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.

The impact of the coronary sinus reducer upon left ventricular function in patients with refractory angina pectoris.

OBJECTIVES: To evaluate the impact of coronary sinus (CS) Reducer implantation upon left ventricular (LV) function. BACKGROUND: CS Reducer implantation is associated with symptomatic relief in patients with refractory angina. The effects of the device upon left ventricular function remains unknown. METHODS: Prior to device implantation and at 4-months, resting ventricular volumes and function were measured using cardiac magnetic resonance (CMR). Stress CMR was performed to extract quantitative indices of myocardial perfusion (myocardial perfusion reserve index-MPRI). RESULTS: Nineteen patients (18 males, 66.0 [IQR 56.0-77.0] years), underwent successful Reducer implantation. Sixteen (84%) patients improved by at least 1 CCS class. Four months after Reducer implantation, we noticed a significant improvement in LV ejection fraction (LVEF) (61 [IQR 47-71] to 66 [IQR 57-72] %; p = .009), a reduction in LV end-diastolic volume (LVEDV)/Body surface area (BSA) (65.7 [IQR 57.4-89.6] to 64.7 [IQR 53.7-74.1] mL/m2 ; p = .036) and a reduction in LV end-systolic volume (LVESV)/BSA (28.7 [IQR 18.6-38.8] to 20.0 [IQR 15.0-31.4] mL/m2 ; p = .007). Patients with reduced EF (EF < 50%, n = 6) presented a greater increase of EF at follow up compared to patients with preserved EF (11.3 [IQR 6.5-54.5] vs. 3.8 [IQR 0.6-9.1] %; p = .029). The observed decrease in LVESV/BSA was greater in patients with reduced EF (23.6 [IQR 11.6-33.8] vs. 4.2 [IQR -2.0 to 8.4] mL/m2 ; p = .005). A significant increase in transmural MPRI was observed 4 months after Reducer implantation (p < .011). CONCLUSIONS: CS Reducer improved angina symptoms and improved left ventricular function. The improvement was pronounced in the subgroup of patients with reduced ejection fraction. Myocardial perfusion improvement could represent the underlying mechanism for the observed benefits.

Percutaneous management of periprocedural coronary sinus Reducer migration.

Coronary sinus Reducer represents a novel therapeutic option for refractory angina. As emerging evidence of both reduction in angina symptoms and reduction of myocardial ischemia burden might lead to increased Reducer implantations, knowledge on how to manage potential complications is of clinical importance. We report a successful management of scaffold migration in right atrium.

The association of interdialytic blood pressure variability with cardiovascular events and all-cause mortality in haemodialysis patients.

BACKGROUND: Long-term pre-dialysis blood pressure variability (BPV) in haemodialysis patients is associated with increased cardiovascular risk. The association of the main haemodynamic culprit in dialysis, that is, short-term BPV, with outcomes has not been investigated. We examine the prognostic role of short-term BPV for mortality and cardiovascular events in this population. METHODS: A total of 227 haemodialysis patients underwent 44-h ambulatory monitoring during a standard interval and were followed-up for 30.17 ± 17.70 months. We calculated SD, weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas. The primary endpoint was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary endpoints were: (i) all-cause mortality, (ii) cardiovascular mortality and (iii) a combination of cardiovascular events. RESULTS: Cumulative freedom from the primary endpoint was similar for quartiles of pre-dialysis and 44-h systolic BP (SBP), but was progressively longer for increasing quartiles of 44-h SBP-SD (P = 0.014), wSD (P = 0.007), CV (P = 0.031) and ARV (83.9, 71.9, 70.2 and 43.9% for quartiles 1-4; P < 0.001). Higher quartiles of 44-h SBP-ARV were associated with higher risk of all studied outcomes. Among diastolic BPV indices, 44-h diastolic BP (DBP)-CV and 44-h DBP-ARV were associated with increased risk for the composite cardiovascular outcome. In Cox regression analysis, SBP-BPV was related to the primary endpoint, independently of SBP levels and interdialytic weight gain [ARV: hazard ratio (HR) 1.115, 95% confidence interval (95% CI) 1.048-1.185]. This association become insignificant after adjustment for pulse wave velocity (PWV; HR 1.061, 95% CI 0.989-1.137), and further attenuated after additional adjustment for age, dialysis vintage, gender, comorbidities and prevalent cardiovascular disease (HR 1.031, 95% CI 0.946-1.122). CONCLUSIONS: Increased BPV during the interdialytic interval is associated with higher risk of death and cardiovascular events, whereas ambulatory BP levels are not. This association was not independent after adjustment for PWV, other risk factors and prevalent cardiovascular disease. Short-term BPV could be a mediator promoting the adverse cardiovascular profile of haemodialysis patients.

Muscle microcirculation alterations and relation to dipping status in newly diagnosed untreated patients with arterial hypertension-A pilot study.

OBJECTIVE: The importance of abnormalities observed in the microcirculation of patients with arterial hypertension (AH) is being increasingly recognized. The authors aimed to evaluate skeletal muscle microcirculation in untreated, newly diagnosed hypertensive patients with NIRS, a noninvasive method that evaluates microcirculation. METHODS: We evaluated 34 subjects, 17 patients with AH (13 males, 49±13 years, BMI: 26±2 kg/m2 ) and 17 healthy controls (12 males, 49±15 years, BMI: 25±3 kg/m2 ). The thenar muscle StO2 (%) was measured by NIRS before, during and after 3-minutes vascular occlusion to calculate OCR (%/min), EF (%/min), and RHT (minute). The dipping status of hypertensive patients was assessed. RESULTS: The RHT differed between AH patients and healthy subjects (2.6±0.3 vs 2.1±0.3 minutes, P<.001). Dippers had higher EF than nondippers (939±280 vs 710±164%/min, P=.05). CONCLUSIONS: The study suggests an impaired muscle microcirculation in newly diagnosed, untreated AH patients.

Effects of High-Intensity Interval Exercise Training on Skeletal Myopathy of Chronic Heart Failure.

BACKGROUND: It remains controversial which type of exercise elicits optimum adaptations on skeletal myopathy of heart failure (HF). Our aim was to evaluate the effect of high-intensity interval training (HIIT), with or without the addition of strength training, on skeletal muscle of HF patients. METHODS AND RESULTS: Thirteen male HF patients (age 51 ± 13 years, body mass index 27 ± 4 kg/m2) participated in either an HIIT (AER) or an HIIT combined with strength training (COM) 3-month program. Biopsy samples were obtained from the vastus lateralis. Analyses were performed on muscle fiber type, cross-section area (CSA), capillary density, and mRNA expression of insulin-like growth factor (IGF) 1 isoforms (ie, IGF-1Ea, IGF-1Eb, IGF-1Ec), type-1 receptor (IGF-1R), and binding protein 3 (IGFBP-3). Increased expression of IGF-1Ea, IGF-1Eb, IGF-1Ec, and IGFBP-3 transcripts was found (1.7 ± 0.8, 1.5 ± 0.8, 2.0 ± 1.32.4 ± 1.4 fold changes, respectively; P < .05). Type I fibers increased by 21% (42 ± 10% to 51 ± 7%; P < .001) and capillary/fiber ratio increased by 24% (1.27 ± 0.22 to 1.57 ± 0.41; P = .005) in both groups as a whole. Fibers' mean CSA increased by 10% in total, but the increase in type I fibers' CSA was greater after AER than COM (15% vs 6%; P < .05). The increased CSA correlated with the increased expression of IGF-1Ea and IGF-1Εb. CONCLUSIONS: HIIT reverses skeletal myopathy of HF patients, with the adaptive responses of the IGF-1 bioregulation system possibly contributing to these effects. AER program seemed to be superior to COM to induce muscle hypertrophy.

Evaluation of a novel brachial cuff-based oscillometric method for estimating central systolic pressure in hemodialysis patients.

BACKGROUND/AIMS: Elevated wave reflections and arterial stiffness, as well as ambulatory blood pressure (BP) are independent predictors of cardiovascular risk in end-stage-renal-disease. This study is the first to evaluate in hemodialysis patients the validity of a new ambulatory oscillometric device (Mobil-O-Graph, IEM, Germany), which estimates aortic BP, augmentation index (AIx) and pulse wave velocity (PWV). METHODS: Aortic SBP (aSBP), heart rate-adjusted AIx (AIx(75)) and PWV measured with Mobil-O-Graph were compared with the values from the most widely used tonometric device (Sphygmocor, ArtCor, Australia) in 73 hemodialysis patients. Measurements were made in a randomized order after 10 min of rest in the supine position at least 30 min before a dialysis session. Brachial BP (mercury sphygmomanometer) was used for the calibration of Sphygmocor's waveform. RESULTS: Sphygmocor-derived aSBP and AIx(75) did not differ from the relevant Mobil-O-Graph measurements (aSBP: 136.3 ± 19.6 vs. 133.5 ± 19.3 mm Hg, p = 0.068; AIx(75): 28.4 ± 9.3 vs. 30.0 ± 11.8%, p = 0.229). The small difference in aSBP is perhaps explained by a relevant difference in brachial SBP used for calibration (146.9 ± 20.4 vs. 145.2 ± 19.9 mm Hg, p = 0.341). Sphygmocor PWV was higher than Mobil-O-Graph PWV (10.3 ± 3.4 vs. 9.5 ± 2.1 m/s, p < 0.01). All 3 parameters estimated by Mobil-O-Graph showed highly significant (p < 0.001) correlations with the relevant measurements of Sphygmocor (aSBP, r = 0.770; AIx(75), r = 0.400; PWV, r = 0.739). The Bland-Altman Plots for aSBP and AIx(75) showed acceptable agreement between the two devices and no evidence of systemic bias for PWV. CONCLUSION: As in other populations, acceptable agreement between Mobil-O-Graph and Sphygmocor was evident for aSBP and AIx(75) in hemodialysis patients; PWV was slightly underestimated by Mobil-O-Graph.

Exercise intolerance in chronic heart failure: the role of cortisol and the catabolic state.

Chronic heart failure (CHF) is a complex clinical syndrome leading to exercise intolerance due to muscular fatigue and dyspnea. Hemodynamics fail to explain the reduced exercise capacity, while a significant skeletal muscular pathology seems to constitute the main underlying mechanism for exercise intolerance in CHF patients. There have been proposed several metabolic, neurohormonal and immune system abnormalities leading to an anabolic/catabolic imbalance that plays a central role in the pathogenesis of the wasting process of skeletal muscle myopathy. The impairment of the anabolic axes is associated with the severity of symptoms and the poor outcome in CHF, whereas increased cortisol levels are predictive of exercise intolerance, ventilatory inefficiency and chronotropic incompetence, suggesting a significant contributing mechanism to the limited functional status. Exercise training and device therapy could have beneficial effects in preventing and treating muscle wasting in CHF. However, specific anabolic treatment needs more investigation to prove possible beneficial effects.

Maximum inspiratory pressure, a surrogate parameter for the assessment of ICU-acquired weakness.

BACKGROUND: Physical examination has been advocated as a primary determinant of ICU-acquired weakness (ICU-AW). The purpose of the study is to investigate ICU-AW development by using Maximum Inspiratory Pressure (MIP) as a surrogate parameter of the standardized method to evaluate patients' peripheral muscle strength. METHODS: Seventy-four patients were recruited in the study and prospectively evaluated in a multidisciplinary university ICU towards the appearance of ICU-AW. APACHE II admission score was 16 ± 6 and ICU stay 26 ± 18 days. ICU-AW was diagnosed with the Medical Research Council (MRC) scale for the clinical evaluation of muscle strength. MIP was measured using the unidirectional valve method, independently of the patients' ability to cooperate. RESULTS: A significant correlation was found between MIP and MRC (r = 0.68, p < 0.001). Patients that developed ICU-AW (MRC<48) had a longer weaning period compared to non ICU-AW patients (12 ± 14 versus 2 ± 3 days, p < 0.01). A cut-off point of 36 cmH2O for MIP was defined by ROC curve analysis for ICU-AW diagnosis (88% sensitivity,76% specificity). Patients with MIP below the cut-off point of 36 cmH2O had a significant greater weaning period (10 ± 14 versus 3 ± 3 days, p = 0.004) also shown by Kaplan-Meier analysis (log-rank:8.2;p = 0.004). CONCLUSIONS: MIP estimated using the unidirectional valve method may be a potential surrogate parameter for the assessment of muscle strength compromise, useful for the early detection of ICU-AW.

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.

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.

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.

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.

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.

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.

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.

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.