Prevalence of statin intolerance: a meta-analysis.

AIMS: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI. METHODS AND RESULTS: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI. CONCLUSION: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

Efficacy and safety of colchicine in patients with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta-analysis was to evaluate the efficacy and safety of colchicine in patients with CAD. METHODS: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all-cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers. RESULTS: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta-analysis. At mean follow-up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P < .001), recurrent myocardial infarction (3.41 vs. 4.41%; P = .005), stroke (0.40 vs. 0.90%; P = .002) and hospitalization due to CV events (0.90 vs. 2.87%; P = .02) compared to the control group. The 2 patient groups had similar risk for all-cause mortality (2.08 vs. 1.88%; P = .82) and CV mortality (0.71 vs. 1.01%; P = .38). Colchicine significantly reduced high-sensitivity C-reactive protein (-4.25, P = .001) compared to controls but did not significantly affect interleukin (IL)-ß1 and IL-18 levels. CONCLUSION: Colchicine reduced CV events and inflammatory markers, high-sensitivity C-reactive protein and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation.

Carotid Atherosclerosis in Predicting Coronary Artery Disease: A Systematic Review and Meta-Analysis.

[Figure: see text].

Correction to: Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis.

An amendment to this paper has been published and can be accessed via the original article.

Left Ventricular Diastolic and Systolic Functions in Patients with Hypothyroidism.

Background and objectives: Long standing hypothyroidism may impair myocardial relaxation, but its effect on systolic myocardial function is still controversial. The aim of this study was to investigate left ventricular (LV) systolic and diastolic function in patients with hypothyroidism. Materials and Methods: This study included 81 (age 42 ± 13 years, 92% female) patients with hypothyroidism, and 22 age and gender matched controls. All subjects underwent a detailed clinical examination followed by a complete biochemical blood analysis including thyroid function assessment and anthropometric parameters measurements. LV function was assessed by 2-dimensional, M-mode and Tissue-Doppler Doppler echocardiographic examination performed in the same day. Results: Patients had lower waist/hip ratio (p< 0.001), higher urea level (p = 0.002), and lower white blood cells (p = 0.011), compared with controls. All other clinical, biochemical, and anthropometric data did not differ between the two groups. Patients had impaired LV diastolic function (lower E wave [p< 0.001], higher A wave [p = 0.028], lower E/A ratio [p< 0.001], longer E wave deceleration time [p = 0.01], and higher E/e' ratio [p< 0.001]), compared with controls. Although LV global systolic function did not differ between groups, LV longitudinal systolic function was compromised in patients (lateral mitral annular plane systolic excursion-MAPSE [p = 0.005], as were lateral and septal s' [p< 0.001 for both]). Conclusions: In patients with hypothyroidism, in addition to compromised LV diastolic function, LV longitudinal systolic function is also impaired compared to healthy subjects of the same age and gender. These findings suggest significant subendocardial function impairment, reflecting potentially micro-circulation disease that requires optimum management.

Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis.

BACKGROUND: The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins' prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. METHODS: We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. RESULTS: Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72-0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76-0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69-0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68-0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69-0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79-0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77-0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64-0.99, P = 0.04 and HR 0.76 95% CI: 0.61-0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies' analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. CONCLUSIONS: In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.

Left atrial compliance index predicts exercise capacity in patients with heart failure and preserved ejection fraction irrespective of right ventricular dysfunction.

BACKGROUND AND AIM: Predictors of exercise capacity in heart failure (HF) with preserved ejection fraction (HFpEF) remain of difficult determination. The aim of this study was to identify predictors of exercise capacity in a group of patients with HFpEF and right ventricle (RV) dysfunction METHODS: In 143 consecutive patients with HFpEF (age 62 ± 9 years, LV EF ≥45) and 41 controls, a complete echocardiographic study was performed. In addition to conventional measurements, LA compliance was calculated using the formula: [LAV max - LAV min/LAV min × 100]. Exercise capacity was assessed using the six-minute walking test (6-MWT). Tricuspid annular plane systolic excursion (TAPSE) < 1.7 cm was utilized to categorize patients with RV dysfunction (n = 40) from those with maintained RV function (n = 103). RESULTS: Patients with RV dysfunction were older (P = 0.002), had higher NYHA class (P = 0.001), higher LV mass index (P = 0.01), reduced septal and lateral MAPSE (all P < 0.001), enlarged LA (P = 0.001) impaired LA compliance index (P < 0.001) and exhibited a more compromised 6-MWT (P = 0.001). LA compliance index correlated more closely with 6-MWT (r = 0.51, P < 0.001) compared with the other LA indices (AP diameter, transverse diameter and volume indexed; r = -0.30, r = -0.35 and r = -0.38, respectively). In multivariate analysis, LA compliance index <60% was 88% sensitive and 61% specific (AUC 0.80, CI = 0.67-0.92 P = 0.001) in predicting exercise capacity. CONCLUSION: An impairment in LA compliance was profound in patients with HFpEF and RV dysfunction and seems to be most powerful independent predictor of limited exercise capacity.

Different determinants of exercise capacity in HFpEF compared to HFrEF.

BACKGROUND: Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic determinants of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF. METHODS: In 111 HF patients (mean age 63 ± 10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m). RESULTS: Group I were older (p = 0.008), had higher prevalence of diabetes (p = 0.027), higher baseline heart rate (p = 0.004), larger left atrium - LA (p = 0.001), longer LV filling time - FT (p = 0.019), shorter isovolumic relaxation time (p = 0.037), shorter pulmonary artery acceleration time - PA acceleration time (p = 0.006), lower left atrial lateral wall myocardial velocity (a') (p = 0.018) and lower septal systolic myocardial velocity (s') (p = 0.023), compared with Group II. Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p = 0.007), higher baseline heart rate (p = 0.005), higher NT-ProBNP (p = 0.001), larger LA (p = 0.004), lower septal s', e', a' waves, and septal mitral annular plane systolic excursion (MAPSE), shorter PA acceleration time (p < 0.001 for all), lower lateral MAPSE, higher E/A & E/e', and shorter LVFT (p = 0.001 for all), lower lateral e' (p = 0.009), s' (p = 0.006), right ventricular e' and LA emptying fraction (p = 0.012 for both), compared with HFpEF patients. In multivariate analysis, only LA diameter [2.676 (1.242-5.766), p = 0.012], and diabetes [0.274 (0.084-0.898), p = 0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012-1.137), p = 0.018] and LA diameter [3.685 (1.348-10.071), p = 0.011], but in HFpEF, lateral s' [0.295 (0.099-0.882), p = 0.029], and hemoglobin level [0.497 (0.248-0.998), p = 0.049] independently predicted poor 6-MWT performance. CONCLUSIONS: In HF patients determinants of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main determinants.

Left atrial changes in early stages of heart failure with preserved ejection fraction.

BACKGROUND AND AIM: Increased left atrial (LA) mass was introduced as a compensatory mechanism in heart failure (HF) patients. Furthermore, atrial conduction time and LA emptying fraction is are deteriorated in HF with preserved ejection fraction (HFpEF). The aim of this study was to assess the early LA changes in HFpEF patients. METHODS: In 79 consecutive patients with HFpEF (age 61±8 years, NYHA class I-III, LV EF ≥45%), a complete 2-dimensional, M-mode, and Doppler echocardiographic study was performed. According to the diastolic dysfunction (DD), patients were divided into three groups: Group I-29 healthy subjects (control group); Group II-HFpEF patients with mild DD; and Group III-HFpEF patients with moderate DD. RESULTS: The LV mass was increased (P<.05), septal s', lateral s', septal and lateral MAPSE were decreased (P<.05, for all), E/e' ratio was increased (P<.001), LA mass and minimal volume were increased (P<.001, P<.05), LA emptying fraction was decreased (P<.05), and LA dyssynchrony was deteriorated (P<.05) in patients with mild DD compared to controls. These changes were of the same nature in patients with moderate LV DD. CONCLUSIONS: In early stage of DD, in patients with HFpEF, in addition to LV hypertrophy and compromised LV longitudinal systolic function, the LA emptying fraction is reduced, LA mass and LAV min are increased and LA dyssynchrony is significant, despite normal LA dimensions. These findings suggest early LA function deterioration irrespective of normal cavity measurements, hence a need for optimum therapy.

One-Month Dual Antiplatelet Therapy Reduces Major Bleeding Compared With Longer-Term Treatment Without Excess Stent Thrombosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Dual antiplatelet therapy (DAPT) remains the gold standard in patients who underwent percutaneous coronary intervention (PCI). This meta-analysis aims to evaluate the clinical safety of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor after PCI with drug-eluting stents (DES). We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Registry, and ClinicalTrials.gov databases and identified 5 randomized controlled trials with 29,831 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary end point was major bleeding, and the co-primary end point was stent thrombosis. The secondary end point included all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events. Compared with >1-month DAPT, the 1-month DAPT was associated with a lower rate of major bleeding (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 to 0.97, p = 0.03, I2 = 71%), whereas stent thrombosis had a similar rate in both study groups (OR 1.08, 95% CI 0.81 to 1.44, p = 0.60, I2 = 0.0%). The study groups had similar risks for all-cause mortality (OR 0.89, 95% CI 0.77 to 1.04, p = 0.14, I2 = 0.0%), cardiovascular death (OR 0.84, 95% CI 0.59 to 1.19, p = 0.32, I2 = 0.0%), myocardial infarction (OR 1.04, 95% CI 0.89 to 1.21, p = 0.62, I2 = 0.0%), and stroke (OR 0.82, 95% CI 0.64 to 1.05, p = 0.11, I2 = 6%). The risk of major adverse cardiovascular or cerebrovascular events was lower (OR 0.86, 95% CI 0.76 to 0.97, p = 0.02, I2 = 25%) in the 1-month DAPT compared with >1-month DAPT. In conclusion, in patients who underwent PCI with DES, 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor reduced major bleeding with no risk of increased thrombotic risk compared with longer-term DAPT.

Management and clinical outcome of myocardial infarction in Kosovo: A cross-sectional study.

Background and Aims: Myocardial infarction (MI) is a major cause of mortality worldwide, irrespective of its presentation as non-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). The objective of this study was to assess national results of management and clinical outcome of acute MI patients in Kosovo. Methods: This cross-sectional descriptive study, conducted at the Clinic of Cardiology of the University Clinical Center of Kosovo, in Prishtina, included all patients hospitalized with acute MI over a period of 7 years (2014-2020). The primary outcome of the study was in-hospital mortality. Results: Among 7353 admitted patients with acute MI (mean age 63 ± 12 years, 29% female) and according to the final diagnosis, 4436 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. More patients with STEMI received primary percutaneous intervention (PPCI) than those with NSTEMI (50% vs. 41%, p < 0.001). In-hospital mortality was higher in no PPCI patients compared to PPCI both in NSTEMI (10.7% vs. 2.6%, p < 0.001) and STEMI (20.9% vs. 6.8%, p < 0.001). Age ≥65 years [0.399 (0.267-0.597), p ˂ 0.001], hemoglobin level [0.889 (0.815-0.970), p = 0.008], STEMI [0.491 (0.343-0.704), p ˂ 0.001], lack of PPCI [2.636 (1.798-3.866), p ˂ 0.001], cardiogenic shock [0.002 (0.001-0.006), p < 0.001], reduced left ventricular ejection fraction (LV EF) [0.966 (0.951-0.980), p < 0.001], and heart rate at admission [1.009 (1.000-1.017), p = 0.047], independently predicted mortality. In STEMI, cardiogenic shock (p ˂ 0.001), lack of PPCI (p = 0.006), female gender (p = 0.01), and low LV EF (p = 0.04) predicted mortality but age ≥65 years (p = 0.02), female gender (p = 0.02), low LV EF (p = 0.007), and low hemoglobin (p = 0.04) predicted mortality in NSTEMI. Conclusion: Between 2014 and 2020, half of patients with acute MI were not treated with PPCI, who had high mortality, particularly when presenting with STEMI. Age, cardiogenic shock, anemia, low LV EF, STEMI and no PPCI independently predicted mortality. Cardiogenic shock and lack of PPCI independently predicted mortality, only in STEMI.

The Rationale and Design of the KOSovan Acute Coronary Syndrome (KOS-ACS) Registry.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: (1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; (2) to create a national database with information on health care in ACS patients treated in Kosovo; (3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, the length of hospital stay, and the quality of clinical care; and (4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (unstable angina, NSTEMI, or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on the post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the registry.

Smoking and Hypertriglyceridemia Predict ST-Segment Elevation Myocardial Infarction in Kosovo Patients with Acute Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI), presented as ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is influenced by atherosclerosis risk factors. AIM: The aim of this study was to assess the patterns of presentation of patients with acute MI in Kosovo. METHODS: This was a cross-sectional study conducted at the University Clinical Center of Kosovo, which included all patients hospitalized with acute MI over a period of 7 years. RESULTS: Among the 7353 patients admitted with acute MI (age 63 ± 12 years, 29% female), 59.4% had STEMI and 40.6% had NSTEMI. The patients with NSTEMI patients less (48.3% vs. 54%, p < 0.001), but more of them had diabetes (37.8% vs. 33.6%, p < 0.001), hypertension (69.6% vs. 63%, p < 0.001), frequently had a family history of coronary artery disease (CAD) (40% vs. 38%, p = 0.009), and had more females compared to the patients with STEMI (32% vs. 27%, p < 0.001). The patients with NSTEMI underwent less primary percutaneous interventions compared with the patients with STEMI (43.6% vs. 55.2%, p < 0.001). Smoking [1.277 (1.117-1.459), p ˂ 0.001] and high triglycerides [0.791 (0.714-0.878), p = 0.02] were independent predictors of STEMI. CONCLUSIONS: In Kosovo, patients with STEMI are more common than those with NSTEMI, and they were mostly males and more likely to have diabetes, hypertension, and a family history of CAD compared to those with NSTEMI. Smoking and high triglycerides proved to be the strongest predictors of acute STEMI in Kosovo, thus highlighting the urgent need for optimum atherosclerosis risk control and education strategies.

2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP).

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.

Percutaneous Coronary Intervention Is Not Superior to Optimal Medical Therapy in Chronic Coronary Syndrome: A Meta-Analysis.

(1) Background and Aim: Conflicting evidence exists regarding the benefits of percutaneous coronary intervention (PCI) on survival and symptomatic relief of patients with chronic coronary syndrome (CCS) compared with optimal medical therapy (OMT). This meta-analysis is to evaluate the short- and long-term clinical benefit of PCI over and above OMT in CCS. (2) Methods: Main endpoints were major adverse cardiac events (MACEs), all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), urgent revascularization, stroke hospitalization, and quality of life (QoL). Clinical endpoints at very short (≤3 months), short- (<12 months), and long-term (≥ 12 months) follow-up were evaluated. (3) Results: Fifteen RCTs with a total of 16,443 patients with CCS (PCI n = 8307 and OMT n = 8136) were included in the meta-analysis. At mean follow-up of 27.7 months, the PCI group had similar risk of MACE (18.2 vs. 19.2 %; p < 0.32), all-cause mortality (7.09 vs. 7.88%; p = 0.56), CV mortality (8.74 vs. 9.87%; p = 0.30), MI (7.69 vs. 8.29%; p = 0.32), revascularization (11.2 vs. 18.3%; p = 0.08), stroke (2.18 vs. 1.41%; p = 0.10), and hospitalization for anginal symptoms (13.5 vs. 13.9%; p = 0.69) compared with OMT. These results were similar at short- and long-term follow-up. At the very short-term follow-up, PCI patients had greater improvement in the QoL including physical limitation, angina frequency, stability, and treatment satisfaction (p < 0.05 for all) but such benefits disappeared at the long-term follow-up. (4) Conclusions: PCI treatment of CCS does not provide any long-term clinical benefit compared with OMT. These results should have significant clinical implications in optimizing patient's selection for PCI treatment.

The GLVC scoring system: a single-center model for predicting survival and hospitalization in patients with heart failure.

BACKGROUND: Heart failure (HF) is the only cardiovascular disease with an ever-increasing incidence. AIMS: The aim of this study was to assess the predictors of adverse clinical events (CE) and the creation and evaluation of the prognostic value of a novel personalized scoring system in patients with HF. METHODS: The study included 113 HF patients (median age 64 years (IQR 58-69); 57.52% male). The new novel prognostic score named GLVC (G, global longitudinal peak strain (GLPS); L, left ventricular diastolic diameter (LVDD); V, oxygen pulse (VO2/HR); and C, high sensitivity C-reactive protein (hs-CRP)) was created. The Kaplan-Meier method and log-rank test were used to compare the CE. RESULTS: Results from final analyses showed that low GLPS (< 13.9%, OR = 2.66, 95% CI = 1.01-4.30, p = 0.002), high LVDD (> 56 mm, OR = 2.37, 95% CI = 1.01-5.55, p = 0.045), low oxygen pulse (< 10, OR = 2.8, 95% CI = 1.17-6.70, p = 0.019), and high hs-CRP (> 2.38 µg/ml, OR = 2.93, 95% CI = 1.31-6.54, p = 0.007) were independent prognostic factors for adverse CE in HF population. All the patients were stratified into a low-risk or high-risk group according to a novel "GLVC" scoring system. The Kaplan-Meier analyses demonstrated that patients in the high-risk group were more predisposed to having higher adverse clinical events compared to patients in the low-risk group. CONCLUSIONS: A novel and comprehensive personalized "GLVC" scoring system is an easily available and effective tool for predicting the adverse outcomes in HF.

Ventricular septal defect associated with aortic regurgitation and ascending aortic aneurysm: a case report.

INTRODUCTION: Ventricular septal defect (VSD) is one of the most common congenital cardiac anomalies. Patients with perimembranous VSD may have aortic regurgitation (AR) secondary to prolapse of the aortic cusp. CASE PRESENTATION: We present a case of 23-year-old White man with VSD, AR and ascending aortic aneurysm. The patient presented to outpatient clinic with weakness and gradual worsening shortness of breath for the past 5 years. Clinical examination revealed regular heart rhythm and loud continuous systolic-diastolic murmur (Lewin's grade 6/6), heard all over the precordium, associated with a palpable thrill. The ECG showed right axis deviation, fractionated QRS in V1 and signs of biventricular hypertrophy. The chest X-ray showed cardiomegaly. Transthoracic and transesophageal echocardiograms showed a perimembranous VSD with moderate restrictive shunt (Qp/Qs = 1.6), aortic regurgitation (AR), and ascending aortic aneurysm. Other clinical and laboratory findings were within normal limits. CONCLUSIONS: Perimembranous VSD, may be associated with aortic regurgitation and ascending aortic aneurysm as secondary phenomenon if it is not early diagnosed and successfully treated.

Diagnostic Usefulness of Spiroergometry and Risk Factors of Long COVID in Patients with Normal Left Ventricular Ejection Fraction.

The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic has brought forth various clinical manifestations and long-term complications, including a condition known as long COVID. Long COVID refers to a persistent set of symptoms that continue beyond the acute phase of the disease. This study investigated the risk factors and the utility of spiroergometry parameters for diagnosing patients with long COVID symptoms. The 146 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with normal left ventricular ejection fraction and without respiratory diseases were included and divided into two groups: the group demonstrating long COVID symptoms [n = 44] and the group without long COVID symptoms [n = 102]. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. ClinicalTrials.gov Identifier: NCT04828629. Patients with long COVID symptoms had significantly higher age [58 (vs.) 44 years; p < 0.0001], metabolic age [53 vs. 45 years; p = 0.02)], left atrial diameter (LA) [37 vs. 35 mm; p = 0.04], left ventricular mass index (LVMI) [83 vs. 74 g/m2, p = 0.04], left diastolic filling velocity (A) [69 vs. 64 cm/s, p = 0.01], the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') [7.35 vs. 6.05; p = 0.01], and a lower ratio of early to late diastolic transmitral flow velocity (E/A) [1.05 vs. 1.31; p = 0.01] compared to the control group. In cardiopulmonary exercise testing (CPET), long COVID patients presented lower forced vital capacity (FVC) [3.6 vs. 4.3 L; p < 0.0001], maximal oxygen consumption measured during incremental exercise indexed per kilogram (VO2max) [21 vs. 23 mL/min/kg; p = 0.04], respiratory exchange ratio (RER) [1.0 vs. 1.1; p = 0.04], forced expiratory volume in one second (FEV1) [2.90 vs. 3.25 L; p = 0.04], and a higher ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) [106 vs. 100%; p = 0.0002]. The laboratory results pointed out that patients with long COVID symptoms also had a lower rate of red blood cells (RBC) [4.4 vs. 4.6 × 106/uL; p = 0.01]; a higher level of glucose [92 vs. 90 mg/dL; p = 0.03]; a lower glomerular filtration rate (GFR) estimate by Modification of Diet in Renal Disease (MDRD) [88 vs. 95; p = 0.03]; and a higher level of hypersensitive cardiac Troponin T (hs-cTnT) [6.1 vs. 3.9 pg/mL; p = 0.04]. On the multivariate model, only FEV1/FVC% (OR 6.27, 95% CI: 2.64-14.86; p < 0.001) independently predicted the long COVID symptoms. Using the ROC analysis, the FEV1/FVC% ≥ 103 was the most powerful predictor of spiroergometry parameters (0.67 sensitive, 0.71 specific, AUC of 0.73; p < 0.001) in predicting the symptoms of long COVID. Spiroergometry parameters are useful in diagnosing long COVID and differentiating it from cardiovascular disease.

Acute pericarditis as a major clinical manifestation of long COVID-19 syndrome.

BACKGROUND: The long COVID-19 syndrome has been recently described and some reports have suggested that acute pericarditis represents important manifestation of long COVID-19 syndrome. The aim of this study was to identify the prevalence and clinical characteristics of patients with long COVID-19, presenting with acute pericarditis. METHODS: We retrospectively included 180 patients (median age 47 years, 62% female) previously diagnosed with COVID-19, exhibiting persistence or new-onset symptoms ≥12 weeks from a negative naso-pharyngeal SARS CoV2 swamp test. The original diagnosis of COVID-19 infection was determined by a positive swab. All patients had undergone a thorough physical examination. Patients with suspected heart involvement were referred to a complete cardiovascular evaluation. Echocardiography was performed based on clinical need and diagnosis of acute pericarditis was achieved according to current guidelines. RESULTS: Among the study population, shortness of breath/fatigue was reported in 52%, chest pain/discomfort in 34% and heart palpitations/arrhythmias in 37%. Diagnosis of acute pericarditis was made in 39 patients (22%). Mild-to-moderate pericardial effusion was reported in 12, while thickened and bright pericardial layers with small effusions (< 5 mm) with or without comet tails arising from the pericardium (pericardial B-lines) in 27. Heart palpitations/arrhythmias (OR:3.748, p = 0.0030), and autoimmune disease and allergic disorders (OR:4.147, p = 0.0073) were independently related to the diagnosis of acute pericarditis, with a borderline contribution of less likelihood of hospitalization during COVID-19 (OR: 0.100, p = 0.0512). CONCLUSION: Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome. Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.

Strain Rate Changes during Stress Echocardiography Are the Most Accurate Predictors of Significant Coronary Artery Disease in Patients with Previously Treated Acute Coronary Syndrome.

BACKGROUND AND AIMS: Dobutamine stress echocardiography (DSE) is a well-established non-invasive investigation for the detection of ischemic myocardial dysfunction. The aim of this study was to evaluate the accuracy of myocardial deformation parameters measured by speckle tracking echocardiography (STE) in predicting culprit coronary artery lesions in patients with prior revascularization and acute coronary syndrome (ACS). METHODS: We prospectively studied 33 patients with ischemic heart disease, a history of at least one episode of ACS and prior revascularization. All patients underwent a complete stress Doppler echocardiographic examination, including the myocardial deformation parameters of peak systolic strain (PSS), peak systolic strain rate (SR) and wall motion score index (WMSI). The regional PSS and SR were analyzed for different culprit lesions. RESULTS: The mean age of patients was 59 ± 11 years and 72.7% were males. At peak dobutamine stress, the change in regional PSS and SR in territories supplied by the LAD showed smaller increases compared to those in patients without culprit LAD lesions (p < 0.05 for all). Likewise, the regional parameters of myocardial deformation were reduced in patients with culprit LCx lesions compared to those with non-culprit LCx lesions and in patients with culprit RCA legions compared to those with non-culprit RCA lesions (p < 0.05 for all). In the multivariate analysis, the △ regional PSS (1.134 (CI = 1.059-3.315, p = 0.02)) and the △ regional SR (1.566 (CI = 1.191-9.013, p = 0.001)) for LAD territories predicted the presence of LAD lesions. Similarly, in a multivariable analysis, the △ regional PSS and the △SR predicted LCx culprit lesions and RCA culprit lesions (p < 0.05 for all). In an ROC analysis, the PSS and SR had higher accuracies compared to the regional WMSI in predicting culprit lesions. A △ regional SR of -0.24 for the LAD territories was 88% sensitive and 76% specific (AUC = 0.75; p < 0.001), a △ regional PSS of -1.20 was 78% sensitive and 71% specific (AUC = 0.76, p < 0.001) and a △ WMSI of -0.35 was 67% sensitive and 68% specific (AUC = 0.68, p = 0.02) in predicting LAD culprit lesions. Similarly, the △ SR for LCx and RCA territories had higher accuracies in predicting LCx and RCA culprit lesions. CONCLUSIONS: The myocardial deformation parameters, particularly the change in regional strain rate, are the most powerful predictors of culprit lesions. These findings strengthen the role of myocardial deformation in increasing the accuracy of DSE analyses in patients with prior cardiac events and revascularization.