Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers.

BACKGROUND: Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection. METHODS: We conducted a prospective, non-controlled, observational study on no-option CLTI diabetic patients that underwent intramuscular PB-MNCs therapy, which consisted of more cell treatments repeated a maximum of three times. The primary endpoint was amputation rate at 1 year following the first treatment with PB-MNCs. We evaluated ulcer healing, walking capability, and mortality during the follow-up period. We assessed angiogenic cells and EVs at baseline and after each cell treatment, according to primary outcome and tissue perfusion at the last treatment [measured as transcutaneous oxygen pressure (TcPO2)]. RESULTS: 50 patients were consecutively enrolled and the primary endpoint was 16%. TcPO2 increased after PB-MNCs therapy (17.2 ± 11.6 vs 39.1 ± 21.8 mmHg, p < .0001), and ulcers healed with back-to-walk were observed in 60% of the study population (88% of survivors) during follow-up (median 1.5 years). Patients with a high level of TcPO2 (≥ 40 mmHg) after the last treatment showed a high frequency of small EVs at enrollment. CONCLUSIONS: In no-option CLTI diabetic patients, PB-MNCs therapy led to an improvement in tissue perfusion, a high rate of healing, and back-to-walk. Coupling circulating cellular markers of angiogenesis could help in the identification of patients with a better clinical benefit over time.

Coronary physiology thresholds associated with microvascular obstruction in myocardial infarction.

OBJECTIVES: To ascertain whether invasive assessment of coronary physiology soon after recanalisation of the culprit artery by primary percutaneous coronary intervention is associated with the development of microvascular obstruction by cardiac magnetic resonance in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Between November 2020 and December 2021, 102 consecutive patients were prospectively enrolled in five tertiary centres in Italy. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the culprit vessel soon after successful primary percutaneous coronary intervention. Optimal cut-off points of IMR and CFR to predict the presence of microvascular obstruction were estimated, stratifying the population accordingly in four groups. A comparison with previously proposed stratification models was carried out. RESULTS: IMR>31 units and CFR≤1.25 yielded the best accuracy. Patients with IMR>31 and CFR≤1.25 exhibited higher microvascular obstruction prevalence (83% vs 38%, p<0.001) and lower left ventricular ejection fraction (45±9% vs 52±9%, p=0.043) compared with those with IMR≤31 and CFR>1.25, and lower left ventricular ejection fraction compared with patients with CFR≤1.25 and IMR≤31 (45±9% vs 54±7%, p=0.025). Infarct size and area at risk were larger in the former, compared with other groups. CONCLUSIONS: IMR and CFR are associated with the presence of microvascular obstruction in STEMI. Patients with an IMR>31 units and a CFR≤1.25 have higher prevalence of microvascular obstruction, lower left ventricular ejection fraction, larger infarct size and area at risk. TRIAL REGISTRATION NUMBER: NCT04677257.

Cardiac magnetic resonance predictors of left ventricular remodelling following acute ST elevation myocardial infarction: The VavirimS study.

BACKGROUND: Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI. METHODS AND RESULTS: patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REMEDV)]; LV-REM by end-systolic volume index increase ≥12% (LV-REMESV) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REMEDV and LV-REMESV were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REMEDV, whilst it decreased in those with LV-REMESV (p < 0.001 for interaction). Considering predictors of LV-REM, IS in the highest tertile was clearly separated from the two lower tertiles. In LV-REMEDV, the highest tertile was associated with significantly higher LV-EDV, LV-ESV, and lower EF. CONCLUSIONS: In a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REMEDV was lower than previously reported. Importantly, our data indicate that LV-REMEDV might not be "adverse" per se, but rather "compensatory", being associated with LV-EF improvement at follow-up. Conversely, LV-REMESV might be an "adverse" phenomenon associated with decreased LV-EF, driven by IS.

Circulating CD4+CD25hiCD127lo regulatory T-Cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis.

OBJECTIVE: Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries. METHODS AND RESULTS: We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3(+)CD4(+)CD25(high)CD127(low)) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (n=65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients). CONCLUSIONS: The results suggest that determination of circulating Treg-cell levels based on flow cytometry or mRNA assessment is not a useful indicator of the extent or severity of atherosclerosis.

Chimney Stenting for Coronary Occlusion During TAVR: Insights From the Chimney Registry.

OBJECTIVES: The aim of this study was to determine the safety and efficacy of chimney stenting, a bailout technique to treat coronary artery occlusion (CAO). BACKGROUND: CAO during transcatheter aortic valve replacement (TAVR) is a rare but often fatal complication. METHODS: In the international Chimney Registry, patient and procedural characteristics and data on outcomes are retrospectively collected from patients who underwent chimney stenting during TAVR. RESULTS: To date, 16 centers have contributed 60 cases among 12,800 TAVR procedures (0.5%). Chimney stenting was performed for 2 reasons: 1) due to the development of an established CAO (n = 25 [41.6%]); or 2) due to an impending CAO (n = 35 [58.3%]). The majority of cases (92.9%) had 1 or more classical risk factors for CAO. Upfront coronary protection was performed in 44 patients (73.3%). Procedural and in-hospital mortality occurred in 1 and 2 patients, respectively. Myocardial infarction (52.0% vs. 0.0%; p < 0.01), cardiogenic shock (52.0% vs. 2.9%; p < 0.01), and resuscitation (44.0% vs. 2.9%; p < 0.01) all occurred more frequently in patients with established CAO compared with those with impending CAO. The absence of upfront coronary protection was the sole independent risk factor for the combined endpoint of death, cardiogenic shock, or myocardial infarction. During a median follow-up time of 612 days (interquartile range: 405 to 842 days), 2 cases of stent failure were reported (1 in-stent restenosis, 1 possible late stent thrombosis) after 157 and 374 days. CONCLUSIONS: Chimney stenting appears to be an acceptable bailout technique for CAO, with higher event rates among those with established CAO and among those without upfront coronary protection.

Sirolimus-eluting and paclitaxel-eluting stents for the treatment of coronary bifurcations.

BACKGROUND: The aim of the study was to compare the outcomes of sirolimus-eluting (SES) and paclitaxel-eluting (PES) stent implantation in coronary bifurcations treated with either a 1-stent or 2-stent strategy. METHODS: The study used a retrospective cohort analysis of consecutive de novo bifurcations, excluding left main, treated with SES or PES between April 2003 and June 2005. RESULTS: We identified 170 bifurcations in 161 patients treated with SES and 119 bifurcations in 112 patients treated with PES. During a median follow-up of 1,061 days (interquartile range 814-1,314), 43 patients (26.7%) in the SES group and 28 (25.0%) in the PES group had a major adverse cardiac event (P = .78). The angiographic restenosis rate per bifurcation was 20.9% and 25.9%, respectively (P = .41). There was no difference overall in the occurrence of target lesion revascularization (TLR) per bifurcation, 22 with SES (12.9%) and 18 with PES (15.1%), P = .61. The TLR rate was similar for SES and PES in bifurcations treated with 1 stent (6.7% vs 11.4%, P = .40) and in bifurcations treated with both branch stenting (20.0% vs 20.4%, P =1.0). CONCLUSIONS: In this cohort, the long-term clinical outcomes appear similar overall between SES and PES in the treatment of coronary bifurcations irrespective of whether a 1-stent or 2-stent strategy was used.

Percutaneous coronary intervention in patients with a single remaining vessel.

Percutaneous coronary intervention in a patient's last remaining coronary conduit is perceived to be high risk, although there are no published data on outcomes in this lesion cohort. We report our experience with 16 patients who underwent intervention in their sole remaining vessel between 1998 and 2005. All patients had previously undergone coronary artery bypass grafting, had a history of myocardial infarction, had impaired left ventricular systolic function, and were symptomatic with unstable angina or minimal effort angina. There was 1 periprocedural death 10 hours after the procedure, and another patient died 4 months after the procedure. At 6-month follow-up, 2 patients had undergone target lesion revascularization. There was a significant and sustained improvement in symptom status, with 75% of patients being asymptomatic or in Canadian Cardiovascular Society class I after 6 months. Given the complexity of the patients and lesions treated in this cohort, periprocedural and long-term outcomes are acceptable with a notable improvement in symptomatic status. In conclusion, these data support percutaneous intervention as a realistic treatment option for this often highly symptomatic and difficult-to-treat patient cohort.

Comparison of SFA lesion treatment with Zilver PTX in diabetics vs. non-diabetics: 2-year clinical and functional results.

BACKGROUND: Prospective single-arm study, aimed at evaluating safety and effectiveness at 12 and 24 months of the paclitaxel-eluting nitinol stent (Zilver PTX), and focused in particular on the treatment of complex lesions and/or diabetic patients. METHODS: Between May 2010 and March 2012, 67 patients (78% males) were treated by Zilver PTX, because of stenosis or occlusions of the superficial femoral artery in one of two centers. The mean age of patients was 70.1±8 years. Thirty-two of 67 (48%) were diabetics, 14 (21%) active smokers and 11 (14.6%) had chronic renal failure (end stage renal disease). The average length of lesions was 104±60 mm. Occlusion was complete in 46.3% of cases, whereas severely calcified lesions were present in 30% of patients (18.8% in diabetics and 31.4% in non-diabetics). Twenty-six patients (39%) had type C or D lesions according to TASC 2. RESULTS: One hundred-two stents were used (1.7±0.9 per patients); median 1 (range 1-4). All patients had successful stent placement. Primary patency, evaluated by Kaplan-Meier method was 88±0.06% at 12 months, and 68±0.1% at 24 months. In particular, the difference between diabetics (D) and non-diabetics (non-D) was not significant (P=0.07, Log-Rank). Patients turned from 4.2±1.3 to 1.6±1.3 Rutherford class. There were 5 deaths due to systemic comorbidities. There also were 3 major amputations, all of them also in the D group. Among the other patients, differences between D and non-D patients were not significant in terms of wound healing, bipedal stay and spontaneous ambulation. The mean follow-up length was 28±5 months (range 24-36 months). There was only one patient who had fracture and stent migration (1.5%). In 13 diabetic patients, tibial PTA was also associated. Additional treatment was required in 6 D and 1 non-D. CONCLUSIONS: The use of Zilver PTX is safe and effective in the treatment of SFA lesions. In particular, both stent patency and functional results on the basis of both clinical and instrumental tools were similar in D and non-D, suggesting a particularly favorable activity of PTX in a subpopulation of diabetics. Further studies are required to confirm these results, which seem to be particularly promising in diabetic patients.

Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients.

OBJECTIVE: Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS: We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group). RESULTS: GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 +/- 3.5% at baseline to 74.9 +/- 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 +/- 0.25 to 4.20 +/- 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 +/- 4.9 to 44.6 +/- 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 +/- 8.3 to 57.2 +/- 4.6 ms, P < 0.05) with higher erythrocytes Na(+)-K(+)-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness. CONCLUSIONS: Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft.

Transcatheter CoreValve implantation for aortic regurgitation in a Jehovah's witness with prior aortic dissection.

Indications for transcatheter valve implantation have been extended to treat native valve aortic regurgitation in case of disproportionate risk for open surgery. Transcatheter aortic valves are also an attractive alternative in patients who refuse blood transfusions. We report the successful off-label implantation of a self-expandable transcatheter valve in a Jehovah's Witness with prior replacement of the ascending aorta for Type A dissection, residual severe aortic regurgitation and refractory heart failure.

Effectiveness of treatment of in-stent restenosis with an 8-French compatible atherectomy catheter.

The study reports the results of directional atherectomy with an 8Fr guiding catheter-compatible atherectomy catheter in a series of 31 in-stent restenotic lesions. This preliminary experience indicates a favorable safety profile, with events limited to non-Q-wave myocardial infarction occurring in 3.6% of patients. The secondary end point regarding the incidence of angiographic restenosis at 6 months showed a high restenosis rate (65%).

Comparison of diamond-like carbon-coated stents versus uncoated stainless steel stents in coronary artery disease.

Stainless steel (SS) and carbon-coated (CC) stents were randomly compared in 347 patients (520 lesions). No differences were observed in in-hospital major adverse cardiac events: 2.8% in the CC group and 4.5% in the SS group (p = 0.286). The 6-month follow-up showed similar rates of binary restenosis (31.8% in the CC group vs 35.9% in the SS group; p = 0.448) and of cumulative major adverse cardiac events (30.5% in the CC group vs 32.7% in the SS group; p = 0.675). In unselected patients and lesions, carbon coating does not provide significant improvements over SS stents with the same design.