Chronic total occlusion in non-ST elevation myocardial infarction - A multi-centre observational study.

OBJECTIVES: To evaluate the characteristics and outcomes of patients with a chronic total occlusion (CTO) in a Non-ST Elevation Myocardial Infarction (NSTEMI) cohort. BACKGROUND: There is limited data on the clinical characteristics, revascularisation strategies and outcomes of patients presenting with a NSTEMI and a CTO. METHODS: Retrospective analysis of a six-centre percutaneous coronary intervention (PCI) registry in the UK between January 2015 and December 2020 was performed. Patients with a NSTEMI with and without a CTO were compared for baseline characteristics and outcomes. RESULTS: There were 17,355 NSTEMI patients in total of whom 1813 patients had a CTO (10.4 %). Patients with a CTO were more likely to be older (CTO: 67.8 (±11.5) years vs. no CTO: 67.2 (±12) years, p = 0.04), male (CTO: 81.1 % vs.71.9 %, p < 0.0001) with a greater prevalence of cardiovascular risk factors. All-cause mortality at 30 days: HR 2.63, 95 % CI 1.42-4.84, p = 0.002 and at 1 year: HR: 1.87, 95 % CI 1.25-2.81, p = 0.003 was higher in the CTO cohort. CTO patients who underwent revascularisation were younger (Revascularisation 66.4 [±11.7] years vs. no revascularisation 68.4 [±11.4] years, p = 0.001). Patients with failed CTO revascularisation had lower survival (HR 0.21, 95 % CI 0.10-0.42, p < 0.0001). The mean time to revascularisation was 13.4 days. There was variation in attempt at CTO revascularisation between the 6 centres for (16 % to 100 %) with success rates ranging from 65 to 100 %. CONCLUSIONS: In conclusion, the presence of a CTO in NSTEMI patients undergoing PCI was associated with worse in-hospital and long-term outcomes.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

A case report of capillary leak syndrome with recurrent pericardial and pleural effusions.

BACKGROUND: Capillary leak syndrome (CLS) is a rare connective tissue disease, triggered by the leak of serous fluid into the interstitial spaces, characterized by a hallmark of oedema and effusions in confined spaces. The limiting factor in CLS management appears to be its diagnosis rather than treatment, which is usually to contain the disease progression rather than a cure. CASE SUMMARY: We report a case of a 51-year-old woman with recurrent life-threatening presentations of pericardial effusions, pleural effusions, and generalized swelling of face and extremities. The only notable past medical history was of Type 1 diabetes. Numerous investigations did not lead to specific disease accounting for pericardial effusions and pleural effusions. Eventually, the diagnosis of CLS was made based on hypovolaemic shock, hypoalbuminaemia, and haemoconcentration without the presence of albuminuria. She was managed with steroids to reduce system inflammation and later with immunoglobulins and tumour necrosis factor to contain the disease process. Since her diagnosis and subsequent appropriate management, she has not had further admissions with cardiac tamponade 16 months of follow-up. DISCUSSION: The diagnosis of CLS is difficult to make unless there is a high degree of suspicion and until other causes have been ruled out. It remains a challenging condition to manage as the treatment options are limited and patients recurrently present with emergencies until the correct diagnosis is made and the optimal treatment is provided.

Mechanical Mitral Valve Replacement during the 2nd Trimester of Pregnancy.

We report the case of a 44-year-old pregnant woman who was diagnosed with symptomatic severe mitral stenosis that did not respond to optimal medical therapy and balloon valvuloplasty. After a multidisciplinary team discussion on the timing and risks of interventions and postoperative optimization of peripartum anticoagulation, the patient underwent mechanical mitral valve replacement during the 2nd trimester of pregnancy. The outcome was excellent for the mother and the infant. This case emphasizes the importance of a multidisciplinary approach in managing unusual cases.

Towards a contemporary, comprehensive scoring system for determining technical outcomes of hybrid percutaneous chronic total occlusion treatment: The RECHARGE score.

OBJECTIVES: This study sought to create a contemporary scoring tool to predict technical outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) from patients treated by hybrid operators with differing experience levels. BACKGROUND: Current scoring systems need regular updating to cope with the positive evolutions regarding materials, techniques, and outcomes, while at the same time being applicable for a broad range of operators. METHODS: Clinical and angiographic characteristics from 880 CTO-PCIs included in the REgistry of CrossBoss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom (RECHARGE) were analyzed by using a derivation and validation set (2:1 ratio). Variables significantly associated with technical failure in the multivariable analysis were incorporated in the score. Subsequently, the discriminatory capacity was assessed and the validation set was used to compare with the J-CTO score and PROGRESS scores. RESULTS: Technical success in the derivation and validation sets was 83% and 85%, respectively. Multivariate analysis identified six parameters associated with technical failure: blunt stump (beta coefficient (b) = 1.014); calcification (b = 0.908); tortuosity ≥45° (b = 0.964); lesion length 20 mm (b = 0.556); diseased distal landing zone (b = 0.794), and previous bypass graft on CTO vessel (b = 0.833). Score variables remained significant after bootstrapping. The RECHARGE score showed better discriminatory capacity in both sets (area-under-the-curve (AUC) = 0.783 and 0.711), compared to the J-CTO (AUC = 0.676) and PROGRESS (AUC = 0.608) scores. CONCLUSIONS: The RECHARGE score is a novel, easy-to-use tool for assessing the risk for technical failure in hybrid CTO-PCI and has the potential to perform well for a broad community of operators. © 2017 Wiley Periodicals, Inc.

One-Year Clinical Outcomes of the Hybrid CTO Revascularization Strategy After Hospital Discharge: A Subanalysis of the Multicenter RECHARGE Registry.

OBJECTIVES: Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) has historically been associated with higher event rates during follow-up. The hybrid algorithm and contemporary wiring and dissection re-entry (DR) techniques can potentially improve long-term outcomes after CTO-PCI. This study assessed the long-term clinical outcomes of the hybrid CTO practice, when applied by operators with varying experience levels. METHODS: We examined the 1-year clinical events after hospital discharge of the RECHARGE population, according to technical outcome and final technique. The primary endpoint was major adverse cardiac event (MACE) rate. Centers that provided ≥90% complete 12-month follow-up were included. RESULTS: Follow-up data of 1067 out of 1165 patients (92%) were provided by 13 centers. Mean follow-up duration was 362.8 ± 0.9 days. One-year MACE-free survival rate was 91.3% (974/1067). MACE included death (1.9%; n = 20), myocardial infarction (1.4%; n = 15), target-vessel failure (5.9%; n = 63), and target-vessel revascularization (TVR) (5.5%; n = 59). Non-TVR was performed in 6.7% (n = 71). MACE was significantly in favor of successful CTO-PCI (8.0% vs 13%; P=.04), even after adjusting for baseline differences (adjusted hazard ratio, 0.59; 95% confidence interval, 0.36-0.98; P=.04). Other events, including individual MACE components, were comparable with respect to technical outcome and final technique (DR vs non-DR techniques). CONCLUSIONS: The use of the hybrid algorithm with contemporary techniques by moderate to highly experienced operators for CTO-PCI is safe and associated with a low 1-year event rate. Successful procedures are associated with a better MACE rate. DR techniques can be used as first-line strategies alongside intimal wiring techniques without compromising clinical outcomes.

Fully Transradial Versus Transfemoral Approach for Percutaneous Intervention of Coronary Chronic Total Occlusions Applying the Hybrid Algorithm: Insights From RECHARGE Registry.

BACKGROUND: Small observational studies demonstrate the feasibility of transradial approach for chronic total occlusion (CTO) percutaneous coronary intervention. The aim of the current study is to assess technical success, complication rates, and procedural efficiency in fully transradial approach (fTRA) and transfemoral approach (TFA) in a large prospective European registry adopting the hybrid algorithm for CTO percutaneous coronary intervention (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom, RECHARGE registry). METHODS AND RESULTS: We analyzed 1253 CTO percutaneous coronary intervention procedures performed according to the hybrid protocol in 17 European centers, comparing fTRA (single or biradial access) and TFA (single or bifemoral or combined radial and femoral access). fTRA was applied in 306 (24%) and TFA in 947 (76%) cases. The average Japanese CTO score was 2.1±1.2 in fTRA and 2.3±1.1 in TFA (P=0.06). Technical success was achieved in 85% in fTRA and 86% in TFA (P=0.51). Technical success was comparable for fTRA and TFA in different Japanese CTO score subgroups after multivariable analysis and after propensity adjustment. In-hospital major adverse cardiac and cerebral events occurred in 2.0% in fTRA and 2.9% in TFA (P=0.40). Major access site bleeding occurred in 0.3% in fTRA and 0.5% in TFA (P=0.66). fTRA compared with TFA had similar procedural duration (80 minutes [54-120 minutes] versus 90 minutes [60-121 minutes]; P=0.07), similar radiation dose (dose area product 89 Gray×cm2 [52-163 Gray×cm2] versus 101 Gray×cm2 [59-171 Gray×cm2]; P=0.06), and lower contrast agent use (200 mL [150-310 mL] versus 250 mL [200-350 mL]; P<0.01). CONCLUSIONS: fTRA CTO percutaneous coronary intervention is a valid alternative to TFA with a high rate of success, low complication rates, and no decrease in procedural efficiency.

The Hybrid Algorithm for Treating Chronic Total Occlusions in Europe: The RECHARGE Registry.

BACKGROUND: The hybrid algorithm for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) was developed to improve procedural outcomes. Large, prospective studies validating the algorithm in a broad multicenter setting with operators of different experience levels are lacking. OBJECTIVES: The RECHARGE (REgistry of Crossboss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom) registry aims to report achievable results using the hybrid algorithm. METHODS: Between January 2014 and October 2015, consecutive patients undergoing hybrid CTO-PCI were prospectively enrolled in 17 centers. Procedural techniques, outcomes, and in-hospital complications were analyzed. RESULTS: A total of 1,253 CTO-PCIs were performed in 1,177 patients, of which 86% were men. Mean age was 66 ± 11 years. The average Japanese CTO score was 2.0 ± 1.0, and was higher in the failure group (2.6 ± 0.6 vs. 1.9 ± 1.0; p < 0.001). Overall procedure success was 86% and major in-hospital complications occurred in 2.6%. Antegrade wire escalation was the preferred primary strategy in 77%, followed by retrograde (17%) and antegrade dissection re-entry strategies (7%). Primary strategies were successful in 60%. Consecutive strategies were applied in 34% and were successful in 74%. Antegrade dissection re-entry and retrograde strategies were the most common bailout strategies and were successful in 67% and 62%, respectively. Median procedure and fluoroscopy time were 90 (interquartile range [IQR]: 60 to 120) min and 35 (IQR: 21 to 55) min, contrast volume was 250 (IQR: 180 to 340) ml, and radiation doses (air kerma and dose area product) were 1.6 (IQR: 1.0 to 2.7) Gy and 98 (IQR: 57 to 168) Gy·cm2, respectively. CONCLUSIONS: High procedure and patient success rates, combined with a low event rate and improved procedural characteristics, support further use of the hybrid algorithm for a broad community of appropriately trained CTO operators.

The effects of inspiratory muscle training in older adults.

PURPOSE: Declining inspiratory muscle function and structure and systemic low-level inflammation and oxidative stress may contribute to morbidity and mortality during normal ageing. Therefore, we examined the effects of inspiratory muscle training (IMT) in older adults on inspiratory muscle function and structure and systemic inflammation and oxidative stress, and reexamined the reported positive effects of IMT on respiratory muscle strength, inspiratory muscle endurance, spirometry, exercise performance, physical activity levels (PAL), and quality of life (QoL). METHODS: Thirty-four healthy older adults (68 ± 3 yr) with normal spirometry, respiratory muscle strength, and physical fitness were divided equally into a pressure-threshold IMT or sham-hypoxic placebo group. Before and after an 8-wk intervention, measurements were taken for dynamic inspiratory muscle function and inspiratory muscle endurance using a weighted plunger pressure-threshold loading device; diaphragm thickness by using B-mode ultrasonography; plasma cytokine concentrations by using immunoassays; DNA damage levels in peripheral blood mononuclear cells by using comet assays; spirometry, maximal mouth pressures, and exercise performance by using a 6-min walk test; PAL by using a questionnaire and accelerometry; and QoL using a questionnaire. RESULTS: Compared with placebo, IMT increased maximal inspiratory pressure (+34% ± 43%, P = 0.008), diaphragm thickness at residual volume (+38% ± 39%, P = 0.03), and peak inspiratory flow (+35% ± 42%, P = 0.049) but did not change other spirometry measures, plasma cytokine concentrations, DNA damage levels in peripheral blood mononuclear cells, dynamic inspiratory muscle function, inspiratory muscle endurance, exercise performance, PAL, or QoL. CONCLUSION: These novel data indicate that in healthy older adults, IMT elicits some positive changes in inspiratory muscle function and structure but neither attenuates systemic inflammation and oxidative stress nor improves exercise performance, PAL, or QoL.

Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts.

In acromegaly, somatostatin receptor ligands (SRLs) can ameliorate left ventricular hypertrophy (LVH) and their use is associated with demonstrable improvements in various parameters of cardiac function. It remains unclear as to whether these beneficial effects are principally attributable to falling GH and IGF-I levels, or whether SRLs exert independent direct effects on the heart via somatostatin receptors. To help address this issue, we have sought to investigate somatostatin receptor expression in human heart. A human heart cDNA library was probed using PCR techniques to determine expression of somatostatin receptor subtypes. Subsequently, human heart biopsies and human cardiac fibroblasts and myocytes were analysed to determine whether expression differed between cardiac chambers or cell types. mRNAs for four of the five somatostatin receptor subtypes (sst1, sst2, sst4 and sst5) were shown to be co-expressed by the human heart. These receptors were present in both atrial and ventricular tissue. Human cardiac myocytes expressed mRNA for only sst1 and sst2, while human cardiac fibroblasts expressed all four subtypes found in whole heart tissue. The expression of functional somatostatin receptors on human cardiac fibroblasts was confirmed by mobilisation of intracellular calcium in response to somatostatin. The presence of cardiac somatostatin receptors raises the possibility of a direct effect of somatostatin analogues on the heart. Furthermore, the differential expression of somatostatin receptor subtypes by human cardiac myocytes and fibroblasts opens up the possibility of differential modulation of the cell types in the heart by subtype-specific somatostatin analogues.

Chronic beta2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism.

OBJECTIVE: The aim of this study was to determine whether chronic beta-adrenergic receptor (beta-AR) stimulation induces proliferation of human cardiac fibroblasts and to investigate the mechanism(s) involved. METHODS AND RESULTS: In vitro cultures of human cardiac fibroblasts were established from biopsies of right atrial appendage. RT-PCR analysis and pharmacological studies demonstrated that these cells express predominantly the beta(2)-AR subtype coupled to activation of adenylyl cyclase and p44/42 mitogen-activated protein kinase (MAPK). Proliferation was determined by cell counting over a 6-day period in medium containing 2.5% fetal calf serum (control) or supplemented with the non-selective beta-AR agonist isoproterenol (ISO). ISO induced a concentration-dependent increase in cardiac fibroblast proliferation, which was maximal at 1 micromol/l. This increased proliferation was inhibited by the beta(2)-AR-selective antagonist ICI-118,551, but not the beta(1)-AR-selective antagonist atenolol. Direct activation of adenylyl cyclase alone (0.1-10 micromol/l forskolin) stimulated cyclic AMP production and MAPK activation, but did not induce cell proliferation. Since catecholamines are not considered to be 'classical' growth factors, we subsequently investigated whether beta(2)-AR stimulation results in secretion of growth factors that are able to stimulate proliferation in an autocrine manner. Conditioned medium obtained from cardiac fibroblasts treated with ISO for 48 h increased proliferation of parallel cultures of fibroblasts in the presence of the beta-AR antagonist alprenolol. Heat-treatment of this conditioned medium fully prevented the increase in cell proliferation, indicating that the autocrine factor(s) are heat-sensitive proteins. CONCLUSIONS: Chronic beta(2)-AR stimulation increases proliferation of human cardiac fibroblasts via a mechanism involving increased secretion of heat-sensitive growth factors.