Contribution of pressure and flow changes to resistance reduction after pulmonary arterial hypertension treatment: a meta-analysis of 3898 patients.

Background: Pulmonary arterial hypertension (PAH)-targeted therapies exert significant haemodynamic changes; however, systematic synthesis is currently lacking. Methods: We searched PubMed, CENTRAL and Web of Science for studies evaluating mean pulmonary artery pressure (mPAP), cardiac index/cardiac output (CI/CO) and pulmonary vascular resistance (PVR) of PAH-targeted therapies either in monotherapy or combinations as assessed by right heart catheterisation in treatment-naïve PAH patients. We performed a random-effects meta-analysis with meta-regression. Results: We included 68 studies (90 treatment groups) with 3898 patients (age 47.4±13.2 years, 74% women). In studies with small PVR reduction (<4 WU), CI/CO increase (R2=62%) and not mPAP reduction (R2=24%) was decisive for the PVR reduction (p<0.001 and p=0.36, respectively, in the multivariable meta-regression model); however, in studies with large PVR reduction (>4 WU), both CI/CO increase (R2=72%) and mPAP reduction (R2=35%) contributed significantly to the PVR reduction (p<0.001 and p=0.01, respectively). PVR reduction as a percentage of the pre-treatment value was more pronounced in the oral+prostanoid intravenous/subcutaneous combination therapy (mean difference -50.0%, 95% CI -60.8- -39.2%), compared to oral combination therapy (-41.7%, -47.6- -35.8%), prostanoid i.v./s.c. monotherapy (-31.8%, -37.6- -25.9%) and oral monotherapy (-21.6%, -25.4- -17.8%). Changes in haemodynamic parameters were significantly associated with changes in functional capacity of patients with PAH as expressed by the 6-min walking distance. Conclusion: Combination therapies, especially with the inclusion of parenteral prostanoids, lead to remarkable haemodynamic improvement in treatment-naïve PAH patients and may unmask the contribution of mPAP reduction to the overall PVR reduction in addition to the increase in CO.

Prognostic implications of thyroid disease in patients with atrial fibrillation.

Atrial fibrillation (AF) is often accompanied by thyroid disease (THD). This study aimed to explore the relationship between THD and the occurrence of significant clinical outcomes in patients with AF. This post hoc analysis utilized data from the MISOAC-AF trial (NCT02941978), which enrolled hospitalized patients with AF. Patients were categorized based on their THD history into hyperthyroidism, hypothyroidism, or euthyroidism. Cox regression models were employed to calculate unadjusted and adjusted hazard ratios (aHRs). The primary outcomes of interest included all-cause mortality, cardiovascular death, and hospitalizations during the follow-up period. The study included 496 AF patients (mean age 73.09 ± 11.10 years) with available THD data, who were followed-up for a median duration of 31 months. Among them, 16 patients (3.2%) had hyperthyroidism, 141 (28.4%) had hypothyroidism, and 339 (68.4%) had no thyroid disease. Patients with hypothyroidism exhibited higher rates of hospitalization during follow-up (aHR: 1.57, 95% CI 1.12 to 2.20, p = 0.025) compared to the euthyroid group. Elevated levels of thyroid-stimulating hormone (TSH) were correlated with an increased risk of cardiovascular mortality (aHR: 1.03, 95% CI 1.01 to 1.05, p = 0.007) and hospitalizations (aHR: 1.06, 95% CI 1.01 to 1.12, p = 0.03). Conversely, lower levels of triiodothyronine (T3) were associated with higher risks of all-cause mortality (aHR: 0.51, 95% CI 0.31 to 0.82, p = 0.006) and cardiovascular mortality (aHR: 0.42, 95% CI 0.23 to 0.77, p = 0.005). Among patients with AF, hypothyroidism was associated with increased hospitalizations. Furthermore, elevated TSH levels and decreased T3 levels were linked to higher cardiovascular and all-cause mortality risks, respectively.

Residual leaks following percutaneous left atrial appendage occlusion and outcomes: a meta-analysis.

BACKGROUND AND AIMS: Residual leaks are not infrequent after left atrial appendage occlusion. However, there is still uncertainty regarding their prognostic implications. The aim of this study is to evaluate the impact of residual leaks after left atrial appendage occlusion. METHODS: A literature search was conducted until 19 February 2023. Residual leaks comprised peri-device leaks (PDLs) on transoesophageal echocardiography (TEE) or computed tomography (CT), as well as left atrial appendage patency on CT. Random-effects meta-analyses were performed to assess the clinical impact of residual leaks. RESULTS: Overall 48 eligible studies (44 non-randomized/observational and 4 randomized studies) including 61 666 patients with atrial fibrillation who underwent left atrial appendage occlusion were analysed. Peri-device leak by TEE was present in 26.1% of patients. Computed tomography-based left atrial appendage patency and PDL were present in 54.9% and 57.3% of patients, respectively. Transoesophageal echocardiography-based PDL (i.e. any reported PDL regardless of its size) was significantly associated with a higher risk of thromboembolism [pooled odds ratio (pOR) 2.04, 95% confidence interval (CI): 1.52-2.74], all-cause mortality (pOR 1.16, 95% CI: 1.08-1.24), and major bleeding (pOR 1.12, 95% CI: 1.03-1.22), compared with no reported PDL. A positive graded association between PDL size and risk of thromboembolism was noted across TEE cut-offs. For any PDL of >0, >1, >3, and >5 mm, the pORs for thromboembolism were 1.82 (95% CI: 1.35-2.47), 2.13 (95% CI: 1.04-4.35), 4.14 (95% CI: 2.07-8.27), and 4.44 (95% CI: 2.09-9.43), respectively, compared with either no PDL or PDL smaller than each cut-off. Neither left atrial appendage patency, nor PDL by CT was associated with thromboembolism (pOR 1.45 and 1.04, 95% CI: 0.84-2.50 and 0.52-2.07, respectively). CONCLUSIONS: Peri-device leak detected by TEE was associated with adverse events, primarily thromboembolism. Residual leaks detected by CT were more frequent but lacked prognostic significance.

Epicardial Versus Endocardial Pacing in Paediatric Patients with Atrioventricular Block or Sinus Node Dysfunction: A Systematic Review and Meta-analysis.

Pacing indications in children are clearly defined, but whether an epicardial (EPI) or an endocardial (ENDO) pacemaker performs better remains to be elucidated. This systematic review and meta-analysis aimed to directly compare the incidence of pacemaker (PM) lead-related complications, mortality, hemothorax and venous occlusion between EPI and ENDO in children with atrioventricular block (AVB) or sinus node dysfunction (SND). Literature search was conducted in MEDLINE (via PubMed), Scopus by ELSEVIER, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and OpenGrey databases until June 25, 2022. Random-effects meta-analyses were performed to assess the pacing method's effect on lead failure, threshold rise, post-implantation infection and battery depletion and secondarily on all-cause mortality, hemothorax and venous occlusion. Several sensitivity analyses were also performed. Of 22 studies initially retrieved, 18 were deemed eligible for systematic review and 15 for meta-analysis. Of 1348 pediatric patients that underwent EPI or ENDO implantation, 542 (40.2%) had a diagnosis of congenital heart disease (CHD). EPI was significantly associated with higher possibility of PM-lead failure [pooled odds ratio (pOR) 3.00, 95% confidence interval (CI) 2.05-4.39; I2 = 0%]; while possibility for threshold rise, post-implantation infection and battery depletion did not differ between the PM types. Regarding the secondary outcome, the mortality rates between EPI and ENDO did not differ. In sensitivity analyses the results were consistent results between the two PM types. The findings suggest that EPI may be associated with increased PM-lead failure compared to ENDO while threshold rise, infection, battery depletion and mortality rates did not differ.

Transcatheter closure of atrial septal defect in the elderly: a systematic review and meta-analysis.

OBJECTIVE: Despite the establishment of transcatheter closure as the treatment of choice in adults with secundum atrial septal defects (ASDs), the effectiveness of this approach in the elderly is disputed. This systematic review and meta-analysis aims to explore the impact of transcatheter ASD closure in patients ≥60 years old. METHODS: We systematically searched four major electronic databases (PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus and Web of Science), ClinicalTrials.gov, article references and grey literature. Primary outcomes were the right ventricular end-diastolic diameter (RVEDD) and the New York Heart Association functional class change, whereas secondary outcomes included systolic pulmonary arterial pressure (sPAP), left ventricular end-diastolic diameter (LVEDD), brain natriuretic peptide (BNP), tricuspid valve regurgitation (TR) change, as well as the rate of atrial arrhythmias and all-cause mortality. RESULTS: In total, 18 single-arm cohorts comprising 1184 patients were included. RVEDD was reduced after ASD closure (standardised mean difference (SMD) -0.9, 95% CI -1.2 to -0.7). Elderly patients had 9.5 times higher odds of being asymptomatic after ASD closure (95% CI 5.06 to 17.79). Furthermore, ASD closure improved sPAP (mean difference (MD) -10.8, 95% CI -14.6 to -7), LVEDD (SMD 0.8, 95% CI 0.7 to 1.0), TR severity (OR 0.39, 95% CI 0.25 to 0.60) and BNP (MD -68.3, 95% CI -114.4 to -22.1). There was a neutral effect of ASD closure on atrial arrhythmias. CONCLUSIONS: Transcatheter ASD closure is beneficial for the elderly population since it improves functional capacity, biventricular dimensions, pulmonary pressures, TR severity and BNP. However, the incidence of atrial arrhythmias did not change significantly after the intervention. PROSPERO REGISTRATION NUMBER: CRD42022378574.

Prescription Rates and Prognostic Implications of Optimally Targeted Guideline-Directed Medical Treatment in Heart Failure and Atrial Fibrillation: Insights From The MISOAC-AF Trial.

ABSTRACT: Heart failure (HF) and atrial fibrillation (AF) commonly coexist in real-life clinical practice. Among patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF), guidelines call for evidence-based target doses of renin-angiotensin-aldosterone system inhibitors and beta-blockers. However, target doses of guideline-directed medical treatment (GDMT) are often underused in real-world conditions, including HF-AF comorbidity. This retrospective cohort study of a randomized trial (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with nonvalvular AF) included hospitalized patients with AF and HFrEF or HFmrEF. Optimally targeted GDMT was defined as intake of evidence-based target doses of renin-angiotensin-aldosterone system and beta-blockers at 3 months after discharge. Rates of optimally targeted GDMT achievement across the baseline estimated glomerular filtration rate (eGFR) were assessed. Independent predictors of nontargeted GDMT and its association with all-cause mortality and the composite of cardiovascular death or HF hospitalization were assessed by regression analyses. In total, 374 patients with AF and HFrEF or HFmrEF were studied. At 3 months after discharge, 30.7% received target doses of GDMT medications. The rate of optimally targeted GDMT was reduced by 11% for every 10 mg/min/1.73 m 2 decrease in baseline eGFR [adjusted ß = 0.99; 95% confidence interval (CI), 0.98-0.99] levels. After a median 31-month follow-up period, 37.8% patients in the optimally targeted GDMT group died, as compared with 67.8% (adjusted hazard ratio: 1.49; 95% CI, 1.05-2.13) in the nontargeted GDMT group. The risk of cardiovascular death or HF hospitalization was also higher in these patients (adjusted hazard ratio: 1.60; 95% CI, 1.17-2.20). Target doses of all HF drugs were reached in roughly one-third of patients with AF and HFrEF or HFmrEF 3 months after hospital discharge. Nontargeted GDMT was more frequent across lower eGFR levels and was associated with worse outcomes.

Prognostic implications of adherence to oral anticoagulants among patients with atrial fibrillation: Insights from MISOAC-AF trial.

OBJECTIVES: To explore the implications of adherence to oral anticoagulants (OACs) on all-cause mortality and cardiovascular outcomes in patients with atrial fibrillation (AF). METHODS: This post-hoc analysis of the MISOAC-AF trial included recently hospitalized patients with AF. Adherence to OACs was assessed by the proportion of days covered (PDC). Good adherence was defined as PDC >80 %. Cox regression models were used to associate PDC with clinical outcomes of all-cause death, cardiovascular death (CVD), stroke, and bleeding. A sub-analysis was performed among adherent patients to compare outcomes between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). RESULTS: During a median 31-month follow-up, 778 cardiac patients with comorbid AF who had been prescribed OACs upon hospital discharge were studied. The mean PDC was 0.78; 66 % of patients had good adherence (>80 %) which was associated with lower risk of all-cause death [adjusted hazard ratio (aHR): 0.64; 95 % confidence interval (CI): 0.46 to 0.84, p < 0.001] and CVD (aHR: 0.70; 95 % CI: 0.50 to 0.97, p = 0.03). The risk of stroke and major or non-major bleeding did not differ by adherence status. Among adherent patients to OACs, VKA use was associated with higher rates of all-cause death (p < 0.001), CVD (p < 0.001), and stroke (p = 0.01); no differences were found regarding major or non-major bleeding risk. CONCLUSIONS: In recently hospitalized patients with AF, good adherence to OACs was associated with a reduced risk of all-cause death and CVD. The rates of stroke or bleeding events were not significantly different. VKAs were associated with more adverse events compared to DOACs.

Sex-Related Differences in Clinical Outcomes in Patients with Atrial Fibrillation and Coronary Artery Disease: A Sub-Study of the MISOAC-AF Randomized Controlled Trial.

BACKGROUND: There is limited "real-world" data on the prognostic role of gender in comorbid atrial fibrillation (AF) and coronary artery disease (CAD). METHODS: In this post-hoc analysis of the MISOAC-AF randomized trial (NCT: 02941978), consecutive patients with AF and CAD who were discharged from the cardiology ward between 2015 and 2018 were included. Multivariable Cox-regression analysis was performed for all-cause mortality and cardiovascular (CV) mortality. Competing-risk analysis was performed for the outcomes of stroke or systemic embolism, major bleeding, AF- or heart failure (HF)-related hospitalization, adjusted for the competing risk of all-cause death. RESULTS: Of 1098 patients with AF, 461 patients with comorbid CAD were analyzed. Women were older and more likely to have a history of diabetes mellitus and valvular heart disease, while men were more likely to have a history of smoking or myocardial infarction. Over a median follow-up of 31 months, 143 (43.4%) men and 71 (53.7%) women died. Women were at a higher risk for all-cause mortality (adjusted hazard ration [aHR] 1.65; 95% confidence interval [CI] 1.14-2.38) and stroke or systemic embolism (aHR 3.52; 95% CI 1.46-8.49) compared to men. The risks of CV mortality, major bleeding, AF-related hospitalization, and HF-related hospitalization were similar between genders. CONCLUSIONS: In recently hospitalized patients with AF and comorbid CAD, the female gender was independently associated with increased all-cause mortality and thromboembolic events.

Polypharmacy and Major Adverse Events in Atrial Fibrillation.

ABSTRACT: Patients with atrial fibrillation (AF) often receive multiple medications daily. The purpose of this study was to examine the prognostic implications of polypharmacy in patients with AF. This is a retrospective post hoc analysis of 1113 AF patients, enrolled in a randomized trial during an acute hospitalization (MISOAC-AF, NCT02941978). The presence of polypharmacy (use of >4 drugs daily) was assessed at hospital discharge. Regression analyses were performed to identify clinical predictors of polypharmacy and compare the outcomes of patients with or without confirmed polypharmacy. The coprimary outcomes were all-cause and cardiovascular (CV) mortality. Among patients with polypharmacy, the difference in the risk of mortality was also assessed per each added drug as a numeric variable. Polypharmacy was found in 36.9% of participants. Dyslipidemia, coronary artery disease, lower left ventricular ejection fraction, and higher glomerular filtration rates were independent predictors of polypharmacy. Polypharmacy was an independent predictor for all-cause death (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.01-1.64) and CV death (aHR: 1.39, 95% CI: 1.05-1.84). Among patients with polypharmacy, each additional concomitant medication was independently associated with a 4% increased risk of all-cause mortality (aHR = 1.04, 95% CI: 1.00-1.08) and a 5% increased risk of CV mortality (aHR = 1.05, 95% CI: 1.00-1.10). Polypharmacy was common among patients with AF hospitalized in a tertiary hospital and was incrementally associated with higher rates of mortality.

Severe mitral regurgitation causing unilateral pulmonary edema: A case report.

This is a case of a 70-year-old male patient with a history of degenerative mitral valve disease who presented to the emergency department with progressively worsening dyspnea. Prominent findings were rapid atrial fibrillation and unilateral pulmonary edema. Transthoracic and transesophageal echocardiography revealed chordal rupture-related severe-eccentric mitral regurgitation. The patient underwent surgical mitral valve repair. Learning objectives: •To acknowledge that the clinical presentation may not be as dramatic when acute mitral regurgitation (MR) is superimposed on chronic MR, due to the increased left atrium compliance•To bear in mind that eccentric jets of severe MR can cause unilateral pulmonary infiltrates, mimicking a primary pulmonary process•To remind that rapid atrial fibrillation might be the result rather than the cause of acute cardiac decompensation.

Association of stress induced hyperglycemia with angiographic findings and clinical outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: Stress induced hyperglycemia (SIH) is common among patients with ST-elevation myocardial infarction (STEMI), even in patients without diabetes mellitus. However, evidence regarding its role on the angiographic outcomes and the prognosis of patients presenting with STEMI is scarce. METHODS: This study included 309 consecutively enrolled STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Patients were diagnosed with SIH if blood glucose on admission was > 140 mg/dl. Also, patients had to fast for at least 8 hours before blood sampling. The objective was to assess whether SIH was associated with major adverse cardiovascular and cerebrovascular (MACCE) events and explore its relationship with angiographic predictors of worse prognosis such as poor initial TIMI flow, intracoronary thrombus burden, distal embolization, and presence of residual thrombus after pPCI. RESULTS: SIH in diabetic and non-diabetic patients was associated with a higher incidence of LTB (aOR = 2.171, 95% CI 1.27-3.71), distal embolization (aOR = 2.71, 95% CI 1.51-4.86), and pre-procedural TIMI flow grade = 0 (aOR = 2.69, 95% CI 1.43-5.04) after adjusting for relevant clinical variables. Importantly, during a median follow-up of 1.7 years STEMI patients with SIH with or without diabetes experienced increased occurrence of MACCE both in univariate (HR = 1.92, 95% CI 1.19-3.01) and multivariate analysis (aHR = 1.802, 95% CI 1.01-3.21). CONCLUSIONS: SIH in STEMI patients with or without diabetes was independently associated with increased MACCE. This could be attributed to the fact that SIH was strongly correlated with poor pre-procedural TIMI flow, LTB, and distal embolization. Large clinical trials need to validate SIH as an independent predictor of adverse angiographic and clinical outcomes to provide optimal individualized care for patients with STEMI.

Education level predicts mortality and morbidity in hospitalised patients with atrial fibrillation.

AIM: Education level has been long considered a life-quality modifier, but little is known about its relation to life expectancy in patients with cardiovascular disease. This study aims to assess possible correlations between education level and survival in patients with atrial fibrillation (AF). METHODS: This retrospective cohort study used data from a randomised trial of 1082 hospitalised patients with AF (mean age of 75 ± 11 years) who were followed up after discharge. Patients were divided into three groups based on their education level: i) none or primary (NPEL), ii) secondary (SEL), and iii) tertiary education level (TEL). Kaplan-Meier curves and multivariable-adjusted hazard ratios (aHRs) were used to compare survival rates between groups. The primary outcome was all-cause mortality. The composite secondary outcome was cardiovascular mortality or any hospitalisation. RESULTS: After a median 31-month follow-up period, 289 (41.9%) patients died in the NPEL group, 75 (31.1%) in the SEL group, and 29 (19.1%) in the TEL group. The aHRs for all-cause mortality were 0.42 (95% CI, 0.27 to 0.66; p < 0.001) for the TEL group compared with the NPEL group, 0.55 (95% CI, 0.33 to 0.93; p = 0.02) for the TEL group compared with the SEL group, and 0.68 (95% CI, 0.50 to 0.93; p = 0.01) for the SEL group compared with the NPEL group. The corresponding aHRs for the composite secondary outcome were 0.36 (95% CI, 0.23 to 0.52; p < 0.001), 0.49 (95% CI, 0.29 to 0.80; p < 0.001), and 0.67 (95% CI, 0.50 to 9.91; p = 0.01). CONCLUSION: Higher education levels were independently associated with fewer fatal and non-fatal outcomes in recently hospitalised patients with AF.