Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis.

BACKGROUND: Novel pacing technologies, such as His bundle pacing (HBP) and left bundle branch area pacing (LBBaP), have emerged to maintain physiological ventricular activation. We investigated the outcomes of LBBP with HBP for patients requiring a de novo permanent pacing. METHODS AND RESULTS: Systematic review of randomized clinical trials and observational studies comparing LBBaP with HBP until March 01, 2023 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included pacing metrics, QRS duration, lead revision, procedure parameters, all-cause mortality and heart failure hospitalization (HFH). Overall, 10 studies with 1596 patients were included. Implant success rate was higher in LBBaP compared with HBP (RR 1.24, 95% CI: 1.08 to 1.42, p = .002). LBBaP was associated with lower capture threshold at implantation (mean difference (MD) -0.62 V, 95% CI: -0.74 to -0.51 V, p < .0001) and at follow-up (MD -0.74 V, 95% CI: -0.96 to -0.53, p < .0001), shorter procedure duration (MD -14.66 min, 95% CI: -23.54 to -5.78, p = .001) and shorter fluoroscopy time (MD -4.2 min, 95% CI: -8.4 to -0.0, p = .05). Compared with HBP, LBBaP was associated with a decreased risk of all-cause mortality (RR: 0.50, 95% CI: 0.33 to 0.77, p = .002) and HFH (RR: 0.57, 95% CI: 0.33 to 1.00, p = .05). No statistical differences were found in lead revisions and QRS duration before and after pacing. CONCLUSION: This meta-analysis found that LBBaP was superior to HBP regarding pacing metrics and implant success rate as an initial pacing strategy, although absence of head-to-head randomized comparison warrants caution in interpretation of the results.

Cardiovascular effects of waterpipe smoking: a systematic review and meta-analysis.

Waterpipe smoking has developed into a major and rapidly growing global tobacco epidemic affecting more than 100 million people worldwide. This study identifies and analyzes comprehensively all available data on the cardiovascular effects of waterpipe smoking. Databases PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for studies published until December 2019 assessing cardiovascular effects of waterpipe smoking. We included experimental, cohort, cross-sectional and case-control studies and excluded systematic reviews, case reports/series and qualitative studies. Studies not conducted in humans or not distinguishing waterpipe smoking from other forms of smoking were also excluded. A total of 42 studies with 46 cardiovascular parameters were eligible for analysis. The meta-analysis included 31 studies with 38,037 individuals. Results showed that one waterpipe smoking session leads to immediate increases in heart rate and blood pressure (P < 0.001). Compared to non-smokers, waterpipe smokers had significantly lower high-density lipoprotein levels (P < 0.001), higher levels of low-density lipoprotein (P = 0.04), triglyceride (P < 0.001) and fasting blood glucose (P = 0.03) and higher heart rate (P = 0.04) with a tendency to have higher blood pressure. Mean heart rate, blood pressure and lipids levels did not differ between waterpipe and cigarette smokers, except for total cholesterol, being higher among waterpipe smokers (P < 0.001). Current level of evidence suggests that waterpipe smoking is associated with substantial adverse effects on cardiovascular system, which seem to be similar to those of cigarette smoking. Longitudinal studies are required to scrutinize the magnitude of these effects.

Hyperkalaemia in Heart Failure-Pathophysiology, Implications and Therapeutic Perspectives.

PURPOSE OF REVIEW: Hyperkalaemia is a frequent and sometimes life-threatening condition that may be associated with arrhythmia and cardiac dysfunction. Evaluating the prevalence of hyperkalaemia in patients with heart failure (HF) and potential treatments of this condition is essential for patients using renin-angiotensin-aldosterone system inhibitors or angiotensin receptor-neprilysin inhibitor and mineralocorticoid receptor antagonists, which represent the cornerstone and highly proven life-saving therapy. RECENT FINDINGS: Novel findings from the past few years include data regarding the epidemiology, pathomechanisms, implications and novel therapeutic approaches to counteract hyperkalaemia in patients with HF. Whilst older potassium-binding agents are associated with serious adverse events, novel potassium-binding drugs are effective in lowering potassium levels and are generally well tolerated. Hyperkalaemia represents both a direct risk of cardiovascular complication and an indirect biomarker of the severity of the underlying disease such as neurohormonal activation and renal dysfunction. Novel potassium-binding drugs such as patiromer and sodium zirconium cyclosilicate may help to optimize therapy in HF and achieve guideline-recommended doses.

True rate of mineralocorticoid receptor antagonists-related hyperkalemia in placebo-controlled trials: A meta-analysis.

BACKGROUND: Mineralocorticoid receptor antagonists (MRA) improve survival in heart failure with reduced ejection fraction but are often underused, mostly due to concerns of hyperkalemia. Because hyperkalemia occurs also on placebo, we aimed to determine the truly MRA-related rate of hyperkalemia. METHODS: We performed a meta-analysis including randomized, placebo-controlled trials reporting hyperkalemia on MRAs in patients after myocardial infarction or with chronic heart failure. We evaluated the truly MRA-related rate of hyperkalemia that represents hyperkalemia on MRA, corrected for hyperkalemia on placebo (Pla), according to the equation: True MRA (%)=(MRA (%) - Pla (%))/MRA (%). RESULTS: A total number of 16,065 patients from 7 trials were analyzed. Hyperkalemia was more frequently observed on MRA (9.3%) vs placebo (4.3%) (risk ratio 2.17, 95% CI 1.92-2.45, P<.0001). Truly MRA-related hyperkalemia was 54%, whereas 46% were non-MRA related. In trials using eplerenone, hyperkalemia was documented in 5.0% on eplerenone and in 2.6% on placebo (P<.0001). In spironolactone trials, hyperkalemia was documented in 17.5% and in 7.5% of patients on placebo (P=.0001). Hypokalemia occurred less frequently in patients on MRA (9.3%) compared with placebo (14.8%) (risk ratio 0.58, CI 0.47-0.72, P<.0001). CONCLUSION: This meta-analysis shows that in clinical trials, 54% of hyperkalemia cases were specifically related to the MRA treatment and 46% to other reasons. Therefore, non-MRA-related rises in potassium levels might be underestimated and should be rigorously explored before cessation of the evidence-based therapy with MRAs.

Effects of catheter-based renal denervation in hypertension: a systematic review and meta-analysis.

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. Aim: To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. Methods: We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Results: Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials. Conclusions: RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication. Clinical Perspective: What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis.

INTRODUCTION: AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses. MATERIAL AND METHODS: We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. RESULTS: FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2 > 50%) between the trials for any of the analyzed outcomes. CONCLUSIONS: Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD, while effects on CVD alone are based on available level of data indeterminate. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.

Device-related risk of atrial fibrillation after closure of patent foramen ovale: a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) represents a frequent complication in patients after interventional closure of patent foramen ovale (PFO). We aimed to compare the incident rate and risk of AF between Amplatzer PFO and GORE (Helex and CARDIOFORM Septal Occluder) device by analyzing the data from randomized trials. METHODS: We included all randomized studies which reported the rate of AF after PFO closure using Amplatzer or GORE occluder in patients suffering cryptogenic stroke and compared the risk of AF between the two devices. PubMed and Cochrane library were searched for eligible studies published until July 2020. RESULTS: Rate of all cases of incident AF from randomized trials with Amplatzer in the interventional group was 3.93% (30/763) vs. 1.46% (11/751) in the respective medical group (RR of 2.57, 95% CI 1.31-5.03, p = 0.006). The incidence of incident AF from randomized trial with GORE device was 6.57% (29/441) vs. 0.44% (1/223) in the respective medical group (RR of 14.66, 95% CI 2.01-106.95, p = 0.008). The p for interaction between the two devices regarding risk of AF was 0.10. CONCLUSIONS: The results suggest lower risk expressed by lower rate of incident AF after PFO closure using Amplatzer PFO Occluder when compared with GORE Occluder. However, these findings are derived from secondary analyses and should be scrutinized using appropriate screening tool for AF following PFO closure in adequately powered randomized clinical trial with a head-to-head design that compares the two devices.

Side effects and treatment initiation barriers of sodium-glucose cotransporter 2 inhibitors in heart failure: a systematic review and meta-analysis.

AIMS: Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium-glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. METHODS AND RESULTS: We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91-1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95-1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51-0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. CONCLUSION: Sodium-glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors.

Sacubitril/valsartan in heart failure: efficacy and safety in and outside clinical trials.

Heart failure (HF) treatment has changed substantially over the last 30 years, leading to significant reductions in mortality and hospital admissions in patients with HF with reduced ejection fraction (HFrEF). Currently, the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve quality of life, mortality, and HF hospitalizations for patients with HFrEF. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) has an important role in the treatment of patients with HFrEF. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) randomized controlled trial has established solid evidence for the treatment of HFrEF in various subgroups. Apart from HFrEF, several studies have been conducted using S/V in various indications: patients hospitalized with acute decompensated HF, HF with preserved ejection fraction, acute myocardial infarction with reduced ejection fraction, uncontrolled and resistant hypertension, and chronic kidney disease. Data from the German Institute for Drug Use Evaluation reveal that implementation of S/V has increased steadily over time and, by the end of 2021, an estimated 266 000 patients were treated with S/V in Germany. The estimated cumulative real-world patient exposure is >5.5 million patient-treatment years worldwide. The number of patients treated with S/V largely exceeds the number of patients treated in clinical trials, and the current indication for S/V is larger than the strict inclusion/exclusion criteria of the randomized trials. Especially elderly patients, women, and patients with more and more severe comorbidities are underrepresented in the clinical trials. We therefore aimed to summarize the importance of S/V in HF in terms of efficacy and safety in clinical trials and daily clinical practice.

Outcomes of conduction system pacing compared to right ventricular pacing as a primary strategy for treating bradyarrhythmia: systematic review and meta-analysis.

BACKGROUND: Right ventricular pacing (RVP) may cause electrical and mechanical desynchrony leading to impaired left ventricular ejection fraction (LVEF). We investigated the outcomes of RVP with His bundle pacing (HBP) and left bundle branch pacing (LBBP) for patients requiring a de novo permanent pacemaker (PPM) for bradyarrhythmia. METHODS AND RESULTS: Systematic review of randomized clinical trials and observational studies comparing HBP or LBP with RVP for de novo PPM implantation between 01 January 2013 and 17 November 2020 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included all-cause mortality, heart failure hospitalization (HFH), LVEF, QRS duration, lead revision, atrial fibrillation, procedure parameters, and pacing metrics. Overall, 9 studies were included (6 observational, 3 randomised). HBP compared with RVP was associated with decreased HFH (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.49-0.94), preservation of LVEF (mean difference [MD] 0.81, 95% CI - 1.23 to 2.85 vs. - 5.72, 95% CI - 7.64 to -3.79), increased procedure duration (MD 15.17 min, 95% CI 11.30-19.04), and increased lead revisions (RR 5.83, 95% CI 2.17-15.70, p = 0.0005). LBBP compared with RVP was associated with shorter paced QRS durations (MD 5.6 ms, 95% CI - 6.4 to 17.6) vs. (51.0 ms, 95% CI 39.2-62.9) and increased procedure duration (MD 37.78 min, 95% CI 20.04-55.51). CONCLUSION: Of the limited studies published, this meta-analysis found that HBP and LBBP were superior to RVP in maintaining physiological ventricular activation as an initial pacing strategy.

Myocardial infarction in a patient with single coronary artery - rare but real.

A 53-year-old woman was referred to our hospital with acute coronary syndrome. The coronary angiography demonstrated a single coronary artery. Culprit lesion was a subtotal occlusion of the proximal left anterior descending coronary artery, which was recanalized and treated with drug-coated balloon angioplasty. The patient recovered quickly after the procedure. A coronary computed tomography angiography visualized the left main coronary artery, which was passing between the ascending aorta and the pulmonary trunk and categorized this anomaly as R-II-B according to Lipton's classification, representing an extremely rare coronary anomaly. .

Off-the-shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID-19) pandemic.

With the spread of SARS-CoV-2, it is expected that cases of acute coronary syndrome in the setting of coronavirus disease 2019 (COVID-19) develop. As expensive and sophisticated protection devices are not widely available, we have been working on a simple, off-the-shelf protection device for endotracheal intubation of potentially infected patients. For this purpose, we used a large transparent plastic bag (such as the sterile protective cover of the lead glass shield) for protection from airborne infections. The cover is moved over the patient's head from cranial to caudal, covering the catheter table including the torso with no need for patient mobilization. The intubation is done conventionally under direct visual control.

Correction to: Off­the­shelf barrier for emergency intubation in the cardiac catheterization laboratory during the coronavirus disease 2019 (COVID­19) pandemic.

During submission the author name Andreas Link was unfortunately omitted. The correct author list reads as follows.

Survival After Coronary Revascularization With Paclitaxel-Coated Balloons.

BACKGROUND: Drug-coated balloons (DCBs) are accepted treatment strategies for coronary in-stent restenosis and are under clinical investigation for lesions without prior stent implantation. A recently published meta-analysis suggested an increased risk of death associated with the use of paclitaxel-coated devices in the superficial femoral artery. The reasons are incompletely understood as potential underlying pathomechanisms remain elusive, and no relationship to the administered dose has been documented. OBJECTIVES: The purpose of this analysis was to investigate the available data on survival after coronary intervention with paclitaxel-coated balloons from randomized controlled trials (RCTs). METHODS: PubMed, Web of science, and the Cochrane library database were searched, and a meta-analysis from RCT was performed comparing DCB with non-DCB devices (such as conventional balloon angioplasty, bare-metal stents, or drug-eluting stents) for the treatment of coronary in-stent restenosis or de novo lesions. The primary outcome was all-cause death. The number of patients lost to follow-up was observed at different time points. Risk estimates are reported as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 4,590 patients enrolled in 26 RCTs published between 2006 and 2019 were analyzed. At follow-up of 6 to 12 months, no significant difference in all-cause mortality was found, however, with numerically lower rates after DCB treatment (RR: 0.74; 95% CI: 0.51 to 1.08; p = 0.116). Risk of death at 2 years (n = 1,477, 8 RCTs) was similar between the 2 groups (RR: 0.84; 95% CI: 0.51 to 1.37; p = 0.478). After 3 years of follow-up (n = 1,775, 9 RCTs), all-cause mortality was significantly lower in the DCB group when compared with control treatment (RR: 0.73; 95% CI: 0.53 to 1.00; p = 0.047) with a number needed to treat of 36 to prevent 1 death. A similar reduction was seen in cardiac mortality (RR: 0.53; 95% CI: 0.33 to 0.85; p = 0.009). CONCLUSIONS: In this meta-analysis, the use of paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality, as has been suggested for peripheral arteries. On the contrary, use of coronary paclitaxel-coated balloons was associated with a trend toward lower mortality when compared with control treatments.

Rate of Cough During Treatment With Angiotensin-Converting Enzyme Inhibitors: A Meta-Analysis of Randomized Placebo-Controlled Trials.

Use of protective angiotensin-converting enzyme inhibitors (ACE-I) in patients with cardiovascular disease (CVD) is sometimes limited by incident coughing. In clinical trials, cough occurred also on placebo. We performed a meta-analysis including randomized, placebo-controlled trials reporting cough on ACE-I in patients with CVD. We evaluated the attributable fraction of cough on ACE-I accounting rate on placebo: placebo-adjusted ACE-I (%) = (ACE-I (%) - Placebo (%)) / ACE-I (%). In total, 65,054 patients from 22 included studies were analyzed. Placebo-adjusted ACE-I cough was 37% of 13.5% reported cases on ACE-I, while 8.5% reported cases on placebo were equivalent to 63% of cases on ACE-I, indicating potential other factors for cough than ACE-I in a substantial number of cough cases on ACE-I. Placebo-adjusted ACE-I cough had the highest rates of arterial hypertension (85%) and the lowest of heart failure (29%). Therefore, other causes of cough, particularly in heart failure, should be excluded before ACE-I withdrawal.

Interventional closure vs. medical therapy of patent foramen ovale for secondary prevention of stroke: updated meta-analysis.

BACKGROUND: We aimed to explore whether interventional closure of patent foramen ovale (PFO) results in reduction of composite outcome [stroke/transitory ischemic attack (TIA), death, and thrombolysis in myocardial infarction-TIMI bleeding], stroke and stroke/TIA compared to medical treatment in patients with cryptogenic stroke. METHODS AND RESULTS: Searching the PUBMED and Cochrane library database, we performed meta-analysis from all randomized controlled studies that compared effects of interventional PFO closure with medical treatment on stroke prevention. 3560 patients from six randomized trials were included. Interventional PFO closure reduced composite outcome (RR of 0.47, 0.26-0.85, p = 0.01), stroke (RR of 0.38, 0.18-0.82, p = 0.01) and stroke/TIA (RR of 0.56, 0.43-0.74, p < 0.0001). Analysis had 70.5% power to detect observed reduction of RR for the primary outcome, 70.6% for stroke and 98.7% for stroke/TIA. Bleeding rates were comparable (RR of 0.91, 0.60-1.38, p = 0.66), while there was higher burden of new AF (RR of 5.54, 3-10.2, p < 0.0001) after interventional closure. Subgroup analysis revealed that patients with large shunts had substantial less recurrent strokes over patients with small shunts (p for interaction = 0.02). Use of Amplatzer PFO device was associated with substantial less AF (RR of 2.36, p = 0.06) compared with other devices (RR of 8.93, p < 0.0001) (p for interaction = 0.04), with comparable benefit for stroke prevention (p for interaction = 0.73). CONCLUSIONS: Interventional closure of PFO resulted in significant reduction of stroke and stroke/TIA compared with antiplatelets/anticoagulants with comparable bleeding rates between the groups, whereas AF occurred more frequently in the intervention group. Patients with large shunts had more benefit from interventional closure.

Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials.

OBJECTIVE: Use of amlodipine for treatment of arterial hypertension and stable coronary artery disease (CAD) is sometimes limited by occurrence of peripheral edema and headache. We aimed to explore the true magnitude of this phenomenon by determining the rate and placebo-adjusted rate of these side effects. METHODS: We performed a meta-analysis by including all randomized, placebo-controlled trials reporting edema and headache with amlodipine in patients with arterial hypertension and CAD. Placebo-adjusted rate (%) was determined as follows: (SE amlodipine % - SE placebo %)/SE amlodipine %. RESULTS: Data from 7226 patients of 22 trials were analyzed. Rate of edema was higher on amlodipine vs. placebo (16.6 vs. 6.2%, risk ratio: 2.9, 95% CI: 2.50-3.36, P < 0.0001). The placebo-adjusted rate was 63%, indicating that 37% of edema cases were unrelated to amlodipine. Treatment with low/medium doses (2.5-5 mg) resulted in lower rates of edema (risk ratio: 2.01, 95% CI: 1.41-2.88, P = 0.0001) vs. high dose (10 mg) (risk ratio: 3.08, 95% CI 2.62-3.60, P < 0.0001, Pforinteraction = 0.03). Incidence of headache was reduced using amlodipine vs. placebo (7.9 vs. 10.9%, risk ratio: 0.77, 95% CI: 0.65-0.90, P = 0.002) and was driven by use of low/medium doses (risk ratio: 0.52, 95% CI: 0.40-0.69, P < 0.00001 vs. risk ratio: 0.92, 95%-CI: 0.74-1.15, P = 0.45, for high doses, Pforinteraction = 0.002). CONCLUSION: Although risks of peripheral edema are three-fold higher on amlodipine, up to one-third of edema cases on amlodipine might not be induced by amlodipine. Headache is reduced on amlodipine treatment, mainly driven by use of this drug at low/medium doses.

Effects of Arteriovenous Fistula on Blood Pressure in Patients With End-Stage Renal Disease: A Systematic Meta-Analysis.

Background Central arteriovenous fistula ( AVF ) creation is under investigation for treatment of severe hypertension. We evaluated the effects of AVF for initiation of hemodialysis on systolic, diastolic, and mean arterial blood pressure in patients with end-stage renal disease. Methods and Results Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review and meta-analysis of peer-reviewed studies reporting the effects of the creation/ligation of an AVF on blood pressure in patients with end-stage renal disease was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), PRISMA -P (PRISMA for systematic review protocols), and ROBINS-I (Risk of Bias in Non-Randomized Studies) criteria by the Cochrane Bias Methods Group. All studies in which the results could have been biased by hemodialysis were excluded. A total of 14 trials including 412 patients with end-stage renal disease ( AVF creation, n=185; AVF ligation, n=227) fulfilled the criteria and were subsequently analyzed. Average blood pressure in patients with no/closed AVF was 140.5/77.6 mm Hg with a mean arterial blood pressure of 96.1 mm Hg. Following creation of AVF , systolic blood pressure significantly decreased by 8.7 mm Hg ( P<0.001), diastolic blood pressure by 5.9 mm Hg ( P<0.001), and mean arterial blood pressure by 6.6 mm Hg ( P=0.02), whereas after ligation systolic blood pressure increased by 5.2 mm Hg ( P=0.07), diastolic blood pressure by 3.8 mm Hg ( P=0.02), and mean arterial blood pressure by 3.7 mm Hg ( P=0.07) during short- to long-term follow-up. Conclusions Creation of AVF significantly decreases blood pressure in patients with end-stage renal disease, whereas blood pressure tends to increase after ligation. These findings illustrate the hemodynamic consequences of AVF which are under investigation for severe hypertension.

Heart rate and its reduction in chronic heart failure and beyond.

Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR >70 b.p.m. increased the risk of hospitalization, and >75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo-controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.