Non-invasive electrical stimulation in patients with neurodegenerative ataxia and spasticity: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: There are limited treatment options for patients with neurodegenerative ataxia and spasticity. Non-invasive electrostimulation (NES) is receiving increasing interest because of its ease of implementation, cost-effectiveness and safety. A meta-analysis was conducted to evaluate the efficacy of NES. METHODS: MEDLINE and Embase were screened for studies using NES in ataxias and spasticity. Key outcome measurements of effectiveness included changes in (1) Modified Ashworth Scale (MAS) scores, (2) cerebellar brain inhibition (CBI), (3) the nine-hole peg test (9HPT), (4) the 8-m walking time (8MWT), (5) International Cooperative Ataxia Rating Scale (ICARS) score and (6) the Scale for Assessment and Rating of Ataxia (SARA) scores. RESULTS: Seven randomized controlled trials involving 203 patients were included. There were significant improvements in MAS (mean difference [MD] -0.42, 95% confidence interval [CI] -0.76 to -0.08, p = 0.015), CBI (MD -0.35%, 95% CI -0.42 to -0.28, p < 0.001), 8MWT (MD -1.88 s, 95% CI -3.26 to -0.49, p = 0.008), ICARS (MD -7.84, 95% CI -11.90 to -3.78, p < 0.001) and SARA (MD -3.01, 95% CI -4.74 to -1.28, p < 0.001). There was almost no heterogeneity across all outcomes except for CBI (I2  = 79%). No significant changes in the 9HPT were observed comparing NES to a sham procedure (MD -3.52 s, 95% CI -9.15 to 2.10, p = 0.220). Most included studies were at low risk of bias, and no severe adverse effects were reported. CONCLUSION: It was demonstrated that NES is an effective treatment for improving coordination and balance and increased exercise capacity in patients with ataxia and spasticity. There was also a significant modulation of CBI in ataxic patients.

Higher mortality in acute coronary syndrome patients without standard modifiable risk factors: Results from a global meta-analysis of 1,285,722 patients.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes, hyperlipidemia, hypertension, and smoking, are used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. METHODS: Embase, Medline and Pubmed were searched for studies comparing SMuRF-less and SMuRF patients with first presentation of ACS. We conducted single-arm analyses to determine the proportion of SMuRF-less patients in the ACS cohort, and compared the clinical presentation and outcomes of these patients. RESULTS: Of 1,285,722 patients from 15 studies, 11.56% were SMuRF-less. A total of 7.44% of non-ST-segment-elevation ACS patients and 12.87% of ST-segment-elevation myocardial infarction (STEMI) patients were SMuRF-less. The proportion of SMuRF-less patients presenting with STEMI (60.71%) tended to be higher than those with SMuRFs (49.21%). Despite lower body mass index and fewer comorbidities such as chronic kidney disease, peripheral arterial disease, stroke and heart failure, SMuRF-less patients had increased in-hospital mortality (RR:1.57, 95%CI:1.38 to 1.80) and cardiogenic shock (RR:1.39, 95%CI:1.18 to 1.65), but lower risk of heart failure (RR:0.91, 95%CI:0.83 to 0.99). On discharge, SMuRF-less patients were prescribed less statins (RR:0.93, 95%CI:0.91 to 0.95), beta-blockers (RR:0.94, 95%CI:0.92 to 0.96), P2Y12 inhibitors (RR: 0.98, 95%CI: 0.96 to 0.99), and angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker (RR:0.92, 95%CI:0.75 to 0.91). CONCLUSION: In this study level meta-analysis, SMuRF-less ACS patients demonstrate higher mortality compared with patients with at least one traditional atherosclerotic risk factor. Underuse of guideline-directed medical therapy amongst SMuRF-less patients is concerning. Unraveling novel risk factors amongst SMuRF-less individuals is the next important step. SUMMARY: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes mellitus, hyperlipidemia, hypertension, and smoking, are often used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. Of 1,285,722 ACS patients, 11.56% were SMuRF-less. Despite lower body mass index and fewer comorbidities, SMuRF-less patients had increased in-hospital mortality and cardiogenic shock. However, despite worse outcomes, SMuRF-less patients were prescribed less guideline-directed medical therapies on discharge.

Meta-Analysis Comparing Risk Factors, Incidence, and Outcomes of Patients With Versus Without Prosthesis-Patient Mismatch Following Transcatheter Aortic Valve Implantation.

Current guidelines on the management of patients with aortic valvular disease have widened the use of transcatheter aortic valve implantation (TAVI) with an emphasis on avoidance of prosthesis-patient mismatch (PPM). This study sought to examine the incidence, risk factors, and all-cause mortality of PPM after TAVI. Medline and Embase databases were searched from inception to August 10, 2021. Patients were compared along 2 arms: (1) any degree of PPM and those without PPM, (2) severe PPM, and nonsevere PPM. A total of 22 articles involving 115,442 patients after TAVI were included. Pooled incidence for any degree of PPM was 30.1% and 10.7% in severe PPM. Incidence was significantly higher (p <0.001) for any degree of PPM in Europe (33.1%) and North America (34.4%) compared with Asia (10.4%). Incidence of severe PPM was higher (p = 0.015) in older generation (13.6%) compared with current-generation valves (6.3%). Severe PPM increased the risk of all-cause mortality relative to nonsevere PPM (hazard ratio: 1.86, 95% confidence interval: 1.05 to 3.29, p = 0.034). Patients of younger age, increased body surface area, lower left ventricular ejection fraction, and classified New York Heart Association Class III/IV were at greater risk of both any degree and severe PPM. Smaller prosthesis size increased the risk of any degree of PPM, whereas postdilation and larger prostheses were protective factors. In conclusion, all-cause mortality was significantly affected in severe PPM compared with nonsevere cases, whereas this excess mortality was not observed between those with any degree of PPM and those without. Closer attention to patient and bioprosthetic valve factors is required to minimize the occurrence of severe PPM.

Prevalence, Risk Factors and Intervention for Depression and Anxiety in Pulmonary Hypertension: A Systematic Review and Meta-analysis.

BACKGROUND: Current guidelines recommend psychological support for patients with pulmonary hypertension suffering from psychological adversity. However, little is known about the prevalence and risk factors of depression and anxiety in patients with pulmonary hypertension (PH). METHODS: Medline and Embase were searched from inception to 6 May 2021. Meta-analysis of proportions using the generalized linear mixed model was conducted to analyze the pooled prevalence rates of depression and anxiety in PH patients. Risk factors for depression and anxiety in PH patients were evaluated using meta regression. RESULTS: A total of 24 studies involving 2,161 PH patients were included. The pooled prevalence of depression in PH was 28.0% (95% CI: 20.5-36.8) and pooled prevalence of anxiety was 37.1% (95% CI: 28.7-46.4). There was a significantly higher prevalence of anxiety (p = 0.0013) amongst PH patients in Asia (61.1%) compared to Europe (40.3%) and North America (22.9%). In terms of risk factors, congenital heart disease-related pulmonary arterial hypertension (PAH-CHD) were significantly associated with both depression (OR: 1.68, 95% CI: 1.27-2.23, p = 0.024) and anxiety (OR: 1.63, 95% CI: 1.45-1.83, p = 0.002). On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH, OR: 1.18, 95% CI: 1.10-1.26, p = 0.004) was significantly associated with depression, whereas worse pulmonary vascular resistance (ß: 0.30, 95% CI: 0.09-0.52, p = 0.005) and cardiac index (ß: -0.96, 95% CI: -1.58 to -0.35, p = 0.002) were significantly correlated with anxiety. CONCLUSION: The prevalence of anxiety and depression in PH patients is alarmingly high, with an increased prevalence of anxiety in Asia compared to Europe or North America. Psychological support is warranted for patients with PH, particularly those with underlying congenital heart disease, CTEPH, and severe disease. SYSTEMATIC REVIEW REGISTRATION: CRD42021251733.

Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention for Multivessel Coronary Artery Disease: A One-Stage Meta-Analysis.

Background and Aims: Data are emerging on 10-year mortality comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with stenting for multivessel disease (MVD) without left main (LM) involvement. We conducted an updated two-stage meta-analysis using reconstructed individual patient data to compare long-term mortality between CABG and PCI for patients with MVD without significant LM coronary disease. Methods: Medline and Embase databases were searched for articles comparing CABG with PCI for MVD. A two-stage meta-analysis was conducted using reconstructed patient level survival data for all-cause mortality with subgroups by SYNTAX score. The shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results: We screened 1,496 studies and included six randomized controlled trials with 7,181 patients. PCI was associated with greater 10-year all-cause mortality risk (HR: 1.282, CI: 1.118-1.469, p < 0.001) compared with CABG. In patients with low SYNTAX score, 10-year all-cause mortality after PCI was comparable to CABG (HR: 1.102, 0.822-1.479, p = 0.516). However, in patients with moderate to high SYNTAX score, 10-year all-cause mortality was significantly higher after PCI compared with CABG (HR: 1.444, 1.122-1.858, p < 0.001; HR: 1.856, 1.380-2.497, p < 0.001, respectively). Conclusion: This updated reconstructed individual patient-data meta-analysis revealed a sustained lower cumulative all-cause mortality of CABG over PCI for multivessel disease without LM involvement.

Clinical, echocardiographic and prognostic outcomes of patients with concordant and discordant high-gradient aortic stenosis in an Asian cohort.

Literature of patients with severe high-gradient aortic stenosis (HG AS) (mean pressure gradient [MPG] ≥ 40 mmHg and aortic valve area [AVA] ≥ 1.0 cm2) remains limited. This study seeks to compare the prognostic outcomes of patients with high-gradient concordant (HGCON-AS) and discordant AS (HGDIS-AS) in an Asian cohort. From 2010 to 2015, patients with moderate-to-severe AS with preserved left ventricular ejection fraction (LVEF ≥ 50%) were recruited and stratified into 3 groups based on index echocardiogram-(1) HGDIS-AS, (2) HGCON-AS and (3) moderate AS (MOD-AS). The primary study endpoints was all-cause mortality, with secondary endpoints of congestive heart failure (CHF) admissions and aortic valve replacement (AVR). Multivariable Cox regression was used and Kaplan-Meier curves were constructed to evaluate associations between HGDIS-AS, HGCON-AS and MOD-AS, and the study outcomes. A total of 467 patients were studied, comprising of 6.2% HGDIS-AS, 13.9% HGCON-AS and 79.9% MOD-AS patients. There was significantly higher AVR rates in the HGCON-AS group (58.5%), followed by HGDIS-AS (31.0%) and MOD-AS (4.6%), p < 0.001) groups. After adjusting for confounders, HGCON-AS was significantly associated with all-cause mortality (HR 3.082, 95% CI 1.479-6.420, p = 0.003) and CHF admissions (HR 12.728, 95% CI 2.922-55.440 p = 0.001) but not HGDIS-AS, with MOD-AS as the reference group. Both HGDIS-AS (HR 7.715, 95% CI 2.927-20.338; p < 0.001) and HGCON-AS (HR 21.960, 95% CI 10.833-44.515, p < 0.001) were independent predictors of AVR. After exclusion of reversible high-flow states, HGDIS-AS patients appear to have a more favourable prognostic profile compared to HGCON-AS patients. Large prospective interventional studies examining the prognostic differences between the two groups will be the next important step.

Meta-Analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Narrowing.

Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p <0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD.