Myocardial injury in patients with SARS-CoV-2 pneumonia: Pivotal role of inflammation in COVID-19.

AIMS: Infection by SARS-CoV-2 may result in a systemic disease and a proportion of patients ranging 15%-44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID-19 in order to identify predisposing and/or protective factors of CI and the outcome. METHODS AND RESULTS: This is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID-19 and at least one high-sensitivity cardiac troponin (hs-cTnt) measurement during hospitalization. CI was defined if at least one hs-cTnt value was above the 99th percentile. The primary end-point was the occurrence of CI during hospitalization. We included 750 patients (median age 67, IQR 56-77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34-147 ng/l) were detected in 390 patients (52%) during the hospitalization. At multivariable analysis age, CKD, cancer, C-reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all-cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI. CONCLUSION: This large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID-19, highlighting the leading role of systemic inflammation for the occurrence of CI.

Pulmonary embolism in patients with COVID-19 pneumonia on adequate oral anticoagulation.

Thrombotic complications are common in patients with severe COVID-19 pneumonia with important consequences on the diagnostic and therapeutic management. We report a consecutive series of five patients on long-term oral anticoagulation therapy who presented to our hospital for severe COVID-19 pneumonia associated with segmental acute pulmonary embolism despite adherence to therapy and with an adequate anticoagulant range at the time of the event. Four patients were receiving a direct oral anticoagulant (two with edoxaban, one with rivaroxaban and one with apixaban) and one patient a vitamin K antagonist. No significant thrombotic risk factors, active cancer, or detectable venous thromboembolism were present. In all cases, elevated d-dimer and fibrinogen levels with a parallel rise in markers of inflammation were documented. The combination of these findings seems to support the hypothesis that considers the local vascular damage determined by severe viral infection as the main trigger of thrombi detected in the lungs, rather than emboli from peripheral veins.

Effects on QT interval of hydroxychloroquine associated with ritonavir/darunavir or azithromycin in patients with SARS-CoV-2 infection.

INTRODUCTION: Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc). OBJECTIVE: To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals. METHODS: At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group). RESULTS: A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia. CONCLUSION: Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.

Ventricular tachycardia triggered by pregnancy in left-ventricular non-compaction cardiomyopathy: a controversial indication to automated defibrillator implantation.

Left-ventricular non-compaction (LVNC) is a rare form of cardiomyopathy. Its clinical presentation is highly variable and during pregnancy is frequently associated with heart failure, embolic events, and arrhythmias. Herein we report a case of a woman with left ventricular non-compaction who had an automated defibrillator implantation for recurrent ventricular arrhythmias during pregnancy. During pregnancy and at long-term follow-up no interventions of the device were documented. In conclusion, the management of malignant arrhythmias during pregnancy is one of the concerns for patients with LVNC and requires a careful approach in third-level centers.

Spontaneous pneumomediastinum in COVID-19 pneumonia.

Spontaneous pneumomediastinum is a benign entity but can worsen the underlying condition with which it is associated. We evaluated the incidence and the clinical relevance of spontaneous pneumomediastinum in a consecutive series of 102 patients with COVID-19 pneumonia. Six cases of pneumomediastinum were identified by high-resolution chest CT-scan. Three patients required early intubation, and one of them died, while in in the remaining subjects the clinical course was benign. The presence of pneumomediastinum required some changes in the management of mechanical ventilation. In conclusion, spontaneous pneumomediastinum is a possible complication of severe COVID-19 pneumonia that can affect patient management and clinical outcomes.

Third generation drug eluting stent (DES) with biodegradable polymer in diabetic patients: 5 years follow-up.

OBJECTIVE: To report the long-term safety and efficacy data of a third generation drug eluting stent (DES) with biodegradable polymer in the complex patient population of diabetes mellitus after a follow-up period of 5 years. BACKGROUND: After percutaneous coronary intervention patients with diabetes mellitus are under higher risk of death, restenosis and stent thrombosis (ST) compared to non-diabetic patients. METHODS: In 126 centers worldwide 3067 patients were enrolled in the NOBORI 2 registry, 888 patients suffered from diabetes mellitus (DM), 213 of them (14%) being insulin dependent (IDDM). Five years follow-up has been completed in this study. RESULTS: At 5 years, 89.3% of the patients were available for follow-up. The reported target lesion failure (TLF) rates at 5 years were 12.39% in DM group and 7.34% in non-DM group; (p < 0.0001). In the DM group, the TLF rate in patients with IDDM was significantly higher than in the non-IDDM subgroup (17.84 vs. 10.67%; p < 0.01). The rate of ST at 5 years was not different among diabetic versus non-diabetic patients or IDDM versus NIDDM. Only 10 (<0.4%) very late stent thrombotic events beyond 12 months occurred. CONCLUSIONS: The Nobori DES performed well in patients with DM. As expected patients with DM, particularly those with IDDM, had worse outcomes. However, the very low rate of very late stent thrombosis in IDDM patients might have significant clinical value in the treatment of these patients. Clinical trial registration ISRCTN81649913; http://www.controlled-trials.com/isrctn/search.html?srch=81649913&sort=3&dir=desc&max=10.

The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence.

The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES.

Does optimal lesion preparation reduce the amount of acute recoil of the Absorbe BVS? Insights from a real-world population.

OBJECTIVES: To evaluate the acute recoil of the ABSORB bioabsorbable vascular scaffold (BVS) and its relationship with procedural characteristics in a real world population. BACKGROUND: In vivo acute recoil of the BVS was evaluated in selected patients. METHODS: Acute recoil was studied with videodensitometry in a consecutive series of patients treated by means of a BVS, and the results were compared with those obtained in subjects receiving an everolimus-eluting stent (EES). Recoil was defined as the difference between the mean diameter of the fully expanded balloon on which the device was mounted (or the mean diameter of the post-dilatation balloon), and the mean luminal diameter of the treated segment immediately after the final inflation. RESULTS: Recoil was assessed in 106 lesions treated with a BVS and 71 treated with an EES. The absolute and percent recoil of the BVS were significantly greater (0.32 ± 0.16 mm and 10% ± 5% vs. 0.17 ± 0.07 and 5% ± 3%; P < 0.001). Multiple regression analysis showed that BVS use was associated with acute recoil (ß = 0.477; P<0.001). Suboptimal lesion preparation (residual stenosis after balloon angioplasty >20%) (ß = 0.217; P = 0.027) and a small vessel reference diameter (ß = 0.335; P = 0.002) were associated with increased BVS but not EES recoil. CONCLUSIONS: In unselected patients, the acute recoil of the BVS was significantly greater than that of the metal EES. In the BVS group, residual stenosis after predilatation correlated with percent recoil, and so optimal lesion preparation seems to be mandatory in order to maximize the mechanical properties of the scaffold.

Cobalt-chromium KAname™ coRonary stEnt system in the treatment of patients with coronary artery disease (KARE study).

OBJECTIVES: To evaluate the safety and effectiveness of the Kaname™ cobalt-chromium (Co-Cr), thin strut, bare metal stent (BMS) system for the treatment of coronary artery lesions. BACKGROUND: Despite widespread use of drug-eluting stents, a certain percentage of patients with coronary artery disease are still treated with BMS. Therefore, it is essential to evaluate their clinical performance. METHODS: Two hundred eighty-two patients were enrolled in this prospective, single-arm study including a predefined subset of 79 patients with small vessels. The primary end-point was freedom from target vessel failure (TVF) at 6 months. Key angiographic and intravascular ultrasound (IVUS) end-points were late loss, diameter stenosis, binary restenosis, and neointimal hyperplasia volume. RESULTS: Freedom from TVF at 6 months was 93.3% and at 1 year 90.8% in total population, and 92.4% and 87.3% in small vessels, respectively. Clinically driven target lesion revascularization (TLR) rates at 6 and 12 months were 4.3% and 6.4% in total population, and 3.8% and 7.6% in small vessels, respectively. At 6 months in-stent late loss was 0.75 ± 0.43 mm and binary restenosis rate was 16.9% in total population, and 0.64 ± 0.40 mm and 26.1% in small vessels, while IVUS assessed neointimal hyperplasia volume at 6 months was 128.9 ± 42.6 mm(3) for total population. There were no definite and probable stent thromboses up to 12 months. CONCLUSIONS: Results indicate good safety and effectiveness of the Kaname™ stent with clinically equivalent results in small and larger vessels, as such providing useful treatment option for patients with ischemic heart disease considered for BMS implantation.

Nobori biolimus-eluting stent vs. permanent polymer drug-eluting stents in patients undergoing percutaneous coronary intervention.

BACKGROUND: Permanent polymer coatings on drug-eluting stents (DES) surface have been identified as triggers of adverse events following percutaneous coronary intervention (PCI). However, efficacy and safety data for the Nobori biolimus-eluting stent (BES), a biodegradable polymer DES, are limited, so the aim of this study was to evaluate clinical outcomes associated with the Nobori BES compared with permanent polymer DES in patients undergoing PCI. METHODS AND RESULTS: Randomized trials comparing Nobori BES vs. other DES were included in the meta-analysis. The 12-month clinical endpoints were: target lesion revascularization (TLR), all-cause mortality, myocardial infarction (MI) and stent thrombosis (ST). Seven trials totaling 12,090 PCI patients met the inclusion criteria. Nobori BES vs. other DES had a comparable risk of TLR (odds ratio [OR] 0.94; 95% confidence interval [CI], 0.66-1.34; P=0.74), mortality (OR 1.00; 95% CI, 0.78-1.28; P=0.98), MI (OR 1.10; 95% CI, 0.87-1.40; P=0.42) and definite/probable ST (OR 1.01; 95% CI, 0.45-2.25; P=0.99). Despite Nobori BES showing similar clinical results to sirolimus-, everolimus- and zotarolimus-eluting stents, it was superior to paclitaxel-eluting stents in reducing the risk of TLR (OR 0.31; 95% CI, 0.10-0.90; P=0.03)CONCLUSIONS:Nobori BES use is associated with a similar safety and efficacy as permanent polymer DES at 1-year follow-up, albeit it is superior to paclitaxel-eluting stents in terms of TLR. Long-term follow-up data are needed in order to establish whether polymer degradation related to Nobori BES implantation improves clinical outcomes.

Long-term follow-up of coronary venous bypass graft lesions treated with a new generation drug-eluting stent with bioabsorbable polymer.

BACKGROUND: To date, no published data are available regarding long-term follow-up of new generation DES implanted in coronary artery bypass graft (CABG) lesions. OBJECTIVES: To assess the long-term clinical outcome of patients receiving the new generation Biolimus A9-coated drug-eluting stent (DES) with biodegradable polymer in saphenous vein grafts (SVG). METHODS: Three thousand sixty-seven patients were included in the NOBORI 2 registry: 71 patients with a total of 117 lesions received at least 1 biolimus A9 DES in SVG lesions and 2,959 patients received percutaneous coronary intervention in other lesions. Clinical follow-up was performed at 1, 6, and 12 months, and annually up to 3 years. RESULTS: Compared to the non-CABG group, patients with CABG lesions were older (P < 0.001), had a higher Charlson Comorbidity Index (P = 0.004), and presented more often with acute coronary syndrome (P = 0.02). At 3-year follow-up, cardiac death occurred in 9.7% versus 2.1% (P < 0.001), myocardial infarction (MI) in 8.3% versus 3.0% (P = 0.02), target lesion failure in 13.9% versus 6.4% (P = 0.03), and major adverse cardiac event in 18.1% versus 8.6% (P = 0.01). No differences were observed in TV-MI and TLR, nor stent thrombosis (ST) which was generally low in both groups (1.4% vs 0.8%, P = NS). CONCLUSION: Albeit 3-year outcomes were less favorable in the CABG group, the higher cardiac mortality was apparently not driven by ST, target vessel MI, or TLR, but is likely due to advanced disease and age as well as comorbidity. The low TLR rate as well as the absence of late and very late ST suggest that BES are safe and effective for the treatment of CABG lesions.

Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis.

A 62-year-old woman with multiple myeloma and light-chain amyloidosis with significant heart involvement developed an in-hospital cardiac arrest. After cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage was restored, and the patient was admitted to the coronary care unit. A cardioverter-defibrillator was implanted, and it successfully intervened in two sustained ventricular tachycardia episodes and one ventricular fibrillation episode, which were recorded during hospitalization. After achieving discrete cardiac compensation, the patient was transferred to the emergency medicine department where she underwent chemotherapy for multiple myeloma. The patient died 40 days after admission from refractory heart failure. In the literature, there are studies that describe the use of cardioverter-defibrillator implantation in cardiac amyloidosis; however, at present, there is no evidence of a beneficial effect on survival with the use of this intervention. A high index of suspicion for amyloid heart disease and early diagnosis are critical to improving outcomes.

The Incidence and Impact of In-Hospital Bleeding in Patients with Acute Coronary Syndrome during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). AIM: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. METHODS: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March-April 2020) and in the same period in the previous two years. RESULTS: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. CONCLUSIONS: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients.

Combined Role of Troponin and Natriuretic Peptides Measurements in Patients With Covid-19 (from the Cardio-COVID-Italy Multicenter Study).

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs' cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.