Erythrocyte Indices in Patients With Takotsubo Syndrome.

BACKGROUND: Although the prognosis of patients with Takotsubo syndrome (TTS) is relatively favorable, serious complications may occur. This study aimed to investigate the relationship between blood parameters and the occurrence of in-hospital complications. METHODS: Clinical charts of 51 patients with TTS were retrospectively evaluated, and data regarding blood parameters assessed during the first 24 hours of hospitalization were studied. RESULTS: Levels of hemoglobin less than 13 g/dL in men and 12 g/dL in women (P < 0.01), levels of mean corpuscular hemoglobin concentration (MCHC) less than 33 g/dL (P = 0.01), and levels of red blood cell distribution width-coefficient of variation higher than 14.5% (P = 0.01) were significantly associated to the occurrence of major adverse cardiovascular events (MACE). Markers, such as, platelets to lymphocytes ratio, lymphocytes to monocytes ratio, neutrophils to lymphocytes ratio, and white blood cell count to mean platelet volume, were unable to differentiate patients with and without complications (P > 0.05). MCHC and estimated glomerular filtration rate were independent predictors of MACE. CONCLUSIONS: Blood parameters may have a role in the stratification risk of patients with TTS. Patients showing low levels of MCHC and decreased estimated glomerular filtration rate were more likely to have in-hospital MACE. This should encourage physicians to closely monitor blood parameters in patients with TTS.

A 'parachute effect' mockingly sealing a spontaneous coronary artery dissection: what we have learnt from intravascular imaging.

Spontaneous coronary artery dissection is often underdiagnosed. It accounts for a certain amount of acute coronary syndromes. Intravascular imaging, either intravascular ultrasound or optical coherence tomography, represents a relevant ally for interventional cardiologist. Here we report an intriguing case of spontaneous coronary artery dissection not immediately diagnosed due to the explained parachute effect, managed invasively according to an algorithm previously published, with a good long-term outcome.

Association between Tpeak-Tend/QT and major adverse cardiovascular events in patients with Takotsubo syndrome.

BACKGROUND: Conflicting results have been described in the scientific literature regarding the relationship between electrocardiographic parameters and complications in patients with Takotsubo syndrome (TTS). Aim of the present study was to investigate whether there is an association between markers of ventricular repolarization and major adverse cardiovascular events (MACE) during hospitalisation. METHODS: A retrospective chart review was conducted on a sample of patients with diagnosis of TTS, based on the fulfilment of the revised Mayo Clinic criteria. MACE included acute heart failure, cardiogenic shock, sustained ventricular tachycardia, ventricular fibrillation, and death. The following parameters, assessed on the admission electrocardiogram, were analysed: ST-segment elevation, ST-segment depression, T wave inversion, presence of Q waves, QT interval, QT interval corrected for heart rate, QT-dispersion, Tpeak-Tend (Tpe) interval, Tpe dispersion, Tpe/QT ratio, and QTpeak/QT ratio. RESULTS: Patients with MACE, compared to patients without MACE, showed more commonly anterior ST-segment elevation and had significantly higher values of Tpe/QT ratio. Low ejection fraction and Tpe/QT ratio > 0.27 identified a sub-population of patients more likely to have MACE during hospitalisation. CONCLUSIONS: Tpe/QT ratio represents a useful electrocardiographic parameter in the acute phase of TTS.

Optimal duration of dual antiplatelet therapy after second-generation drug-eluting stent implantation in patients with diabetes: The SECURITY (Second-Generation Drug-Eluting Stent Implantation Followed By Six- Versus Twelve-Month Dual Antiplatelet Therapy)-diabetes substudy.

BACKGROUND/OBJECTIVES: The randomized SECURITY (Second-Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy) trial showed the non-inferiority of 6 vs. 12-month DAPT after percutaneous coronary intervention (PCI) with second-generation DES in a low-risk population. Nevertheless, diabetes mellitus (DM) remained a major predictor of adverse cardiovascular events. We aimed to assess the interaction between DAPT duration and outcome in DM patients. METHODS: All diabetic patients included in the SECURITY trial treated by second-generation DES PCI were analyzed. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), stroke, definite or probable stent thrombosis (ST), or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 12months. The main secondary endpoint was a composite of cardiac death, MI, stroke, definite or probable ST, or BARC type 2, 3, or 5 bleeding at 24months. RESULTS: Four hundred-twenty nine DM patients received either 6 (n=206) or 12 (n=223) months of DAPT. The primary endpoint occurred in 3.9% and 5.4% of patients in the 6 and 12-month DAPT group, respectively (log-rank test p=0.83). Similarly, no statistically significant difference in the secondary endpoint was observed between the two study groups (5.4% vs. 7.6%, p=0.620). Stent thrombosis rate was low irrespective of DAPT duration at both 12 (0.5% vs. 0.4%; p=0.804) and between 12 and 24months of follow-up (0.5% vs. 0%, p=0.291). At multivariable analysis, female gender (HR: 3.42; 95% CI 1.32-8.85; p=0.011 and HR 2.28; 95% CI 1.09-4.75; p=0.027) and insulin-treated diabetes mellitus (HR: 2.62; 95% CI 1.15-6.75; p=0.004 and HR: 2.23; 95% CI 1.09-6.33; p=0.003) were independent predictors of both primary and secondary endpoint. CONCLUSIONS: In diabetic patients treated by second-generation DES PCI, we failed to find any additional benefit of prolonging DAPT beyond 6months, regardless of insulin-requiring status.

Second-generation drug-eluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: the SECURITY randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) following second-generation drug-eluting stent (DES) implantation is still debated. OBJECTIVES: The aim of this study was to test the noninferiority of 6 versus 12 months of DAPT in patients undergoing percutaneous coronary intervention with second-generation DES. METHODS: The SECURITY (Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy) trial was a 1:1 randomized, multicenter, international, investigator-driven, noninferiority study conducted from July 2009 to June 2014. Patients with a stable or unstable angina diagnosis or documented silent ischemia undergoing revascularization with at least 1 second-generation DES were eligible. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 12 months. The main secondary endpoint was a composite of cardiac death, MI, stroke, definite or probable stent thrombosis, or BARC type 2, 3, or 5 bleeding at 12 and 24 months. RESULTS: Overall, 1,399 patients were enrolled in the study and randomized to receive 6 months (n = 682) versus 12 months (n = 717) DAPT. The primary composite endpoint occurred, respectively, in 4.5% versus 3.7% (risk difference 0.8%; 95% confidence interval [CI]: -2.4% to 1.7%; p = 0.469) at 12 months. The upper 95% CI limit was lower than the pre-set margin of 2%, confirming the noninferiority hypothesis (p < 0.05). Moreover, no differences were observed in the occurrence of the secondary endpoint at 12 months (5.3% vs. 4.0%, difference: 1.2%; 95% CI: -1.0 to 3.4; p = 0.273) and between 12 and 24 months (1.5% vs. 2.2%, difference: -0.7%; 95% CI: -2.1 to 0.6; p = 0.289). Finally, no differences were observed in definite or probable stent thrombosis at 12 months (0.3% vs. 0.4%; difference: -0.1%; 95% CI: -0.7 to 0.4; p = 0.694) and between 12 and 24 months of follow-up (0.1% vs. 0%; difference: 0.1%; 95% CI: -0.1 to 0.4; p = 0.305). CONCLUSIONS: In a low-risk population, the noninferiority hypothesis of 6 vs. 12 months DAPT following second-generation DES implantation appears accepted for the incidence of cardiac death, MI, stroke, definite/probable stent thrombosis, and BARC type 3 or 5 bleeding at 12 months. (Second Generation Drug-Eluting Stent Implantation Followed by Six- Versus Twelve-Month Dual Antiplatelet Therapy; NCT00944333).

Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome.

OBJECTIVE: Small, dense low-density lipoproteins (LDL) are a feature of the metabolic syndrome (MS) but their predictive role still remains to be established. We performed a 2-year follow-up study in 124 subjects with MS (63 +/- 6 years), as defined by the American Heart Association/National Heart, Lung and Blood Institute guidelines, to assess clinical and biochemical predictors of cerebro- and cardio-vascular events. METHODS AND RESULTS: Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Clinical events were registered in the 25% of subjects. At univariate analysis subjects with events had increased prevalence of elevated fasting glucose (P = 0.0117), smoking (P = 0.0015), family history of coronary artery disease (P = 0.0033) and higher levels of total- and LDL-cholesterol (P = 0.0027 and P = 0.0023, respectively); LDL size was lower (P < 0.0001), due to reduced larger subclasses and increased small, dense LDL (all P < 0.0001). At multivariate analysis the following were independent predictors of events (univariate odd ratios were calculated): low HDL-cholesterol (OR 15.4, P = 0.0238), elevated fasting glucose (OR 12.1, P = 0.0102), elevated small, dense LDL (OR 11.7, P = 0.0004), elevated blood pressure (OR 9.2, P = 0.0392), smoking (OR 4.8, P = 0.0054). CONCLUSIONS: This is the first study that assessed the predictive role of small, dense LDL beyond traditional cardiovascular risk factors in subjects with MS.

LDL size and subclasses in patients with abdominal aortic aneurysm.

Since the type of dyslipidemia in patients with abdominal aortic aneurysm (AAA) is still insufficiently defined, we measured plasma lipids and analyzed LDL size and subclasses by gradient gel electrophoresis in 30 male patients (69+/-6 years, BMI: 27+/-3) with newly diagnosed AAA and in 26 age- and BMI-matched male healthy controls. Patients with AAA had lower HDL-cholesterol (p<.0001), increased triglycerides (p=.0002) and smaller LDL size (p<.0001) as well as increased levels of total small, dense LDL (p=.0210) in relation to controls. Multivariate analysis also showed that small LDL size was independently associated with the presence of AAA (p=.0350). Increased levels of small, dense LDL may therefore represent a common feature in patients with AAA.

Atherogenic lipoprotein phenotype and LDL size and subclasses in patients with peripheral arterial disease.

The type of dyslipidemia in patients with peripheral arterial disease (PAD) is still ill defined. PAD patients often show elevated triglycerides and reduced HDL-cholesterol, two lipid abnormalities usually accompanied by decreased LDL size in the "atherogenic lipoprotein phenotype" (ALP). We investigated (1) whether PAD patients have lower LDL size, (2) altered LDL subclass distribution and (3) the prevalence of ALP. We measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis in 31 adults with intermittent claudication and 31 age-BMI-matched controls. Patients had higher prevalence of hypertension (p=.0132), smoking (p<.0020) and diabetes (p=.0024), with lower HDL-cholesterol (p<.0001) and increased triglycerides (p=.0057); LDL size was smaller (p<.0001), with decreased larger subclasses (LDL-I, p<.0001; LDL-IIA, p=.0068) and increased smaller particles (LDL-IIIA, p<.0001; LDL-IIIB, p=.0013; LDL-IVA, p=.0029; LDL-IVB, p<.0001). The presence of PAD was independently associated with smoking (OR 7.2, p=.0099), hypertension (OR 6.5, p=.0362), diabetes (OR 5.5, p=.0450) and elevated small, dense LDL (OR 6.7, p=.0497). The concomitant presence of high triglycerides, low HDL-cholesterol and elevated small, dense LDL in patients was 26% (versus 0% controls, p=.0024). ALP seems to characterize PAD dyslipidemia, but prospective studies are needed to test whether this lipoprotein phenotype may represent a risk factor too.

Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even if significantly, higher TG levels in patients with CAD) and low-density lipoprotein cholesterol levels near optimal values. Nevertheless, patients with CAD had significantly lower high-density lipoprotein cholesterol, smaller low-density lipoprotein peak particle size, and a reduced HDL2b subfraction than controls. In addition, we observed higher concentrations of total TRL in patients with CAD together with a selective increase in apoE-rich particles. All these data were confirmed after correction for TG levels. We also investigated which parameters were associated with the spread of coronary atherosclerosis. Subjects with a single-vessel disease had selectively lower levels of apoE-rich fractions than patients with a multivessel disease. This was confirmed by multivariate analysis. Patients with a premature CAD free of nonlipid conventional risk factors, despite not having elevated lipid levels, show several lipoprotein abnormalities. Besides known atherogenic alterations, the accumulation of apoE-rich TRL subfractions may represent an additive factor that can potentially promote and initiate the atherosclerotic process.

Family history, diabetes and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA: A one-year follow-up study.

BACKGROUND AND AIM: In this study we addressed some open questions in patients with coronary artery disease (CAD). First, we analysed which of the traditional risk factors was associated with the spreading of coronary stenosis and second, we aimed to identify if any variable was predictive of post-percutaneous transluminal coronary angioplasty (PTCA) clinical events. METHODS AND RESULTS: We collected a consecutive series of patients with CAD (n=301) and in the subgroup of patients undergoing PTCA (n=135) we performed a prospective one-year follow-up study recording cardiovascular morbidity and total mortality. According to the extension of coronary atherosclerosis, we found a significant relationship with the prevalence of diabetes in men and with plasma HDL-cholesterol concentrations in women. The follow-up was completed in 95% of patients; we did not document any death whereas clinical events were registered in 16% of patients. At univariate analysis, we found that patients with clinical events had a higher prevalence of family history of CAD (43% vs 14%, p<0.005), diabetes (52% vs 21%, p<0.005) and multivessel disease (52% vs 35%, p<0.05). Multivariate analysis (logistic regression) confirmed that family history of CAD (OR 4.6, 95% CI 1.7-12.8, p<0.005), diabetes (OR 4.0, 95% CI 1.5-10.6, p<0.01) and multivessel disease (OR 2.8, 95% CI 1.1-7.4, p<0.05) were the only variables predictive of clinical events. CONCLUSIONS: In this study, factors associated with the spreading of coronary stenosis were different according to the gender. Moreover, the presence of diabetes and multivessel disease had a negative impact on the long-term prognosis of patients undergoing PTCA. In addition, the family history of CAD represented in our study a strong predictor of clinical events. We suggest that in the management of post-PTCA patients, the role of individual baseline clinical characteristics must be taken into account and that subjects with a family history of premature CAD, diabetes and a wide extension of coronary disease represent those with the highest risk.

[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.

Cutting balloon versus conventional balloon angioplasty for the treatment of in-stent restenosis: results of the restenosis cutting balloon evaluation trial (RESCUT).

OBJECTIVES: The aim of this trial was to compare cutting balloon angioplasty (CBA) with conventional balloon angioplasty (i.e., percutaneous transluminal coronary angioplasty [PTCA]) for the treatment of patients with coronary in-stent restenosis (ISR). BACKGROUND: Retrospective studies suggest CBA might be superior to conventional PTCA in the treatment of ISR. METHODS: The Restenosis Cutting Balloon Evaluation Trial (RESCUT) is a multicenter, randomized, prospective European trial including 428 patients with all types of ISR (e.g., focal, multifocal, diffuse, proliferative). RESULTS: In both groups, the majority of ISR lesions were shorter than 20 mm. The length of restenotic stents was similar (CBA: 18.6 +/- 9.7 mm; PTCA: 18.3 +/- 8.7 mm). The number of balloons used to treat ISR was lower in the CBA group: only one balloon was used in 82.3% of CBA cases, compared with 75% of PTCA procedures (p = 0.03). Balloon slippage was less frequent in the CBA group (CBA 6.5%, PTCA 25%; p < 0.01). There was a trend toward a lower need for additional stenting in the CBA group (CBA 3.9%, PTCA 8.0%; p = 0.07). At seven-month angiographic follow-up, the binary restenosis rate was not different between the groups (CBA 29.8%, PTCA 31.4%; p = 0.82), with a similar pattern of recurrent restenosis. Clinical events at seven months were also similar. CONCLUSIONS: Cutting balloon angioplasty did not reduce recurrent ISR and major adverse cardiac events, as compared with conventional PTCA. However, CBA was associated with some procedural advantages, such as use of fewer balloons, less requirement for additional stenting, and a lower incidence of balloon slippage.

A randomized comparison of direct stenting versus stenting with predilatation in native coronary artery disease: results from the multicentric Crosscut study.

Stenting without predilatation has become possible due to the availability of a new generation of flexible, low-profile, securely crimped, balloon-expandable stents. This study compared the feasibility, efficacy and cost-effectiveness of direct stenting (DS) to the standard predilatation technique (PS) using the premounted Crossflex LC stent (Cordis Corporation, Miami Lakes, Florida). The study is a randomized prospective multicenter evaluation including 271 patients (140 patients in the DS group and 131 patients in the PS group) with 1 or 2 de novo or restenotic lesions located in native coronary arteries. Procedural success was 98.9% and 98.7% in the DS and PS groups, respectively (p = NS); crossover to PS was required in 22/166 lesions (13.2%) enrolled in the DS group because of inability to cross the target lesion without predilatation. Nonsignificant reductions in procedural time (-10.5%), fluoroscopy time (-4.7%) and amount of contrast (-3.8%) were observed in the DS group in comparison to the PS group. The number of balloons used (-76.6%) and the global cost of the procedure (-18.8%) were significantly lower in the DS group (p < 0.01 for both comparisons). After 6 months, no differences were observed in the restenosis rate between the two groups (22.0% for DS group versus 18.1% for PS group; p = NS) and in the incidence of major adverse clinical events (5.0% for DS group versus 3.0% for PS group; p = NS). Direct stenting is safe and feasible for the treatment of lesions in native coronary arteries and obtains a significant reduction in procedural cost, mainly due to the lower number of balloons used. Clinical and angiographic results at 6 months are comparable to those obtained after a conventional predilatation-stenting strategy.

Elective stenting in small coronary arteries: results of the Italian prospective multicenter registry MICROSCOPE.

BACKGROUND: The role of stent implantation in small coronary arteries is still controversial. The MICROSCOPE study (Ministenting in small coronary arteries, a prospective evaluation) is a multicenter registry addressed to prospectively evaluate the immediate and mid-term clinical and angiographic results of elective stenting of lesions located in coronary arteries with an angiographic reference diameter < or = 2.75 mm. METHODS: A total of 146 patients (160 lesions) were included in the study. The percentage of complex lesions (B2 and C lesions) was 49.3%. The clinical indications for stent implantation were: stable angina (55.0%), unstable angina (24.6%), and clinical evidence of myocardial ischemia in asymptomatic patients (20.4%); 60% of patients had multivessel disease. Stent deployment could be performed in 96.2% of lesions. The baseline reference diameter was 2.12 +/- 0.36 mm. In all cases the Ministent (Cordis, a J&J Company, Miami, FL, USA), specifically designed for small coronary arteries, was employed. The stent was pre-mounted on low profile balloons available in three different diameters (2.25, 2.50 and 2.75 mm) and three different lengths (11, 15 e 26 mm). RESULTS: The primary endpoint of successful stent-assisted angioplasty in all study vessels without major adverse cardiac events was achieved in 95.8% of the patients. The minimal lumen diameter increased from 0.64 +/- 0.24 to 2.02 +/- 0.43 mm and the dimensions of the stenosis (expressed as a percentage of the diameter of the coronary vessel) decreased from 68.6 +/- 10.8 to 16.2 +/- 10.7% (< 30% standard deviation in all cases). After the procedure all the patients received double antiplatelet therapy for 4 weeks. Post-procedural complications were limited to 2 patients (1.3%) who had a non-Q wave myocardial infarction at 6 months of follow-up; 13 patients (11%) required target lesion revascularization. No patient died following the procedure. Angiographic control was performed in 44% of lesions. The minimal lumen diameter decreased to 1.12 +/- 0.47 mm and the percent stenosis increased to 45.9 +/- 23.2%. The incidence of binary restenosis (stenosis > or = 50%) was 41%. CONCLUSIONS: Elective stenting of small coronary arteries with the Ministent can be safely performed and is associated with a low incidence of acute or subacute stent thrombosis. The mid-term results indicate a high rate of angiographic restenosis but a low need of target vessel revascularization. These data suggest that stenting cannot be considered the treatment of choice for unselected lesions located in coronary arteries with a small reference diameter, but represents a safe solution if unsatisfactory results are obtained with balloon angioplasty alone.