Patients with Acute Coronary Syndrome are at High Risk Prior to the Event and Lipid Management is Underachieved Pre- and Post- Hospitalization.

BACKGROUND: Current European Guidelines suggest the use of cardiovascular risk categories and also recommend using high-intensity statins for patients with acute coronary syndromes (ACS). OBJECTIVE: We examined the risk of ACS patients prior to the event, as well as the overall use and intensity of statins. METHODS: We enrolled 687 ACS patients (mean age 63 years, 78% males). Low-density lipoprotein cholesterol (LDL-C) levels upon admission were used to assess attainment of LDL-C targets. Patients were categorized as very high, high, moderate and low risk based on their prior to admission cardiovascular (CV) risk. We examined statin use and dosage intensity among patients discharged from the hospital. Patients were followed for a median period of 189 days. RESULTS: The majority of the patients (n=371, 54%) were at very high CV risk prior to admission, while 101 patients were at high risk (15%), 147 (21%) moderate risk and 68 (10%) low risk. Interestingly, LDL-C target attainment decreased as the risk increased (p<0.001). The majority (96%) of patients received statins at discharge; however, most of them (60.4%) received low/moderate intensity statins and just 35.9% received the suggested by the Guidelines high-intensity dose of statins. At follow-up, the rate of patients at high-intensity dose of statins remained similar (34.8%); 6% received no statins at all at follow-up. CONCLUSION: According to our study, the majority of ACS patients are already at high risk prior to their admission. Further, LDL-C targets are underachieved prior to the event and high-intensity statins are underutilized in ACS patients at, and post-discharge.

Epidemiological characteristics, management and early outcomes of acute coronary syndromes in Greece: The PHAETHON study.

INTRODUCTION: In view of recent therapeutic breakthroughs in acute coronary syndromes (ACS) and essential demographic and socioeconomic changes in Greece, we conducted the prospective, multi-center, nationwide PHAETHON study (An Epidemiological Cohort Study of Acute Coronary Syndromes in the Greek Population) that aimed to recruit a representative cohort of ACS patients and examine current management practices and patient prognosis. METHODS: The PHAETHON study was conducted from May 2012 to February 2014. We enrolled 800 consecutive ACS patients from 37 hospitals with a proportional representation of all types of hospitals and geographical areas. Patients were followed for a median period of 189 days. Outcome was assessed with a composite endpoint of death, myocardial infarction, stroke, urgent revascularization and urgent hospitalization for cardiovascular causes. RESULTS: The mean age of patients was 62.7 years (78% males). The majority of patients (n=411, 51%) presented with ST-elevation myocardial infarction (STEMI), whereas 389 patients presented with NSTEMI (n=303, 38%) or UA (n=86, 11%). Overall, 58.8% of the patients had hypertension, 26.5% were diabetic, 52.5% had dyslipidemia, 71.1% had a smoking history (current or past), 25.8% had a family history of coronary artery disease (CAD) and 24.1% had a prior history of CAD. In STEMI patients, 44.5% of patients were treated with thrombolysis, 38.9% underwent a coronary angiogram (34.1% were treated with primary percutaneous coronary intervention) and 16.5% did not receive urgent treatment. The pain-to-door time was 169 minutes. During hospitalization, 301 (38%) patients presented one or more complications, and 13 died (1.6%). During follow-up, 99 (12.6%) patients experienced the composite endpoint, and 21 died (2.7%). CONCLUSIONS: The PHAETHON study provided valuable insights into the epidemiology, management and outcome of ACS patients in Greece. Management of ACS resembles the management observed in other European countries. However, several issues still to be addressed by public authorities for the timely and proper management of ACS.

Cryoablation in persistent atrial fibrillation - a critical appraisal.

Ablation of atrial fibrillation is an established treatment for the management of patients with paroxysmal and persistent atrial fibrillation. The complex pathophysiology of persistent atrial fibrillation has fuelled the concept of adjunctive substrate modification on top of pulmonary vein isolation. However, recent studies have failed to demonstrate additive benefit from complex ablation approaches, thus supporting that standalone pulmonary vein isolation may prove sufficient, at least as the initial ablation strategy in persistent atrial fibrillation. In this premise, the new-generation cryoballoon is an attractive option in this demanding subgroup of patients due to its reliable efficacy in achieving pulmonary vein isolation combined with collateral debulking of the neighbouring atrial myocardium. In this review, we present a critical appraisal of the role of cryoablation in patients with persistent atrial fibrillation, discussing related technical considerations and existing scientific evidence.

Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Blockade of angiotensin II type 1 receptor diminishes cardiac hypertrophy, but does not abolish thyroxin-induced preconditioning.

Growth and stress seem to share common intracellular pathways and activation of growth signaling can increase resistance to stress. Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against ischemia reperfusion injury. The present study investigated whether this response is mediated by renin-angiotensin system (RAS). RAS is shown to be activated in hyperthyroidism and is involved in the development of cardiac hypertrophy. Male Wistar rats were treated with L-thyroxin (25 microg/100 g, sc, od) for fourteen days, while normal rats served as controls. In addition, irbesartan (150 mg/kg po), a potent blocker of angiotensin II type 1 receptor (AT1), was given with L-thyroxin for fourteen days. Isolated hearts were perfused in Langendorff mode; after stabilization, they were subjected to 20 min zero-flow global ischemia and 45 min of reperfusion. Thyroxin induced cardiac hypertrophy, which was diminished with irbesartan administration. Post-ischemic recovery of function was increased in thyroxin-treated hearts as compared to controls while ischemic contracture was accelerated and intensified. Irbesartan did not abolish this response. In conclusion, blockade of angiotensin II type 1 receptor with irbesartan preserves thyroxin-induced cardioprotection while diminishing cardiac hypertrophy. It is likely that thyroxin-induced cardioprotection is due to a direct effect of thyroid hormone.

Propylthiouracil-induced hypothyroidism is associated with increased tolerance of the isolated rat heart to ischaemia-reperfusion.

The present study investigated the response of the hypothyroid heart to ischaemia-reperfusion. Hypothyroidism was induced in Wistar rats by oral administration of propylthiouracil (0.05%) for 3 weeks (HYPO rats), while normal animals (NORM) served as controls. Isolated hearts from NORM and HYPO animals were perfused in Langendorff mode and subjected to zero-flow global ischaemia followed by reperfusion (I/R). Post-ischaemic recovery of left ventricular developed pressure was expressed as % of the initial value (LVDP%). Basal expression of protein kinase C epsilon (PKCepsilon) and PKCdelta and phosphorylation of p46 and p54 c-jun NH(2)-terminal kinases (JNKs) in response to I/R were assessed by Western blotting. LVDP% was found to be significantly higher in HYPO hearts than in NORM. At baseline, PKCepsilon expression was 1.4-fold more in HYPO than in NORM hearts, P<0.05, while PKCdelta was not changed. Furthermore, basal phospho-p54 and -p46 JNK levels were 2.2- and 2.6-fold more in HYPO than in NORM hearts, P<0.05. In response to I/R, in NORM hearts, phospho-p54 and -p46 JNK levels were 5.5- and 6.0-fold more as compared with the baseline values, P<0.05, while they were not significantly altered in HYPO hearts. HYPO hearts seem to display a phenotype of cardioprotection against ischaemia-reperfusion and this is associated with basal PKCepsilon overexpression and attenuated JNK activation after I/R.

Phenylephrine induced aortic vasoconstriction is attenuated in hyperthyroid rats.

BACKGROUND: Abnormal vascular responsiveness to vasoconstrictors may play an important role in peripheral vascular resistance in hyperthyroidism. The aim of the present study was to evaluate whether the vascular response to potassium chloride and phenylephrine is abnormal in a rat model of thyroxine-induced cardiac hypertrophy. METHODS: Left ventricular hypertrophy was induced in Wistar rats by subcutaneous administration of L-thyroxine for two weeks ("THYR"), n=17. Animals treated with normal saline served as controls, ("NORM"), n=20. The thoracic aorta was dissected and cut into rings that were suspended in an isolated organ bath with Krebs-Henseleit buffer. Maximal tension, Tmax, in g was measured in response to KCl and PE at the highest concentration in rings with endothelium (+E) and without endothelium (-E) in both groups. Relaxation response (Relax percent) to acetylcholine administration was expressed as percent of the maximal tension induced by phenylephrine. RESULTS: Left ventricular weight was 0.9 (SEM, 0.04) g for THYR group vs 0.7 (0.02) g for the NORM group, p<0.05. With KCl, Tmax was not different between the THYR and NORM groups with and without endothelium. With PE, there was a difference in Tmax between THYR+E and NORM+E, 1.2 (0.05) g vs 1.5 (0.09) g, p<0.05. Tmax was also different between THYR-E and NORM-E, 1.5 (0.08) g vs 1.7 (0.07) g, p<0.05. Relax percent was not significantly different between THYR+E and NORM+E (45.9 percent vs 42.8 percent, p>0.05). CONCLUSIONS: We conclude that: a) Vascular tension of the thoracic aorta in response to PE is lower in thyroxine-treated rats as compared to controls, probably due to enhanced PE-induced vasorelaxation at high concentration. b) Relaxation response of the thoracic aorta to acetylcholine is not different between THYR and NORM groups.

Long-term thyroxine administration increases heat stress protein-70 mRNA expression and attenuates p38 MAP kinase activity in response to ischaemia.

The present study was undertaken to investigate heat stress protein (HSP)-70 mRNA induction and p38 MAP kinase (MAPK) activity in response to ischaemic stress in the hyperthyroid rat heart. L-Thyroxine (T(4)) (25 microg/100 g body weight) was administered to Wistar rats for 2 days (THYRacute) or 14 days (THYR), while animals treated similarly with normal saline served as controls (NORMacute and NORM). In addition, abdominal aortic banding was performed in another group of rats to produce constriction-induced hypertrophy (HYP), while sham-operated (SOP) animals served as controls. Isolated rat hearts were perfused in a Langendorff mode. Hearts from NORMacute (n=6), THYRacute animals (n=8), NORM (n=6), THYR (n=6), SOP (n=5) and HYP (n=7) animals were subjected to 20 min of zero-flow global ischaemia followed by 45 min of reperfusion. HSP70 mRNA expression and phosphorylated p38 MAPK protein expression were detected in response to ischaemia and protein kinase C-epsilon (PKCepsilon) protein expression was detected at baseline. Thyroid hormones were measured in plasma. Long-term T(4) administration and aortic constriction resulted in the development of cardiac hypertrophy. Thyroid hormones were increased in both THYR and THYRacute as compared with normal groups (P<0.05). HSP70 mRNA induction was increased 2.3-fold in THYR as compared with NORM hearts (P<0.05), whereas there was not any difference between THYRacute and NORMacute hearts (P>0.05). Phosphorylated p38 MAPK protein expression was 2.2-fold more in NORM than in THYR hearts (P<0.05), but it was not different between NORMacute and THYRacute hearts (P>0.05). HSP70 mRNA induction was 1.8-fold greater in HYP than in SOP hearts (P<0.05), whereas phosphorylated p38 MAPK protein expression was similar between the two groups (P>0.05). PKCepsilon protein expression at baseline was 1.7-fold more in NORM than in THYR hearts (P<0.05), and not different between NORMacute and THYRacute hearts (P>0.05) as well as HYP and SOP hearts (P>0.05). This study shows that HSP70 mRNA expression is increased, whereas p38 MAPK activation is attenuated in response to ischaemia in long-term T(4)-treated rat hearts as compared with normal and acute hyperthyroid hearts.

Propranolol diminishes cardiac hypertrophy but does not abolish acceleration of the ischemic contracture in hyperthyroid hearts.

This study was undertaken to define the contributions of left ventricular hypertrophy (LVH) and increased adrenergic activity to the acceleration of ischemic contracture (IC) that occurs in chronic hyperthyroid rat heart. Acute and chronic hyperthyroidism (THYR) were induced by thyroxine administration for 2 and 14 days, respectively, and normal animals (NORM) served as controls. Isolated hearts were perfused in a Langendorff mode. NORM alpha acute, n = 6; THYR alpha acute, n = 8; and THYR alpha, n = 13; and NORM alpha, n = 13 were subjected to 20-min zero-flow global ischemia (I) and 45-min reperfusion (R). Additional THYR and NORM hearts treated with propranolol (prop) were subjected to 30-min I; THYR beta prop, n = 6 and NORM beta prop, n = 8, and THYR beta, n = 6, NORM beta, n = 8 served as controls. Acceleration of IC was measured by the time to peak contracture (Tmax). Left ventricular hypertrophy (LVH) was assessed by the ratio of left ventricular weight in milligrams (LVW) to animal body weight (BW) in grams. Cardiac hypertrophy developed in chronic but not acute hyperthyroidism. Propranolol reduced the extent of LVH. Contracture occurred earlier in chronic than in acute hyperthyroid and normal hearts. Propranolol did not alter contracture. In conclusion, IC is accelerated by thyroxine administration, and this is probably not due to LVH or increased beta-adrenergic activity. Propranolol diminishes LVH in hyperthyroidism.

Hyperthyroidism is associated with preserved preconditioning capacity but intensified and accelerated ischaemic contracture in rat heart.

BACKGROUND: The present study was undertaken to define the effects of thyroxine administration on ischaemic preconditioning (PC) and the ischaemic contracture. METHODS: Hyperthyroidism was induced by administration of L-thyroxine in rats (THYR) while normal animals served as controls (NORMa). Isolated rat hearts were perfused in a Langendorff preparation. NORMa control (n = 16) and THYR control (n = 9) hearts underwent 20 min of ischaemia and 45 min reperfusion while NORMa PC (n = 16) and THYR PC (n = 14) were subjected to PC before ischaemia. Additional normal hearts were subjected to 30 min of ischaemia with and without PC, NORMb control, n = 8 and NORMb PC, n = 6. Postischaemic recoveries of left ventricular (LV) developed pressure were expressed as % of the initial value (LVDP%). Severity of contracture was measured by the time (Tmax) and magnitude (Cmax) of peak contracture. RESULTS: LVDP% was significantly higher after PC, both in NORMa and THYR rats. In NORMa control hearts, ischaemic contracture had not yet reached a plateau at 20 min of ischaemia. Contracture appeared earlier in THYR control and PC than in NORMa control and PC groups. Tmax was 22.1 (0.9) vs 16.8 (1.4) min for NORMb control and PC, p < 0.05 and 12.5 (1.0) vs 9.3 (1.1) min for THYR control and PC hearts, p < 0.05. Tmax was earlier in both THYR groups compared to NORMb groups, p < 0.05. Cmax was significantly higher in both THYR groups compared to both NORMb groups. CONCLUSION: Ischaemic contracture is both accelerated and accentuated in thyroxine treated hearts while preconditioning capacity is preserved. Preconditioning and thyroxine administration shorten Tmax in an additive way, whereas Cmax in hyperthyroid hearts did not further increase by preconditioning.