G-CSF for Extensive STEMI.

RATIONALE: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term. OBJECTIVE: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain. METHODS AND RESULTS: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006). CONCLUSIONS: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

Concordance between Coronary Artery Computed Tomography and Invasive Coronary Angiography in a Real-World Population with Suspected Chronic Coronary Syndrome.

BACKGROUND: Coronary computed tomographic angiography (CCTA) is a non-invasive imaging technique that possesses the ability to provide detailed anatomical information about coronary arteries, avoiding unnecessary invasive procedures. Our aim was to assess the ability of CCTA to identify coronary artery disease compared to invasive coronary angiography (ICA) in a real-life setting. METHODS: We examined 137 consecutive patients who underwent ICA after CCTA. The latter was conducted in various non-selected centers, and data regarding stenosis were taken from individual reports without further analysis. RESULTS: A total of 60.5% of patients who underwent CCTA were found to have at least one critical stenosis, while the remaining 39.5% underwent ICA due to concurrent clinical or instrumental indications. Among these, 29.5% had angiographically critical pathology, 20.3% underwent a percutaneous coronary intervention (PCI), and 1.8% had coronary artery bypass grafting. Among the 83 patients with positive CCTA results, 34.9% had negative ICA findings. CCTA demonstrated low sensitivity (57.8%) and a positive predictive value of 42.6%. However, it retained high specificity (83.6%) and a negative predictive value of 90.4% for identifying critical stenosis. Among the 18.2% of patients who underwent CCTA without a specific indication, 60% had critical coronary lesions on their ICA and 86.6% of these subsequently underwent a PCI. CONCLUSIONS: CCTA performed in non-selective centers has a low concordance with ICA.

The "Woggle" Technique for Venous Access Site Management: An Old Technique for a New Need.

BACKGROUND: Several closure devices are routinely used for percutaneous arterial access, while a relatively low number is available for the management of large bore venous accesses. The Woggle technique is a modification of the purse-string suture which was introduced several years ago in patients undergoing hemodialysis. METHODS: A population of 45 patients who underwent transvenous femoral structural heart interventions was retrospectively evaluated. The Woggle technique consists of a purge string suture with a collar to maintain the tension as stable over time and a suture lock to tighten the suture. RESULTS: Sheaths magnitude ranged from 8 French (F) to 14 F. A rapid post-procedural hemostasis was achieved in the whole population, and in 95% of cases, definite hemostasis was obtained after the first single release; the mean time of release was 302 ± 83 min. Although no relevant bleedings were reported, a significant reduction in hemoglobin levels was found in the whole population. This decrement was statistically significant only in the group with sheaths higher than 12 F. A single mild local hematoma was recorded in the group in which smaller sheaths were used. Seventy-two percent of patients were pre-treated with a dual antiplatelet therapy. CONCLUSIONS: The Woggle technique has shown to be a simple, effective, and safe approach for the management of large bore venous in percutaneous structural heart interventions.

Right Heart Catheterization: An Antecubital Vein Approach to Reduce Fluoroscopy Time, Radiation Dose, and Guidewires Need.

Antecubital access for right heart catheterization (RHC) is a widespread technique, even though there is a need to clarify if there are differences and significant advantages compared to proximal vein access. To pursue this issue, we retrospectively identified patients who underwent RHC in our clinic over a 7 year period (between January 2015 and December 2022). We revised demographic, anthropometric, and procedural data, including the fluoroscopy time, the radiation exposure, and the use of guidewires. The presence of any complications was also assessed. In patients with antecubital access, the fluoroscopy time and the radiation exposure were lower compared to proximal vein access (6 vs. 3 min, mean difference of 2 min, CI 95% 1-4 min, p < 0.001 and 61 vs. 30 cGy/m2, mean difference 64 cGy/m2, CI 95% 50-77, p < 0.001). The number of patients requiring the use of at least one guidewire was lower in the group undergoing RHC through antecubital access compared to proximal vein access (55% vs. 43%, p = 0.01). The feasibility was optimal, as just 0.9% of procedures switched from antecubital to femoral access, with a negligible rate of complications. The choice of the antecubital site exhibits advantages, e.g., a shorter fluoroscopy time, a reduced radiation dose, and a lower average number of guidewires used compared to proximal vein access.

Atrial fibrillation and ischemic heart disease: (un)solved therapeutic dilemma?

Concomitant presence of atrial fibrillation and coronary artery disease requiring percutaneous coronary intervention is a frequent occurrence. The choice of optimal antithrombotic therapy, in this context, is still challenging. To offer the best protection both in terms of stroke and stent thrombosis, triple therapy with oral anticoagulation and dual antiplatelet therapy would be required. Several drug combinations have been tested in recent years, including direct oral anticoagulants, with the aim of balancing ischemic and bleeding risk. Both pharmacokinetic aspects of the molecules and patient's characteristics should be analyzed in choosing oral anticoagulation. Then, as suggested by guidelines, triple therapy should start with a seven-day duration and the aim to prolong to thirty days in high thrombotic risk patients. Dual therapy should follow to reach twelve months after coronary intervention. Even not fully discussed by the guidelines, in order to balance ischemic and bleeding risk it should also be considered: 1) integrated assessment of coronary artery disease and procedural complexity of coronary intervention; 2) appropriateness to maintain the anticoagulant drug dosage indicated in technical data sheet; the lack of data on the suspension of antiplatelet drugs one year after percutaneous intervention; 3) the possibility of combination therapy with ticagrelor; and 4) the need to treat the occurrence of paroxysmal atrial fibrillation during acute coronary syndrome. With data provided clinician should pursue a therapy as personalized as possible, both in terms of drug choice and treatment duration, in order to balance ischemic and bleeding risk.

Induced myocardial ischemia in candidates to liver transplantation without evidence of heart disease.

BACKGROUND: Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether stress echocardiography and coronary computed tomography angiography (CCTA) could detect CAD in end-stage liver disease (ESLD) patients without previous evidence of heart disease. METHODS: LT candidates ≥30 years underwent a cardiovascular (CV) assessment through stress echocardiography. CCTA was performed in patients ≥50 years with two or more CV risk factors (e.g. diabetes, CAD family history, dyslipidaemia). Coronary angiography (CAG) was scheduled when stress echocardiography and/or CCTA were positive. Sensibility, specificity, positive and negative predictive values of stress echocardiography and CCTA were assessed by numbers of coronary revascularization (true positives) and lack of acute coronary events over a mean follow-up of 3 years (true negatives). RESULTS: Stress echocardiography was performed in 273 patients, CCTA in 34 and CAG in 41. Eight patients had critical coronary lesions, and 19 not-critical lesions. Sensitivity, specificity, positive and negative predictive values were 50.0%, 90.2%, 13.3% and 98.4% for stress echocardiography and 100%, 76.7%, 36.4% and 100% for CCTA. Among 163 patients who underwent LT (57.6%), 16 died and 5 had major adverse CV events over a mean follow-up of 3 years. CONCLUSIONS: A very low prevalence of CAD in a selected population of ESLD at intermediate to high CV risk was found. A screening based on stress echocardiography and CCTA resulted in low incidence of post-LT acute coronary events in ELSD patients. CAD has no impact on mid-term survival.

Percutaneous cutting balloon angioplasty for the treatment of renovascular hypertension in children and adolescents.

OBJECTIVE: Percutaneous transluminal renal angioplasty (PTRA), the recommended treatment in children with renovascular hypertension (RVH), often has unsatisfactory outcomes. Cutting balloons may improve the results of angioplasty in different vascular beds with complex and resistant lesions. We retrospectively analysed the effects of percutaneous cutting balloon angioplasty (PCBA) on blood pressure, cardiac mass and renal artery acceleration time in children/adolescents referred to our centre for RVH. PATIENTS AND METHODS: Thirteen patients (aged 9-19 years) with renal artery stenosis (RAS) and severe hypertension were identified. RASs were focal fibromuscular (FMD) or FMD-like dysplasia (in six cases bilateral, in five associated with mid aortic syndrome). Ten patients had uncontrolled hypertension, in nine cases associated with left ventricular hypertrophy (LVH). Acceleration time was abnormal in all stenotic arteries. Eighteen PCBA were performed, in three arteries associated with stent implantation. RESULTS: PCBA was technically successful in all individuals without major complications. In one patient, an intra-stent restenosis occurred, successfully redilated with conventional angioplasty without recurrence at 4 years distance. One year after PCBA, mean SBP and DBPs were markedly reduced from 146 ±â€Š25 to 121 ±â€Š10 mmHg and from 87 ±â€Š11 to 65 ±â€Š12 mmHg, respectively ( P  < 0.001 for both). At that time, hypertension was cured in seven children and controlled in five individuals. This favourable outcome was confirmed with ambulatory blood pressure measurement in four patients. At the latest follow-up, left ventricular mass and acceleration time were normal in all patients. CONCLUSION: PCBA proved to be a well tolerated and effective procedure that can be considered as an alternative to PTRA to treat hypertensive children/adolescents with recurrent or resistant RAS.

Renal artery embolization for kidney trauma.

Kidney trauma occurs in approximately 1-5% of all traumas with the male to female ratio being 3:1. In this paper we reported two cases of male patients with kidney trauma treated by renal artery embolization. Endo-vascular embolization is an efficient method for the treatment of patient with severe renal haemorrhage preserving loss of renal parenchyma and renal function.

Preservation of the baroreceptor heart rate reflex by chemical sympathectomy in experimental heart failure.

BACKGROUND: The mechanisms underlying impaired baroreflex sensitivity in congestive heart failure (CHF) are incompletely understood. The purpose of the present study was to test the hypothesis that this alteration depends on the marked degree of sympathetic overactivity known to characterize the CHF syndrome. METHODS AND RESULTS: Eight-week-old rats were subjected to induction of postmyocardial infarction CHF obtained by coronary ligation (Lig), chronic chemical sympathectomy by 6-hydroxydopamine (Sx), both interventions (Sx-Lig), or neither intervention (Veh-Sham, sham surgery, and vehicle administration). Four weeks after infarction, in conscious state, baroreflex sensitivity was assessed from the bradycardic responses to graded phenylephrine-induced elevations in blood pressure (BP). Left ventricular (LV) diameter was assessed by echocardiography, and plasma catecholamines were assayed to estimate sympathetic activity. Lungs were eventually excised and weighed (LW). CHF was associated with the following: (1) no changes in BP and heart rate; (2) sympathetic overactivity (norepinephrine, 320.2+/-53.8 pg/mL for Veh-Lig versus 173.4+/-20.5 pg/mL for Veh-Sham, P<0.01), prevented by Sx (181.2+/-35.5 pg/mL for Sx-Lig versus 159.8+/-33.1 pg/mL for Sx-Sham, P=NS); (3) LV enlargement (10.3+/-0.7 mm for Veh-Lig versus 6.8+/-0.6 mm for Veh-Sham, P<0.01), irrespective of Sx (9.7+/-0.7 mm for Sx-Lig versus 6.6+/-0.5 mm for Sx-Sham, P<0.01); (4) pulmonary congestion (LW, 7.55+/-0.40 mg per gram of body weight for Veh-Lig versus 5.21+/-0.44 mg per gram of body weight for Veh-Sham, P<0.01), marginally attenuated by Sx (6.54+/-0.28 mg per gram of body weight for Sx-Lig versus 4.98+/-0.22 mg per gram of body weight for Sx-Sham, P<0.05); (5) reduction in baroreflex sensitivity (0.443+/-0.032 ms/mm Hg for Veh-Lig versus 0.860+/-0.420 ms/mm Hg for Veh-Sham, P<0.01), entirely prevented by Sx (1.217+/-0.058 ms/mm Hg for Sx-Lig versus 1.345+/-0.093 ms/mm Hg for Sx-Sham, P=NS). CONCLUSIONS: In early post-MI CHF, sympathectomy only partially attenuated LV dysfunction and entirely prevented baroreflex sensitivity impairment that arises from enhanced sympathetic activity.

Influence of left ventricular mass, uremia and hypertension on vagal tachycardic reserve.

BACKGROUND: Left ventricular (LV) hypertrophy, arterial hypertension and end-stage renal disease (ESRD) are associated with deranged cardiac parasympathetic regulation and increased cardiovascular risk. These conditions often co-exist but little is known about the relative contribution of LV mass, arterial blood pressure and ESRD to impaired cardiac vagal tone. We evaluated the vagal tachycardic reserve (VTR) in subjects with normal renal function (age 58.4 +/- 6.6 years, n = 19) and in patients under chronic hemodialysis (HD) (age 62.6 +/- 13.2 years, n = 30) having wide ranges of LV mass and blood pressure. METHODS: VTR was estimated from the tachycardic response to atropine (15 microg/kg intravenously) administered during a dipyridamole-atropine stress-echo test performed as part of the diagnostic work-up for identification of inducible myocardial ischemia. LV hypertrophy (defined as LV mass index > 125 g/m2 in both genders) was present in 20 HD patients and in nine control patients. Only patients free of inducible myocardial ischemia were included in the study. RESULTS: The atropine-mediated tachycardia was: (i) significantly smaller in HD patients than in control patients (34.7 +/- 7.6 versus 60.8 +/- 10.5 beats/min, P < 0.01); (ii) independently and inversely related to LV mass (multiple regression; partial coefficients, -0.139 in HD patients and -0.382 in controls, both P < 0.01) and to mean blood pressure (-0.171 in HD patients and -0.268 in controls, both P < 0.01). CONCLUSIONS: LV mass is the strongest (inverse) determinant of VTR. Blood pressure as well as the patient's renal status are also independent correlates of VTR, and the concomitance of LV hypertrophy and ESRD exacerbates the impairment of VTR.

Dynamic QT interval analysis in uraemic patients receiving chronic haemodialysis.

OBJECTIVE: To analyse the duration of the QT interval and its relationship with heart rate changes in patients with uraemia, before and during haemodialysis. METHODS: QT and RR intervals were measured automatically using a dedicated algorithm with 24-h Holter recordings in 29 patients (15 women) receiving chronic haemodialysis. QT corrected for heart rate (QTc) and the slope of QT/RR linear regression were calculated. Arterial blood pressure (ABP) was measured before and during haemodialysis. Plasma concentrations of K+, Mg2+ and Ca2+ were assessed before and after haemodialysis. RESULTS: ABP decreased significantly from baseline (102.7 +/- 11.0 mmHg) during the first (100.6 +/- 8.8 mmHg, P < 0.05), second (95.6 +/- 10.6 mmHg, P < 0.05), and third (94.9 +/- 10.3 mmHg, P < 0.05) hours of haemodialysis. QTc was longer during haemodialysis than during a 4-h period of no dialysis (447 +/- 28 ms compared with 429 +/- 22 ms, P < 0.001), and increased progressively during haemodialysis, with the greatest value during the last hour of haemodialysis (454 +/- 32 ms compared with 426 +/- 22 ms, P < 0.001). QT/RR slopes and correlation coefficients were lower during haemodialysis than during the period of no dialysis (0.13 +/- 0.08 compared with 0.20 +/- 0.07, P < 0.001 and 0.48 +/- 0.30 compared with 0.81 +/- 0.20, respectively; P < 0.001), suggesting a reduced ability to adapt the QT interval in response to changes in heart rate. The effects of haemodialysis on QT interval and the QT/RR relationship were greater in women than in men. QTc variations during dialysis were not correlated with changes in ABP, but were inversely related to changes in Ca2+ concentration (r2 = 0.35; P = 0.001). CONCLUSIONS: In patients with uraemia, the haemodialysis session induces a progressive increase in QT interval and modifies its relationship with heart rate. These effects may predispose some individuals to ventricular arrhythmias at the end of and immediately after the haemodialysis session.

Dipyridamole stress echocardiography in diagnosis and prognosis of hemodialysis patients with asymptomatic coronary disease.

The prevalence of coronary artery disease (CAD) is high in hemodialysis (HD) patients. The aim of the study was to assess the diagnostic and prognostic value of dipyridamole stress echocardiography (DSE) in nondiabetic HD patients without signs or symptoms of CAD. In 51 out of 158 evaluated HD patients (21 females, age 67 [33-85] years, HD duration 38 [9-271] months), resting echocardiography and DSE were performed. Exclusion criteria were known CAD, diabetes mellitus, and pulmonary and oncologic pathologies. Logistic regression analysis was carried out to identify predictors of abnormal DSE response, while Cox regression analysis was performed to determine variables associated with total and cardiovascular mortality, after 43.3 (11-60) months of follow-up. Seven patients (14%) showed a positive response to DSE (DSE+). In 5/7, CAD was documented by angiography: All of them underwent coronary revascularization. DSE+ patients had significantly smaller body mass index than patients with a negative response (DSE-): 21.7 ± 1.9 vs. 25.1 ± 3.4 kg/m(2) (p = 0.018). During follow-up, 16 (31%) patients died. Older age hazard ratio [HR = 1.07; confidence interval (CI) = 1.01-1.12; p = 0.02] and higher plasma phosphate levels (HR = 10.41; CI = 2.30-47.17; p < 0.01) were predictors of total mortality. Male gender (HR = 22.7; CI = 1.45-354.4; p = 0.03), older age (HR = 1.24; CI = 1.03-1.50; p = 0.02), longer HD duration (HR = 1.13; CI = 1.01-1.26; p = 0.04), and positive response to DSE (HR = 5.82; CI = 1.04-32.65; p = 0.04) were associated with cardiovascular mortality. Ten percent of asymptomatic HD patients had significant CAD, but timely diagnosis did not seem to improve their prognosis. Total survival was associated with age and higher levels of plasma phosphate, while male gender, older age, longer HD duration, and DSE+ were predictors of cardiovascular mortality.

Granulocyte colony-stimulating factor attenuates left ventricular remodelling after acute anterior STEMI: results of the single-blind, randomized, placebo-controlled multicentre STem cEll Mobilization in Acute Myocardial Infarction (STEM-AMI) Trial.

AIMS: The aim of this study was to assess the effect of granulocyte colony-stimulating factor (G-CSF) on left ventricular (LV) function and volumes in patients with anterior ST-elevation myocardial infarction (STEMI) and depressed LV ejection fraction (EF). METHODS AND RESULTS: Sixty consecutive patients with anterior STEMI, undergoing primary angioplasty percutaneous coronary intervention (PCI), with symptom-to-reperfusion time of 2-12 h and EF ≤45% after PCI, were randomized to G-CSF 5 µg/kg b.i.d. subcutaneously (n = 24) or placebo (n = 25) for 5 days, starting <12 h after PCI. The primary endpoint was an increase from baseline to 6 months of 5% in left ventricular ejection fraction (LVEF), as measured by magnetic resonance imaging (MRI). Co-primary endpoint was a ≥20 mL difference in end-diastolic volume (EDV). Infarct size and perfusion were evaluated with late gadolinium enhancement (LGE) and gated (99m)Technetium Sestamibi single-photon emission computed tomography (SPECT). Left ventricular EDV and end-systolic volume (ESV) increased from baseline to 6 months in the placebo group (81.7 ± 24.4 to 94.4 ± 26.0 mL/m(2), P < 0.00005 and 45.2 ± 20.0 to 53.2 ± 23.8 mL/m(2), P = 0.016) but were unchanged in the G-CSF group (82.2 ± 20.3 to 85.7 ± 23.7 mL/m(2), P = 0.40 and 46.0 ± 18.2 to 48.4 ± 20.8 mL/m(2), P = 0.338). There were no significant differences in EF or perfusion between groups. A significant reduction in transmural LGE segments was seen at 6 months in the G-CSF vs. placebo groups (4.38 ± 2.9 to 3.3 ± 2.6, P = 0.04 and 4.2 ± 2.6 to 3.6 ± 2.7, P = 0.301, respectively). Significantly more placebo patients had a change in left ventricular end-diastolic volume abovethe median (9.3 mL/m(2)) when reperfusion time exceeded 180 min (median time-to-reperfusion) (P = 0.0123). Severe adverse events were similar between groups. CONCLUSION: Early G-CSF administration attenuates ventricular remodelling in patients with anterior STEMI and EF ≤45% after successful PCI.

Lowering of elevated ambulatory blood pressure by HMG-CoA reductase inhibitors.

Controversial results were reported as to a possible blood pressure-lowering effect of statins. This may relate to methodological limitations (blood pressure measuring techniques) or to putative different effects of statins in different biologic conditions (cholesterol or blood pressure levels, age, etc). Patients with cholesterol>200 mg/dL and no previous statin treatment underwent 24-hour ambulatory blood pressure (ABP) monitoring and were classified as normotensives or hypertensives according to their ABP. They were randomized to statin (n=51, simvastatin or pravastatin, 10-20 mg/d; atorvastatin, 5-10 mg/d) or control treatment (n=23, soy lecithin, 20 g/d) for 2 months, after which ABP assessment was repeated. No consistent treatment-related reduction in ABP was observed in lecithin-treated patients (either hypertensives or normotensives) or in statin-treated normotensive patients (-0.7+/-5.1/-1.0+/-4.6 mm Hg, both P=ns). In contrast, statin-treated hypertensive patients showed lower systolic and diastolic blood pressure (-5.7+/-5.8/-3.5+/-3.9 mm Hg, both P<0.001), the effect was entirely accounted for by reduced daytime values with no change in nighttime values, and it was unrelated to the concomitant statin-induced cholesterol reduction. Statins moderately but significantly lower blood pressure in patients with high (but not with normal) ABP; the effect is confined to the daytime period and is unrelated to the extent of the cholesterol lowering.