Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

BACKGROUND: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. AIMS: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. METHODS: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. RESULTS: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). CONCLUSIONS: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome: A multicenter registry of the Tokyo Cardiovascular Care Unit Network.

BACKGROUND: Hypoalbuminemia is common in critically ill patients and is associated with poor outcomes. However, the relationship between serum albumin levels and clinical outcomes in patients with takotsubo syndrome remains unclear. We examined the impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome. METHODS: Using the multicenter registry of the Tokyo Cardiovascular Care Unit Network between January 2017 and December 2020, we identified 631 eligible patients with takotsubo syndrome (median age, 78 years; male proportion, 22 %) and documented serum albumin levels at admission, which were used to allocate patients to hypoalbuminemia (serum albumin <3.5 g/dL) or normal albumin (serum albumin ≥3.5 g/dL) groups. Patient characteristics and in-hospital mortality were compared between the groups. RESULTS: Hypoalbuminemia was detected in 200 (32 %) patients at admission. The hypoalbuminemia group was older and had a higher proportion of men and preceding physical triggers than the normal albumin group. In-hospital all-cause mortality was greater in the hypoalbuminemia group than in the normal albumin group (9.5 % vs. 1.9 %, p < 0.001). Both cardiac (3.0 % vs. 0.5 %, p = 0.015) and non-cardiac (6.5 % vs. 1.4 %, p = 0.002) mortality was greater in the hypoalbuminemia group. In multivariable logistic regression analysis, hypoalbuminemia was independently associated with increased in-hospital mortality, even after adjusting for confounders, including age, sex, and triggering events (odds ratio, 3.23; 95 % confidence interval, 1.31-7.95; p = 0.011). CONCLUSIONS: In patients with takotsubo syndrome, hypoalbuminemia is a common comorbidity and is associated with a substantial risk of in-hospital death. Close monitoring and comprehensive critical care are required in these patients.

A study of takotsubo syndrome over 9 years at the Tokyo Cardiovascular Care Unit Network Registry.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiovascular disease with clinical manifestations similar to those of acute myocardial infarction (AMI), and TTS sometimes occurs just after catastrophes. Large-scale studies of TTS in Japan are scarce, so we examined data over 9 years from Tokyo metropolitan acute cardiovascular care hospital network registry. METHODS: A total of 1626 patients were diagnosed with TTS between 2010 and 2018 at Tokyo Cardiovascular Care Unit Network facilities, and data from all these patients were analyzed. We investigated annual and monthly captured incidence of TTS, temporal trend of the captured incidence proportion of TTS versus AMI, the occurrence of TTS on the day of the great earthquake, and we elucidated the prognostic factors for in-hospital death. RESULTS: The annual incidence proportion of TTS versus AMI increased from 2.3 % to 4.5 % (p < 0.001) over 9 years. The mean TTS patient age was 74.4 years: the peak incidence of TTS was at 80 to 84 years of age for both male and female; females accounted for 78.5 % of patients. The monthly variation of the incidence of TTS was found (p = 0.009). In 2011, a total of 137 cases of TTS occurred, with as many as 6 occurring on March 11, the day of the Great East Japan Earthquake. There was a definable trigger for TTS in 64 % (physical: 36 %; emotional: 27 %; others: 2 %). All-cause in-hospital mortality was 5.3 % and was higher in males than in females (10.3 % vs 3.9 %; p < 0.001). Non-cardiac causes accounted for 62 % of in-hospital mortality. Factors at presentation that were associated with in-hospital all-cause mortality were male sex, low body mass index, and a high C-reactive protein level. CONCLUSIONS: This study elucidated the clinical features, in-hospital outcomes, and their attributed factors in patients with TTS in real-world clinical practice in Japan.

Heart Team risk assessment with angiography-derived fractional flow reserve determining the optimal revascularization strategy in patients with multivessel disease: Trial design and rationale for the DECISION QFR randomized trial.

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography-derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR-based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD.

Quality indicators of palliative care for cardiovascular intensive care.

Healthcare providers working for cardiovascular intensive care often face challenges and they play an essential role in palliative care and end-of-life care because of the high mortality rates in the cardiac intensive care unit. Unfortunately, there are several barriers to integrating palliative care, cardiovascular care, and intensive care. The main reasons are as follows: cardiovascular disease-specific trajectories differ from cancer, there is uncertainty associated with treatments and diagnoses, aggressive treatments are necessary for symptom relief, and there is ethical dilemma regarding withholding and withdrawal of life-sustaining therapy. Quality indicators that can iterate the minimum requirements of each medical discipline could be used to overcome these barriers and effectively practice palliative care in cardiovascular intensive care. Unfortunately, there are no specific quality indicators for palliative care in cardiovascular intensive care. A few indicators and their domains are useful for understanding current palliative care in cardiovascular intensive care. Among them, several domains, such as symptom palliation, patient- and family-centered decision-making, continuity of care, and support for health care providers that are particularly important in cardiovascular intensive care.Historically, the motivation for using quality indicators is to summarize mechanisms for external accountability and verification, and formative mechanisms for quality improvement. Practically, when using quality indicators, it is necessary to check structural indicators in each healthcare service line, screen palliative care at the first visit, and integrate palliative care teams with other professionals. Finally, we would like to state that quality indicators in cardiovascular intensive care could be useful as an educational tool for practicing palliative care, understanding the minimum requirements, and as a basic structure for future discussions.

Temporal trends in clinical outcomes after percutaneous coronary intervention: a systematic review of 66,327 patients from 25 all-comers trials.

BACKGROUND: With the improvements of percutaneous coronary intervention (PCI) technology and post-PCI patient management, several registry studies reported temporal trends in post-PCI clinical outcomes. However, their results are inconclusive, potentially reflecting region-specific trends, based on site-reported events without external validity. AIMS: This study aimed to investigate temporal trends in post-PCI clinical outcomes in all-comers randomised controlled trials (RCTs) involving coronary stents. METHODS: We performed a systematic review identifying RCTs comparing a clinical outcome as a primary endpoint among different coronary stents with an all-comers design and independent clinical event adjudication, extracting the study start year, patient baseline characteristics, and one- and five-year clinical outcomes. Temporal trends in clinical outcomes (cardiac death, myocardial infarction [MI], target lesion revascularisation [TLR], stent thrombosis [ST]) were assessed using random-effects meta-regression analyses, estimating the relationship between clinical outcomes and study start year. RESULTS: Overall, 25 all-comers trials (51 device arms, 66,327 patients) conducted between 2003 and 2018 fulfilled the eligibility criteria. Random-effects meta-regression analysis revealed significant decreasing trends in one- and five-year cardiac death, one-year TLR, and five-year ST incidences (relative risk per 10-year increase: 0.69 [0.51-0.92], 0.66 [0.44-0.98], 0.60 [0.41-0.88], and 0.18 [0.07-0.44], respectively). There was no significant trend in myocardial infarction incidences. CONCLUSIONS: This is the first attempt to clarify and quantify the temporal trends of post-PCI outcome incidence. The 15-year improvements in PCI therapy and post-therapeutic patient management are associated with reduced incidences of cardiac death and PCI-related adverse events.

The relationship between coronary stent strut thickness and the incidences of clinical outcomes after drug-eluting stent implantation: A systematic review and meta-regression analysis.

BACKGROUND: Drug-eluting stents (DESs) have been developed with thinner stent struts, and more biocompatible polymers and anti-proliferative drugs to improve the clinical performance. However, it remains unclear whether thinner struts are associated with favorable short- and long-term clinical outcomes such as target lesion revascularization (TLR), periprocedural myocardial infarction (PMI), and stent thrombosis (ST). METHODS: We searched MEDLINE, Embase and other online sources for randomized controlled trials (RCTs) comparing clinical outcomes between a DES and other stent(s), with independent clinical event adjudication. We investigated stent-related events (TLR, PMI, and ST) in 5 years. Each outcome was analyzed with random-effects meta-regression model against strut thickness, then adjusted for DES generation and patient and lesion characteristics. RESULTS: We identified 49 RCTs enrolling 97,465 patients, of which strut thickness ranged from 60 to 140 µm. Incidences of 1-year TLR, PMI, and early ST were reduced with thinner stent struts, when adjusted for stent generation (adjusted relative risk [RR] per 10 µm increase 1.12 [95% CI 1.04-1.21], 1.15 [95% CI 1.05-1.26], and 1.15 [95% CI 1.06-1.25], respectively). Strut thickness was not independently associated with incidences of 5-year TLR, late and very late ST. In addition, early DESs contributed to a higher incidence of very late ST (adjusted RR 2.97 [95% CI 1.36-6.50]). CONCLUSIONS: In this meta-regression analysis, a thinner strut thickness was associated with reduced incidences of early stent-related adverse events (1-year TLR, PMI, and early ST), but not with later events (5-year TLR, late ST, and very late ST).

Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first-line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP-1RA and SGLT2i may exert positive effects on patients with known CVD. OBJECTIVES: To systematically review the available evidence on the benefits and harms of DPP4i, GLP-1RA, and SGLT2i in people with established CVD, using network meta-analysis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP-1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, all-cause mortality, hospitalisation for heart failure (HF), and safety outcomes. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta-analyses and network meta-analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope. MAIN RESULTS: We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta-analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP-1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow-up duration. 1. DPP4i versus placebo Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high-certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high-certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high-certainty evidence), and all-cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high-certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate-certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low-certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate-certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate-certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate-certainty evidence). 2. GLP-1RA versus placebo Our findings indicate that GLP-1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high-certainty evidence), all-cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high-certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high-certainty evidence). GLP-1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate-certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high-certainty evidence). GLP-1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low-certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low-certainty evidence). We are uncertain about the effect of GLP-1RA on hypoglycaemia and bone fractures. 3. SGLT2i versus placebo This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate-certainty evidence), all-cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate-certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high-certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high-certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate-certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate-certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate-certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high-certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low-certainty evidence). 4. Network meta-analysis Because we failed to identify direct comparisons between each class of the agents, findings from our network meta-analysis provided limited novel insights. Almost all findings from our network meta-analysis agree with those from the standard meta-analysis. GLP-1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate-certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta-analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all-cause mortality. AUTHORS' CONCLUSIONS: Findings from both standard and network meta-analyses of moderate- to high-certainty evidence suggest that GLP-1RA and SGLT2i are likely to reduce the risk of CVD mortality and all-cause mortality in people with established CVD; high-certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate-certainty evidence likely supports the use of GLP-1RA to reduce fatal and non-fatal stroke. Future studies conducted in the non-diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose-lowering effects.