Dual vs. triple antithrombotic treatment after percutaneous coronary intervention in patients with non-valvular atrial fibrillation: a meta-analysis on current evidence.

OBJECTIVE: Combination and duration of antithrombotic therapy in order to prevent both stent thrombosis and thromboembolic complications after coronary artery stenting (PCI) in non-valvular atrial fibrillation (AF) is still debated. This uncertainty can be attributed mainly to the fact that the reference trials were open-label and not adequately powered in order to reach a definitive conclusion on ischemic endpoints (i.e., stent thrombosis). On these grounds, data from real-life studies could support evidence on dual antithrombotic treatment (DAT) safety (bleeding risk) and efficacy (stent thrombosis prevention). The aim of the meta-analysis is to investigate in both randomized controlled trials (RCTs) and observational studies (Obs) the risks and/or benefits related to DAT vs. triple antithrombotic treatment (TAT) regimens in patients affected by AF undergoing PCI. MATERIALS AND METHODS: RCTs and Obs were retrieved through PubMed database. The risk ratio with 95% confidence interval was used to compare the primary and the safety endpoints. RESULTS: Meta-analysis demonstrated no significant differences between DAT vs. TAT for mortality. However, a two-fold higher mortality rate was registered in Obs than in RCTs. The Obs did not confirm the expected significant reduction in bleeding risk shown by the RCTs; however, the bleeding rates in Obs were more than three-fold those of RCTs. In Obs, a significant greater risk for stent thrombosis was observed in DAT than in TAT. CONCLUSIONS: The safety and efficacy outcomes observed in RCTs are unrealistic with respect to the current clinical practice. So, more evidence is needed to have more exhaustive guidelines based on RCTs with homogeneous designs and protocols that should mimic real-life population and practice.

Takotsubo cardiomyopathy and flecainide toxicity: a case report and brief literature review.

OBJECTIVE: Takotsubo syndrome, also known as stress cardiomyopathy, is predominantly reported in postmenopausal women and it is often triggered by a physical or emotional stressor. CASE REPORT: We present the case of a 44-year-old Caucasian woman admitted to the emergency department after voluntary intake of 20 tablets of flecainide 150 mg to commit suicide. During the in-hospital stay in the Cardiac Intensive Care Unit, the patient developed Takotsubo syndrome. CONCLUSIONS: The relative role of flecainide as a possible trigger of the syndrome is discussed in the context of the current literature evidence.

Effectiveness of the new generation transcatheter aortic valve in the real life studies. Review and meta-analysis.

OBJECTIVE: The aim of the meta-analysis was to assess post-procedural outcome of the new generation of transcatheter aortic valve implantation (TAVI) devices, focusing on the transfemoral and balloon-expandable SAPIEN 3 (Edwards Lifesciences Inc., Irvine, CA, USA), the self-expanding CoreValveTM Evolut series R and PRO (R/PRO)TM (Medtronic Inc., Minneapolis, MN, USA) and ACURATE neoTM transcatheter aortic valve (Symetis SA, a Boston Scientific company, Ecublens, Switzerland). MATERIALS AND METHODS: All observational studies were retrieved through PubMed computerized database from January 2014 until June 30th, 2019. The risk difference (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. The primary end point was 30-day mortality. Safety end points included: (i) stroke, (ii) moderate/severe paravalvular leak, and (iii) the need for new permanent pacemaker implantation. RESULTS: Meta-analysis demonstrated no significant differences as regards to either 30-day mortality or stroke for all the groups of prostheses under comparison. ACURATE neo was associated with significantly less new permanent pacemaker implantation compared to SAPIEN 3 (RD: -0.06; 95% CI -0.08 to -0.03; p<0.0001; I2=0%) or to EVOLUT R/PRO (RD: -0.06; 95% CI -0.09 to -0.02; p=0.0009; I2=0%). A significant reduction of new permanent pacemaker need was observed in the group of patients implanted with SAPIEN 3 compared to EVOLUT R/PRO (RD: -0.07; 95% CI -0.09 to -0.04; p<0.00001; I2=7%). The occurrence of moderate/severe leak was significantly increased in the group of patients implanted with ACURATE neo vs. SAPIEN 3 (RD: 0.04; 95% CI 0.02 to 0.05; p<0.00001; I2=0%). No significant differences were found between ACURATE neo vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.02; p=0.69; I2=0%) and between SAPIEN 3 vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.01; p=0.28; I2=73%). CONCLUSIONS: The results of the meta-analysis show that: (1) ACURATE neo was associated with significantly less new permanent pacemaker implantation than SAPIEN 3 and EVOLUT R/PRO; (2) SAPIEN 3 had significantly lower occurrence of moderate/severe valvular leak than ACURATE neo.

Meta-analysis of the impact on early and late mortality of TAVI compared to surgical aortic valve replacement in high and low-intermediate surgical risk patients.

OBJECTIVE: We studied the impact of transcatheter aortic valve implantation (TAVI) compared to the surgical aortic valve replacement (SAVR) on 30-day and one-year mortality from randomized controlled trials (RCTs) in patients with severe aortic stenosis at high or low-intermediate surgical risk. MATERIALS AND METHODS: All RCTs were retrieved through PubMed computerized database and the site https://www.clinicaltrials.gov from January 2010 until March 31st, 2019. The absolute risk reduction (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. We evaluated overall mortality rates at 30-day and one-year follow-up in the comparison between TAVI vs. SAVR. We also evaluated the role played by the site access for TAVI performed through the femoral or subclavian artery (TV-TAVI) vs. SAVR, or transapically (TA-TAVI) vs. SAVR. RESULTS: In the "as-treated population" the overall 30-day mortality was significantly lower in TAVI (p=0.03) with respect to SAVR. However, the analysis for TAVI subgroups showed that 30-day mortality was (1) significantly lower in TV-TAVI vs. SAVR (p=0.006), (2) increased, not significantly, in TA-TAVI vs. SAVR (p=0.62). No significant differences were found between TAVI vs. SAVR at one-year follow-up. CONCLUSIONS: The results of our meta-analysis suggest that TV-TAVI is a powerful tool in the treatment of severe aortic stenosis at high or low-intermediate surgical risk, with a significant lower mortality with respect to SAVR. On the contrary, SAVR seems to provide better results than TA-TAVI.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

OBJECTIVE: Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. MATERIALS AND METHODS: Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. RESULTS: Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. CONCLUSIONS: Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

The natural history of prehypertension. A 20-year follow-up.

OBJECTIVE: According to the JNC7 report, prehypertension category includes subjects with systolic blood pressure between 120 and 139 mmHg and/or diastolic blood pressure between 80 and 89 mmHg that would be at risk for developing hypertension and its untoward sequelae as myocardial infarction and cerebrovascular disease. Moreover, ambulatory blood pressure monitoring made it possible to detect subjects with masked hypertension, who are at risk of greater target organ damage than those with normal ambulatory or home blood pressure. The aim of this study was to evaluate the risk of cardiac, cerebral and vascular events in a group of prehypertensive subjects, with and without masked hypertension. PATIENTS AND METHODS: We studied 204 consecutive asymptomatic prehypertensive subjects without history and signs of cardiovascular disease or diabetes. All the subjects underwent clinical evaluation, electrocardiogram, routine laboratory tests and ambulatory blood pressure monitoring. They were followed-up for a maximum of 237 months or until a cardiovascular event occurred. RESULTS: Twenty-seven cardiovascular events (13.2%) occurred, including 4 abdominal aortic aneurysms. Age (p<0.0001), total cholesterol (p=0.004), smoking (p=0.03) and clinically overt hypertension development (p=0.011) were related to cardiovascular events. Prognosis was not related to masked hypertension. CONCLUSIONS: The results of this study suggest that, in subjects with prehypertension, followed for 20 years, traditional cardiovascular risk factors and development of clinically overt hypertension could be more relevant than ambulatory hypertension in the prediction of an adverse outcome.

Blood pressure control and clustering of cardiovascular risk factors in Mediterranean post-menopausal hypertensive women.

BACKGROUND: Control of hypertension is unsatisfactory among older women. Data about Mediterranean countries are not currently reported. AIM: The aim of the present study was to describe the features of blood pressure (BP) control and the clustering of other cardiovascular (CV) risk factors in Mediterranean post-menopausal hypertensive women. PATIENTS AND METHODS: We consecutively selected 516 post-menopausal female patients (mean age 69±11 years) with drug-treated essential hypertension (ESH/ESC grade 1 and 2) for this cross-sectional study. All patients were divided in 4 groups: < 60 years; 60-69 years; 70-79 years; ≥ 80 years. RESULTS: The Kruskal-Wallis analysis of variance showed a significant difference among the 4 age groups both for systolic BP (p < 0.001) and diastolic BP (p < 0.01). Mann-Whitney test for multiple comparisons of each age group vs. octogenarians demonstrated that there is a significant incremental trend of SBP through the age decades. Mean diastolic BP values were significantly higher in younger patients (age decades < 60 and 60-69 years, p < 0.01 and p < 0.05 respectively), while in patients aged 70-79 years there was no difference vs. octogenarians. Dyslipidemia was the more prevalent clustered risk factor with a peak rate of 49% in patients aged 60-69 years, statistically different (p < 0.05) from octogenarians. Global BP control (i.e. treated BP < 140/90 mmHg) was low (33.5% in the whole population) and there was no trend through age decades. CONCLUSIONS: BP control varied across age groups, but was poor. Nevertheless, the studied population appeared to be at low cardiovascular risk, due to a modest clustering of traditional risk factors.

Skin iron deposition characterises lipodermatosclerosis and leg ulcer.

BACKGROUND: It is commonly reported that chronic venous disease (CVD) increases the skin iron content in which the excess is stored as haemosiderin. Despite increasing interest in the role of haemosiderin in venous ulceration, no study has systematically evaluated the occurrence of iron overload in the limbs of patients with CVD. PURPOSE: To evaluate skin haemosiderin deposition in relation to the presence and severity of skin changes in CVD legs designated according to the clinical, etiologic, anatomic and pathophysiologic (CEAP) classification. METHODS: A total of 85 skin biopsies were taken from the medial aspect of 49 limbs with CVD of CEAP clinical stages C2, C3, C4 and C6. The content of ferric ions was assessed by Perl's Prussian Blue (PPB) stain. RESULTS: No haemosiderin deposition was found in normal skin of C2, C3 and C4A legs, in less severe regions of pigmentation and in some parts of more severely affected limbs. Haemosiderin was always present in lipodermatosclerotic skin and ulcers. Occasionally, haemosiderin was found in the apparently normal perilesional skin of C4b and C6 legs. The regenerating dermis at the base of healing ulcers showed none or light haemosiderin deposition. CONCLUSION: Iron overload is not present in the less severe stages of skin damage due to CVD but lipodermatosclerosis and leg ulcers are always accompanied by haemosiderin deposition. In fact, no severe skin changes occur in CVD legs until iron overload occurs. Our results are in agreement with previous reports suggesting that a genetic inability to counteract skin iron overload is present in these patients. A more detailed analysis of disordered iron metabolism should be undertaken in CVD patients.

Cigarette smoking and ambulatory blood pressure: a case-control study in normotensives.

The aim of our study was the evaluation of the effects of cigarette smoking on ambulatory blood pressure (ABP) in normotensive subjects participating to a cardiovascular prevention program. All subjects were followed up for an average time of 97+/-42 months to assess the event of hypertension development. Prevalence of hypertension development was higher in smokers even if regression logistic analysis was not able to predict hypertension development.

Evaluation of systolic blood pressure control in elderly patients with isolated systolic hypertension.

The aim of this retrospective study was the evaluation of systolic blood pressure (SBP) control in elderly patients (pts) with isolated systolic hypertension (ISH). We assessed SBP control (i.e. average of 2 clinic BP measurements < 140 mmHg) in 152 pts (44 M, 108 F, 75 +/- 6 years) with ISH (149/84 +/- 17/6 mmHg), treated for at least 3 months by general practitioners or specialists with treatments of their choice. Most antihypertensive drugs were used at starting doses in monotherapy or combination treatment, as usual in clinical practice. ECG was abnormal in 82/152 pts (54.0%). All pts were divided in 2 groups according to SBP control. The 2 groups were compared by chi-square test for categorical variables and by Mann-Whitney test for quantitative variables. A p value < 0.05 was considered statistically significant. The global SBP control rate was 41.4% (63/152 pts). BP was higher in pts with poor SBP control, as expected, but the 2 groups were similar for sex distribution, age, prevalence of other cardiovascular risk factors and type of care (general practitioner or specialist). Pts with poor SBP control had a higher prevalence of abnormal ECG tracings (p = 0.003), a lower prevalence of combination regimes (p = 0.007) and prescriptions of dihydropyridine calcium antagonists or thiazide diuretics (p = 0.006). Global SBP control rate in our retrospective study in pts with ISH was unsatisfactory. Use of dihydropyridines or thiazides, drugs of choice in the management of ISH according to ESH/ESC and JNCVII guidelines, as single drugs or in combination regimes, can improve BP control and prevent cardiac damage.

Early carotid endarterectomy after ischemic stroke: the results of a prospective multicenter Italian study.

OBJECTIVES: To evaluate safety of early carotid endarterectomy (CEA) in patients with acute brain ischemia presenting to the emergency department stroke units (EDSU). METHODS: The neurologists, neuroradiologists and vascular surgeons on duty in emergency departments enrolled 96 patients who underwent very early CEA according to a predefined protocol within two years. The protocol included evaluation of neurological status by National Institute of Health Stroke Scale (NIHSS), neuroimaging assessment, ultrasound of the carotid arteries and Transcranial Doppler. Patients with NIHSS>22 or whose neuroimaging showed brain infarct >2/3 of the middle cerebral artery territory were excluded. All eligible patients underwent CEA as soon as possible. Primary end points of the study were mortality, neurological morbidity by NIHSS and postoperative hemorrhagic conversion on neuroimaging. Statistical analysis was performed by univariate analysis. RESULTS: The mean time elapsing between the onset of stroke and endarterectomy was 1.5 days (+/-2 days). The overall 30-day morbidity mortality rate was 7.3% (7/96). No neurological mortality occurred. On hospital discharge, three patients (3%) experienced worsening of the neurological deficit (NIHSS score 1 to 2, 1 to 3 and 9 to 10 respectively). Postoperative CT demonstrated there were no new cerebral infarcts nor hemorrhagic transformation. At hospital discharge 9/96 patients (9%) had no improvement in NHISS scores, 37 were asymptomatic and 45 showed a median decrease of 4.5 NIHSS points (range 1-18). By univariate analysis none of the considered variables influenced the clinical outcome. CONCLUSION: Our protocol selected patients who can safely undergo very early (<1.5 days) surgery after acute brain ischemia. Large randomized multicenter prospective trials are warranted to compare very early CEA versus best medical therapy.

Collateral flow prevents unintentional myocardial ischemia during antegrade cardioplegia in patients undergoing coronary artery bypass grafting.

OBJECTIVE: We evaluated, in the prevention of perioperative unintentional myocardial ischemia, the role of coronary collateral flow in patients with left anterior descending coronary artery stenosis or occlusion who underwent elective coronary artery bypass grafting. METHODS: Coronary lesions and collaterals were assessed by coronary angiography in 21 patients. Anteroseptal myocardial viability was evaluated by dobutamine echocardiography. Antegrade perfusion of cardioplegic solution was assessed by myocardial contrast echocardiography. Time-intensity curves were generated from the anteroseptal region. Twelve parameters were measured and averaged in the following four groups of patients: those with stenosis of the left anterior descending artery and poor collaterals; those with stenosis of the left anterior descending artery and good collaterals; those with occlusion of the left anterior descending artery and good collaterals; and those with occlusion of the left anterior descending artery and poor collaterals. RESULTS: Time-intensity curves were significantly different in patients with stenosis versus occlusion of the left anterior descending artery (p < 0.005); multiple comparisons with Bonferroni's correction showed that this difference was mainly a result of the impact of collateral circulation (p < 0.01). However, the role of collaterals was nonsignificant within the groups with stenosis and occlusion of the left anterior descending artery. Patients with occlusion of the left anterior descending artery and good collaterals had perfusion parameters similar to those of patients with stenosis of the left anterior descending artery (p = not significant), except for the ascending slope and time to peak values (p < 0.05 and p < 0.01, respectively), which reflected a higher flow resistance in the collateral circulation. Regional systolic function after coronary artery bypass grafting was depressed in patients with poor collaterals and poor perfusion of cardioplegic solution, as compared with findings in other subgroups. CONCLUSIONS: Incomplete myocardial protection may impair the early recovery of function after coronary artery bypass grafting.

Risk factors of incomplete distribution of cardioplegic solution during coronary artery grafting.

Myocardial distribution of cardioplegic solution infused by combined antegrade/retrograde routes was assessed with myocardial contrast echocardiography in 18 patients with chronic stable angina and three-vessel disease undergoing elective coronary artery bypass grafting. Overall myocardial opacification was significantly greater in retrograde than in antegrade cardioplegia (77.7% +/- 13.4% versus 59.1% +/- 15.7%; p = 0.0009). The difference was affected by collateral circulation, as pointed out by the significant interaction between coronary collateral circulation and percent of myocardial opacification after antegrade and retrograde cardioplegia (p = 0.002). When we performed multiple comparisons, in patients with good collaterals the opacification difference between antegrade and retrograde cardioplegia was not statistically significant (66.4% +/- 10.2% versus 76.0% +/- 15.2%; p = not significant), whereas in patients with poor collaterals myocardial opacification during retrograde cardioplegia was significantly greater (44.3% +/- 15.0% versus 81.2% +/- 9.0%; p < 0.02). During antegrade cardioplegia, patients with poor collaterals showed a lower degree of myocardial opacification than patients with good collaterals (44.3% +/- 15.0% versus 66.4% +/- 10.2%; p < 0.01). Our results show that retrograde cardioplegia in patients undergoing elective coronary artery bypass grafting offers no advantage over antegrade cardioplegia when collateral circulation is well developed. On the other hand, conventional aortic root infusion may not provide adequate myocardial protection in the subset of patients with significantly narrowed or occluded coronary arteries and poor collaterals.

[Anterograde and retrograde cardioplegia in myocardial revascularization. An intraoperative contrast echographic study]. / Cardioplegia anterograda e retrograda nella rivascolarizzazione miocardica. Studio ecocontrastografico intraoperatorio.

The aim of this study was to assess the distribution of antegrade and retrograde cardioplegia with intraoperative contrast echocardiography in patients undergoing coronary artery bypass grafting. Fifteen patients with chronic stable angina pectoris and severe coronary artery disease were studied. The severity of coronary artery disease was assessed at coronary angiography, using the Jeopardy Score System. The presence and the extent of collateral circulation was evaluated on the basis of preoperative coronary angiography and graded as: absent or poor; good or excellent. Coronary revascularization was carried out during extracorporeal circulation and myocardial protection was performed with antegrade (aortic root) and retrograde (right atrial) cardioplegia. The echo contrast agent was sterilely prepared 1 hour prior to surgery and consisted of a solution of sonicated 5% human albumin microbubbles. Two ml of sonicated albumin were injected along with antegrade cardioplegia and 4 ml with retrograde cardioplegia. The echocardiographic images were obtained with transesophageal echocardiography in the transgastric left ventricular short-axis view. Images were recorded on videotape for off-line planimetric measurement of percent myocardial opacification. Data were analyzed with the analysis of variance. Multiple comparisons were made with Student's paired t test and using Bonferroni's correction. Myocardial opacification was 58.9 +/- 12.9% during antegrade cardioplegia and 77.5 +/- 16.4% during retrograde cardioplegia (p = 0.003). This overall difference was mainly due to the impact of collateral circulation in the distribution of antegrade cardioplegia. Patients with absent or poor collateral circulation showed a lower degree of myocardial opacification than patients with good or excellent myocardial opacification (44.3 +/- 12.0% versus 64.2 +/- 8.6%; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)