Inflammation- and Tissue Remodeling-Related Gene Responses in Skeletal Muscle of Heart Failure Patients Following High-Intensity Interval Training.

Background: Peripheral myopathy consists a hallmark of heart failure (HF) and has been associated with poor prognosis. Inflammation has been suggested to dominate this pathology, while exercise training is typically associated with the induction of anti-inflammatory mechanisms. However, the current knowledge regarding the involvement of inflammation-related genes in the exercise training-induced muscle adaptations in HF patients is very limited. Given that high-intensity interval training (HIIT) alone or combined with strength training (COM) has gained ground in HF cardiac rehabilitation, this study aimed to investigate the local muscle expression of inflammatory and tissue remodeling factors in HF patients, who underwent 3 months of these training schemes. In addition, we examined whether these exercise training-induced gene expression responses are associated with changes in exercise capacity in those patients. Methods: Thirteen male patients with chronic HF (age: 51 ± 13 y; body mass index (BMI): 27 ± 4 kg/ m 2 ) were randomly assigned to a 3-month exercise program consisted of either HIIT (N = 6) or COM training (N = 7). Muscle tissue biopsies were obtained from vastus lateralis pre- and post-training and transcriptional changes in interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-1 alpha (TNF-1 α ), urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), and transforming growth factor-beta 1 (TGF- ß 1) were quantified by RT-PCR. Results: An overall increase in the expression levels of selected inflammatory (IL-8, TNF-1 α ) and remodeling factors (uPAR) was found post-training (p < 0.05), while IL-6, uPA and TGF- ß 1 gene expression remained unchanged (p > 0.05). The observed alterations did not differ between training groups. Additionally, IL-8 changes were found to be correlated with the improvement in exercise capacity post-training (p < 0.05). Conclusions: This is the first study demonstrating an increase in intramuscular inflammatory and remodeling key factors induced by HIIT or COM training in HF patients. Combining these observations with our previous findings of improved muscle hypertrophy and capillarization post-training in these patients, the findings of the present study may suggest that inflammatory responses are part of an ongoing remodeling process in the exercising skeletal muscle. Clinical Trial Registration: NCT02387411.

Insights Into Coronary Sinus Reducer Non-Responders.

BACKGROUND: Refractory angina affects an increasing proportion of the population with advanced coronary artery disease and microvascular dysfunction. Limited effective pharmacological and interventional therapies exist for this patient cohort. The coronary sinus (CS) reducer, recently recommended in the 2019 guidelines of the European Society of Cardiology for the management of chronic refractory angina, is a balloon-expandable, stainless-steel device designed for implantation in the CS. It acts by increasing CS pressure, thereby redistributing blood to ischemic myocardium, relieving symptoms, and improving quality of life. However, between 15%-30% of patients do not respond to this treatment. Six mechanisms appear to explain this poor response to CS reducer therapy: (1) inappropriate patient selection; (2) cardiac venous system heterogeneity; (3) CS size; (4) incomplete device endothelialization; (5) coronary artery disease phenotype and progression; and (6) limited myocardial ischemia at baseline. We hereby review these mechanisms in detail and highlight key areas that should be addressed in order to try and reduce the burden of non-responders following CS reducer implantation.

Coronary sinus size and ischemia improvement after reducer implantation; "one size to fit them all?"

AIM: Coronary sinus (CS) reducer implantation is associated with symptomatic relief of patients with refractory angina. However, 15% to 30% of the patients do not respond to this treatment. Aim if this study was to evaluate the effect of CS size in the effectiveness of the device. METHODS: Prior to device implantation and at 4-month resting ventricular function was assessed by stress cardiac magnetic resonance. Ischemia was assessed by the myocardial perfusion reserve index (MPRI). RESULTS: Fifteen patients (66 ± 10 years) underwent successful CS Reducer implantation, with improvements in angina class and exercise tolerance. Patients with a smaller CS size (<5.8 mm) presented a significantly higher percentage increase in MPRI (63 ± 51 vs 9 ± 30%, P = .03) and a higher reduction in left ventricle end-diastolic volumes. CONCLUSIONS: Greater benefits, in terms of ischemia improvement, after CS Reducer implantation were seen in patients with smaller CS sizes, suggesting a potential mechanism underlying the observed rates of reducer non-responsiveness.

Feature tracking and mapping analysis of myocardial response to improved perfusion reserve in patients with refractory angina treated by coronary sinus Reducer implantation: a CMR study.

Coronary sinus (CS) Reducer implantation improves myocardial perfusion and symptoms in patients with debilitating refractory angina. Its impact on myocardial remodeling remain uncertain. Aim of the present study was to assess possible impact of CS Reducer on myocardial systolic-diastolic deformation and microstructural remodeling, as assessed through cardiac magnetic resonance (CMR) feature tracking and mapping analysis. Twenty-eight consecutive patients with refractory angina underwent multiparametric stress CMR before and 4 months after CS Reducer implantation. Eight patients were excluded (6 for absence of inducible ischemia, 2 for artifacts). Modifications in 3D systo-diastolic myocardial deformation were evaluated using feature tracking analysis on rest cine images. Myocardial microstructural remodeling was assessed by native T1 mapping, cellular and matrix volume and extracellular volume fraction (ECV). Collaterally, the percentage of ischemic myocardium (ischemic burden %) and the myocardial perfusion reserve index (MPRI) were measured. After CS Reducer implantation, myocardial contractility improved (ejection fraction rose from 61 to 67%; p = 0.0079), along with longitudinal (from - 16 to - 19%; p = 0.0192) and circumferential strain (from - 18 to - 21%; p = 0.0017). Peak diastolic radial, circumferential and longitudinal strain rate did not change (p > 0.05), and no changes in native T1, ECV, cellular and matrix volume were observed. Myocardial perfusion improved, with a reduction of ischemic burden (13-11%; p = 0.0135), and recovery of intramural perfusion balance in segments with baseline ischemia (MPRi endocardial/epicardial ratio from 0.67 to 0.96; p = 0.0107). CS Reducer improves myocardial longitudinal and circumferential strain, without microstructural remodeling and no impact on diastolic proprieties.

POT-sideDCB-POT: A novel technique for treating coronary bifurcation lesions.

The rePOT technique is a novel and easily applied approach for coronary bifurcations. Drug-Coated Balloon (DCB) angioplasty is increasingly being utilized in management of small vessels and coronary bifurcation lesions. Herein, we propose a new approach for treating coronary bifurcation lesions with the application of DCB to treat the side-branch in addition to the rePOT technique: the POT-sideDCB-POT technique.

Dapagliflozin Does Not Affect Short-Term Blood Pressure Variability in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Increased blood pressure variability (BPV) is associated with increased cardiovascular and all-cause mortality in patients with type-2 diabetes mellitus (T2DM). Sodium-glucose co-transporter 2 (SGLT-2) inhibitors decrease the incidence of cardiovascular events, renal events, and death in this population. This study aimed to evaluate the effect of dapagliflozin on short-term BPV in patients with T2DM. METHODS: This is a secondary analysis of a double-blind, randomized, placebo-controlled trial in 85 patients with T2DM. Subjects were randomized to dapagliflozin 10 mg/day or placebo for 12 weeks. All participants underwent 24-hour ambulatory blood pressure (BP) monitoring with Mobil-O-Graph-NG device at baseline and study-end. SD, weighted SD (wSD), coefficient of variation, average real variability (ARV), and variation independent of mean were calculated for the 24-hour, daytime and nighttime periods. RESULTS: Dapagliflozin reduced 24-hour brachial BP compared with placebo. From baseline to study-end 24-hour brachial BPV indexes did not change with dapagliflozin (SBP-ARV: 11.51 ± 3.45 vs. 11.05 ± 3.35; P = 0.326, SBP-wSD: 13.59 ± 3.60 vs. 13.48 ± 3.33; P = 0.811) or placebo (SBP-ARV: 11.47 ± 3.63 vs. 11.05 ± 3.00; P = 0.388, SBP-wSD: 13.85 ± 4.38 vs. 13.97 ± 3.87; P = 0.308). Similarly, no significant changes in BPV indexes for daytime and nighttime were observed in any group. At study-end, no between-group differences were observed for any BPV index. Deltas (Δ) of all indexes during follow-up were minimal and not different between groups (SBP-wSD: dapagliflozin: -0.11 ± 3.05 vs. placebo: 0.12 ± 4.20; P = 0.227). CONCLUSIONS: This study is the first to evaluate the effects of an SGLT-2 inhibitor on short-term BPV in T2DM, showing no effect of dapagliflozin on all BPV indexes studied. CLINICAL TRIALS REGISTRATION: Trial Number NCT02887677.

Transradial Crossover Balloon Occlusion Technique for Primary Access Hemostasis During Transcatheter Aortic Valve Replacement: Initial Experience With the Oceanus 140 cm and 200 cm Balloon Catheters.

OBJECTIVES: The crossover balloon occlusion technique (CBOT) facilitates primary access hemostasis in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). The CBOT is usually performed through the contralateral femoral artery. The aim of this study was to evaluate, in patients undergoing TAVR, the safety and feasibility of transradial CBOT using the new Oceanus balloon dilatation catheter (iVascular). METHODS: This multicenter study included 104 patients (mean age, 81 ± 7 years; 43% women) undergoing transfemoral TAVR. A modified CBOT through the radial artery was performed in all patients with the Oceanus balloon catheter. Data regarding transradial CBOT, balloon performance, vascular complications, and 30-day clinical events were recorded. RESULTS: Up to 21% of patients had a height >170 cm and 17% presented with severe aortic/iliofemoral tortuosity. The transradial CBOT (left radial 74%, right radial 26%) was performed using either the 140 cm Oceanus (37.5%) or the 200 cm Oceanus (62.5%) balloon catheter. The balloon reached the femoral artery in all patients, and balloon inflation achieved an appropriate vessel closure in 98%. There were no complications related to the balloon catheter, and only 1 patient (1.0%) suffered a minor vascular complication related to the secondary radial access. The 30-day rates of primary access major vascular complications and death were 3.8% and 1.9%, respectively. CONCLUSION: In patients undergoing transfemoral TAVR, transradial CBOT with the Oceanus balloon dilatation catheter was feasible and safe. A balloon length up to 200 cm allowed the use of this technique (from right or left radial access) in all patients regardless of patient height or the presence of a challenging vascular anatomy.

Ambulatory blood pressure profile and blood pressure variability in peritoneal dialysis compared with hemodialysis and chronic kidney disease patients.

Hypertension in end-stage renal disease patients is highly prevalent and poorly controlled. Data on the ambulatory blood pressure (BP) profile and BP variability (BPV) in peritoneal dialysis (PD) patients are absent. This study examined the BP profile and BPV of patients undergoing PD in comparison with hemodialysis (HD) and predialysis chronic kidney disease CKD patients. Thirty-eight PD patients were matched for age, sex, and dialysis vintage with 76 HD patients and for age and sex with 38 patients with CKD stage 2-4. Patients under PD or HD underwent 48-h and CKD patients 24-h ambulatory BP monitoring. BP levels and BPV indices were compared for the 48-h, first and second 24 h, daytime and nighttime periods. Two-way mixed ANOVA for repeated measurements was used to evaluate the effects of dialysis modality and time on ambulatory BP in PD and HD. During all periods studied, SBP and DBP were numerically higher but not significantly different in PD than in HD patients. Systolic BP was significantly higher in PD or HD than in predialysis CKD (PD: 138.38 ± 20.97 mmHg; HD: 133.75 ± 15.5 mmHg; CKD: 125.52 ± 13.4 mmHg, p = 0.003), a difference evident also during daytime and nighttime periods. Repeated-measurements ANOVA showed no effect of dialysis modality on ambulatory BP during any period studied. All BPV indices studied were similar between PD and HD patients, in whom they were higher than in CKD individuals (first 24-h systolic-ARV: PD: 11.86 ± 3.19 mmHg; HD: 11.23 ± 3.45 mmHg; CKD: 9.81 ± 2.49 mmHg, p = 0.016). Average BP levels and BPV indices are similar between PD and HD patients, in whom they are higher than in their CKD counterparts. The dialysis modality has no effect on the ambulatory BP profile. These results suggest that PD is no better than HD with regard to overall BP control or BP fluctuations over time.

Solving Challenging Situations and Complications in Everyday Percutaneous Coronary Intervention Using Chronic Total Occlusion Techniques.

The field of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has witnessed a dramatic evolution in the last decade. The challenging nature of CTO interventions involves regularly dealing with support-related issues, uncrossable/undilatable lesions, manipulation of equipment in the subadventitial (also known as "subintimal") space, and the treatment of complications such as perforation and equipment loss or entrapment. The CTO experience has provided numerous techniques to the creative operator facing challenges in the non-CTO PCI setting. Herewith, we discuss an armamentarium of techniques routinely used in CTO-PCI, which can also be utilized in interventions for non-occlusive coronary artery disease and have the potential to improve the efficacy and safety of these procedures.

Refractory Angina: From Pathophysiology to New Therapeutic Nonpharmacological Technologies.

Despite optimal combination of guideline-directed anti-ischemic therapies and myocardial revascularization, a substantial proportion of patients with stable coronary artery disease continues to experience disabling symptoms and is often referred as "no-option." The appraisal of the pathways linking ischemia to symptom perception indicates a complex model of heart-brain interactions in the generation of the subjective anginal experience and inspired novel approaches that may be clinically effective in alleviating the angina burden of this population. Conversely, the prevailing ischemia-centered view of angina, with the focus on traditional myocardial revascularization as the sole option to address ischemia on top of medical therapy, hinders the experimental characterization and broad-scale clinical implementation of strongly needed therapeutic options. The interventionist, often the first physician to establish the diagnosis of refractory angina pectoris (RAP) following coronary angiography, should be aware of the numerous emerging technologies with the potential to improve quality of life in the growing population of RAP patients. This review describes the current landscape and the future perspectives on nonpharmacological treatment technologies for patients with RAP, with a view on the underlying physiopathological rationale and current clinical evidence.

Coronary artery disease in renal transplant recipients: an angiographic study.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in renal transplant recipients (RT). Coronary artery disease (CAD) in such patients is poorly studied. METHODS: During 2012-2017, 50 patients with a renal graft (functioning for a minimum of 6 months) were subjected to coronary angiography in our institution. They were matched (for age, gender, diabetes, and indication for angiography) with 50 patients with end-stage renal disease (ESRD) undergoing chronic dialysis and 50 patients with normal renal function who were subjected to coronary angiography during the same period. The extent and severity of CAD were assessed by using the SYNTAX score. RESULTS: RT had a significantly longer duration of ESRD than patients on dialysis (17.5±7.1 vs. 8.5±8.7 years, p<0.01). Mean SYNTAX score was 13.3±12.0 in RT, 20.6±17.5 in patients on dialysis, and 9.4±9.2 in control patients (p<0.01). At least one significantly calcified lesion was present in 75.7% of RT recipients, 92.1% of patients on dialysis, and 15.8% of control patients (p<0.01). Percutaneous coronary intervention (PCI) was successful in 93.8% of the attempted cases in RT, 75% of patients on chronic dialysis, and 100% of control patients (p=0.04). In the RT group, SYNTAX score significantly correlated with smoking (p=0.02) and the total vintage of ESRD (p=0.04). CONCLUSIONS: In this angiographic study, CAD was less severe in RT than in patients on long-term dialysis despite a longer duration of ESRD. Coronary artery calcification was highly prevalent after renal transplantation. PCI in RT had a high rate of angiographic success.

Technical aspects in coronary sinus Reducer implantation.

Refractory angina is a growing problem, predominantly due to advanced coronary artery disease, associated with a reduced quality of life and an increased hospitalisation rate with a corresponding impact on healthcare resources. There is an unmet clinical need to be addressed by novel therapeutic approaches. Over the last few years, a treatment approach causing a controlled coronary sinus narrowing by implantation of a balloon-expandable, hourglass-shaped, stainless steel mesh (i.e., the coronary sinus Reducer) has arisen with promising initial short-term and midterm results, in terms of reducing angina and ischaemia burden and improving quality of life. Guidance with proper implantation algorithms and knowledge on how to address potential complications will improve interventional outcomes and foster a wider application of this novel therapeutic approach. In this review, we summarise the implantation technique, the causes of potential complications, and algorithms focusing upon their practical management, based on the experience of the authors.