Computed tomography-derived membranous septum length as predictor of conduction abnormalities and permanent pacemaker implantation after TAVI: A meta-analysis of observational studies.

BACKGROUND: Permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is associated with higher risk of mortality and rehospitalization for heart failure. Efforts to prevent conduction abnormalities (CA) requiring PPI after TAVI should be made. The membranous septum (MS) length and its interaction with implantation depth (ID-ΔMSID) could provide useful information about the risk of CA/PPI following TAVI. OBJECTIVES: To identify MS length and ΔMSID as predictors of CA/PPI following TAVI. METHODS: Study-level meta-analysis of studies published by September 30, 2022. RESULTS: Eighteen studies met our eligibility including 5740 patients. Shorter MS length was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: odds ratio [OR] 1.60, 95% confidence interval [CI] 1.28-1.99, p < 0.001). Similarly, lower ΔMSID was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: OR 1.75, 95% CI 1.32-2.31, p < 0.001). Meta-regression analyses revealed a statistically significant modulation of the effect of shorter MS length and lower ΔMSID on the outcome (CA/PPI) by balloon postdilatation (positive regression coefficients with p < 0.001); with increasing use of balloon postdilatation, the effect of shorter MS length and lower ΔMSID on the outcome increased. MS length and ΔMSID demonstrated excellent discriminative abilities, with diagnostic ORs equaling 9.49 (95% CI 4.73-19.06), and 7.19 (95% CI 3.31-15.60), respectively. CONCLUSION: Considering that short MS length and low ΔMSID are associated with higher risk of CA and PPI, we should include measurement of MS length in the pre-TAVI planning with MDCT and try to establish optimal ID values before the procedure to avoid CA/PPI.

Interventional Management of Venous Thromboembolism: State of the Art.

OBJECTIVE: The purpose of this article is to describe the indications for and approach to catheter-based treatment of acute venous thromboembolism (VTE). CONCLUSION: Catheter-based treatment of VTE is a viable adjunct to anticoagulant therapy and is being rapidly adopted around the United States. Early data suggest that these therapies reduce postthrombotic sequelae and improve quality of life, but bleeding events are still frequent, particularly at low-volume centers. Protocols need to be standardized to improve patient care.

Impact of Institutional Volume on Outcomes of Catheter Directed Thrombolysis in the Treatment of Acute Proximal Deep Vein Thrombosis: A 6-Year US Experience (2005-2010).

BACKGROUND: The use of catheter-directed thrombolysis (CDT) in the treatment of acute proximal lower-extremity deep vein thrombosis is increasing in the United States and has been linked to higher bleeding rates. Whether this relationship is interrelated with institution volume of CDT is unknown. METHODS AND RESULTS: The Nationwide Inpatient Sample database was used to identify all patients admitted with a principal diagnosis of proximal or inferior vena caval deep vein thrombosis and treated with CDT from 2005 to 2010. Institutions were divided into high-volume (≥6 procedures a year) and low-volume (<6 procedures a year) centers. Propensity score matching was used to create 2 matched groups for comparative analysis. A total of 90 618 patients were hospitalized for proximal lower-extremity deep vein thrombosis, and 3649 patients (4.1%) underwent CDT. In-hospital mortality was significantly lower at high-volume centers (0.6% versus 1.5%; P=0.04) with a trend toward lower intracranial hemorrhage rates compared with low-volume centers (0.4% versus 1%; P=0.07). No significant difference was seen with blood transfusion (10.4% versus 10.8%; P=0.70), gastrointestinal bleeding (1.4% versus 1.8%; P=0.35), or pulmonary embolism rates (18.4% versus 17.9%; P=0.72). Median length of stay was similar (6 days) and hospital charges were higher ($65 500 versus $75 870) at high-volume centers. CONCLUSIONS: In this observational study, we found that an increase in institutional volume of CDT was associated with lower in-hospital mortality and lower intracranial hemorrhage rates. Further studies are needed to assess whether standardization of CDT protocols across all institutions in the United States improves outcomes.

Chronic ß1-adrenergic blockade enhances myocardial ß3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective ß1-blocker therapy.

The ß1-adrenergic antagonist metoprolol improves cardiac function in animals and patients with chronic heart failure, isolated mitral regurgitation (MR), and ischemic heart disease, though the molecular mechanisms remain incompletely understood. Metoprolol has been reported to upregulate cardiac expression of ß3-adrenergic receptors (ß3AR) in animal models. Myocardial ß3AR signaling via neuronal nitric oxide synthase (nNOS) activation has recently emerged as a cardioprotective pathway. We tested whether chronic ß1-adrenergic blockade with metoprolol enhances myocardial ß3AR coupling with nitric oxide-stimulated cyclic guanosine monophosphate (ß3AR/NO-cGMP) signaling in the MR-induced, volume-overloaded heart. We compared the expression, distribution, and inducible activation of ß3AR/NO-cGMP signaling proteins within myocardial membrane microdomains in dogs (canines) with surgically induced MR, those also treated with metoprolol succinate (MR+ßB), and unoperated controls. ß3AR mRNA transcripts, normalized to housekeeping gene RPLP1, increased 4.4 × 10(3)- and 3.2 × 10(2)-fold in MR and MR+ßB hearts, respectively, compared to Control. Cardiac ß3AR expression was increased 1.4- and nearly twofold in MR and MR+ßB, respectively, compared to Control. ß3AR was detected within caveolae-enriched lipid rafts (Cav3(+)LR) and heavy density, non-lipid raft membrane (NLR) across all groups. However, in vitro selective ß3AR stimulation with BRL37344 (BRL) triggered cGMP production within only NLR of MR+ßB. BRL induced Ser (1412) phosphorylation of nNOS within NLR of MR+ßB, but not Control or MR, consistent with detection of NLR-specific ß3AR/NO-cGMP coupling. Treatment with metoprolol prevented MR-associated oxidation of NO biosensor soluble guanylyl cyclase (sGC) within NLR. Metoprolol therapy also prevented MR-induced relocalization of sGCß1 subunit away from caveolae, suggesting preserved NO-sGC-cGMP signaling, albeit without coupling to ß3AR, within MR+ßB caveolae. Chronic ß1-blockade is associated with myocardial ß3AR/NO-cGMP coupling in a microdomain-specific fashion. Our canine study suggests that microdomain-targeted enhancement of myocardial ß3AR/NO-cGMP signaling may explain, in part, ß1-adrenergic antagonist-mediated preservation of cardiac function in the volume-overloaded heart.

Impact of prior coronary artery bypass grafting and coronary lesion complexity on outcomes of transcatheter aortic valve replacement for severe aortic stenosis.

OBJECTIVE: To investigate the impact of prior coronary artery bypass grafting (CABG) and coronary lesion complexity on transcatheter aortic valve replacement (TAVR) outcomes for aortic stenosis. METHODS: Clinical outcomes of TAVR were retrospectively compared between patients with and without prior CABG, and between patients with prior CABG and without coronary artery disease (CAD). The impact of the CABG SYNTAX score was also evaluated in patients with prior CABG. RESULTS: The study included 1042 patients with a median age and follow-up of 82 years and 25 (range: 0-72) months, respectively. Of these, 175 patients had a history of CABG, while 401 were free of CAD. Patients with prior CABG were more likely to be male and had higher rates of diabetes, peripheral artery disease and atrial fibrillation compared with patients without prior CABG. After 2 : 1 propensity score matching, all-cause mortality (P = 0.17) and the composite of all-cause mortality, stroke and coronary intervention (P = 0.16) were similar between patients with (n = 166) and without (n = 304) prior CABG. A 1 : 1 propensity score-matched analysis, however, showed lower rates of all-cause mortality (P = 0.04) and the composite outcome (P = 0.04) in patients with prior CABG (n = 134) compared with patients without CAD (n = 134). The median CABG SYNTAX score was 16 (interquartile range: 9.0-23), which was not associated with better/worse clinical outcomes in patients with prior CABG. CONCLUSION: Prior CABG may positively affect mid-term TAVR outcomes for aortic stenosis compared with no CAD when adjusted for other comorbidities. The CABG SYNTAX score did not influence the prognosis after TAVR.

Impact of coronary artery disease and revascularization on outcomes of transcatheter aortic valve replacement for severe aortic stenosis.

BACKGROUND/PURPOSE: To evaluate the impact of coronary artery disease (CAD), percutaneous coronary intervention (PCI), and coronary lesion complexity on outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS/MATERIALS: This retrospective study included 1042 patients divided into two groups by the presence or absence of CAD (SYNTAX score 0, no history of revascularization). Propensity score matching was used to compare the two groups. The effect of PCI, SYNTAX score, and residual SYNTAX score was also analyzed. RESULTS: The median age of the cohort was 82 years, and 641 patients had CAD. After propensity score matching, 346 pairs were analyzed. During 5 years of follow-up (median: 25, range 0-72 months), the rate of coronary intervention was significantly higher in CAD patients (p = 0.018). However, all-cause mortality, composite of all-cause mortality, stroke, and coronary intervention, and overt bleeding defined by VARC-3 were comparable. After stratification, in patients with creatinine ≥1.5 mg/dl, CAD was associated with a worse composite outcome (p = 0.016). Neither PCI nor SYNTAX score was associated with all-cause mortality in CAD patients. Similarly, residual SYNTAX score showed no association with mortality in patients undergoing PCI (all p values >0.7). PCI did not reach a significant difference in overt bleeding in CAD patients (adjusted p = 0.06). CONCLUSIONS: Despite a higher incidence of coronary interventions, major clinical outcomes were similar between patients with and without CAD after TAVR. In patients with chronic kidney disease, CAD may be associated with an adverse composite outcome. Neither PCI nor SYNTAX/residual SYNTAX score influenced all-cause mortality.

Impact of mitral stenosis on early and late outcomes of transcatheter aortic valve replacement for aortic stenosis: a single-center analysis.

OBJECTIVES: To assess the impact of concomitant mitral stenosis (MS) on early and late outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS: This study involved 952 patients undergoing TAVR for severe tricuspid aortic stenosis. The patients were classified into 3 groups: without MS, with progressive MS, and severe MS (mitral valve area ≤ 1.5 cm2). Clinical outcomes between these groups were compared. RESULTS: The median age of the overall cohort was 82 years, and patients in the progressive (n = 49) and severe (n = 24) MS groups were more likely to be female than those in the no-MS group (n = 879). Periprocedural mortality rate was lowest in the no-MS group (1.8%) compared with the progressive (4.1%) and severe (4.2%) MS groups, which were not significantly different (P = .20). During 5 years of follow-up (median: 27, range: 0-72 months), there was no significant difference in all-cause mortality (log-rank P = .99), a composite of all-cause mortality or rehospitalization for heart failure (log-rank P = .84), or cardiovascular death (log-rank P = .57) between groups. Although crude analysis showed a significant difference in rehospitalization for heart failure in the severe MS group compared with the no-MS group (P = .049), the difference was not significant in the multivariate analysis (adjusted hazard ratio: 1.36 [95% CI, 0.66-2.80], P = .41). CONCLUSIONS: TAVR can be safely performed in patients with severe tricuspid aortic stenosis and concomitant MS, with early and mid-term outcomes comparable to those in patients without MS.

Antibiotics for exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. OBJECTIVES: To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. MAIN RESULTS: Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I(2) = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I(2) = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I(2) = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence).Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference -9.60 days; 95% CI -12.84 to -6.36 days). One trial showed no effect of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between the treatment and control group.Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high-quality evidence). AUTHORS' CONCLUSIONS: Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient-reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.

Association of Right Ventricular Longitudinal Strain with Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Conventional right ventricular (RV) echocardiographic measurements of systolic function (SF) have demonstrated conflicting results when their association with long-term outcomes after transcatheter aortic valve replacement (TAVR) is evaluated. RV free-wall (FW) longitudinal strain (LS) is a novel, single parameter to measure RV SF and may provide a better evaluation than fractional area change, tricuspid annular plane systolic excursion, and myocardial velocity (S'). The value of RV FW LS in patients undergoing TAVR and its association with 1-year mortality are unknown. The aim of this study was to test the hypothesis that RV FW LS would be associated with 1-year all-cause mortality in patients undergoing TAVR. METHODS: Consecutive patients who underwent TAVR between 2007 and 2014 in whom RV FW LS was measurable were included; a subgroup that had 1-year follow-up echocardiographic evaluation of RV FW LS was analyzed. FW LS was derived from speckle-tracking analyses. The standard reference was determined as normal or impaired RV SF, the latter defined as the presence of ≥50% of tricuspid annular plane systolic excursion < 1.7 cm, S' < 9.5 cm/sec, and fractional area change < 35%. Cox proportional-hazards regression analysis was used to assess the association of RV FW LS with 1-year all-cause mortality. RESULTS: Of 612 patients, 334 were included for RV FW LS analysis on pre-TAVR echocardiography (feasibility 55%); exclusion criteria included atrial fibrillation (n = 92 [15%]), pacemaker (n = 73 [12%]), and poor image quality (n = 113 [18%]). Baseline impaired RV SF was present in 19% of cases. RV FW LS did not change significantly at 1-year follow-up, in both the groups with baseline impaired and normal function. Cox regression analysis showed that RV FW LS was associated with all-cause mortality at 1 year (hazard ratio, 1.06; 95% CI, 1.01-1.11). For each unit increase in RV FW LS, there was a 6% higher risk for 1-year mortality. CONCLUSIONS: In a high-risk TAVR population, RV FW LS should be considered a single echocardiographic parameter for the assessment of RV SF. When measurable, RV FW LS is associated with all-cause mortality at 1 year after TAVR.

Pulmonary Hypertension in HIV.

Human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) is important to recognize given its association with significant morbidity and mortality. With the introduction of antiretroviral therapy, the focus of disease management has largely shifted from treating immunodeficiency-related opportunistic infections to managing chronic cardiopulmonary complications. Symptoms are nonspecific, and a high index of clinical suspicion is needed to avoid significant delay in the diagnosis of HIV-PAH. Although several viral proteins have been implicated in the pathogenesis of HIV-PAH, the exact mechanism remains uncertain. Further studies are needed to elucidate precise pathogenic mechanisms, early diagnostic tools, and novel therapeutic targets to improve prognosis of this severe complication.

HIV-associated pulmonary hypertension.

PURPOSE OF REVIEW: HIV-associated pulmonary arterial hypertension (HIV-PAH) is a well-recognized severe cardiovascular complication of HIV infection that confers an adverse prognosis irrespective of the stage of disease. This review will summarize the available data on HIV-PAH epidemiology and provide insights into the pathophysiology and therapeutic strategies currently available. RECENT FINDINGS: Patients with HIV are several thousand times more likely to develop HIV-PAH compared to the incidence of idiopathic PAH. Several HIV viral proteins are implicated in the pathogenesis although the exact mechanism remains unknown. In the past two decades, there have been several new treatment strategies that appear effective in treating HIV-PAH. Novel pathophysiologic mechanisms implicating the transforming growth factor ß receptor family may offer novel therapeutic targets in the future. SUMMARY: As antiretroviral therapy continues to improve health outcomes for patients with HIV, there needs to be a shift in focus of care toward chronic noncommunicable diseases. Among cardiovascular disease-complicating chronic HIV infection, HIV-PAH is a severe progressive disease that leads to right heart failure and death. Currently available treatment strategies are effective, however, furthering our understanding of HIV-PAH will be critical as it is likely to become the commonest cause of PAH worldwide.