% (13.3) for TMZ-REP vs 53.8% (7.7) for NORM, P < 0.05. This effect was associated with decreased myocardial lactate content early at reperfusion. In conclusion, preischemic administration of TMZ protects against I/R injury while TMZ given only at reperfusion accelerates recovery of function without reducing the extent of injury.

Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure.

BACKGROUND: High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels. METHODS: We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively. RESULTS: Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively). CONCLUSIONS: Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.

Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor alpha1.

Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated rat hearts were perfused in Langendorff mode and subjected to 20 minutes of zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' Triiodothyronine remained unchanged while body weight and food intake were reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial glycogen content was increased in both DRON and HYPO. In DRON, resting heart rate and contractility were reduced and ischemic contracture was significantly suppressed while postischemic left ventricular end-diastolic pressure and lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. In conclusion, dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism. This is accompanied by a reduction in body weight because of the suppression of food intake. TRs might prove novel pharmacologic targets for the treatment of cardiovascular illnesses.

Complete stent fracture 1 year after LIMA PCI due to LIMA and subclavian artery dissection.

Stent platforms are prone to fracture while incidental data are demonstrating a potential unfavorable outcome. Predisposing factors usually involve long lesions and tortuous vessels requiring more than one stent. This issue is magnified when it involves a periprocedural iatrogenic left internal mammary artery (LIMA) and subclavian artery dissection. In such complex clinical scenarios, the risk of potential complications including stent fractures is thought to be higher, though there is no data to determine the prognosis or to outline the outcomes of any management option. We present a case of complete stent fracture 1 year after LIMA percutaneous coronary intervention due to LIMA and subclavian artery dissection highlighting the circumstantial evidence in the literature that guided our management decisions.

Insulin receptor number is reduced in healthy offspring of patients with essential hypertension.

BACKGROUND: Epidemiologic studies have shown that healthy offspring of hypertensive patients exhibit many features of the metabolic syndrome, such as hyperinsulinemia, insulin resistance, and lipid disorders. Patients with essential hypertension have reduced numbers of insulin receptors. The aim of this study was to examine whether the number of insulin receptors is reduced in the erythrocytes of healthy offspring of hypertensive patients in comparison to the offspring of healthy normotensive subjects. METHODS: The study population consisted of 25 healthy offspring of patients with essential hypertension (group A) and 28 healthy offspring of healthy normotensive individuals (group B). The two groups were matched for sex, age, and body mass index. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), resting heart rate (HR), plasma insulin levels, and human insulin receptor (hINR) number in erythrocytes were determined in each participant. RESULTS: Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (121 +/- 13 v 110 +/- 10 mm Hg, 78 +/- 6 v 73 +/- 8 mm Hg, and 76 +/- 4 v 72 +/- 6 beats/min; P < .01, P < .05, and P < .01, respectively). Plasma insulin levels were significantly higher, whereas hINR density was significantly lower, in group A than in group B (21 +/- 7 v 15 +/- 6 pIU/mL, P < .01, and 5.6 +/- 1.4 v 6.8 +/- 1.3 receptors x 10(3)/red cell, P < .01, respectively). CONCLUSIONS: Our findings suggest that increased SBP, DBP, HR, plasma insulin levels, and decreased erythrocyte hINR density preexist in healthy offspring of patients with essential hypertension.

Thyroxine pretreatment increases basal myocardial heat-shock protein 27 expression and accelerates translocation and phosphorylation of this protein upon ischaemia.

Thyroxine pretreatment increases the tolerance of the heart to ischaemia, and heat-shock protein 27 (HSP27) is considered to play an important role in cardioprotection. The present study investigated whether long-term thyroxine administration can induce changes in the expression, translocation and phosphorylation of HSP27 at baseline and upon ischaemic stress. L-Thyroxine (T(4)) was administered to Wistar rats (25 microg/100 g/day s.c.) for 2 weeks, while normal animals served as controls. Hearts from normal and thyroxine-treated rats were perfused in Langendorff mode and subjected to 10 or 20 min of zero-flow global ischaemia only or to 20 min of ischaemia followed by 45 min of reperfusion. Total and phospho-HSP27 expression were assessed at different times in the Triton-soluble (cytosol-membrane), S fraction, and the Triton-insoluble (cytoskeleton-nucleus) fraction, P fraction. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value. In hearts from thyroxine-treated animals, the levels of basal total HSP27 and phospho-HSP27 in the P fraction were significantly increased as compared to normal. In response to ischaemia, in hearts from thyroxine-treated rats, the levels of total HSP27 and phospho-HSP27 were found to be significantly increased in the P fraction at 10 and 20 min of ischaemia as compared to preischaemic values, whereas in normal hearts, the levels of total HSP27 and phospho-HSP27 were significantly increased at 20 min only. Postischaemic functional recovery was significantly greater in thyroxine-treated than in untreated hearts. In summary, long-term thyroxine pretreatment results in an increased basal expression and phosphorylation of HSP27 and in an earlier and sustained redistribution of HSP27 from the S to the P fraction in response to ischaemia. This effect might be of important therapeutic relevance.

Helicobacter pylori seroprevalence in patients with chronic bronchitis.

BACKGROUND: A high Helicobacter pylori seroprevalence has been found in many extragastrointestinal disorders. Moreover, it has been reported that the risk of chronic bronchitis may be increased in H. pylori-infected patients. The aim of this study was to assess the H. pylori seroprevalence in patients with chronic bronchitis. METHODS: We evaluated 144 patients with chronic bronchitis (81 men and 63 women, aged 53.2+/-12.7 years) and 120 age and sex-matched control subjects. All enrolled subjects (bronchitic patients and controls) underwent an enzyme-linked immunosorbent assay (ELISA) IgG serologic test for H. pylori diagnosis. RESULTS: A correlation between age and H. pylori IgG level was detected for both bronchitic patients (r = 0.42; P = 0.004) and controls (r = 0.44; P = 0.004). H. pylori seropositivity in the chronic bronchitis group was significantly higher than that in controls (83.3% vs 60%; P = 0.007). The mean serum concentration of IgG antibodies against H. pylori was also significantly higher in patients with chronic bronchitis than in the control subjects (38.7+/-24.1 U/ml vs 25.9+/-19.3 U/ml; P = 0.02). CONCLUSIONS: Helicobacter pylori infection may be associated with chronic bronchitis. Further studies should be undertaken to confirm our results and to clarify the potential underlying pathogenetic mechanisms.

Long-term thyroxine administration protects the heart in a pattern similar to ischemic preconditioning.

We have previously shown that long-term thyroxine administration can protect the heart against ischemia. In the present study, we investigated whether thyroxine-induced cardioprotection can mimic the pattern of protection that is afforded by a well-established cardioprotective means such as ischemic preconditioning. In a Langendorff-perfused rat heart preparation, after an initial stabilization, normal and thyroxine-treated hearts were subjected to 20 minutes of zero-flow global ischemia followed by 45 minutes of reperfusion. In thyroxine-treated hearts, phospho-p38 mitogen-activated protein kinase (MAPK) was found to be less at the end of the ischemic period, whereas ischemic contracture was accelerated and postischemic recovery was increased in comparison to normal hearts. In addition, normal hearts were subjected to a four-cycle preconditioning protocol before ischemia. Phospho-p38 MAPK was found to be less at the end of the ischemic period in preconditioned hearts, whereas ischemic contracture was accelerated and postischemic functional recovery was increased in those hearts in comparison to nonpreconditioned hearts. An increase in basal expression and phosphorylation of PKCdelta was also found to occur after long-term thyroxine administration. We conclude that long-term thyroxine administration can protect the heart from ischemic injury through a pattern of protection that closely resembles that of ischemic preconditioning.

The Athens TAVR Registry of newer generation transfemoral aortic valves: 30-day outcomes.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is a documented treatment for patients with symptomatic aortic stenosis who are at very high or prohibitive operative risk. We sought to investigate the outcomes of transfemoral procedures with the newer generation valves in four TAVR centres in Athens, Greece. METHODS: The ATHENS TAVR Registry included all patients who underwent transfemoral implantation of the newer generation valves in 4 Athens TAVR centres (self-expanding valve 67 patients, balloon-expandable valve 59 patients). We present the procedural and echocardiographic data and the 30-day clinical outcomes according to valve type. RESULTS: A total of 126 patients underwent 126 procedures (67 CoreValve, Medtronic; 59 SAPIEN XT, Edwards Lifesciences). The mean age and logistic EuroSCORE were 80 ± 8 years and 25 ± 13%. The procedural and device success rates were 100% and 98%, respectively. The 30-day mortality was 1% (n=1), the major vascular event rates 9% (similar for both valve types), and a new permanent pacemaker was implanted more often during the same hospitalisation after CoreValve (33% vs. 9%, p=0.001). The mean effective aortic valve area increased and the mean transvalvular pressure gradient declined post implantation (from 0.66 ± 0.15 cm(2) to 1.61 ± 0.43 cm(2), p<0.001; from 51 ± 14 mm Hg to 10 ± 3 mm Hg, p<0.001). The mean grade of aortic insufficiency increased after CoreValve (from 1.2 ± 0.6 to 1.5 ± 0.7, p=0.03) but remained stable after SAPIEN XT (1.0 ± 0.8 and 1.0 ± 0.6, p=0.88) implantation. CONCLUSIONS: TAVR outcomes with both the newer generation transfemoral valves in the ATHENS Registry were excellent. We observed a greater need for a new permanent pacemaker and a greater degree of aortic valve insufficiency after CoreValve implantation.

Percutaneous coronary intervention for chronic total occlusions: the role of side-branch obstruction.

AIMS: The aim of this study was to review all percutaneous coronary interventions (PCI) performed in our department for chronic total occlusions (CTO) over the last three years, and analyse the success rate and complications. METHODS AND RESULTS: We retrospectively studied all PCls for total occlusions of more than four weeks duration, performed between 2004 and 2006, after excluding multivessel PCI, venous grafts and in-stent restenosis (n=106 cases). The in-hospital complications were recorded; periprocedural myocardial infarction (MI) was defined as elevation of troponin I more than 3 times the upper reference limit. Procedural success was defined as angiographic success and absence of major adverse cardiac events (MACE: death, large MI, emergency bypass). Logistic regression analysis was used to determine predictors of success and complications. The procedural success was 77%, and was mainly associated with duration of occlusion less than three months (OR 4.17, 95% CI 1.23-14.28, p = 0.02), preprocedural TIMI 1 coronary flow (OR 3.29, 95% CI 1.00-10.82, p = 0.05) and absence of ipsilateral collaterals (OR 4.54, 95% CI 1.35-16.67, p = 0.01). Periprocedural MI occurred in 12 cases (12%), while MACE occurred in 3 (3%). The only parameter significantly associated with periprocedural MI was the obstruction of side-branches (with diameter >1 mm) within 5 mm of the CTO (OR 10.00, 95% CI 1.76-56.67, p < 0.01). CONCLUSIONS: In our CTO cohort the success rate was 77%, with a low complication rate. Periprocedural MI was mainly due to obstruction of side-branches.

Involvement of p38 MAPK and JNK in heat stress-induced cardioprotection.

The present study investigated whether heat stress-induced cardioprotection involves alterations in the pattern of p38 mitogen activated protein kinase (p38MAPK) and c-Jun NH2 - terminal kinase (JNK) activation during ischaemia - reperfusion in a model of isolated perfused rat heart. Wistar rats were subjected to whole-body hyperthermia at 42 degrees C for 15 min (HS), while untreated animals served as controls (CON). Twenty four hours later, CON and HS isolated hearts were perfused in a Langendorff mode and subjected to 20 min of zero-.ow global ischaemia followed by 45 min of reperfusion. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value (LVDP%). Activation of p38 MAPK and JNK was assessed by standard Western blotting techniques using a dual phospho-p38 MAPK and phospho-p46 JNK and p54 JNK antibodies. The levels of phospho-p38 MAPK at the end of reperfusion were not different in HS as compared to CON hearts. The levels of phospho-p46 JNK and p54 JNK were 1.4- and 1.6-fold less in HS than in CON hearts respectively, p < 0.05. LVDP% was 60.3 (s.e.m., 6.3) for HS and 42.9 (4.1) for CON, p < 0.05. In summary, heat stress pretreatment improves postischaemic recovery of function in isolated rat hearts and this is associated with suppressed JNK activation in response to ischaemia-reperfusion.

Thyroid hormone and cardioprotection: study of p38 MAPK and JNKs during ischaemia and at reperfusion in isolated rat heart.

It has been recently shown that long-term thyroxine administration increases the tolerance of the heart to ischaemia. The present study investigated whether thyroxine induced cardioprotection involves alterations in the pattern of p38 mitogen activated protein kinase (p38MAPK) and c-Jun NH2-terminal kinases (JNKs) activation during ischaemia-reperfusion. L-thyroxine (T4) was administered in Wistar rats (25 microg/100 g/day, subcutaneously) for 2 weeks (THYR), while normal animals served as controls (NORM). NORM and THYR isolated rat hearts were perfused in Langendorff mode and subjected to 10 or 20 min of zero-flow global ischaemia only and also to 20 min of ischaemia followed by 10, 20 or 45 min of reperfusion. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value. Activation of p38 MAPK and JNKs was assessed at the different times of the experimental setting by standard Western blotting techniques using a dual phospho p38MAPK and phospho JNKs (p46/p54) antibodies. Activation of p38 MAPK was significantly attenuated during ischaemia and reperfusion in thyroxine treated hearts compared to normal hearts. JNKs were found to be activated only during the reperfusion period. The levels of phospho JNKs were found to be lower in thyroxine treated hearts as compared to untreated hearts, though not at a statistically significant level. Postischaemic functional recovery was higher in THYR as compared to NORM, p < 0.05. In summary, in hearts pretreated with thyroxine, p38 MAPK was attenuated during ischaemia and at reperfusion and this was associated with improved postischaemic recovery of function.