Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. METHOD: We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. RESULTS: We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. CONCLUSION: Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

Long-Term Outcomes of Women With Peripartum Cardiomyopathy Having Subsequent Pregnancies.

BACKGROUND: Long-term maternal outcomes of subsequent pregnancies (SSPs) in patients with peripartum cardiomyopathy (PPCM) have not been analyzed. OBJECTIVES: The goal of this study was to evaluate the long-term survival of SSPs in women with PPCM. METHODS: We conducted a retrospective review of 137 PPCMs in the registry. The clinical and echocardiographic findings were compared between the recovery group (RG) and nonrecovery group (NRG), defined as left ventricular ejection fraction ≥50% and <50% after an index of pregnancy, respectively. RESULTS: Forty-five patients with SSPs were included with a mean age of 27.0 ± 6.1 years, 80% were of African American descent, and 75.6% from a low socioeconomic background. Thirty (66.7%) women were in the RG. Overall, SSPs were associated with a decrease in mean left ventricular ejection fraction from 45.1% ± 13.7% to 41.2% ± 14.5% (P = 0.009). At 5 years, adverse outcomes were significantly higher in the NRG compared with the RG (53.3% vs 20%; P = 0.04), driven by relapse PPCM (53.3% vs 20.0%; P = 0.03). Five-year all-cause mortality was 13.33% in the NRG compared with 3.33% in the RG (P = 0.25). At a median follow-up of 8 years, adverse outcomes and all-cause mortality rates were similar in the NRG and RG (53.3% vs 33.3% [P = 0.20] and 20% vs 20%, respectively). CONCLUSIONS: Subsequent pregnancies in women with PPCM are associated with adverse events. The normalization of left ventricular function does not guarantee a favorable outcome in the SSPs.

Qualitative and Quantitative Effects of PCSK9 Inhibitors in familial Hypercholesterolemia: a Synthetic Review.

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused most commonly by mutations in the gene coding for LDL receptors. This results in increased circulating cholesterol, and clinical consequences of premature stroke, myocardial infarction, etc. FH remains underdiagnosed and thus undertreated, leading to a high health care burden. A newer group of agents, the PCSK9 inhibitors, effectively reduces plasma cholesterol, especially when combined with other lipid lowering agents. The purpose of this narrative review is to synthesize all existing qualitative and quantitative data on the utility of PCSK9 inhibitors in familial hypercholesterolemia, in order to clarify standards of care and identify areas needing further research. Through PubMed/MEDLINE keyword searching, we identified 12 existing randomized controlled trials comparing PCSK9 inhibitor to placebo in FH patients, and pooled their outcomes across a total 2533 patients. We also reviewed quantitative effect on ASCVD outcomes and cost/benefit ratios. In FH patients, PCSK9 inhibitors caused a mean LDL reduction of -49.1%, compared to -3.5% with placebo (weighted average was calculated to account for different study sizes). These findings are comparable to trial results in the non-FH ASCVD population. However, there are no data on PCSK9 inhibitors' effect on hard cardiovascular outcomes in FH. Furthermore, in order for PCSK9 inhibitors to qualify as high-value care, price must be significantly reduced or LDL goals increased. PCSK9 inhibitors are potent reducers of LDL in FH patients. However, dedicated randomized trials are needed to assess whether this translates into statistically significant ASCVD prevention long-term.

Flow-driven right-to-left cardiac shunting in a patient with carcinoid heart disease and patent foramen ovale without elevated right atrial pressure: a case report and literature review.

BACKGROUND: Carcinoid heart disease is present in approximately 20% of the patients with carcinoid syndrome and is associated with poor prognosis. It usually manifests with right-sided valvular involvement including tricuspid insufficiency and pulmonary stenosis. Patent foramen ovale (PFO) is present in approximately 50% of the patients with carcinoid heart disease which is twice higher than the general population. Right-to-left shunting through a PFO can occur either due to higher right atrial pressure than left (pressure-driven) or when the venous flow is directed towards the PFO (flow-driven) in the setting of normal intracardiac pressures. We report a rare case of flow-driven right-to-left atrial shunting via PFO in a patient with carcinoid heart disease. CASE SUMMARY: A 54-year-old male with a metastatic neuroendocrine tumour to liver presented with progressive shortness of breath for 5 months. Patient was found to be hypoxic with oxygen saturation of 78% and examination revealed a holosystolic murmur. Arterial blood gas showed oxygen tension of 43 mmHg. A transthoracic and transoesophageal echocardiogram showed aneurysmal inter-atrial septum with a PFO, severe tricuspid regurgitation directed anteriorly towards the inter-atrial septum leading to a marked right-to-left shunt. Right heart catheterization showed right atrial pressure of 8 mmHg, mean pulmonary artery pressure of 12 mmHg, and normal oxygen saturations in the right atrium, right ventricle, and pulmonary arteries. The patient then underwent closure of the PFO along with tricuspid valve and pulmonary valve replacement at an experienced cardiovascular surgical centre and has been asymptomatic since. CONCLUSION: Right-to-left shunting through a PFO in patients with normal right atrial pressure can be successfully treated with closure of the PFO. Thus, understanding the mechanism of intracardiac shunts is important to accurately diagnose and treat this rare and fatal condition.

Renal Denervation in the Management of Hypertension: A Meta-Analysis of Sham-Controlled Trials.

INTRODUCTION: Sympathetic renal denervation (RD) can potentially reduce blood pressure (BP) in people with resistant hypertension (RH) and uncontrolled hypertension (UH). While a large sham-controlled trial (SCT) showed similar outcomes of RD vs. sham control, in the recent trials, RD was effective in reducing BP in hypertensive people. We performed a meta-analysis of SCTs of RD vs. sham in hypertensive patients. METHODS: Multiple electronic databases were searched since inception through September 2018 for SCTs that compared RD vs. sham. Change in 24-hour, daytime and nighttime ambulatory and office BP were efficacy outcomes. Various adverse events were safety outcomes. RESULTS: A total of 7 SCTs were included in the analysis. RD vs. sham significantly reduced 24-hour ambulatory SBP by 3.45 mmHg [95% CI (-5.01, -1.88); P < 0.0001] and DBP by 1.87 mmHg [(-3.59, -0.15); P = 0.01], office DBP by 2.97 mmHg [(-4.76, -1.18); P = 0.001] and daytime ambulatory SBP by 4.03 mmHg [(-6.37, -1.68); P = 0.0008] and DBP by 1.53 mmHg [(-2.69, -0.37); P = 0.01]. RD vs. sham caused non-significant reduction in office SBP by 3.99 mmHg [(-8.10, 0.11); P = 0.06] and nighttime ambulatory SBP by 3.05 mmHg [(-6.86, 0.75), P = 0.12] and DBP by 1.03 mmHg [(-3.01, 0.96); P = 0.31]. There was no difference in the risk of hypertensive crisis/emergency [0.62; 0.24-1.60; P = 0.33] between the two strategies. CONCLUSIONS: Current meta-analysis shows that RD reduces ambulatory BP and office DBP in patients with hypertension. Future trials with longer follow-up should confirm these findings.

Ischemic and bleeding outcomes of triple therapy in patients on chronic anticoagulation undergoing percutaneous coronary intervention: A meta-analysis of randomized trials.

BACKGROUND: Triple therapy (TT) that includes oral anticoagulation and dual antiplatelet therapy is recommended in patients who are on chronic anticoagulation and undergo percutaneous coronary intervention (PCI). The randomized clinical trials (RCTs) comparing the effectiveness and safety of TT compared to double therapy (DT), which consists of an oral anticoagulation and one of the P2Y12 inhibitors, have shown increased risk of bleeding; however, none of the individual studies were powered to show a difference in ischemic outcomes. To compare the clinical outcomes of TT and DT, we performed this meta-analysis of RCTs. METHODS: Electronic search of PubMed, EMBASE and Cochrane CENTRAL databases was performed for RCTs comparing TT and DT in patients who were on oral anticoagulation (Vitamin K antagonist or non-vitamin K antagonist oral anticoagulant) who underwent PCI. All-cause and cardiovascular mortality, myocardial infarction (MI), stroke, stent thrombosis (ST) and TIMI major and minor bleeding were the major outcomes. RESULTS: An analysis of 5 trials including 10,592 total patients showed that TT, compared to DT, resulted in non-significant difference in risk of all-cause [odds ratio (OR); 1.14;95% confidence interval (CI):(0.80-1.63); P = 0.46) and cardiovascular mortality [1.43(0.58-3.36); P = 0.44], MI [0.88 (0.64-1.21); P = 0.42], stroke [1.10(0.75-1.62); P = 0.63] and ST [0.82(0.46-1.45); P = 0.49]. TT, compared to DT resulted in higher risk of TIMI major bleeding [1.61(1.09-2.37); P = 0.02], TIMI minor bleeding [1.85(1.23-2.79); P = 0.003] and TIMI major and minor bleeding [1.81 (1.38-2.38); P < 0.0001; I2 = 52%]. CONCLUSION: Compared to DT, the patients receiving TT are at a higher risk of major and minor bleeding with no survival benefit or impact on thrombotic outcomes.

Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated meta-analysis of randomized trials.

BACKGROUND: A few randomized clinical trials (RCT) and their meta-analyses have found patent foramen ovale closure (PFOC) to be beneficial in prevention of stroke compared to medical therapy. Whether the benefit is extended across all groups of patients remains unclear. AIM: To evaluate the efficacy and safety of PFOC vs medical therapy in different groups of patients presenting with stroke, we performed this meta-analysis of RCTs. METHODS: Electronic search of PubMed, EMBASE, Cochrane Central, CINAHL and ProQuest Central and manual search were performed from inception through September 2018 for RCTs. Ischemic stroke (IS), transient ischemic attack (TIA), a composite of IS, TIA and systemic embolism (SE), mortality, major bleeding, atrial fibrillation (AF) and procedural complications were the major outcomes. Random-effects model was used to perform analyses. RESULTS: Meta-analysis of 6 RCTs including 3560 patients showed that the PFOC, compared to medical therapy reduced the risk of IS [odds ratio: 0.34; 95% confidence interval: 0.15-0.78; P = 0.01] and the composite of IS, TIA and SE [0.55 (0.32-0.93); P = 0.02] and increased the AF risk [4.79 (2.35-9.77); P < 0.0001]. No statistical difference was observed in the risk of TIA [0.86 (0.54-1.38); P = 0.54], mortality [0.74 (0.28-1.93); P = 0.53] and major bleeding [0.81 (0.42-1.56); P = 0.53] between two strategies. Subgroup analyses showed that compared to medical therapy, PFOC reduced the risk of stroke in persons who were males, ≤ 45 years of age and had large shunt or atrial septal aneurysm. CONCLUSION: In certain groups of patients presenting with stroke, PFOC is beneficial in preventing future stroke compared to medical therapy.

Electrocardiographic findings in peripartum cardiomyopathy.

BACKGROUND: There is limited data on electrocardiographic (ECG) abnormalities and their prognostic significance in women with peripartum cardiomyopathy (PPCM). We sought to characterize ECG findings in PPCM and explore the association of ECG findings with myocardial recovery and clinical outcomes. HYPOTHESIS: We hypothesized that ECG indicators of myocardial remodeling would portend worse systolic function and outcomes. METHODS: Standard 12-lead ECGs were obtained at enrollment in the Investigations of Pregnancy-Associated Cardiomyopathy study and analyzed for 88 women. Left ventricular ejection fraction (LVEF) was measured by echocardiography at baseline, 6 months, and 12 months. Women were followed for clinical events (death, mechanical circulatory support, and/or cardiac transplantation) until 1 year. RESULTS: Half of women had an "abnormal" ECG, defined as atrial abnormality, ventricular hypertrophy, ST-segment deviation, and/or bundle branch block. Women with left atrial abnormality (LAA) had lower LVEF at 6 months (44% vs 52%, P = 0.02) and 12 months (46% vs 54%, P = 0.03). LAA also predicted decreased event-free survival at 1 year (76% vs 97%, P = 0.008). Neither left ventricular hypertrophy by ECG nor T-wave abnormalities predicted outcomes. A normal ECG was associated with recovery in LVEF to ≥50% (84% vs 49%, P = 0.001) and event-free survival at 1 year (100% vs 85%, P = 0.01). CONCLUSIONS: ECG abnormalities are common in women with PPCM, but a normal ECG does not rule out the presence of PPCM. LAA predicted lower likelihood of myocardial recovery and event-free survival, and a normal ECG predicted favorable event-free survival.

Acute De Novo Multivessel Spontaneous Coronary Artery Dissection: A Case Report and Review of Literature.

Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome, especially in young women. Recurrent SCAD can be due to extension of dissection or de novo dissection of unrelated vessel. The authors present a case of acute de novo recurrent SCAD treated conservatively and with coronary intervention. (Level of Difficulty: Intermediate.).

Reduction of vascular complication rates from femoral artery access in contemporary women undergoing cardiac catheterization.

BACKGROUND: Femoral arterial access (FAA) during diagnostic coronary angiography (CAG) and percutaneous coronary interventions (PCI) are associated with several vascular complications (VC). VC rate in our experience a decade ago was 3.02% and higher in women (4.7% in women, and 1.67% in men, p < 0.0006), with an OR of 2.81 (95% CI: 1.51-5.22). METHODS: Patients who underwent CAG and PCI utilizing FAA (n = 2617) were separated into Period 1 (2005 to 2008; 1970 patients; Male 1045; Female 925) and Period 2 (2016-2017; 647 patients; Male 357; Female 290). FA access was preceded by anatomic FA localization during Period 1 vs. additional fluoroscopic marking of femoral head during Period 2. Ultrasound guidance was not utilized during either period. VCs were defined as hematoma>3 cm, major bleeding requiring blood transfusion or hemoglobin drop >2 g, retroperitoneal bleed, pseudoaneurysm, AV fistula, arterial thrombosis, distal embolism, dissection, and transient limb ischemia. RESULTS: Rate of VCs did not differ from Periods 1 to 2 (2.44% vs. 2.32%, p = 1.0). An elevated rate of VCs experienced by women in Period 1 (Female 3.68% vs. Male 1.34%, p < 0.05) is no longer noted in Period 2(Female 2.07% vs. Male 2.52%, p = 0.79). Vascular closure device (VCD) use was protective in both Periods 1 and 2. CONCLUSIONS: The use of fluoroscopic marking of femoral head prior to access, smaller sheath size, and being a high femoral volume center may have contributed to the reduced incidence of VCs in women. VCD utilization is continuing to reduce VC rates in both men and women.

Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure: A Systematic Review and Meta-analysis.

Importance: Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. Objectives: To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. Data Sources: PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. Study Selection: Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. Main Outcomes and Measures: The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. Results: In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, -0.43 to 3.24; P = .13). Conclusions and Relevance: Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.

Does micropuncture technique really help reduce vascular complications?

BACKGROUND: Micropuncture technique (MPT) is being adapted nationally to reduce vascular complications (VC). We initiated a quality improvement project in our cath lab to reduce VCs utilizing MPT. METHODS: We utilized MPT on all of our non-STEMI femoral artery (FA) access cases starting September 2016. As a comparator group, we collected data from April to August 2016. Anatomic localization of FA and fluoroscopic marking of femoral head was utilized in all cases. VCs were defined by BARC definitions for bleeding/hematomas, retroperitoneal bleed, pseudoaneurysm, AV fistula, arterial thrombosis, distal embolism, dissection, and transient limb ischemia. RESULTS: A total of 647 patients (Male 357, Female 290; MPT 333) were included in the analysis. MPT as compared to regular 18-gauge needle access did not demonstrate a reduction in VCs (2.4% vs. 2.2%; p = 1.0). MPT utilization did not affect the risk of VCs on univariate (OR 1.08; 95% CI 0.38-3.01; p = 0.88) or multivariate analysis (OR 0.91, 95% CI 0.28-2.93; p + 0.87). Vascular closure device (VCD) utilization as compared to manual/fem-stop hemostasis was the only factor that demonstrated a statistically significant and lower VC rate on both univariate (OR 0.28; 95% CI: 0.08-0.89; p = 0.03), and multivariate (OR 0.24; 95% CI 0.06-0.93; p = 0.039) analysis. CONCLUSION: Utilization of MPT in conjunction with fluoroscopic marking of the femoral head and without ultrasound guidance did not contribute to statistically significant reduction in the VC rate. The only factor found to be beneficial is utilization of VCDs. Further large randomized studies are required to demonstrate benefit of routinely utilizing MPT.

Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease.

Hydrogen sulfide (H2S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of H2S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H2S in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of H2S. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfur levels were significantly reduced in Caucasian males with CVD compared with those without the disease. Surprisingly, gender differences of H2S bioavailability were not observed in African Americans, although H2S bioavailability was significantly lower overall in this ethnic group compared to Caucasians. We also performed SNP analysis of H2S synthesizing enzymes and found a significant increase in cystathionine gamma-lyase (CTH) 1364 G-T allele frequency in patients with CVD compared to controls. Lastly, plasma H2S bioavailability was found to be predictive for cardiovascular disease in Caucasian subjects as determined by receiver operator characteristic analysis. These findings reveal that plasma H2S bioavailability could be considered a biomarker for CVD in an ethnic and gender manner. Cystathionine gamma-lyase 1346 G-T SNP might also contribute to the risk of cardiovascular disease development.

Comparison of manual compression and vascular hemostasis devices after coronary angiography or percutaneous coronary intervention through femoral artery access: A meta-analysis of randomized controlled trials.

OBJECTIVES: To compare the efficacy and safety of manual compression (MC) with vascular hemostasis devices (VHD) in patients undergoing coronary angiography (CA) or percutaneous coronary intervention (PCI) through femoral artery access. INTRODUCTION: The use of femoral artery access for coronary procedures may result in access-related complications, prolonged immobility and discomfort for the patients. MC results in longer time-to-hemostasis (TTH) and time-to-ambulation (TTA) compared to VHDs but its role in access-related complications remains unclear in patients undergoing coronary procedures. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL and relevant references for English language randomized controlled trials (RCT) from inception through September 30, 2016. We performed the meta-analysis using random effects model. The outcomes were time-to-hemostasis, time-to-ambulation, major bleeding, large hematoma >5cm, pseudoaneurysm and other adverse events. RESULTS: The electronic database search resulted in a total of 44 RCTs with a total of 18,802 patients for analysis. MC, compared to VHD resulted in longer TTH [mean difference (MD): 11.21min; 95% confidence interval (CI) 8.13-14.29; P<0.00001] and TTA [standardized mean difference: 1.2 (0.79-1.62); P<0.00001] along with excess risk of hematoma >5cm formation [risk ratio (RR): 1.38 (1.15-1.67); P=0.0008]. MC resulted in similar risk of major bleeding [1.01 (0.64-1.60); P=0.95] pseudoaneurysm [0.99 (0.75-1.29); P=0.92], infections [0.52 (0.25-1.10); P=0.09], need of surgery [0.60 (0.29-1.22); P=0.16), AV fistula [0.93 (0.68-1.27); P=0.63] and ipsilateral leg ischemia [0.95 (0.57-1.60); P=0.86] compared to VHD. CONCLUSION: Manual compression increase time-to-hemostasis, time-to-ambulation and risk of hematoma formation compared vascular hemostasis devices.

A comparison of standard versus low dose heparin on access-related complications after coronary angiography through radial access: A meta-analysis of randomized controlled trials.

BACKGROUND: Transradial access (TRA) is preferred for coronary angiography (CA) or percutaneous coronary intervention due to reduced access-related complications, and mortality especially for patients with ST elevation myocardial infarction. Radial artery occlusion (RAO) is a known complication of TRA, and precludes its use as a future access site, conduit for coronary artery bypass grafting or for hemodialysis fistula placement. Although a standard dose (SD) heparin of 5000 Units is used during TRA, the risks of RAO and hematoma compared to lower dose (LD) remain unclear. To compare the risks of RAO and hematoma using SD vs. LD heparin after CA through TRA, we performed a meta-analysis of randomized controlled trials (RCT). METHODS: We searched PubMed, EMBASE, CINAHL and CENTRAL for RCTs since inception through 06/30/2017 and used random effects model for analysis. The outcomes analyzed were RAO, hematoma formation and radial artery compression time (RACT). RESULTS: We identified a total of 6 RCTs with a total of 2239 patients. SD heparin resulted in a trend toward a lower risk of RAO [4.2% vs. 10.7%; risk ratio (RR): 0.40, 95% confidence interval (CI): 0.16-1.0; P=0.05], a trend toward increased risk of hematoma [2.2% vs. 1.1%; 1.83 (0.91-3.66); P=0.09], and a longer duration of RACT [mean difference: 9.64min (4.01-15.28); P=0.0008] compared to LD. CONCLUSIONS: The current meta-analysis showed a trend towards reduction in the risk of RAO with the use of standard dose heparin. Larger randomized trials should explore the appropriate dosing of heparin to prevent radial artery occlusion.

Comparison of prasugrel and ticagrelor in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A meta-analysis of randomized and non-randomized studies.

BACKGROUND: The newer oral P2Y12 receptor antagonists (i.e. prasugrel and ticagrelor) are recommended over clopidogrel for patients with acute coronary syndrome (ACS) going for percutaneous coronary intervention (PCI). As the superiority of one agent over the other remains unclear, we designed a systematic review and meta-analysis of these agents in patients with ACS undergoing PCI. METHODS: PUBMED, EMBASE, Cochrane CENTRAL, CINAHL and manual search were performed through 11/02/2016. Mortality, myocardial infarction (MI), stroke, repeat revascularization, stent thrombosis (ST) and BARC bleeding ≥2 were the major outcomes. RESULTS: A total of 9 studies with 21,360 total patients were included in the meta-analysis. Compared to ticagrelor, prasugrel was associated with lower rate of MI [0.8% vs. 1.9%; 0.54 (0.29-0.99); P=0.05] but no difference was noted in mortality [2.1% vs. 2.4%; 0.84 (0.64-1.09); P=0.19], repeat revascularization [1.6% vs. 2.1%; 0.82 (0.61-1.10); P=0.19] and stroke [0.2% vs. 0.3%; 0.68 (0.25-1.83); P=0.44] between two agents. In addition, prasugrel was associated with lower risk of BARC ≥2 bleeding [2.5% vs. 3.8%; 0.75 (0.59-0.95); P=0.02] and showed a trend toward a lower risk of ST [0.3% vs. 0.6%; 0.55 (0.28-1.07); P=0.08] in comparison with ticagrelor. CONCLUSIONS: Based on this meta-analysis of observational and randomized studies, prasugrel appears to be equivalent or superior to ticagrelor in patients with ACS undergoing PCI on the 30-day follow up. Larger randomized trials with longer follow-ups are needed to establish superiority of one agent over the other.

Gender-based outcomes of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions: Meta-analysis of randomized controlled trials.

OBJECTIVES: We aimed to perform a gender-based meta-analysis of the outcome of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions (PCI). BACKGROUND: Bivalirudin has been shown to decrease major bleeding when compared to heparin ± glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing PCI. It is unclear, however, if those differences in outcomes are the same for men and women. METHODS: We included randomized controlled trials (RCTs) that compared bivalirudin to heparin with or without GPI in patients undergoing PCI and reported outcome data that were stratified by gender. Random effect model was used to pool odds ratio (OR) and 95% confidence intervals (CI). RESULTS: We included 9 trials with 33,224 patients. Bivalirudin decreased major bleeding when compared to heparin plus routine GPI in both men (OR: 0.51, P < 0.001) and women (OR: 0.55, P < 0.001). However, when GPI were used selectively with heparin, the bleeding lowering effect of bivalirudin was statistically significant in men (OR: 0.69, P = 0.02) but not in women (OR: 0.71, P = 0.21). When compared to heparin ± GPI, there was a nonstatistically significant trend toward lower all-cause mortality with bivalirudin in both men (OR: 0.76, P = 0.055) and women (OR: 0.79, P = 0.21). There were no significant differences in major adverse cardiovascular events between heparin and bivalirudin in both men and women. CONCLUSION: Bivalirudin decreases major bleeding in both men and women when compared to heparin plus routine GPI. However, when compared to heparin alone, the bleeding lowering benefit of bivalirudin is less evident in women. © 2017 Wiley Periodicals, Inc.

Combined Use of Bivalirudin and Radial Access in Acute Coronary Syndromes Is Not Superior to the Use of Either One Separately: Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The aim of this meta-analysis was to study the relation between access site and bivalirudin use on outcomes in patients with acute coronary syndrome (ACS). BACKGROUND: Bivalirudin and radial access use are 2 strategies that are increasingly used to lower major bleeding in patients with ACS undergoing invasive approaches. The interaction between these 2 strategies and the benefit of using them in combination are unclear. METHODS: This analysis included randomized controlled trials that compared bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with ACS and reported outcomes stratified by arterial access site. Meta-analyses of outcome data were performed on the basis of access site and anticoagulation regimen. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from event rates using random-effects models. RESULTS: Eight trials with a total of 27,491 patients were included. Bivalirudin reduced major bleeding risk in patients with femoral access (OR: 0.51; 95% CI: 0.46 to 0.6; p < 0.001) but not in patients with radial access (OR: 0.75; 95% CI: 0.45 to 1.26; p = 0.28). Moreover, radial access reduced major bleeding risk in patients treated with heparin (OR: 0.57; 95% CI: 0.43 to 0.77; p < 0.001) but not in patients treated with bivalirudin (OR: 0.96; 95% CI: 0.65 to 1.41; p = 0.83). There were no differences in major adverse cardiovascular events or all-cause mortality between bivalirudin and heparin, regardless of access site. CONCLUSIONS: Bivalirudin reduces bleeding risk only with femoral access, and radial access reduces bleeding risk only with heparin anticoagulation. Therefore, there is no additional benefit to the combined use of bivalirudin and radial access strategies in patients with ACS.

Right Ventricular Function in Peripartum Cardiomyopathy at Presentation Is Associated With Subsequent Left Ventricular Recovery and Clinical Outcomes.

BACKGROUND: Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery. We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome. METHODS AND RESULTS: Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) <45% within 13 weeks after delivery. Baseline RV function was assessed by echocardiographic end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane excursion, and RV speckle-tracking longitudinal strain. LV recovery was defined as LVEF of ≥50% at 1 year, persistent severe LV dysfunction as LVEF of ≤35%, and major events as death, transplant, or LV assist device implantation. RV measurements were feasible for 90 of the 96 patients (94%) with echocardiograms available. Mean baseline LVEF was 36±9%. RV fractional area change was <35% in 38% of patients. Of 84 patients with 1-year follow-up data, 63 (75%) had LV recovery and 11 (13%) had LVEF of ≤35% or a major event (4 LV assist devices and 2 deaths). Tricuspid annular plane excursion and RV strain did not predict outcome. Baseline RV fractional area change by multivariable analysis was independently associated with subsequent LV recovery and clinical outcome. CONCLUSIONS: Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year. RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important.