Safety and Efficacy of Dapagliflozin in Patients with Heart Failure with Reduced Ejection Fraction: Multicentre Retrospective Study on Echocardiographic Parameters and Biomarkers of Heart Congestion.

Objectives: Dapagliflozin has shown efficacy in clinical trials in patients with heart failure and reduced ejection fraction (HFrEF). However, real-world data on its use and outcomes in routine clinical practice are limited. We aimed to evaluate the utilisation and safety profile of dapagliflozin in a real-world population of HFrEF patients within the Marche region. Methods: Nine cardiology departments within the Marche region retrospectively included HFrEF patients who were initiated on dapagliflozin therapy in an outpatient setting. Data on medical history, comorbidities, echocardiographic parameters, and laboratory tests were collected at baseline and after 6 months. Telephone follow-up interviews were conducted at 1 and 3 months to assess adverse events. We defined the composite endpoint score as meeting at least 50% of four objective measures of improvement among: weight loss, NYHA decrease, ≥50% Natriuretic peptides (NP) decrease, and guideline/directed medical therapy (GDMT) up titration. Results: We included 95 HFrEF patients aged 66 ± 12 years, 82% were men, 48% had ischemic heart disease, and 20% had diabetes. At six months, glomerular filtration rate declined (p = 0.03) and natriuretic peptides levels decreased, on average, by 23% (p < 0.001). Echocardiographic measurements revealed a decrease in pulmonary artery pressure (p < 0.001) and E/e' (p < 0.001). In terms of drug therapy, furosemide dosage decreased (p = 0.001), and the percentage of the target dose achieved for angiotensin receptor-neprilysin inhibitors increased (p = 0.003). By multivariable Cox regression, after adjustment for age, sex, the presence of diabetes/prediabetes, and HF duration, higher baseline Hb concentrations (HR 1.347, 95% CI 1.038-1.746, p = 0.025), and eGFR levels (HR 1.016, 95% CI 1.000-1.033, p = 0.46). Conclusions: In a real-life HFrEF population, dapagliflozin therapy is safe and well-tolerated, improves echocardiographic parameters and biomarkers of congestion, and can also facilitate the titration of drugs with a prognostic impact.

Acute myocarditis following Comirnaty vaccination in a healthy man with previous SARS-CoV-2 infection.

Myopericarditis following mRNA Covid-19 vaccination has recently been reported to health authorities in a lot of countries. They can occur in very rare cases after either the Moderna (mRNA-1273 - Spikevax) or Pfizer-BioNTech (BNT162b2 - Comirnaty) vaccination. Cases predominately occur in younger adult men within 14 days following the second dose. In this article, we present a 56 year-old man with no prior medical history, whit the exception of a mild Covid-19 infection 4 months earlier, who experienced an episode of acute epigastric pain, profuse sweating, tachycardia, hypotension 4 days after the first dose of BNT162b2 vaccine. Troponin I level was elevated. Chest X-ray, electrocardiogram, echocardiogram, coronary angiography didn't show significant abnormalities. Cardiac Magnetic Resonance showed a pattern of acute myocarditis. The condition appeared to be self-limited and the patient recovered without specific therapy. No report of acute myocarditis was observed in the BNT162b2 and mRNA-1273 trials and very rare cases, in comparison to given doses, have been reported to pharmacovigilance systems worldwide. Further surveillance and evaluation of this side effect are warranted to establish the correct balance of benefits and risks of Covid-19 mRNA vaccines, above all in children and younger people (categories with the higher reactogenicity and the lower risk of Covid-19 complications). At the present time the benefits of Covid-19 vaccination significantly exceed possible risks.

Percutaneous coronary implantation of sirolimus-eluting stents in unselected patients and lesions: clinical results and multiple outcome predictors.

BACKGROUND: Sirolimus-eluting stents (SES) prevent restenosis and repeat percutaneous coronary intervention (PCI), but safety data in unselected patients are limited, especially for intermediate-term follow-up. METHODS: All patients undergoing SES implantation at 4 Italian centers were enrolled into a dedicated database. Baseline, procedural, and outcome data at discharge and at follow-up were abstracted. Outcomes of interest were the occurrence of major adverse cerebrocardiovascular events (MACCE) at 6 months, as well as long-term event-free survival and multivariable event predictors. RESULTS: One thousand four hundred twenty-four patients were enrolled (2,915 lesions, treated with 3,305 stents). Specifically, 1,074 (75.4%) subjects had multivessel disease, 399 (28.1%) had diabetes, 89 (6.3%) had ST-elevation myocardial infarction, and 44 (3.1%) underwent unprotected left main intervention. At 6 months, MACCE had occurred in 121 (9.0%) patients. After a median of 48.7 months (first-third quartile 41.8-55.3), MACCE-free survival was 69.2%+/-2.6%, with definite stent thrombosis occurring acutely in 6 (0.4%), subacutely in 11 (0.8%), after 30 days in 12 (0.8%), and cumulatively in 28 (2.0%). Major multivariable outcome predictors were diabetes (target lesion revascularization [TLR], MACCE), ejection fraction (TLR, MACCE), and maximal balloon length (TLR). CONCLUSIONS: This large cohort of unselected patients supports the overall safety of unrestricted percutaneous SES implantation, as shown by the low rates of stent thrombosis. Event attrition remains, however, high at long-term follow-up, driven mainly by target vessel revascularization, with diabetes and ejection fraction as the most important prognostic factors.

Early and long-term clinical results of AngioJet rheolytic thrombectomy in patients with acute pulmonary embolism.

Anticoagulant and thrombolytic therapies are a mainstay in the management of acute pulmonary embolism (PE), especially when hemodynamic compromise is present. However, systemic drugs cannot achieve timely and effective treatment of acute PE in all patients. In such a setting, mechanical removal of thrombus from the pulmonary circulation holds the promise of significant clinical benefits, although it remains untested. We report early and long-term outcome of patients with massive or submassive acute PE treated with rheolytic thrombectomy by means of the 6Fr Xpeedior AngioJet device at our institution. Three main groups were defined pre hoc: subjects with severe (i.e., shock), moderate, or mild hemodynamic compromise. Technical and procedural successes, obstruction, perfusion and Miller indexes, and clinical events were appraised. In total 25 patients were treated with thrombectomy (8 in severe, 12 in moderate, and 5 in mild hemodynamic compromise). Technical and procedural successes were obtained in all patients, as confirmed by the significant improvement in obstruction, perfusion and Miller indexes overall, and in each subgroup (all p values <0.001). Improvement in obstruction, perfusion, and Miller indexes at the end of the procedure could also be confirmed in patients (n = 8) treated with local fibrinolysis and in the absence of concomitant thrombolysis (n = 17, p <0.05). Four patients died in hospital, all other patients but 1 were safely discharged after an appropriate hospital stay, and all were alive at long-term follow-up (median 61 months). In conclusion, this study supports at early and long-term follow-up the effectiveness and safety of rheolytic thrombectomy for PE.

Outlook of drug-eluting stent implantation for unprotected left main disease: insights on long-term clinical predictors.

BACKGROUND: Percutaneous coronary intervention (PCI) has been increasingly employed to treat unprotected left main coronary artery (LMCA) stenosis, with variable success. This strategy has been applied to patients undergoing drug-eluting stent (DES) implantation for unprotected LMCA stenosis. METHODS: From April 2003 to June 2006, 114 consecutive patients with de novo unprotected LMCA stenosis underwent PCI with DES, and were followed over a mean period of 17.1 +/- 9.1 months. The primary endpoint of the study was the occurrence of major adverse cardiovascular events (MACE) (cardiac death, myocardial infarction [MI] or target lesion revascularization [TLR]). RESULTS: LMCA stenting was successfully performed in all patients. In-hospital mortality was 3.5%, with no in-hospital non-fatal MI or emergency coronary artery bypass grafts. During the follow-up period, the all-cause mortality rate was 7.9%, with 3.5% cardiac-related deaths. TLR was performed in 7.9% of patients, and the MACE rate was 14.9%. All non-surviving patients were at high surgical risk (EuroSCORE > 6) and had a significantly higher EuroSCORE than surviving patients that patients with a EuroSCORE < or = 11 had significantly improved survival rates over those with a EuroSCORE > 11 (p < 0.0001). Moreover, most of the patients who died of cardiac causes were diabetic (71.4% vs. 26.6%; p < 0.05). Acute coronary syndromes, as clinical presentation, and non-ostial LMCA disease were also significantly more common within non-surviving patients (100% vs. 67%; p < 0.05, and 92.3% vs. 66.3%; p = 0.05, respectively). CONCLUSIONS: Stenting of unprotected LMCA appears to be associated with a favorable mid-term outlook, especially in selected patients.

Single-center randomized evaluation of paclitaxel-eluting versus conventional stent in acute myocardial infarction (SELECTION).

OBJECTIVES: To evaluate the superiority of the paclitaxel-eluting stent (PES) in reducing neointimal hyperplasia (NIH) over its corresponding bare metal stent (BMS) during primary percutaneous coronary intervention (PCI). BACKGROUND: Primary PCI with stent implantation is the repercussion strategy of choice for ST-elevation myocardial infarction (STEMI); nonetheless restenosis rate is still high. Drug-eluting stents have been proven to reduce restenosis rate in many settings, but their use during primary PCI is still controversial. METHODS: Consecutive patients with STEMI <12 hours were randomized to receive PES or BMS. The primary end-point was the percentage of the stent volume obstructed by neointimal proliferation (NIH) measured by intravascular ultrasound (IVUS) at a 7-month angiographic follow-up. Secondary end-points were binary restenosis rate and major adverse cardiac events (MACE, i.e., death, nonfatal myocardial infarction, and target lesion revascularization). RESULTS: Eighty patients with STEMI were randomized into the PES or BMS group. Patients were well matched for baseline characteristics and the index procedure was always successful. In-hospital and 1-month MACE were 2.5% per group. NIH at 7 months was 4.6% versus 20% (P< 0.01), late lumen loss 0.1 versus 1.01 mm (P = 0.01). MACE were 7.5% versus 42.5% (P = 0.001) with no difference in death and recurrent myocardial infarction rates. Late-acquired incomplete stent apposition (ISA) rate was 5.1% versus 2.7% (P = 0.65). One subacute stent thrombosis was reported in each group. CONCLUSIONS: PES was superior to its corresponding BMS in reducing NIH in the STEMI setting without any increase in early and long-term clinical adverse events.

Thrombus aspiration with export catheter in ST elevation myocardial infarction.

BACKGROUND: Many thrombectomy devices have failed to confirm initial promising results during primary angioplasty. This may be due to device complexity and operator experience. The objective of this study was to assess the safety and efficacy of the EXPORT catheter for thrombus aspiration in patients with ST elevation myocardial infarction (STEMI). METHODS: EXPORT catheter was used in patients with STEMI and angiographic evidence of thrombus in vessels with a reference diameter > or =1.5 mm. Direct stenting and glycoprotein IIb/IIIa inhibitors were liberally employed to optimize angiographic and clinical results. Epicardial and myocardial angiographic parameters, in-hospital major adverse cardiac events (MACE, i.e., cardiac death, myocardial infarction, target vessel revascularization) were assessed. RESULTS: EXPORT catheter was used in 129 patients without any device-related complications. Angiographic analysis following thrombus aspiration revealed a significant improvement in TIMI frame count (P = 0.0001), myocardial perfusion (P = 0.0001), TIMI thrombus grade (P = 0.0001), and TIMI flow (P = 0.0001). Stent implantation did not significantly improve myocardial perfusion, TIMI thrombus grade, or TIMI flow, but improved TIMI frame count, minimal lumen, and reference vessel diameter. When compared to a historical STEMI control group not undergoing thrombus aspiration, our EXPORT population showed significant improvements in reperfusion parameters. In-hospital MACE were uncommon (4.5%) despite high-risk patient characteristics. CONCLUSIONS: Our study demonstrates that routine use of EXPORT catheter in patients with STEMI and coronary thrombosis is feasible, safe, and associated with significant improvements in flow-related angiographic parameters. The relative simplicity of this approach makes it an attractive option in this challenging situation.

Incidence, predictors, and outcomes of coronary dissections left untreated after drug-eluting stent implantation.

AIMS: Coronary dissections left untreated after percutaneous coronary intervention are associated with unfavourable outcomes. However, their role after drug-eluting stent (DES) implantation is still undescribed. We assessed incidence, predictors, and outcomes of residual dissections in DES-treated lesions. METHODS AND RESULTS: Consecutive patients undergoing DES implantation were enrolled in four Italian centres, with baseline, procedural, and outcome data entered into a dedicated database. Residual dissections were classified according to the National Heart Lung and Blood Institute criteria. End-points of interest were in-hospital, 1-month, and 6-month major adverse cardiovascular events (MACE, i.e. death, myocardial infarction, or target vessel revascularization), and stent thrombosis (ST). Among the 2418 included patients (4630 lesions), a total of 77 (1.7%) final dissections occurred in 67 (2.8%) subjects. Dissections were more frequent in longer and complex lesions and in the left anterior descending, and were associated with increased rates of in-hospital (11.9 vs. 5.2%, P=0.017) and 1-month MACE (13.4 vs. 6.0%, P=0.013), with similar 6-month trends. Cumulative ST was also greater in patients with dissections (6.3 vs. 1.3%, P=0.011). Even non-obstructive dissections with thrombolysis in myocardial infarction 3 flow conferred a significantly worse prognosis. CONCLUSION: This study, reporting for the first time on incidence, predictors, and outcomes of residual dissections in DES-treated coronary lesions, demonstrates their adverse clinical impact and supports the pursuit of a strategy of sealing dissection flaps with other DES.

Safety and efficacy of the AngioJet in patients with acute myocardial infarction: results from the Florence Appraisal Study of Rheolytic Thrombectomy (FAST).

OBJECTIVES: To assess the safety and efficacy of the AngioJet coronary device, given the uncertain risk-benefit balance of rheolytic thrombectomy in patients with acute myocardial infarction (AMI). BACKGROUND: Current risk of inadequate myocardial perfusion for thrombus embolization in primary coronary interventions is not negligible. The AngioJet thrombectomy device showed promising results in terms of safety and efficacy, but failed to confirm them in a large, multicenter, randomized trial, and the risk-benefit balance is still uncertain. METHODS: The AngioJet device was employed in 116 consecutive patients with AMI and angiographic evidence of extensive thrombosis in a vessel with a reference diameter > 2.5 mm. Stents and glycoprotein IIb/IIIa inhibitors were liberally used. Epicardial and myocardial reperfusion angiographic parameters, and in-hospital major adverse cardiac events (MACE, i.e., cardiac death, myocardial infarction, target vessel revascularization) were assessed. RESULTS: The AngioJet was successfully used in all patients. Angiographic analysis showed that the AngioJet significantly improved epicardial coronary flow (p < 0.01), frame count (p < 0.01) and myocardial blush (p < 0.01), while stenting yielded significant improvements only in diameter stenosis, minimum lesion diameter and correlated vessel parameters (p < 0.01). In-hospital MACE were uncommon [9 (8%)], despite the patientsO characteristics. When compared to an AMI population with similar thrombus burden but not undergoing thrombectomy, our AngioJet population showed significant improvement of reperfusion parameters. Moreover, there was greater AngioJet benefit in the high versus moderate thrombus burden subset; laboratory and operator experience also correlated significantly with final angiographic results. CONCLUSIONS: Our study supports the favorable risk-benefit profile of AngioJet device use in selected patients with AMI when used in experienced laboratories and by trained operators.

Validation of predictors of intraprocedural stent thrombosis in the drug-eluting stent era.

Although predictors of acute intraprocedural stent thrombosis (IPST) in the drug-eluting stent era have been proposed, external validation is lacking. We thus analyzed the occurrence of IPST in the RECIPE study and found that, among 1,320 patients who underwent drug-eluting stent implantation, IPST occurred in 6 (0.5%), with in-hospital major adverse events in 4 (67%). IPST was predicted by number and total length of implanted stents, baseline minimal lumen diameter, and, in a pooled analysis that incorporated values from the present study and a previous study, use of elective glycoprotein IIb/IIIa inhibitors. Such results may provide useful information to guide prevention of this complication.

Safety and efficacy of two types of influenza vaccination in heart transplant recipients: a prospective randomised controlled study.

BACKGROUND: Influenza may cause severe disease in immunosuppressed patients. Different vaccines have been proved to be efficacious to prevent influenza in tranplant recipients. Since the last five years the addition of adjuvants to improve the immune response to vaccine preparations has been proposed and evaluated. In this study, two antigenically identical vaccines, but different for the presence of adjuvants were randomised among a cohort of heart transplant recipients to evaluate their safety and immunogenicity. METHODS: 58 patients, receiving an heart transplant more than 6 months before, were randomised to receive one shoot vaccination with Fluad (containing the MF59 adjuvant) or Agrippal (no adjuvant added) or to enter the control, not-vaccinated, group. The immune response to influenza was evaluated separately for type A and type B viruses and for the IgG and the IgM antibodies. Patients were clinically evaluated at least monthly up to 6 months. RESULTS: Influenza symptoms were reported by 33% of patients receiving Fluad, 29% of the Agrippal and 63% of the control group. 4 episodes of acute myocardial rejection >/=3A were identified without difference between the three groups. CONCLUSIONS: The superior efficacy of vaccines containing adjuvants was not found and the data clearly confirmed that vaccination against influenza is safe and effective in heart transplant recipients. The use of vaccine containing adjuvant substances do not ameliorate the clinical performance of the immunisation suggesting that less expensive influenza vaccine preparation without adjuvant substances could be equally useful to protect heart transplant recipients.

Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study.

BACKGROUND: Transplant coronary artery disease (TxCAD) is a major cause of long-term mortality after heart transplantation. Although vascular remodeling has been implicated in the pathophysiology of TxCAD, its determinants remain unknown. METHODS: Twenty-nine consecutive heart-transplant recipients prospectively received intravascular ultrasound (IVUS) of the left-anterior descending artery 1 and 12 months after transplant, with volumetric reconstruction of the proximal 30 mm. RESULTS: Overall, patients exhibited intimal volume increase (+83%, P<0.001), wheras vessel volume remained largely unchanged (+4%, P=0.270); consequently, overall lumen volume decreased (-6%, P=0.058). Among the clinical and laboratory variables, cytomegalovirus (CMV) infection requiring treatment (occurring in 12 patients), as assessed by pp65 antigenemia, was independently associated with the impaired ability of the vessel wall to enlarge in response to intimal volume increase, ultimately resulting in lumen loss (OR [95% CI]=0.098 [0.010-0.920]; P=0.042). However, adequate vessel response to intimal hyperplasia with consequent lumen preservation was observed in the remaining 17 patients who did not present CMV infection requiring treatment. CONCLUSIONS: The present study demonstrates that either adequate or inadequate coronary remodeling may occur during the first year after transplantation. Moreover, for the first time, it strongly suggests that remodeling modalities may be negatively influenced by the occurrence of clinically relevant CMV infection. Randomized prospective trials are warranted to investigate whether aggressive treatment of CMV infection may help prevent TxCAD.