Characteristics of coronary microcirculatory function in patients with Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TS) is a recently described cardiac syndrome whose pathogenesis is still unclear. We investigated the characteristics of coronary microcirculatory function in patients with TS through the analysis of the TIMI frame count (TFC) compared to normal subjects and with to subjects with microvascular angina (MA). METHODS: We enrolled 71 TS patients (F:M =69:2, mean age of 65.27±9.53 years), 70 controls (F:M =34:36, mean age of 56.63±13.5 years) and 71 patients with MA, (F:M =69:2, mean age of 65.9±9.2 years). The assessment of the microcirculation was carried out through the TFC. RESULTS: microcirculation was significantly altered in patients with TS compared with healthy controls [left anterior descending coronary artery (LAD) 25.16±6.91 vs. 17.30±3.76, P<0.001; circumflex artery (CX) 25.48±6.10 vs. 17.05±4.60, P<0.001; right coronary artery (RCA) 26.43±8.95 vs. 15.74±4.27, P<0.001, average TFC in TS 25.70±5.34 vs. 16,70±3.26, P<0.001). A TFC >20 frames was able to discriminate TS patients from controls with a specificity of 88.57% and sensitivity of 85.92% (AUC 0.927, P<0.0001). Microvascular dysfunction was diffuse in TS as well as in MA and slightly more severe in this last (mean TFC in MA 28.25±9.3 vs. 25.7±5.34 in TS, P<0.046). CONCLUSIONS: Coronary microcirculation in TS patients is diffuse and milder compared to MA patients. Cut-off values >20 frames discriminate between patients with normal microcirculation and patients with TS.

Climatic variables in Takotsubo cardiomyopathy: role of temperature.

BACKGROUND: Recent studies documented a seasonal (summer) and circadian (morning) temporal distribution of takotsubo cardiomyopathy (TTC). AIM: The aim of our study was to investigate whether there is a relationship among season, temperature and the occurrence of TTC. A second aim of our study was the comparison of climatic variables in Takotsubo cardiomyopathy versus acute myocardial infarction (AMI). METHODS: We enrolled consecutive patients with TTC in three Italian centres and, for comparison consecutive patients with AMI. The frequency of TTC and AMI patients according to month, season and quartiles of temperature (I quartile: 9.8-15°, II quartile: 15-19°, III quartile: 19-25° and IV quartile: 25-38°C) was reported. Climatic variables of TTC and AMI patients were compared. RESULTS: We included in the study 85 patients with TTC and 900 patients with AMI. It was not observed a significant peak in the occurrence of TTC during summer time; however, when compared with AMI, TTC was more frequent in summer. We found an absolute higher frequency of TTC cases with warmer temperatures. TTC cases occurred during warmer temperatures than AMI. CONCLUSION: Our study does not confirm a summer preference for TTC occurrence, as reported by previous studies, even if, compared with AMI, TTC is more frequent in summer. During warmest days, it was recorded the highest incidence of TTC.

G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is an increasingly reported clinical syndrome that mimics acute myocardial infarction without obstructive coronary artery disease and is characterized by transient systolic dysfunction of the apical and/or mid-segments of the left ventricle. The syndrome mainly occurs in postmenopausal women with high adrenergic state conditions. Nowadays, the pathophysiology of TTC is not yet known and the possibility of a genetic predisposition is controversial. AIMS: The purpose of this study was to assess the genetic susceptibility to TTC through analysis of the L41Q polymorphism of the G-protein-coupled receptor kinase 5 (GRK5). METHODS AND RESULTS: In a cohort of 20 patients enrolled in two tertiary Italian centers with diagnosis of TTC, accordingly to the commonly accepted Mayo Clinic criteria and in 22 healthy individuals (control) we have evaluated the polymorphism in GRK5 gene. The TTC patients had a mean age of 65 ±â€Š9 years and 19 of 20 were women. The presence of one or two L41 alleles of GRK5 was significantly more frequent in TTC group than in the control group (40 vs. 8%, P = 0.0372). CONCLUSION: In our study, we have found a significant difference in the frequency of GRK5 polymorphism between TTC patients and controls, supporting a genetic predisposition to this cardiac syndrome.

Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function: preliminary findings.

BACKGROUND: beta-blockers in ST-segment elevation myocardial infarction (STEMI) are indicated for patients without a contraindication, particularly in patients with high heart rates (HR) or blood pressures. Epidemiological studies have shown that elevated HR represents a risk factor for cardiovascular morbidity. The study investigates the feasibility, tolerability, and the effects after 30 days of follow-up of ivabradine (IVA) versus metoprolol (METO) in early phases of anterior STEMI reperfused by percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients with a first anterior STEMI, Killip class I-II, an acceptable echocardiographic window, and admitted within 4hours of the onset of symptoms, with an ejection fraction <50%. METO or IVA, 12hours after PCI (double blind), were administered twice per day. Blood pressure (BP), heart rate (HR), electrocardiogram (ECG), and laboratory parameters were monitored during the study. At entry, day 10, day 30, and day 60, by echocardiography, the ESV, EDV, E/A ratio, E wave deceleration time, isovolumetric relaxation time were measured. A total of 155 (50 females, 105 males) patients were randomized in 2 groups: a group received METO (76 patients) 12hours after PCI and a group received IVA (79 patients) 12hours after PCI. The 2 groups were similar for clinical characteristics. No difference was evidenced in HR, systolic blood pressure, diastolic blood pressure, age (range, 39-73 years), sex, ejection fraction (EF), creatine kinase peak, between the 2 groups at entry. Both groups were similar for time to angiography and interventional procedures and number of vessels diseased. IVA group: the 79 patients showed 2 side effects and 5 readmissions: 4 for ischemic events and 1 for heart failure, and 1 sudden death; METO group: the 76 patients had 4 ischemic events, 2 side effects, and 1 patient died during re-acute MI (intrastent thrombosis) and 8 readmissions for heart failure signs. The systolic blood pressure and diastolic blood pressure showed a significant reduction in both groups, P < .0001, respectively), and significant lower values were observed in METO group, P=.0001). The HR was significantly reduced in both groups, P < .0001). IVA group showed a significant increase in EF, P=.0001, with concomitant reduction in ESV and EDV (P=.0001, and .048, respectively). The diastolic parameters were similar in both groups during study period. CONCLUSIONS: Our results suggest that ivabradine may be administered early (12hours after PCI) to patients with successful PCI for anterior STEMI with an impaired left ventricular function and high HR and sinus rhythm. A larger sample of patients and further studies are required to evaluate the effects of ivabradine on clinical end points.

Combination of indomethacin and statin compared with indomethacin and placebo in patients with a first episode of acute pericarditis: preliminary findings.

The aim of the present study was to evaluate the safety and efficacy of the combination of indomethacin and statin compared with indomethacin plus placebo in patients with a first episode of pericarditis. A total of 55 consecutive patients with acute pericarditis were randomized in a double-blind manner into two groups: group 1 (statin group) was treated with 150 mg of indomethacin plus 10 mg of rosuvastatin, and group 2 (placebo group) was treated with 150 mg of indomethacin plus placebo. Both groups received treatment up to the normalization of inflammation markers and for the following week. Clinical and laboratory assessments [white cell count, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), troponin I, creatine kinase and brain natriuretic peptide plasma levels], ECG and echocardiogram were performed at baseline and daily up to discharge. All of the patients were followed as outpatients for 3 months to evaluate any recurrence of pericarditis. The two groups were similar in age, sex and laboratory parameters [group 1 (the statin group), n=28 patients; gender, 18 male and ten female; and age, 29.5+/-5.7 years; group 2 (placebo group), n=27 patients; gender, 16 male/11 female; and age, 29.2+/-4.8 years]. The statin group, when compared with the placebo group, had a significantly faster reduction in CRP values (5.0+/-1.0 compared with 6.0+/-2.0 days respectively; P=0.022), ST segment normalization (3.5+/-1.0 compared with 4.5+/-1.0 days respectively; P=0.001), pericardial effusion (4.5+/-1.0 compared with 5.5+/-1.0 days respectively; P=0.001) and ESR (5.0+/-1 compared with 6.0+/-2 days respectively; P=0.022). Our results show that the combination of statin and indomethacin treatment in patients with acute pericarditis is feasible, with a significant reduction in inflammatory markers and a favourable trend in hospitalization time (5.5+/-2.0 compared with 6.5+/-2.0 days respectively; P=0.069). However, these preliminary findings require further studies in a larger sample of patients.

Is delayed facilitated percutaneous coronary intervention better than immediate in reperfused myocardial infarction? Six months follow up findings.

BACKGROUND: There are several new strategies proposed to improve the outcome of patients with ST-elevation myocardial infarction (STEMI). One approach is the resurgent use of facilitated percutaneous coronary interventions (PCI). Until recently, deciding whether immediate PCI after combined treatment (facilitated PCI) is more appropriate than delayed PCI (short time) has not been investigated. The aim of this study, therefore, was to investigate the outcomes in patients initially successfully treated pharmacologically and immediate PCI < 2 hr, and in patients initially successfully treated with pharmacological therapy and with delayed PCI (12-72 h). METHODS: 451 reperfused STEMI patients, aged 18 to 75 years, class I-II Killip, with an acceptable echocardiographic window and admitted within 12 hs of the onset of symptoms were randomized into two groups. All patients had to have successful reperfusion, to receive the combination of a standard tirofiban infusion or abciximab plus half dose rtPA. Thereafter, patients were sub-grouped as follows:group 1 (immediate PCI) patients had PCI within 2 h; and group 2 (delayed PCI) patients in which PCI was performed after 12 hs and within 72 hs. RESULTS: The 225 reperfused (immediate-PCI) and 226 reperfused (delayed-PCI) patients (time from randomization to PCI 165 +/- 37 min in immediate PCI versus 45.1 +/- 20.2 h in delayed PCI group) showed similar results in ejection fraction, CK release and patency of the IRA. In addition, the delayed PCI group showed a significant reduction in ischemic events, restenosis and bleedings (P = 0.005, 0.01, 0.01 respectively) and significant reduced angiographic evidence of thrombus formation in the infarction-related artery (IRA) (p = 0.001). CONCLUSION: Our data suggest the safety and possible use of delayed facilitated PCI in patients with STEMI, and that delayed PCI in patients treated with combined lytic and IIb/IIIa inhibitors appears to be as effective and possibly superior (reduced ischemic events and repeat PCI) as immediate PCI. The patients in this study were successfully reperfused, with TIMI-3 flow and our data may not apply to patients with TIMI 0-2 flow. This strategy could allow transferring the reperfused patients and performing PCI after hours < 72 hours and not immediately, thereby reducing the number of urgent PCI and costs, obtaining similar results, but mostly causing less discomfort to the patient. Our results had to be interpreted with caution, because current guidelines do not recommend the combined therapy, but suggest further studies. The study was aimed to investigate the outcomes in patients initially successfully treated pharmacologically and immediate PCI < 2 h, and in patients initially successfully treated with pharmacological therapy and delayed PCI (12-72 h). All patients had to have successful reperfusion, to receive the combination of a standard abciximab or tirofiban infusion plus half dose rtPA. Similar results were observed in both groups. Delayed PCI group showed a significant lower incidence in restenosis (0.01), minor bleedings (0.005), ischemic events (0.01) and a reduced angiographic evidence of thrombus formation in IRA (0.001). Our data suggest the safety and possible use of delayed facilitated PCI in patients with STEMI. Our results had to be interpreted with caution, because current guidelines do not recommend the combined therapy, but suggest further studies.

Effects of canrenoate plus angiotensin-converting enzyme inhibitors versus angiotensin-converting enzyme inhibitors alone on systolic and diastolic function in patients with acute anterior myocardial infarction.

BACKGROUND: Aldosterone (ALDO) exerts profibrotic effects, acting via the mineralocorticoid receptors in cardiovascular tissues. Aldosterone antagonism in combination with angiotensin-converting enzyme inhibition may better protect against the untoward effects of ALDO than angiotensin-converting enzyme inhibition alone. METHODS: In a double-blind randomized study, the tolerability and efficacy of canrenoate (25 mg/d) plus captopril versus captopril alone were evaluated in 510 patients with an acute anterior myocardial infarction (MI), a serum creatinine concentration < 2.0 mg/dL, and a serum potassium level < 5.0 mmol/L. Three hundred forty-one patients received captopril and 25-mg canrenoate (group A). Group B (346 patients) received captopril and placebo. At baseline and at 10, 90, and 180 days after admission, Doppler echocardiography was performed. RESULTS: Clinical and demographic aspects were similar in both groups. In addition, baseline cardiac enzyme levels, left ventricular function, and incidence of surgical interventions and angioplasty were comparable. Overall, creatinine, blood urea, and serum potassium levels did not show significant differences between groups. However, in 18 patients in group A, increases in serum potassium levels to > 5.5 mEq/L and creatinine levels to > 2.0 mg/L after 10 days of treatment were observed. At 180 days, the mitral E-wave-A-wave ratio was higher (P = .0001) and left ventricular end-systolic volume was smaller (P = .0001) in patients treated with canrenoate than in those receiving placebo. No further side effects were observed during the study period. CONCLUSIONS: Our data suggest that the combination of captopril plus canrenoate is well tolerated after an acute MI and has beneficial effect on systolic and diastolic parameters and may decrease post-MI remodeling.

Immediate versus delayed facilitated percutaneous coronary intervention: a pilot study.

The study was aimed to investigate the outcomes in patients initially successfully treated pharmacologically and immediate PCI <2 hours, and in patients initially successfully treated with pharmacological therapy and delayed PCI (12-72 hours). All patients had to have successful reperfusion, to receive the combination of a standard abciximab infusion plus half dose rtPA. Similar results were observed in both groups. Delayed PCI group showed a favorable trend in restenosis and bleedings (ns) and a significant reduced angiographic evidence of thrombus formation in IRA. Our very preliminary data suggest the safety and possible use of delayed facilitated PCI in patients with STEMI. The studied patients have successful reperfusion and TIMI-3 flow and our data may not apply to patients with TIMI 0-2 flow.

[Potential impact of drug-eluting stents in Sicily: results from a multicenter survey and cost-benefit analysis of drug-eluting stents versus bare metal stents]. / Impatto potenziale dello stent medicato nella pratica clinica siciliana: risultati di una "survey" multicentrica e di un'analisi costo-beneficio rispetto allo stent metallico.

BACKGROUND: The recent introduction of drug-eluting stents (DES) has shown, in randomized controlled trials, to reduce the incidence of restenosis as compared to bare metal stents (BMS). Since their cost is considerably higher than that of BMS, the study assessed the economic impact of the adoption of this new therapy in the Sicilian clinical practice. METHODS: An economic evaluation was carried out by means of a linear decision model developed in Excel that simulated and compared costs and clinical pathway, within 1 year of the intervention, of hypothetical groups of patients with de novo lesions undergoing angioplasty with DES or BMS. Clinical data were obtained from the available literature and adapted to the Sicilian reality, using data from an original survey conducted in 7 local cath labs. The survey collected information on the anatomical case-mix of the population treated, the average number of stents used in the various procedures and the methods of treatment for in-stent restenosis. RESULTS: Compared to BMS, DES allows to avoid, on average, 11.8 revascularizations out of 100 patients over a period of 1 year, but requires to bear an incremental net cost of Euro 931 for the annual treatment of each patient. The cost-benefit ratio is more favorable for those categories of patients/lesions in which the risk of in-stent restenosis is higher and, at the same time, the number of stents implanted per procedure is lower (single-vessel diabetics and small vessels). CONCLUSIONS: The results of the study show how, within the scope of a policy that has tended more and more to rationalize the use of available health resources, the use of the expensive DES is not justified from an economic point of view in groups of patients and types of lesions in which a BMS is also associated with a lower likelihood of revascularization. Therefore, the study provides a starting point for consideration by hospital centers, suggesting the use of a mixture of DES for the treatment of lesions/patients at the highest risk of restenosis and BMS for the treatment of lesions/patients at lower risk of re-intervention.

Relationship between ACE-DD polymorphism and diastolic performance in healthy subjects.

BACKGROUND: The ACE-D allele has been associated with cardiovascular disease. The study evaluates the relationship between the ACE-ID genotypes and diastolic function in healthy subjects after 6 years of follow-up. METHODS: Two hundred and seventy-five healthy volunteers aged 25-55 years had normal physical examination, 12-lead ECG, acceptable echocardiographic windows and echocardiogram at entry. Venous blood was drawn for DNA analysis. RESULTS: Two hundred and forty-two subjects completed 6 years of follow-up. Three genetically distinct groups were obtained: ACE-DD group (n=71, 26F/45M, mean age 48 +/- 7 years); ACE-ID (n=115, 39F/76M, mean age 40 +/- 7 years); and ACE-II (n=56, 20F/36M, mean age 47 +/- 6 years). Significant differences in E/A ratio were found between ACE-DD and ACE-ID, and ACE II (p=0.028, <0.0001, 0.0001), respectively. After 6 years, echocardiography showed a significant reduction of E/A ratio in the ACE-DD group, p=0.0001. CONCLUSION: The data suggest that ACE-DD is associated with deteriorating myocardial diastolic properties.

Safety and tolerability of abciximab in patients with acute myocardial infarction and failed thrombolysis.

AIM: The aim of this study was to evaluate glycoprotein IIb/IIIa receptor inhibitor effectiveness in AMI patients with unsuccessful thrombolysis. METHODS: Eighty-four patients hospitalised within 4 h of symptom onset were randomised (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa inhibitors were administered to patients who did not present with reperfusion signs 30 min after starting thrombolysis and 30-60 min after the end of full thrombolysis in patients with pain recurrence and ST-segment elevation. Reperfusion was assessed by the creatine kinase peak occurring within 12 h, by the observation of rapid ST-segment reduction (50-70% within 1 h) in 12-lead ECG continuous monitoring, by the rapid regression of pain and by the development of early ventricular arrhythmias. Group 1 (GP IIb/IIIa) (42 patients) received treatment with GP IIb/IIIa inhibitors i.v., heparin according to TIMI-14 trial and aspirin during failed thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence and ST segment elevation. Group 2 (placebo) (42 patients) received a full dose of rtpA (100 mg) and placebo either during failed thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence and ST segment elevation and standard heparin treatment and aspirin. RESULTS: Thirty-nine group 1 (GP IIb/IIIa) patients showed rapid reperfusion (6 +/- 4 min) after abciximab treatment; 22 patients received rtpA 65 mg and 20 patients received rtpA 100 mg and subsequent GP IIb/IIIa inhibitor treatment. Coronarography, performed after 3-12 h, showed patency of infarct related artery (IRA) in 39 patients whose clinical picture was suggestive of rapid reperfusion during administration of a bolus of GP IIb/IIIa inhibitors. No group 2 (placebo) patients showed reperfusion and they were submitted to rescue PTCA. SIDE EFFECTS: Four cases in the GP IIb/IIIa group and two cases in placebo group (major bleeding). Patients receiving GIIb/IIIa inhibitors showed a reduced incidence of stent treatment (ns) and a significant reduction of events (angina) within 30 days of treatment. CONCLUSION: Our data suggest the possibility of using IIb/IIIa glycoprotein receptor inhibitors in patients with AMI and failed thrombolysis. The increased risk of bleeding was acceptable. The most important results were the safety of this combination.