Novel Magnetic Resonance Imaging Tools for Hypertrophic Cardiomyopathy Risk Stratification.

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder with a well described risk of sudden cardiac death; however, risk stratification has remained a challenge. Recently, novel parameters in cardiac magnetic resonance imaging (CMR) have shown promise in helping to improve upon current risk stratification paradigms. In this manuscript, we have reviewed novel CMR risk markers and their utility in HCM. The results of the review showed that T1, extracellular volume, CMR feature tracking, and other miscellaneous novel CMR variables have the potential to improve sudden death risk stratification and may have additional roles in diagnosis and prognosis. The strengths and weaknesses of these imaging techniques, and their potential utility and implementation in HCM risk stratification are discussed.

Retrograde Revascularization of Tibial Arteries in Patients with Critical Limb Ischemia: Plantar-Arch Versus Transpedal Approach.

PURPOSE: To compare retrograde plantar-arch and transpedal-access approach for revascularization of below-the-knee (BTK) arteries in patients with critical limb ischemia (CLI) after a failed antegrade approach. MATERIALS AND METHODS: Retrospectively we identified 811 patients who underwent BTK revascularization between 1/2014 and 1/2020. In 115/811 patients (14.2%), antegrade revascularization of at least 1 tibial artery had failed. In 67/115 (58.3%), patients retrograde access to the target vessel was achieved via the femoral access and the plantar-arch (PLANTAR-group); and in 48/115 patients (41.7%) retrograde revascularization was performed by an additional retrograde puncture (TRANSPEDAL-group). Comorbidities, presence of calcification at pedal-plantar-loop/transpedal-access-site, and tibial-target-lesion was recorded. Endpoints were technical success (PLANTAR-group: crossing the plantar-arch; TRANSPEDAL-group: intravascular placement of the pedal access sheath), procedural success [residual stenosis <30% after plain old balloon angioplasty (POBA)], and procedural complications limb salvage and survival. Correlations between calcification at access site/tibial-target-lesion and technical/procedural-success were tested. RESULTS: Technical success was achieved in 50/67 (75%) patients of the PLANTAR-group and in 39/48 (81%) patients of the TRANSPEDAL-group (p=0.1). Procedural success was obtained in 23/67 (34%) patients of the PLANTAR-group and in 25/48 (52%) patients of the TRANSPEDAL-group (p=0.04). In 14/49 (29%) cases with calcification at the pedal-plantar loop, technical success was not achieved (p=0.04), and in 33/44 (75%) patients with calcification at the tibial-target-lesion, procedural success was not attained (PLANTAR-group) (p=0.026). In the TRANSPEDAL-group, correlations between calcification at access site/tibial-target-lesion and technical/procedural-success were not observed (p=0.2/p=0.4). In the PLANTAR-group, minor complications occurred in 13/67 (19%) and in the TRANSPEDAL-group in 4/48 patients (8%) (p=0.08). Limb salvage at 12 (18) months was 90% (82%) (PLANTAR-group; 95%CI 15.771-18.061) and 84% (76%) (TRANSPEDAL-group; 95%CI 14.475-17.823) (Log-rank p=0.46). Survival at 12 (18) months was 94% (86%) (PLANTAR-group; 95%CI 16.642-18.337) and 85% (77%) (TRANSPEDAL; 95%CI 14.296-17.621) (Log-rank p=0.098). CONCLUSION: Procedural success was significantly higher using the transpedal-access approach. Calcifications at pedal-plantar loop and target-lesion significantly influenced technical/procedural failure using the plantar-arch approach. No significant difference between both retrograde techniques in terms of feasibility, safety, and limb salvage/survival was found.

[Cryptogenic organizing pneumonia versus secondary organizing pneumonia]. / Kryptogen organisierende Pneumonie versus sekundäre organisierende Pneumonie.

Organizing pneumonia (OP) describes a histological pattern of acute or subacute lung damage. Clinically, patients present with cough, fever, and dyspnea. A distinction is made between idiopathic or cryptogenic organizing pneumonia (COP) and secondary organizing pneumonia (OP). In COP, neither clinical/radiological nor histological causes can be determined. It is classified as an interstitial idiopathic pneumonia (IIP) according to the criteria of the American Thoracic Society (ATS) and the European Respiratory Society (ERS). Secondary organizing pneumonia has a known triggering mechanism, such as infectious agents, certain medications, or concomitant symptoms of other primary pulmonary diseases and diseases of other organ systems. Common to both forms is the histological picture of intra-alveolar mesenchymal buds. These are myofibroblast proliferates that branch out along the alveolar spaces. They are usually accompanied by a moderate interstitial and alveolar, chronic, and macrophage-rich inflammatory cell infiltrate. The most important differential diagnosis is common interstitial pneumonia (UIP). It also shows fibroblast proliferates, which are, however, located in the interstitium. The correct classification of an IIP as a COP by means of clinical, radiological, and histological findings is essential, since the COP, in contrast to the UIP, responds very well to corticosteroids and therefore has an excellent prognosis compared to the UIP. The course of secondary organizing pneumonia depends on the respective underlying disease. Here it is important for the pathologist to correctly identify potential accompanying histological characteristics in order to be able to provide clues to a possible cause of OP.

Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine.

It has become practically impossible to survey the literature on cells derived from adipose tissue for regenerative medicine. The aim of this paper is to provide a comprehensive and translational understanding of the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) and its application in regenerative medicine. We provide profound basic and clinical evidence demonstrating that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue. ADRCs contain the same adult stem cells ubiquitously present in the walls of blood vessels that are able to differentiate into cells of all three germ layers. Of note, the specific isolation procedure used has a significant impact on the number and viability of cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to specifically isolate and separate stem cells from the initial mixture of progenitor and stem cells found in ADRCs. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for more than minimally manipulating, stimulating and/or (genetically) reprogramming the cells for a broad range of clinical applications. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use as defined by the regulatory authorities.

Unmodified autologous stem cells at point of care for chronic myocardial infarction.

BACKGROUND: Numerous studies investigated cell-based therapies for myocardial infarction (MI). The conflicting results of these studies have established the need for developing innovative approaches for applying cell-based therapy for MI. Experimental studies on animal models demonstrated the potential of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) for treating acute MI. In contrast, studies on the treatment of chronic MI (CMI; > 4 wk post-MI) with UA-ADRCs have not been published so far. Among several methods for delivering cells to the myocardium, retrograde delivery into a temporarily blocked coronary vein has recently been demonstrated as an effective option. AIM: To test the hypothesis that in experimentally-induced chronic myocardial infarction (CMI; > 4 wk post-MI) in pigs, retrograde delivery of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) into a temporarily blocked coronary vein improves cardiac function and structure. METHODS: The left anterior descending (LAD) coronary artery of pigs was blocked for 180 min at time point T0. Then, either 18 × 106 UA-ADRCs prepared at "point of care" or saline as control were retrogradely delivered via an over-the-wire balloon catheter placed in the temporarily blocked LAD vein 4 wk after T0 (T1). Effects of cells or saline were assessed by cardiac magnetic resonance (CMR) imaging, late gadolinium enhancement CMR imaging, and post mortem histologic analysis 10 wk after T0 (T2). RESULTS: Unlike the delivery of saline, delivery of UA-ADRCs demonstrated statistically significant improvements in cardiac function and structure at T2 compared to T1 (all values given as mean ± SE): Increased mean LVEF (UA-ADRCs group: 34.3% ± 2.9% at T1 vs 40.4 ± 2.6% at T2, P = 0.037; saline group: 37.8% ± 2.6% at T1 vs 36.2% ± 2.4% at T2, P > 0.999), increased mean cardiac output (UA-ADRCs group: 2.7 ± 0.2 L/min at T1 vs 3.8 ± 0.2 L/min at T2, P = 0.002; saline group: 3.4 ± 0.3 L/min at T1 vs 3.6 ± 0.3 L/min at T2, P = 0.798), increased mean mass of the left ventricle (UA-ADRCs group: 55.3 ± 5.0 g at T1 vs 71.3 ± 4.5 g at T2, P < 0.001; saline group: 63.2 ± 3.4 g at T1 vs 68.4 ± 4.0 g at T2, P = 0.321) and reduced mean relative amount of scar volume of the left ventricular wall (UA-ADRCs group: 20.9% ± 2.3% at T1 vs 16.6% ± 1.2% at T2, P = 0.042; saline group: 17.6% ± 1.4% at T1 vs 22.7% ± 1.8% at T2, P = 0.022). CONCLUSION: Retrograde cell delivery of UA-ADRCs in a porcine model for the study of CMI significantly improved myocardial function, increased myocardial mass and reduced the formation of scar tissue.