Rationale : New therapies for refractory angina are needed. Objective : Assessment of transendocardial delivery of bone marrow CD133 ⁺ cells in patients with refractory angina. Methods and Results : Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P =0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P =0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P =0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P =0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P =0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P =0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P =0.68), 4 (50% versus 33.3%; P =0.63), 6 (70% versus 50.0%; P =0.42), and 12 months (55.6% versus 81.8%; P =0.33) and use of nitrates after 12 months. Conclusion : Transendocardial CD133 ⁺ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01660581.

Oscillometry has been around for almost 70 years, but there are still many unknowns. The test is performed during tidal breathing and is therefore free from patient-dependent factors that could influence the results. The Forced Oscillation Technique (FOT), which requires minimal patient cooperation, is gaining ground, particularly with elderly patients and children. In pulmonology, it is a valuable tool for assessing obstructive conditions (with a distinction between central and peripheral obstruction) and restrictive disorders (intrapulmonary and extrapulmonary). Its sensitivity allows the assessment of bronchodilator and bronchoconstrictor responses. Different lung diseases show different patterns of changes in FOT, especially studied in asthma and chronic obstructive pulmonary disease. Because of these differences, many studies have analysed the usefulness of this technique in different areas of medicine. In this paper, the authors would like to present the basics of oscillometry with the areas of its most recent clinical applications.

Background:The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina. Methods:Thirty-one patients (63.0 +/- 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (>= one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment. Results:The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period. Conclusions:Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

Chronic periodontitis (CP) is associated with cardiovascular disease and mortality in different populations. The aim of this study was to examine an association of CP with hard endpoints in patients after kidney transplantation during a 15-year follow-up period. Study group consist of 117 patients (77M/40F, median age 44 years) divided into two subgroups: those with initially advanced CP (CPITN 3–4) and those with no or moderate CP (CPITN 0–2). All cardiovascular events, graft losses, and re-transplantations were recorded. All deaths were noted and verified, including those occurred after the return to dialysis therapy, the causes of death were identified. Cox regression with Firth’s penalized maximum likelihood models were used for data analysis. During the observation period, 49 deaths occurred. Advanced CP (n = 35) was not associated with overall mortality but was associated with increased risk of death with functioning graft (DWFG) [HR 3.54 (1.20–10.45); p < 0.05]. Risk of graft loss was not associated with CP status. In conclusion, an advanced CP was independently associated with increased risk of DWFG, but not all-cause or cardiovascular mortality after renal transplantation.

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. For developing new therapies, a better understanding of the underlying pathology is required. Historically, such insights have been primarily derived from pathological studies. In the 21st century, thanks to the advent of cardiovascular positron emission tomography (PET), which depicts the presence and activity of pathophysiological processes, it is now feasible to assess disease activity in vivo. By targeting distinct biological pathways, PET elucidates the activity of the processes which drive disease progression, adverse outcomes or, on the contrary, those that can be considered as a healing response. Given the insights provided by PET, this non-invasive imaging technology lends itself to the development of new therapies, providing a hope for the emergence of strategies that could have a profound impact on patient outcomes. In this narrative review, we discuss recent advances in cardiovascular PET imaging which have greatly advanced our understanding of atherosclerosis, ischemia, infection, adverse myocardial remodeling and degenerative valvular heart disease.