Effects of Promotility Agents on Gastric Emptying and Symptoms: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Studies have reported a lack of association between improvements in gastric emptying (GE) and upper gastrointestinal (UGI) symptoms with promotility drugs. However, GE test methods were suboptimal in some studies. We assessed improvements in GE and UGI symptoms in patients given promotility agents in studies with optimal or moderate test methods (scintigraphy or breath test, solid meal, >2 hours duration) compared to studies with suboptimal GE test methods. METHODS: With an expert librarian, we completed an extensive search of publications in the Ovid MEDLINE (1946 to present), EMBASE (1988 to January 2018), and EBM Reviews Cochrane Central Register of Controlled Trials, without restrictions on language or year. Two independent reviewers evaluated the following inclusion criteria: randomized, blinded, parallel, or crossover trials of 5HT4 agonists, D2 receptor antagonist, or ghrelin agonists; trials that measured change in GE (T1/2) or composite UGI symptoms; trials of patients with functional dyspepsia and gastroparesis; and trials of GE test methods. Standardized mean differences (units expressed as SD) were used to standardize symptom assessments that were not uniform across studies. Random effects model was used to analyze data and meta-regression was used to evaluate the association between change in GE and UGI symptoms. RESULTS: Of 899 studies considered, 22 studies assessed change in GE; 23 evaluated UGI symptoms; and 14 evaluated GE and UGI symptoms. Promotility agents significantly accelerated GE (T1/2) in all studies (mean reduction in T1/2, 16.3 minutes; 95% confidence interval, -22.1 to -10.6 minutes) and in studies that used optimal GE test methods (mean reduction in T1/2, 23.6 minutes; 95% confidence interval, -32.3 to -14.9 minutes). Promotility agents also significantly reduced UGI symptoms (mean reduction, 0.25 SD; 95% confidence interval, -0.37 to -0.13 SD). Meta-regression found no significant association between change in GE and UGI symptoms. However, when only studies with optimal GE test methods were evaluated, there was a significant positive association between improvement in GE and UGI symptoms (P = .02). CONCLUSIONS: In a meta-analysis of published trials, we found promotility agents to significantly accelerate GE (when optimal test methods were used) and to produce significant improvements in UGI symptoms.

Opportunities for enhancing the care of older patients with ST-elevation myocardial infarction presenting for primary percutaneous coronary intervention: Rationale and design of the SAFE-STEMI for Seniors trial.

Advanced age is directly related to worse outcomes following ST-elevation myocardial infarction (STEMI) and higher complication rates from antithrombotic therapies and primary percutaneous coronary intervention (PCI). Often excluded from clinical trials, seniors presenting with STEMI remain an understudied population despite contributing to 140,000 hospital admissions annually. The SAFE-STEMI for Seniors study is a prospective, multicenter, unblinded, randomized clinical trial designed to examine the efficacy and safety of instantaneous wave-free ratio-guided complete revascularization in multivessel disease, while also investigating other components of STEMI care for patients ≥60 years including the efficacy and safety of zotarolimus-eluting stents for primary PCI and transradial PCI with the Glidesheath Slender and TR band. The SAFE-STEMI trial represents North America's first and only prospective randomized investigational device exemption study to use a Coordinated Registry Network infrastructure with collaborative partnering across industry manufacturers, promoting both efficiency and reduced cost of evidence development for regulatory decisions related to both diagnostic and therapeutic technologies in a single study design. The study has been powered to evaluate 2 independent co-primary end points in a population of older patients with STEMI: (1) third-generation drug-eluting stents for primary PCI and (2) instantaneous wave-free ratio-guided complete revascularization versus infarct-related artery-only revascularization.

Safety of pacemaker implantation in nonagenarians: an analysis of the healthcare cost and utilization project-nationwide inpatient sample.

BACKGROUND: Data are scarce on outcomes of pacemaker implantation in nonagenarians (age≥90 years). METHODS AND RESULTS: We identified patients >70 years of age (n=115 683) who underwent initial pacemaker implantation in the 2004 to 2008 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. Outcomes included in-hospital mortality, complications, length of stay, and charges. Unadjusted outcomes were compared using χ(2) and Mantel-Haenszel tests. Multivariate hierarchical logistic models and stepwise linear regression models adjusted for case-mix variation and clustering. Eleven percent (12 917) were >90 years of age. Relative to patients aged 70 to 79 years, patients >90 years of age were more likely to have moderate/severe comorbidity (Charlson score >1; 43.2% versus 40.1%) and less likely to be admitted electively (17.5% versus 29.9%), all P<0.001. The unadjusted mortality and complication rates in patients aged 70 to 79 years were 0.60% (confidence interval [CI], 0.53-0.67%) and 5.61% (CI, 5.40-5.82%), respectively, and in patients aged >90 years were 1.87% (CI, 1.63-2.11%) and 6.31% (CI, 5.89-6.72%). Length of stay and charges in patients aged 70 to 79 years were 3.22 days (CI, 3.20-3.24 days) and $38 871 (CI, $38 700-$39 043), and in patients aged >90 years, 4.27 days (CI, 4.25-4.30 days) and $41 373 (CI, $41 190-$41 556). Multivariable analysis revealed severe comorbidity (odds ratio, 5.00; 95% CI, 4.05-6.17) was a greater predictor of mortality than increasing age (odds ratio, 2.81 per decade; CI, 2.35-3.35), all P<0.001. Similarly, severe comorbidity (Charlson score >5) was more strongly associated with complications, length of stay, and charges than age. CONCLUSIONS: Although increasing age predicts worsening outcomes in the elderly, the absolute rates are modest, even in nonagenarians, and comorbidity is a stronger predictor.

Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and signaling and exerts synergistic antimyeloid activity in combination with CXCR4 antagonists.

Stromal cell derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are involved in the directional homing to the bone marrow niches and in peripheral mobilization of normal and transformed hematopoietic stem and myeloid progenitor cells. Elevated CXCR4 expression confers poor prognosis, whereas inhibition of CXCR4 signaling overcomes stroma-mediated chemoresistance in acute myeloid leukemia (AML). Here, we demonstrate that treatment with the pan-histone deacetylase inhibitor panobinostat (PS) depleted the mRNA and protein levels of CXCR4 in the cultured and primary AML cells. PS-induced acetylation of the heat shock protein (hsp) 90 reduced the chaperone association between CXCR4 and hsp90, directing CXCR4 to degradation by the 20S proteasome. PS treatment also depleted G protein-coupled receptor kinase 3, as well as attenuated the phosphorylation of AKT and ERK1/2 in AML cells, which was not affected by cotreatment with CXCL12. Compared with each agent alone, cotreatment with PS and CXCR4 antagonist AMD3100 or FC-131 synergistically induced apoptosis of cultured and primary AML cells. PS and FC-131 exerted more lethal effects on primary AML versus normal CD34(+) bone marrow progenitor cells. These findings support the rationale to test the in vivo efficacy of PS in enhancing the lethal effects of CXCR4 antagonists against AML cells.

Endovascular repair is associated with superior clinical outcomes in patients transferred for treatment of ruptured abdominal aortic aneurysms.

PURPOSE: To compare in a population-based analysis the in-hospital mortality and complications following endovascular aneurysm repair (EVAR) vs. open repair in patients transferred for the management of ruptured abdominal aortic aneurysm (RAAA). METHODS: Interrogation of the 2003-2007 Nationwide Inpatient Sample database identified 271 patients (205 men; mean age 71.7 years) who were transferred for RAAA treatment. Demographic, patient, and hospital characteristics were analyzed. Hierarchical multivariate logistic regression analyses were employed to identify predictors of in-hospital mortality and complications; results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: In comparison to open repair (n=207), endovascular repair (n=64) was associated with lower in-hospital mortality (36% vs. <18%, p<0.01) and a lower complication rate (78% vs. 66%, p<0.05). Transferred RAAA patients undergoing EVAR had lower in-hospital mortality (OR 0.21, 95% CI 0.09 to 0.49, p<0.01) and fewer complications (OR 0.49, 95% CI 0.26 to 0.95, p<0.05) than transferred patients having open repair. CONCLUSION: Compared to open repair, EVAR led to superior short-term clinical outcomes in transferred RAAA patients. In this clinical situation, transfer of stable RAAA patients to institutions capable of performing EVAR is recommended.

Recovery of left ventricular function is associated with improved outcomes in LVAD recipients.

BACKGROUND: The significance of recovered left ventricular ejection fraction (LVEF) in LVAD recipients, outside of pump explantation, is unclear. METHODS: Patients undergoing first LVAD implantation at Duke University Hospital between 2006 and 2017 were evaluated for LVEF recovery up to 2 years following implant. Occurrence of gastrointestinal bleeding (GIB), hospitalization for heart failure (HF), pump thrombosis and death were assessed before and after LVEF recovery. RESULTS: Of 286 patients who met inclusion criteria, 9.8% reached a "threshold" of recovery with an LVEF ≥ 40%. 17.4% achieved "relative" recovery with an increase in LVEF ≥ 10% since LVAD implantation. For either definition, recovered patients had a lower incidence of a composite endpoint of GIB, HF hospitalization, pump thrombosis, or death compared to patients without recovery. Patients with "threshold" recovery had 4.7 events per 100 patient-years (95% CI, 0.7-33.6) compared to 48.8 events per 100 patient-years (95% CI, 39.5-60.3) without "threshold" recovery [p = .020]. Those with "relative" recovery had 14.1 events per 100 patient-years [95% CI, 5.9-33.8] versus 50.7 events per 100 patient-years (95% CI, 40.7-63.0) without "relative" recovery [p = 0.005]. However, improved outcomes in the "relative" recovery group were limited to those who also met the "threshold" definition. Importantly, among patients who achieved "threshold" recovery, the incidence of the composite endpoint declines in the postrecovery period, suggesting that LVEF recovery mechanistically results in improved outcomes. CONCLUSIONS: An LVEF ≥ 40% associates with better outcomes in LVAD recipients. Methods to promote recovery could reduce morbidity and mortality related to LVAD support.

Comparative analysis of therapeutic options used for myasthenia gravis.

OBJECTIVE: To compare clinical and economic outcomes following plasma exchange (PLEX) and intravenous immunoglobulin (IVIG) in U.S. patients with primary diagnoses of myasthenia gravis (MG). METHODS: Our cohort was identified from the Nationwide Inpatient Sample database for years 2000-2005 using codes from the International Classification of Diseases, 9th edition. Multivariate regression analyses were used to identify predictors of mortality, complications, length of stay, and total inpatient cost. RESULTS: Among 1,606 hospitalized patients, the unadjusted mortality rate of MG crisis remained higher than those without crisis (0.44% vs 4.44%, p < 0.001), as well as the unadjusted complication rate (26.36% vs 11.23%, p < 0.001). MG crisis patients receiving PLEX had significantly more complications than those receiving IVIG (30.06% vs 14.79%, p < 0.001). Among the whole cohort, adjusted mortality and complication rates were not significantly different between the treatment groups (p > 0.05). Acute respiratory failure, major cardiac complications, and acute renal failure were associated with an increased mortality rate (p < 0.001). Age and respiratory failure were associated with an increased complication rate (p < 0.001). Length of stay was significantly longer for MG (6 vs 4 days, p < 0.001) and MG crisis (10 vs 5 days, p < 0.001) patients receiving PLEX. Inpatient costs were higher for MG ($26,662 vs $21,124, p < 0.01) and MG crisis ($53,801 vs $33,924, p < 0.001) patients receiving PLEX. INTERPRETATION: Compared to PLEX, IVIG appears of similar clinical (mortality and complications) and perhaps of superior economic (length of stay and total inpatient charges) outcomes in the treatment of MG. Elderly and those with complex comorbid diseases including acute respiratory failure may be better treated with IVIG.

Outcome of plasmapheresis in myasthenia gravis: delayed therapy is not favorable.

INTRODUCTION: The purpose of this study was to compare the in-hospital mortality and complication rates after early and delayed initiation of plasma exchange (PLEX) in patients with myasthenia gravis (MG). METHODS: Our cohort was identified from the Nationwide Inpatient Sample database for the years 2000 through 2005. Early treatment was defined as therapy with PLEX administered within the first 2 days from hospital admission. Univariate and multivariate analyses were employed. RESULTS: One thousand fifty-three patients were treated and included in the analysis. A delay in receiving PLEX was associated with higher mortality (6.56% vs. 1.15%, P < 0.001) and increased complications (29.51% vs. 15.29%, P < 0.001). Adjusted analysis showed increased mortality [odds ratio (OR) 2.812; 95% confidence interval (CI) 1.119-7.069] and complications (OR 1.672; 95% CI 1.118-2.501) with delayed PLEX therapy. CONCLUSIONS: Delaying PLEX therapy for MG by more than 2 days after admission may lead to higher mortality and complication rates, and thus prompt therapy is warranted.

Progression of Myocardial Fibrosis in Nonischemic DCM and Association With Mortality and Heart Failure Outcomes.

OBJECTIVES: The purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes. BACKGROUND: Myocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM. METHODS: In total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant. RESULTS: On CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase >1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p < 0.01), in 60% of these cases the change in LVEF was minimal (<5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p < 0.01) and heart failure-related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p < 0.01) after adjustment for clinical covariates including LVEF. CONCLUSIONS: Once myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.

HDAC6 inhibition enhances 17-AAG--mediated abrogation of hsp90 chaperone function in human leukemia cells.

Histone deacetylase 6 (HDAC6) is a heat shock protein 90 (hsp90) deacetylase. Treatment with pan-HDAC inhibitors or depletion of HDAC6 by siRNA induces hyperacetylation and inhibits ATP binding and chaperone function of hsp90. Treatment with 17-allylamino-demothoxy geldanamycin (17-AAG) also inhibits ATP binding and chaperone function of hsp90, resulting in polyubiquitylation and proteasomal degradation of hsp90 client proteins. In this study, we determined the effect of hsp90 hyperacetylation on the anti-hsp90 and antileukemia activity of 17-AAG. Hyperacetylation of hsp90 increased its binding to 17-AAG, as well as enhanced 17-AAG-mediated attenuation of ATP and the cochaperone p23 binding to hsp90. Notably, treatment with 17-AAG alone also reduced HDAC6 binding to hsp90 and induced hyperacetylation of hsp90. This promoted the proteasomal degradation of HDAC6. Cotreatment with 17-AAG and siRNA to HDAC6 induced more inhibition of hsp90 chaperone function and depletion of BCR-ABL and c-Raf than treatment with either agent alone. In addition, cotreatment with 17-AAG and tubacin augmented the loss of survival of K562 cells and viability of primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) samples. These findings demonstrate that HDAC6 is an hsp90 client protein and hyperacetylation of hsp90 augments the anti-hsp90 and antileukemia effects of 17-AAG.

Molecular and biologic characterization and drug sensitivity of pan-histone deacetylase inhibitor-resistant acute myeloid leukemia cells.

Hydroxamic acid analog pan-histone deacetylase (HDAC) inhibitors (HA-HDIs) have shown preclinical and clinical activity against human acute leukemia. Here we describe HA-HDI-resistant human acute myeloid leukemia (AML) HL-60 (HL-60/LR) cells that are resistant to LAQ824, vorinostat, LBH589, and sodium butyrate. HL-60/LR cells show increased expression of HDACs 1, 2, and 4 but lack HDAC6 expression, with concomitant hyperacetylation of heat shock protein 90 (hsp90). Treatment with HA-HDI failed to further augment hsp90 acetylation, or increase the levels of p21 or reactive oxygen species (ROSs), in HL-60/LR versus HL-60 cells. Although cross-resistant to antileukemia agents (eg, cytarabine, etoposide, and TRAIL), HL-60/LR cells are collaterally sensitive to the hsp90 inhibitor 17-AAG. Treatment with 17-AAG did not induce hsp70 or deplete the hsp90 client proteins AKT and c-Raf. HL-60/LR versus HL-60 cells display a higher growth fraction and shorter doubling time, along with a shorter interval to generation of leukemia and survival in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Thus, resistance of AML cells to HA-HDIs is associated with loss of HDAC6, hyperacetylation of hsp90, aggressive leukemia phenotype, and collateral sensitivity to 17-AAG. These findings suggest that an hsp90 inhibitor-based antileukemia therapy may override de novo or acquired resistance of AML cells to HA-HDIs.

Comorbid health conditions in women with syncope.

OBJECTIVE: We determine the comorbid conditions associated with syncope in women. In addition, we hypothesize a higher proportion of autonomic comorbid conditions during the female reproductive age. METHODS: We identified a cohort of patients admitted to US hospitals with the principal diagnosis of syncope. We compare patient demographics stratified by gender as well as syncope associated comorbidities. We compared these comorbidities in female of reproductive age (15-45) to men as control. RESULTS: From a total sample of 305,932, females constituted 56.7% (n = 173,434). Females were slightly older (mean age 70.9 +/- 17.9 vs. 66.7 +/- 17.3; P < 0.0001); with similar racial distribution (white 57.8 vs. 57.5%), and similar length of hospital stay (mean 2.66 +/- 2.63 vs. 2.68 +/- 2.72 days; P > 0.05). Females had higher proportion of migraine (1.65 vs. 1.29%; odds ratio 'OR' 1.29; 95% confidence interval 'CI' 1.21, 1.36); chronic fatigue syndrome (1.73 vs. 1.3%; OR 1.32; 95% CI 1.25, 1.4); gastroparesis (0.2 vs. 0.12%; OR 1.64; 95% CI 1.35, 1.98); interstitial cystitis (0.07 vs. 0.01%; OR 7.44; 95% CI 4.10, 13.5); and postural tachycardia syndrome (0.49 vs. 0.44%; OR 1.1; 95% CI 1.001, 1.23). Orthostatic hypotension was not different between the groups (P = 0.24). When the sample was stratified by age category, the odds ratio for gastroparesis, orthostatic hypotension, and postural tachycardia syndrome was increased (P < 0.05). INTERPRETATION: A higher proportion of autonomic dysfunction was present in women compared to men. In addition, these comorbid autonomic conditions were especially prominent during the female reproductive age.

Hydroxamic acid analogue histone deacetylase inhibitors attenuate estrogen receptor-alpha levels and transcriptional activity: a result of hyperacetylation and inhibition of chaperone function of heat shock protein 90.

PURPOSE: The molecular chaperone heat shock protein (hsp)-90 maintains estrogen receptor (ER)-alpha in an active conformation, allowing it to bind 17beta-estradiol (E2) and transactivate genes, including progesterone receptor (PR)-beta and the class IIB histone deacetylase HDAC6. By inhibiting HDAC6, the hydroxamic acid analogue pan-HDAC inhibitors (HA-HDI; e.g., LAQ824, LBH589, and vorinostat) induce hyperacetylation of the HDAC6 substrates alpha-tubulin and hsp90. Hyperacetylation of hsp90 inhibits its chaperone function, thereby depleting hsp90 client proteins. Here, we determined the effect of HA-HDIs on the levels and activity of ERalpha, as well as on the survival of ERalpha-expressing, estrogen-responsive human breast cancer MCF-7 and BT-474 cells. EXPERIMENTAL DESIGN: Following exposure to HA-HDIs, hsp90 binding, polyubiquitylation levels, and transcriptional activity of ERalpha, as well as apoptosis and loss of survival, were determined in MCF-7 and BT-474 cells. RESULTS: Treatment with HA-HDI induced hsp90 hyperacetylation, decreased its binding to ERalpha, and increased polyubiquitylation and depletion of ERalpha levels. HA-HDI treatment abrogated E2-induced estrogen response element-luciferase expression and attenuated PRbeta and HDAC6 levels. Exposure to HA-HDI also depleted p-Akt, Akt, c-Raf, and phospho-extracellular signal-regulated kinase-1/2 levels, inhibited growth, and sensitized ERalpha-positive breast cancer cells to tamoxifen. CONCLUSIONS: These findings show that treatment with HA-HDI abrogates ERalpha levels and activity and could sensitize ERalpha-positive breast cancers to E2 depletion or ERalpha antagonists.

Clinical and Echocardiographic Predictors of Outcomes in Patients With Pulmonary Hypertension.

In pulmonary hypertension (PH), measurement of various echocardiographic parameters that assess right heart function is recommended by current clinical guidelines. Limited data exists on the combined value of clinical and echocardiographic parameters in precapillary PH in the modern era of therapy. We examined the association of clinical and echocardiographic parameters with surrogate outcomes (6-minute walk distance) and hard outcomes (hospitalization or death) in patients with precapillary PH. A cohort of patients with an established diagnosis of precapillary PH who underwent transthoracic echocardiography at the Duke Echo Lab were prospectively enrolled from 2010 to 2014. Univariable and multivariable models were constructed to examine the relation of clinical and echocardiographic parameters with surrogate and hard outcomes. Of the 98 patients with analyzable echocardiograms with good image quality, 85 were woman, mean age was 59.4 years, and 47% had ≥World Health Organization functional class III symptoms. The mean 6-minute walk distance was 354(±132) m, and 83% were on pulmonary arterial hypertension medications. At 24 months, the cumulative incidence rate for hospitalization or death was 47%. In univariable analyses, the REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) risk score (HR 1.72 per 1 SD (2.81) increment, 95% CI 1.34, 2.22; p=<0.001), RV global longitudinal strain (RVGLS) (HR 1.54 per 1 SD (5.31) worsening, 95% CI , 2.12; p=0.008) and log-2 NT proBNP (HR 1.43 per 1-fold increase, 95% CI 1.25, 1.63; p=<0.001) were significantly associated with hospitalization or death.

Clinical Utility and Prognostic Value of Right Atrial Function in Pulmonary Hypertension.

Background Although right atrial (RA) enlargement is an established marker for adverse outcomes, the prognostic importance of RA dysfunction independent of RA size in pulmonary arterial hypertension is not known. Methods and Results Study subjects with pulmonary arterial hypertension were prospectively enrolled from 2010 to 2014. RA function was measured using RA speckle-tracking longitudinal strain and strain rate (SR) during each phase of the cardiac cycle: (1) RA reservoir (peak longitudinal strain, peak systolic SR), (2) RA conduit (peak early diastolic SR), and (3) RA active contraction (peak active contraction strain, peak contraction SR). The primary outcome was a composite of time to hospitalization or death assessed on follow-up. A total of 63 subjects had complete echocardiographic data. Of these, 91% were females, and the mean age was 58±12 years. During the follow-up period (range: 1-58 months), 39 were hospitalized or had died. After multivariable adjustment for age, sex, and left atrial size, peak longitudinal strain, peak active contraction strain, and peak early diastolic SR were significantly associated with increased risk of the composite outcome ( P=0.0005, P=0.0167, and P=0.0054, respectively). Conclusions RA dysfunction independently predicts mortality and hospitalizations in patients with pulmonary arterial hypertension.

Percutaneous Mechanical Circulatory Support Devices in Cardiogenic Shock.

Despite a high rate of early revascularization and use of intra-aortic balloon pump counterpulsation therapy, the prognosis of patients with cardiogenic shock has remained poor. In the hopes of improving outcomes, clinicians are increasingly turning to percutaneous left and right mechanical circulatory support devices. Until recently, the evidence base for these devices had consisted only of observational data, meta-analyses, and small feasibility trials. In this article, we describe the contemporary outcomes of patients with cardiogenic shock, the hemodynamics of cardiogenic shock, and hemodynamic effects of percutaneous mechanical circulatory support devices. We then use this discussion to provide clinicians with a useful framework for understanding when selecting between or while managing patients with a percutaneous mechanical circulatory support devices. We critically review the recently published data for and against the use of commercially available devices-the intra-aortic balloon pump counterpulsation, the Impella system, the TandemHeart, and venous-arterial extracorporeal membrane oxygenation-and highlight gaps in our understanding. Given such gaps, a consensus multidisciplinary approach that combines expertise from interventional cardiologists, heart failure specialists, cardiac surgeons, and cardiac anesthesiologists may help pair the right patient with the right device at the right time.

A Nationwide Assessment of the Association of Smoking Bans and Cigarette Taxes With Hospitalizations for Acute Myocardial Infarction, Heart Failure, and Pneumonia.

Multiple studies claim that public place smoking bans are associated with reductions in smoking-related hospitalization rates. No national study using complete hospitalization counts by area that accounts for contemporaneous controls including state cigarette taxes has been conducted. We examine the association between county-level smoking-related hospitalization rates and comprehensive smoking bans in 28 states from 2001 to 2008. Differences-in-differences analysis measures changes in hospitalization rates before versus after introducing bans in bars, restaurants, and workplaces, controlling for cigarette taxes, adjusting for local health and provider characteristics. Smoking bans were not associated with acute myocardial infarction or heart failure hospitalizations, but lowered pneumonia hospitalization rates for persons ages 60 to 74 years. Higher cigarette taxes were associated with lower heart failure hospitalizations for all ages and fewer pneumonia hospitalizations for adults aged 60 to 74. Previous studies may have overestimated the relation between smoking bans and hospitalizations and underestimated the effects of cigarette taxes.