Labile plasma iron and echocardiographic parameters are associated with cardiac events in ß-thalassemic patients.

BACKGROUND AND AIM: Notwithstanding the improvement in therapies, patients affected by thalassemia major (TM) and intermedia (TI) are still at high risk of cardiac complications. This study aimed at evaluating the incidence and predictive factors for developing cardiac events in adult ß-TM and TI patients. POPULATION AND METHODS: Data on diagnosis and clinical history were collected retrospectively; prospective data on new-onset cardiac failure and arrhythmias, echocardiographic parameters, biochemical variables including non-transferrin-bound iron (NTBI) and labile plasma iron (LPI), magnetic resonance imaging (MRI) T2* measurement of hepatic and cardiac iron deposits, and iron chelation therapy were recorded during a 6-year follow-up. RESULTS: Thirty-seven patients, 29 TM and 8 TI, were included. At baseline, 8 TM patients and 1 TI patient had previously experienced a cardiac event (mainly heart failure). All patients were on chelation therapy and only 3 TM patients had mild-to-severe cardiac siderosis. During follow-up, 11 patients (29.7%) experienced a new cardiac event. The occurrence of cardiac events was correlated to high LPI levels (OR 12.0, 95% CI 1.56-92.3, p .017), low mean pre-transfusion haemoglobin (OR 0.21, 95% C.I. 0.051-0.761, p .21) and echocardiographic parameters suggestive of myocardial hypertrophy. Multivariate analysis disclosed high LPI and left ventricle mass index (LVMI) as independent variables significantly associated with cardiac events. Cardiac iron deposits measured by MRI T2* failed to predict cardiac events. CONCLUSION: LPI, Hb levels and echocardiographic parameters assessing cardiac remodelling are associated with cardiac events in adult TM and TI patients. LPI might represent both a prognostic marker and a potential target for novel treatment strategies. Further studies are warranted to confirm our findings on larger populations.

Endovascular treatment of femoro-popliteal occlusions with retrograde tibial access after failure of the antegrade approach.

BACKGROUND: Despite the development in endovascular technologies and the introduction of new tools in clinical practice, the endovascular crossing of femoropopliteal occlusions is not always possible with the antegrade approach, with a failure rate that can be up to 20%. This study aims to assess the feasibility, safety, and efficacy in terms of acute outcome of the endovascular retrograde crossing of femoro-popliteal occlusions with tibial access. METHODS: This study is a single-centre, retrospective analysis of prospectively collected data of 152 consecutive patients, who had undergone, from September 2015 to September 2022, endovascular treatment of femoro-popliteal arterial occlusions with retrograde tibial access after the failure of the antegrade approach. RESULTS: The median lesion length was 25 cm and 66 patients (43.4%) had a calcium grading according to the peripheral arterial calcium scoring system of 4. Angiographically, 44.7% of the lesions were TASC II category D. In all cases, successful cannulation and sheath introduction were performed with an average cannulation time of 150.4 s. Femoropopliteal occlusions were successfully crossed with the retrograde route in 94.1% of cases; the intimal approach was performed in 114 patients (79.7%). The mean time from puncture to retrograde crossing was 20.5 min. Acute vascular access-site complications were noted in 7 (4.6%) patients. Thirty-day major adverse cardiovascular events rate and 30-day major adverse limb events rate of 3.3% and 2%, respectively, were observed. CONCLUSIONS: The results of our study indicate that retrograde crossing of femoro-popliteal occlusions with tibial access is a feasible, effective, and safe approach in case of failed antegrade approach. The results presented represent one of the largest investigations ever published on tibial retrograde access and contribute to the small body of literature present on this topic to date.

Effects of sildenafil on right ventricle remodelling in Portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is a clinical condition associated with end-stage liver disease, described by the coexistence of pulmonary arterial hypertension (PAH) and portal hypertension. In PoPH patients, there is a right ventricle (RV) remodeling to compensate for the increased resistance in the lung circulation. There are no studies on the effects of the PAH-targeted pharmacological treatment on the RV dimension and function. The present study summarizes our experience in patients with PoPH treated with sildenafil in a period of 6 years (from 2013 to 2019). We enrolled 64 consecutive patients identified as PoPH, all treated with sildenafil (57.6% in monotherapy; in the other cases in association with macitentan; in 19.0% with initial combination therapy). A hemodynamic invasive cardiopulmonary study was performed at baseline and after 6 months of sildenafil treatment. In our population we showed a significative improvement in RV performance, with a significant increase in RV stroke volume (+33%), RV ejection fraction (+31%) and RV stroke work index (+17.5%). We registered the reduction of the RV cavity dimension over time in all patients treated with sildenafil (RV end diastolic diameter decreased by 15% after 6 months of follow-up). Regarding diastolic function, we highlighted a very significant reduction in RV end-diastolic pressure (-50% concerning baseline). Sildenafil was effective both when used as monotherapy and in combination with macitentan. In conclusion, Sildenafil had a positive impact on RV systolic and diastolic function in patients with PoPH and was able to conditionate the reverse remodeling of the RV.

Efficacy and Safety of Distal Radial Access for Transcatheter Arterial Chemoembolization (TACE) of the Liver.

BACKGROUND: The distal radial artery has emerged as an alternative vascular-access site to conventional transfemoral and transradial approaches. The main advantage over the conventional transradial route is the reduced risk of radial artery occlusion, especially in those patients who, for various clinical reasons, have to undergo repeated endovascular procedures. This study aims to assess the efficacy and safety of distal radial access for transcatheter arterial chemoembolization of the liver. METHODS: This investigation is a single-center retrospective analysis of 42 consecutive patients who had undergone, from January 2018 to December 2022, transcatheter arterial chemoembolization of the liver with distal radial access for intermediate-stage hepatocellular carcinoma. Outcome data were compared with a retrospectively constituted control group of 40 patients undergoing drug-eluting beads-transcatheter arterial chemoembolization with femoral access. RESULTS: Technical success was achieved in all cases, with a 2.4% conversion rate for distal radial access. A superselective chemoembolization was performed in 35 (83.3%) cases of distal radial access. No episode of radial artery spasm or radial artery occlusion occurred. No significant differences in efficacy and safety were observed between the distal radial access group and the femoral access group. CONCLUSIONS: Distal radial access is effective, safe, and comparable to femoral access in patients undergoing transcatheter arterial chemoembolization of the liver.

Effects of Ivabradine on Right Ventricular Systolic Function in Patients With Chronic Obstructive Pulmonary Disease and Cor Pulmonale.

Cor pulmonale is a clinical syndrome associated with pulmonary hypertension, frequently complicated by congestive heart failure, commonly caused by chronic obstructive pulmonary disease (COPD). Most patients with cor pulmonale have tachycardia. However, heart rate (HR) reduction represents a primary treatment goal to improve the survival and quality of life in these patients. Ivabradine can selectively slow HR at rest and during exercise. In this prospective study, we tested the hemodynamic effects, invasively determined using right-sided cardiac catheterization, of reducing HR with ivabradine. We selected 18 patients (13 men [72.2%], mean age 67 ± 10 years) with COPD and cor pulmonale, presenting with sinus tachycardia. All patients performed clinical evaluation, electrocardiogram, spirometry, echocardiogram, 6-minute walking distance, and right-sided cardiac catheterization within 1 month of enrollment. All tests were repeated after 6 months of ivabradine treatment (median assumed dose 11.9 mg/die). We noticed a significant decrease of HR (from 98 ± 7 to 77 ± 8 beats/min, p = 0.0001), with a concomitant reduction of the congestion index (from 25.9 ± 5.1 to 19.4 ± 5.7 mm Hg, p = 0.001), and the consequent improvement of the right ventricular systolic performance (right ventricular stroke volume augmented from 56.7 ± 7.9 to 75.2 ± 8.6 ml/beat, p = 0.0001). This allows an improvement in clinical status and exercise tolerance (Borg scale score decreased from 5.2 ± 1.4 to 4.1 ± 1.3, p = 0.01 and the 6-minute walking distance increased to 252 ± 65 to 377 ± 59 m, p = 0.001). In conclusion, HR reduction significantly improves hemodynamic and clinical status of patients with tachycardia affected by COPD and cor pulmonale.

Low Levels of Vitamin D and Silent Myocardial Ischemia in Type 2 Diabetes: Clinical Correlations and Prognostic Significance.

Vitamin D deficiency has a pathogenetic and prognostic role in coronary artery disease and a key role in pain transmission. Diabetic patients have a higher risk of silent myocardial ischemia (SMI) due to diabetic neuropathy. We evaluated the correlation between SMI and Vitamin D serum levels in type 2 diabetic patients and assessed whether SMI patients had a worse survival rate than their symptomatic counterpart. We enrolled 253 patients admitted in our Cardiology Unit and compared them with 50 healthy volunteers. We created three sub-groups: symptomatic MI group (125, 32.4%); SMI group (78, 25.7%), and no-MI group (50, 41.9%). 25(OH)D levels (nmol/L) were lower in the SMI group (34.9 ± 5.8) compared to those in the symptomatic MI (49.6 ± 6.1; p = 0.01), no MI (53.1 ± 6.2; p = 0.001), and control groups (62.1 ± 6.7; p = 0.0001). 25(OH)D levels predicted SMI in diabetic patients, with an inverted odds ratio of 1.11 (p = 0.01). Symptomatic MI group survival was higher than the SMI one (6-year survival rate: 83 vs. 69%; p = 0.01). Diabetic patients with SMI had a higher mortality risk and showed lower 25(OH)D levels than the symptomatic group. This suggests the crucial role that vitamin D has in the pathogenesis of SMI.

Red Cell Distribution Width and Patient Outcome in Cardiovascular Disease: A ''Real-World'' Analysis.

Red cell distribution width (RDW) has been shown to predict adverse outcomes in specific scenarios. We aimed to assess the association between RDW and all-cause death and a clinically relevant composite endpoint in a population with various clinical manifestations of cardiovascular diseases. We retrospectively analyzed 700 patients (median age 72.7 years [interquartile range, IQR, 62.6-80]) admitted to the Cardiology ward between January and November 2016. Patients were divided into tertiles according to baseline RDW values. After a median follow-up of 3.78 years (IQR 3.38-4.03), 153 (21.9%) patients died and 247 (35.3%) developed a composite endpoint (all-cause death, acute coronary syndromes, transient ischemic attack/stroke, and/or thromboembolic events). With multivariate Cox regression analysis, the highest RDW tertile was independently associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 2.73, 95% confidence interval [CI] 1.63-4.56) and of the composite endpoint (adjusted HR 2.23, 95% CI 1.53-3.24). RDW showed a good predictive ability for all-cause death (C-statistics: 0.741, 95% CI 0.694-0.788). In a real-world cohort of patients, we found that higher RDW values were independently associated with an increased risk of all-cause death and clinical adverse cardiovascular events thus proposing RDW as a prognostic marker in cardiovascular patients.

Endovascular recanalization of chronic total occlusions of the native superficial femoral artery after failed femoropopliteal bypass in patients with critical limb ischemia.

BACKGROUND: Femoropopliteal bypass occlusions are a significant issue in patients with critical limb ischemia and chronic total occlusion of the native superficial femoral artery, which challenges vascular surgeons and interventional radiologists. Performing a secondary femoropopliteal bypass is still considered the standard of care, although it is associated with a higher complication rate and lower patency rate in comparison with primary bypass. Over the past few years, angioplasty has been commonly used, with the development in endovascular technologies, to treat chronic total occlusions of the native superficial femoral artery, with a good technical success rate and clinical prognosis. The purpose of the study is to assess the outcome of endovascular recanalization of chronic total occlusions of the native superficial femoral artery, in patients unfit for surgery with critical limb ischemia after failed femoropopliteal bypass. RESULTS: A total of 54 patients were treated. 77.8 % of the conduits were PTFE grafts; the remainder were single-segment great saphenous veins. The most common clinical presentation was rest pain. Technical success was achieved in 51 (94.4 %) of 54 limbs. Angiographically, 77.8 % of the lesions were TASC II category D, while 22.2 % were TASC II category C. The average length of the native SFA lesions was 26.8 cm. Clinical success, with improved Rutherford classification staging, followed each case of technical success. The median follow-up value was 5.75 years (IQR, 1.5-7). By Kaplan-Meier survival analysis, primary patency rates were 61 % (± 0.07 SE) at 1 year and 46 % (± 0.07 SE) at 5 years. Secondary patency rates were 93 % (± 0.04 SE) at 1 year and 61 % (± 0.07 SE) at 5 years. Limb salvage rates were 94 % (± 0.03 SE) at 1 year and 88 % (± 0.05 SE) at 5 years. CONCLUSIONS: The endovascular recanalization of chronic total occlusions (CTO) of the native superficial femoral artery (SFA) after a failed femoropopliteal bypass is a safe and effective therapeutic option in patients unfit for surgery with critical limb ischemia.

Percutaneous treatment of vascular access-site complications: a ten years' experience in two centres.

BACKGROUND: The spread of percutaneous arterial catheterization in diagnostic and therapeutic procedures has led to a parallel increase of vascular access site complications. The incidence of these events is between 0.2-1%. A detailed analysis of injuries by type of procedure shows a higher incidence of injuries after therapeutic procedures (3%) than those observed for diagnostic ones (1%), due to the greater size of the vascular devices used and the necessity to frequently administer anticoagulant and antiplatelet therapy during procedures. The iatrogenic arterial injuries requiring treatment are the pseudoaneurysm, arteriovenous fistula, arterial rupture and dissection. Less frequent complications include distal embolization of the limbs, nerve damage, abscess and lymphocele. Moreover, the use of percutaneous vascular closure devices (VCD) has further expanded the types of complications, with an increased risk of stenosis, thrombosis, distal embolism and infection. Our work aims to bring the personal 10 years' experience in the percutaneous treatment of vascular access-site complications. RESULTS: Ninety-two pseudoaneurysms (PSA), 12 arteriovenous fistulas (AVF), 15 retrograde dissections (RD) and 11 retroperitoneal bleedings (RB) have been selected and treated. In 120/130 cases there were no periprocedural complications with immediate technical success (92.3%). Nine femoral PSA, treated with percutaneous ultrasound-guided thrombin injection, showed a failure to close the sac and therefore they were treated by PTA balloon inflation with a contralateral approach and cross-over technique. Only one case of brachial dissection, in which the prolonged inflation of the balloon has not led to a full reimbursement of the dissection flap, was then surgically repaired. At the 7 days follow-up, complications were two abscesses in retroperitoneal bleedings, treated by percutaneous drainage. At 3 months, acute occlusion of 3 covered femoral stents occurred, then treated by loco-regional thrombolysis and PTA. A total of 18 major complications was recorded at 2 years, with a complication rate at 2 years of 13.8%. CONCLUSIONS: The percutaneous treatment of vascular access-site complications is the first-choice treatment. It represents a safe and effective option, validated by a high technical success rate and a low long-term complication rate, that allows avoiding the surgical approach in most cases.

Effect on mortality of different routes of administration and loading dose of aspirin in patients with ST-segment elevation acute myocardial infarction treated with primary angioplasty.

BACKGROUND: Aspirin is the cornerstone of the anti-platelet therapy during the acute phase of ST-segment elevation myocardial infarction (STEMI), and it can be administrated orally or intravenously. The oral loading dose of aspirin is well characterized, whereas there are little data on the optimal intravenous (IV) loading dose. AIM: To confirm if the mortality of patients treated with a loading dose of IV aspirin was comparable to that of patients treated with the most usual aspirin per os. PATIENTS AND METHODS: We analyzed the overall mortality during hospitalization and at 1 year follow-up among 756 consecutive patients with STEMI. Four hundred seventy-eight (63.2%) patients received per os and 278 (36.8%) IV aspirin. We divided the 278 patients of the IV aspirin group into two subgroups, based on the median value of the dose of aspirin used as a load. RESULTS: The per os aspirin group took 234 ± 138 mg of aspirin per os at the first medical contact; the IV low-dose group 194 ± 87 mg, and the IV high-dose group 483 ± 194 mg of IV aspirin. No differences were observed in mortality rate after 1-year of follow-up. In-hospital mortality resulted significantly higher (9.3%) in the IV high-dose group respect to the IV low-dose one (5.0%) and per os aspirin group (6.0%) (P < 0.01 for both). CONCLUSION: In this retrospective study, high dose IV aspirin loading in STEMI increased intra-hospital mortality. Further study is necessary to define the optimal dose of intravenous aspirin in STEMI.

Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes.

Lamin A/C gene mutations can be associated with cardiac diseases, usually referred to as 'cardiolaminopathies' characterized by arrhythmic disorders and/or left ventricular or biventricular dysfunction up to an overt picture of heart failure. The phenotypic cardiac manifestations of laminopathies are frequently mixed in complex clinical patterns and specifically may include bradyarrhythmias (sinus node disease or atrioventricular blocks), atrial arrhythmias (atrial fibrillation, atrial flutter, atrial standstill), ventricular tachyarrhythmias and heart failure of variable degrees of severity. Family history, physical examination, laboratory findings (specifically serum creatine phosphokinase values) and ECG findings are often important 'red flags' in diagnosing a 'cardiolaminopathy'. Sudden arrhythmic death, thromboembolic events or stroke and severe heart failure requiring heart transplantation are the most dramatic complications of the evolution of cardiolaminopathies and appropriate risk stratification is clinically needed combined with clinical follow-up. Treatment with cardiac electrical implantable devices is indicated in case of bradyarrhythmias (implant of a device with pacemaker functions), risk of life-threatening ventricular tachyarrhythmias (implant of an ICD) or in case of heart failure with wide QRS interval (implant of a device for cardiac resynchronization). New technologies introduced in the last 5 years can help physicians to reduce device-related complications, thanks to the extension of device longevity and availability of leadless pacemakers or defibrillators, to be implanted in appropriately selected patients. An improved knowledge of the complex pathophysiological pathways involved in cardiolaminopathies and in the determinants of their progression to more severe forms will help to improve clinical management and to better target pharmacological and non-pharmacological treatments.