Acute mitral regurgitation is a heterogeneous and life-threatening pathology, with severe hemodynamic consequences and extremely adverse outcomes. Traditionally, the definitive treatment is prompt surgical intervention after hemodynamic stabilization. Nowadays, however, percutaneous repair of mitral valve with MitraClip device has emerged as a safe and effective therapeutic option. Evidences in this field are still scarce. Hereby, we report the case of an 82-year-old woman with lateral ST-elevation myocardial infarction determining severe acute mitral regurgitation (MR) with an asymmetric leaflet tethering mechanism. Due to prohibitive operative risk and unstable hemodynamic status, the patient underwent a successful urgent MitraClip procedure with optimal reduction of MR and immediate hemodynamic improvement. Moreover, we provide a review of the available literature regarding the echocardiographic assessment of acute MR, results of published cases and possible management of this complex pathology.
Percutaneous repair of mitral regurgitation (MR) with the MitraClip device (Abbott Vascular, Abbott Park, Illinois, USA) is an established therapeutic option for patients with prohibitive surgical risk and anatomically suitable mitral valve (MV)[
Hereby, we present a case of acute severe ischemic mitral regurgitation successfully treated with MitraClip procedure.
We report the case of an 82-year-old female patient, who presented to emergency department for chest pain lasting for 72 h. The EKG revealed a latecomer lateral ST-elevation myocardial infarction, with ST-depression in V1-V4, ST-elevation and q waves in V7-V9. She had a history of arterial hypertension, rheumatoid arthritis, thalassemia minor, and radiotherapy-treated tongue cancer.
A bedside echocardiogram showed a left ventricular ejection fraction (LVEF) of 40% due to akinesia of posterior and lateral walls, normal left ventricular and atrial dimensions, mild MR, normal right ventricular function and size. Urgent coronary angiography was performed and showed a flow-limiting stenosis in the proximal tract of a dominant circumflex coronary artery. The coronary lesion was treated with balloon angioplasty and implantation of two drug-eluting stents. A severe no-reflow followed and prompted the use of intraortic balloon pump (IABP) for hemodynamic stabilization and the intracoronary injection of nitroprusside and adrenaline. The patient was transferred to Coronary Care Unit and remained hemodynamically stable for the subsequent 24 h.
Then, a sudden hemodynamic collapse occurred, with pulmonary congestion and hypotension requiring intubation and high-dose vasopressors. Trans-thoracic and trans-esophageal echocardiogram (TEE) showed acute severe MR with eccentric jet directed towards the posterior wall of left atrium, due to extreme tethering of the posterior leaflet with partial posteromedial papillary muscle rupture and pseudoprolapse of the anterior leaflet
Baseline trans-esophageal echocardiogram showing partial postero-medial papillary muscle rupture (A, circle), extreme tethering of posterior leaflet with pseudoprolapse of anterior leaflet (B) and wide eccentric jet of severe mitral regurgitation mainly originating from A3-P3 (C, arrow) and extended to the medial section of A2-P2 (C, arrowhead)
The patient underwent an urgent percutaneous edge-to-edge procedure under general anaesthesia, with IABP and vasopressor support, and using fluoroscopic and TEE guidance. An XTR Clip was first implanted in A3-P3 position with residual moderate MR and mean gradients of 3 mmHg
Intraprocedural trans-esophageal echocardiogram of XTR clip implantation: A3-P3 grasping (A), residual moderate mitral regurgitation located laterally to the clip (B) and transmitral gradients (C)
Intraprocedural trans-esophageal echocardiogram of NTR clip implantation: A2-P2 grasping (A), residual minimal mitral regurgitation (B) and transmitral gradients (C)
The patient’s hemodynamics progressively improved, and she was successfully weaned off mechanical ventilation and pharmacological support. Her post-operative recovery was uncomplicated and the patient was discharged on the tenth post-procedural day with residual mild MR and mean gradients of 5 mmHg
Discharge trans-thoracic echocardiogram showing residual mild mitral regurgitation and mean gradient of 5 mmHg
Acute MR is a medical and surgical emergency. Indeed, differently from chronic valvular diseases, acute MR occurs suddenly in normal sized hearts, without time for adaptative left atrial and ventricular enlargement. This results in a rapid increase of left atrial pressure with consequent pulmonary congestion and, despite initial hyperdynamic ventricular contraction, a risk of progressive reduction of cardiac output with hypotension and peripheral hypoperfusion[
Timely diagnosis may be insidious, due to nonspecific clinical pattern and equalization of left ventricular and atrial pressures leading to a soft or absent murmur[
Traditional management involves medical stabilization and surgical intervention, with a timing strictly related to the specific etiology of valve dysfunction[
In the following sections, the main aspects of acute MR will be analysed with a focus on the amenability and use of percutaneous edge-to-edge repair technique in this condition.
Identifying the precise mechanism and cause of acute MV disease is fundamental to tailor the most appropriate therapeutic strategy for each patient. Acute MR counts few mechanisms and many possible causes, as detailed in
Classification of acute mitral regurgitation mechanisms and causes
Mechanism | Cause |
---|---|
Organic/structural damage | |
Carpentier type I (normal leaflet motion): perforation | Infective endocarditis
|
Carpentier type II (excessive leaflet motion): prolapse/flail (papillary muscle rupture, chordal rupture) | Infective endocarditis
|
Functional alteration | |
Carpentier type III (restricted leaflet motion): symmetric/asymmetric systolic restriction | Myocardial ischemia |
Carpentier type IV: systolic anterior motion of the leaflets | Hypertrophic cardiomyopathy
|
“Carpentier types” refer to expanded Carpentier classification[
One major organic cause is chordal rupture which may occur in an otherwise totally normal valve or in a MV affected by Barlow’s disease or fibroelastic deficiency.
Device-related MR is a rare yet possible complication of left ventricular mechanical support devices due to catheter impingement in the chordal apparatus or leaflet tissue[
Infective endocarditis can cause leaflet perforation and tears, papillary muscle and chordal rupture or may reduce systolic coaptation due to masses or abscesses interfering with leaflets’ apposition.
Extremely rare etiologies include chest traumas, systemic inflammatory diseases or acute rheumatic fever which remains a serious concern in endemic areas[
Ischemic papillary muscle rupture is another major cause of acute massive MR, with more frequent involvement of the posterior papillary muscle during inferior myocardial infarctions.
Acute myocardial ischemia or infarction may cause acute functional MR with systolic symmetrical or asymmetrical leaflet tethering, due to global or regional ventricular systolic dysfunction.
Another functional cause of MR is systolic anterior motion (SAM) of mitral leaflets in hypertrophic obstructive cardiomyopathy or Takotsubo cardiomyopathy[
Echocardiography is essential for diagnosis. As opposed to chronic MR, left atrial and ventricular sizes are usually normal in acute MR, except for preexisting conditions influencing chambers’ dimension, compliance and hemodynamic tolerance. For instance, patients with a history of chronic MR and preserved ventricular systolic function have enlarged cardiac volumes and tolerate the further volumetric increase better than patients with normal sized hearts or with preexisting reduced LVEF. Color Doppler may underestimate the severity of MR, owing either to rapid equalization of left atrial and ventricular pressures or to an eccentric direction of the regurgitant jet with “Coanda” effect. Consequently, the use of color Doppler-based quantitative measures such as regurgitant volume and effective regurgitant orifice area may be misleading and even challenging, due to severe acute congestive heart failure with tachycardia. Vena contracta width and continuous wave Doppler signal represent reliable semiquantitative tools to quickly evaluate the significance of MR. A triangular and dense continuous wave Doppler curve supports the diagnosis of acute MR. It mirrors the rapid decline in late systolic velocity as a consequence of the abrupt increase in left atrial pressure. Systolic pulmonary venous flow reversal in one or both pulmonary veins can be found but tachycardia or atrial fibrillation can mask these findings. Any measure or value should be interpreted in the clinical context, as patients with acute heart failure and acute MR may appear to have only moderate MR when assessed by semi-quantitative and quantitative methods. Indeed, an acute significant MR should be suspected in patients with a clinical pattern of acute heart failure, with evidence of hyperdynamic LV without systolic or diastolic dysfunction, and with anatomic imaging of MV lesions[
Trans-thoracic echocardiography is the first-line examination in the assessment of acute dyspnea, feasible at bedside and sufficient to raise the clinical suspicion, but often inconclusive regarding the identification of the mechanism of MR, the evaluation of the MV anatomy and preoperative planning, which all require TEE. As such, three-dimensional (3D) echocardiography should always be adopted, as it provides anatomical details not detectable with two-dimensional (2D) imaging, enabling a dynamic and comprehensive assessment of MV tissue, and seizes dataset for off-line multiplanar reconstructions[
The first step of echocardiographic evaluation of MR mechanism is the distinction between organic/structural damage and functional alteration of MV
A structural lesion with normal leaflet motion is generally due to a leaflet perforation. In this case, TEE should evaluate the position, shape and dimensions of the perforation, detect any sign suggestive of endocarditis, such as masses, vegetations or abscesses and explore mitral-aortic junction, left ventricular outflow tract and the position of other intracardiac devices. Indeed, an ambitious combined percutaneous procedure of MitraClip plus occluder would be contraindicated in the presence of active endocarditis, and an accurate preoperative planning should take into account the risk of iatrogenic obstruction of ventricular outflow or interference with proximally-located prostheses[
Leaflet flails and prolapse are categorised as Carpentier type II mechanism and occur through sudden rupture of chordae tendineae or papillary muscles due to many possible causes[
Papillary muscle rupture is a severe, albeit rare, mechanical complication of acute myocardial infarction. This anatomic lesion is challenging given the large flail width and flail gap with frequent commissural localization requiring an extensive grasping with a concomitant high risk of chordal entanglement[
Among functional alterations of MV, the main cause of acute MR is myocardial ischemia. Indeed, in the very acute phase of myocardial infarction, even modest valve tenting due to regional and/or global left ventricular dysfunction may result in hemodynamically-significant MR[
An infrequent cause of acute MR is SAM of mitral leaflet, which represents a life-threatening condition and may result also in critical left ventricular outflow tract obstruction. Hypertrophic obstructive cardiomyopathy is the main pathology associated with SAM and is characterized by abnormalities of MV and subvalvular apparatus, such as malpositioned papillary muscles, elongated chordae and thickened leaflets[
Finally, rheumatic heart disease is commonly regarded as a contraindication to MitraClip procedures, owing to high risk of mitral stenosis. However, a recently published case report has shown the feasibility of percutaneous MV repair in a rheumatic MV with baseline mean gradients inferior to 4 mmHg[
As outlined above, absolute anatomic limitations are very few. Hahn[
Real-world experience on percutaneous edge-to-edge repair of acute MR is uniquely derived from case reports and small-size registries, listed and synthetized in
Case reports and registries of MitraClip in patients with acute MR
Title | Ref. | Cause and mechanism of acute MR | Patients | Hemodynamic setting | Procedure and acute result | Early outcomes | Discharge | Follow-up |
---|---|---|---|---|---|---|---|---|
Case reports | ||||||||
Percutaneous mitral valve repair using the MitraClip in acute cardiogenic shock | Zuern |
Acute cardiogenic shock and MOF in ischemic cardiomyopathy (2 previous anterior wall myocardial infarctions) | 51-year-old male
|
Cardiogenic shock and MOF
|
1 clip (A2-P2)
|
Device success | Alive (postop day 7)
|
3-month
|
Successful Percutaneous Mitral Valve Repair with the MitraClip System of Acute Mitral Regurgitation due to Papillary Muscle Rupture as Complication of Acute Myocardial Infarction | Bilge |
Posterolateral STEMI, successful primary PCI of proximal circumflex artery with loss of marginal branch
|
60-year-old female
|
Pulmonary edema and cardiogenic shock
|
7 days after admission
|
Minor hemorrhagic stroke 2 days after MitraClip | Alive (postop day 9) | 30-day
|
MitraClip for Papillary Muscle Rupture in Patient With Cardiogenic Shock | Wolff |
Latecomer lateral STEMI, with occlusion of large first obtuse marginal artery
|
68-year-old male
|
Cardiogenic shock and ventricular arrhythmias
|
2 clips (A2-P2)
|
Device success | MR grade = 1-2+
|
3-month
|
MitraClip Implantation After Acute Ischemic Papillary Muscle Rupture in a Patient With Prolonged Cardiogenic Shock | Bahlmann |
Lateral NSTEMI
|
77-year-old male
|
Cardiogenic shock and pulmonary edema
|
3 clips
|
Device success | Alive (postop day 16) | - |
Percutaneous Mitral Valve Repair With Mitraclip System in a Patient With Acute Mitral Regurgitation After Myocardial Infarction | Rodríguez-Santamarta |
Inferolateral STEMI, successful primary PCI of proximal circumflex artery
|
76-year-old male
|
Pulmonary edema | 2 clips (A2-P2; lateral to the first one)
|
MR grade (4th day) = 1+ | Alive
|
NYHA I |
Effective Percutaneous “Edge-to-Edge” Mitral Valve Repair With MitraClip in a Patient With Acute Post-MI Regurgitation Not Related to Papillary Muscle Rupture | Tarsia |
Inferior STEMI, successful primary PCI of right coronary artery and marginal branch, complete revascularization of left anterior descending artery after 48 hours
|
65-year-old female
|
Cardiogenic shock and pulmonary edema
|
1 clip (A2-P2)
|
Device success
|
Alive (postop day 7) | 6-month
|
Acute Mitral Regurgitation Secondary to Papillary Muscle Tear Is Transcatheter Edge-to-Edge Mitral Valve Repair a New Paradigm? | Valle |
Inferior STEMI, successful primary PCI of saphenous vein graft to right coronary artery
|
84-year-old male
|
Cardiogenic shock and MOF
|
3 clips in a “zipper” approach
|
- | Alive | 6-week
|
Use of MitraClip for Postmyocardial Infarction Mitral Regurgitation Secondary to Papillary Muscle Dysfunction | Yasin |
Inferior NSTEMI
|
68-year-old male | Cardiogenic shock and pulmonary edema
|
5 day after admission
|
MR grade (3th day) = 1+
|
Alive | 30-day
|
Edge-to-edge mitral valve repair for acute mitral valve regurgitation due to papillary muscle rupture: a case report | Papadopoulos |
Anterior STEMI, successful primary PCI of intermediate artery
|
85-year-old female
|
Cardiogenic shock and pulmonary edema
|
2 clips (A2-P2, A1-P1) with a “zipping” of the lateral commissure
|
Device success | Alive (postop day 7) | 20-month
|
One-stop-shop totally percutaneous approach for severe aortic and mitral regurgitation in cardiogenic shock | Pagnotta |
Latecomer anterior STEMI, successful primary PCI of proximal right coronary artery and left circumflex artery (proximal left anterior descending artery occluded)
|
57-year-old male
|
Cardiogenic shock
|
1 XTR clip
|
- | Alive | 30-day
|
Successful MitraClip XTR for Torrential Mitral Regurgitation Secondary to Papillary Muscle Rupture as a Complication of Acute Myocardial Infarction | Villablanca |
Lateral NSTEMI, successful primary PCI of proximal and mid-circumflex artery
|
70-year-old male
|
Cardiogenic shock and pulmonary edema
|
1 XTR clip (A2-P2)
|
- | Alive (postop day 3) | 6-month
|
Transcatheter Mitral Valve Edge-to-Edge Repair with the New MitraClip XTR System for Acute Mitral Regurgitation Caused by Papillary Muscle Rupture | Komatsu |
Inferior STEMI, successful primary PCI of culprit single-vessel disease
|
55-year-old male
|
Pulmonary edema, cardiogenic shock and acute kidney injury
|
2 clip XTR (A2-P2)
|
- | Alive | 3-month
|
Case series or registries | ||||||||
Percutaneous Mitral Valve Repair for Acute Mitral Regurgitation After an Acute Myocardial Infarction | Estévez-Loureiro |
AMI without papillary muscle rupture:
2 STEMI 3 NSTEMI 8-12 days = 3 pts 33-49 = 2 pts |
N of patients = 5
|
Cardiogenic shock = 3
|
N of clips:
1 clip = 1 (20%) 2 clips = 3 (60%) 3 clips = 1 (20%) |
Device success = 5/5
|
Deaths = 1 (20%) (due to MOF 1 week after MitraClip) | Median follow-up = 317 days
I = 1 (20%) II = 3 (60%) 2+ = 2 (40%) 1+ = 2 (40%) |
Percutaneous edge-to-edge mitral valve repair for the treatment of acute mitral regurgitation complicating myocardial infarction: A single centre experience | Adamo |
AMI without papillary muscle rupture:
3 STEMI 2 NSTEMI |
N of patients = 5
|
Cardiogenic shock = 4
|
53 ± 33 days from admission
1 clip = 2 2 clips = 3 |
Device success = 5/5 | Deaths = 0 | 1 death due to non-cardiovascular causes 57 days after MitraClip
|
Percutaneous edge-to-edge mitral valve repair may rescue select patients in cardiogenic shock: findings from a single center case series | Flint |
Cardiogenic shock:
AMI = 3 acute papillary muscle rupture = 1 chordal rupture = 1 acute leaflet flail = 1 acute worsening of functional and degenerative MR = 1 acute worsening of functional MR = 1 |
N of patients = 12
|
Cardiogenic shock
|
N of clips = 2.3 ± 0.7
0 = 1 1+ = 8 2+ = 3 |
- | Death (6th day) = 1
|
Deaths = 4 (26-282 days) |
Salvage MitraClip in severe secondary mitral regurgitation complicating acute myocardial infarction: data from a multicentre international study | Haberman |
AMI within 90 days:
12 STEMI 8 NSTEMI 11 anterior 9 inferior-posterior |
N of patients = 20
|
Cardiogenic shock = 8
|
Days after MI = 32 (7-90)
|
Device success = 19/20
|
Death = 1 | Median follow-up = 15 months
|
Transcatheter mitral valve repair in patients with acute
|
Estévez-Loureiro |
STEMI
anterior = 10 (22.7%) inferior = 17 (38.6%) lateral = 10 (22.7%) undetermined = 2 (4.5%) 3+ = 4 (10.3%) 4+ = 35 (89.7%) A1-P1 = 3 (7.5%) A2-P2 = 36 (90%) A3-P3 = 6 (15%) |
N of patients = 44
|
Mechanical support
ECMO = 2 (4.5%) IABP = 14 (31.8%) |
Median n of clips = 2 (1-2)
|
Device success = 86.6%
|
- | 30-day
0/1+ = 31.1% 2+ = 41.4% 3+ = 17.2% 4+ = 10.3% I = 13.8% II = 62.1% III = 17.2% IV = 6.9% |
AMI: acute myocardial infarction; CI: cardiac index; CO: cardiac output; ECMO: extracorporeal membrane oxygenation; HF: heart failure; IABP: intraortic balloon pump; LAP: left atrial pressure; LV: left ventricular; LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVESD: left ventricular end-systolic diameter; MG: mean gradient; MOF: multiorgan failure; MR: mitral regurgitation; MV: mitral valve; N: number; NYHA: New York Heart Association; NSTEMI: non-ST-elevation myocardial infarction; PAP: pulmonary artery pressure; PCI: percutaneous coronary intervention; postop: post-operatory; sPAP: systolic pulmonary artery pressure; STEMI: ST-elevation myocardial infarction; STS: Society of Thoracic Surgery; TAPSE: tricuspid annular plane systolic excursion
The vast majority of cases occurred as complications of acute myocardial infarction, due to either ischemic leaflet tethering or papillary muscle ruptures (more often the posteromedial one). A primary PCI was always performed, except for late presentations due to the likely risk of reperfusion injury of already necrotic walls. The hemodynamic status was generally critical with evidence of cardiogenic shock and pulmonary edema requiring intubation, inotropes and mechanical support, mainly IABP and only in few cases veno-arterial extracorporeal membrane oxygenation. The Heart Team’s decision to proceed with MitraClip was primarily guided by the high surgical risk due to hemodynamic instability, acute/subacute ischemia, dual antiplatelet therapy, advanced age or comorbidities in a few cases, and the favourable risk-benefit balance of percutaneous edge-to-edge approach. Hemodynamic stabilization and likeliness of MR improvement with revascularization or medical therapy were the main determinants of the timing of procedure. One to three clips were deployed with an almost complete procedural success, due to significant reduction of MR, huge reduction of left atrial pressures and increase of cardiac output. Haberman
We propose a flow-chart that may be helpful for acute MR decision-making and management
Proposed flow-chart for acute MR decision-making and management. “Carpentier type” refers to Carpentier classification of MR mechanisms, as exposed in
Once acute MR is diagnosed, the initial goal is hemodynamic stabilization through inotropes/vasopressors and temporary mechanical circulatory supports (IABP, Impella and extracorporeal membrane oxygenation) in cases of cardiogenic shock, intravenous diuretic therapy and non-invasive/invasive ventilation for massive pulmonary edema with acute respiratory distress. Hypertensive or normotensive patients benefit from afterload reduction with intravenous vasodilator therapy, which reduces MR, diminishing pulmonary congestion and increases forward cardiac output[
Then, an accurate trans-esophageal echocardiographic characterization of acute MR is needed to tailor the subsequent actions. The finding of a Carpentier type I lesion, as a leaflet perforation, should lead to exclude an active acute endocarditis, which represents a contraindication for MitraClip procedure and an indication for cardiac surgery[
A Carpentier type II mechanism (leaflet prolapse/flail, rupture of chordae or papillary muscle) warrants a wide differential diagnosis between multiple potential causes. As already reported for Carpentier type I, active endocarditic processes should be excluded, as well. Myocardial ischemia or infarction may cause partial or complete rupture of a papillary muscle and could be targeted with medical therapy or percutaneous myocardial revascularization, before treating the MV lesion. A case-by-case judgement is fundamental and should consider the presence of ongoing myocardial ischemia, the timing of onset of myocardial infarction, the extension of coronary artery disease, the type of MV lesion (partial versus complete rupture), and the differential burden between ischemic and valvular diseases. Primary percutaneous coronary intervention for an ST-elevation myocardial infarction is always indicated, except for delayed infarctions without evidence of ongoing ischemia, as they would not yield significant benefits from revascularization and yet be complicated by reperfusion injury[
The observation of a Carpentier type III mechanism is related to regional or global LV systolic dysfunction. Medical therapy and percutaneous coronary intervention can acutely reduce the degree of ischemic MR, and an earlier reperfusion time is associated with greater reduction in MR severity[
A Carpentier type IV mechanism, namely a SAM of mitral leaflets, observed in hypertrophic and Takotsubo cardiomyopathies, represents an insidious cause of acute MR. Echocardiographic diagnosis is exceedingly important, as vasodilators, inotropes or IABP worsen the clinical and hemodynamic status. Beta-blockers, volume expansion, inotrope discontinuation, afterload augmentation with vasopressors and lastly mechanical circulatory supports (Impella and extracorporeal membrane oxygenation) are the weapons to turn to[
After the initial phases of echocardiographic diagnosis, hemodynamic stabilization, medical therapy implementation and eventually percutaneous coronary revascularization, it is time for Heart Team assessment. Interventionalists, cardiac surgeons, imagers, intensivists and heart failure specialists must meet to tailor the best therapeutic pathway, weighing all clinical and anatomical factors: age, comorbidities, hemodynamic status, response to medical therapy, MR mechanism, surgical risk, other surgical targets and single centre’s experience. In cases of low surgical risk, presence of an indication for concomitant cardiac surgery and organic MV disease, cardiac surgery is the first-choice treatment. Differently, in our opinion, MitraClip should be always attempted in a stepwise approach, as it is a safe procedure and does not preclude a delayed surgical intervention. Even in low-risk patients undergoing isolated MV surgery with a low probability of surgical repair, MitraClip may be attempted, above all in high-volume centers. Eligibility for percutaneous edge-to-edge procedure requires only three conditions: possibility to grasp and approximate the leaflets, low risk of MV stenosis, and good-quality TEE imaging[
Acute MR is a life-threatening condition, traditionally treated as a medical and surgical emergency. Percutaneous edge-to-edge repair of MV is a safe and effective therapeutic option, does not preclude delayed cardiac surgery and is potentially able to solve almost any type of MV disease, with very few contraindications. Echocardiographic identification of the precise valvular lesion and Heart Team evaluation are pivotal to tailor the best therapeutic pathway for each patient. Literature confirms optimal results of MitraClip in acute MR, but further studies are warranted to shed light on feasibility and limitations of this powerful procedure.
Involved in clinical care: Sanz-Sánchez J, Chiarito M, Briani M, Fazzari F, Corrada E, Bragato RM, Pagnotta PA, Regazzoli D
Wrote the manuscript: Cannata F, Regazzoli D
Supervised and coordinated all aspects of the research: Stefanini GG, Reimers B
Contributed to critical revision of the manuscript and approved the final version of the manuscript: Cannata F, Sanz-Sánchez J, Chiarito M, Briani M, Fazzari F, Bertoldi LF, Ferrante G, Corrada E, Bragato RM, Stefanini GG, Pagnotta PA, Reimers B, Regazzoli D
Not applicable.
None.
All authors declared that there are no conflicts of interest.
Not applicable.
A written informed consent for publication was obtained.
© The Author(s) 2020.