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.

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.

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.

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.

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.

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.

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.

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.

Financial stress and outcomes after acute myocardial infarction.

BACKGROUND: Little is known about the association between financial stress and health care outcomes. Our objective was to examine the association between self-reported financial stress during initial hospitalization and long-term outcomes after acute myocardial infarction (AMI). MATERIALS AND METHODS: We used prospective registry evaluating myocardial infarction: Event and Recovery (PREMIER) data, an observational, multicenter US study of AMI patients discharged between January 2003 and June 2004. Primary outcomes were disease-specific and generic health status outcomes at 1 year (symptoms, function, and quality of life (QoL)), assessed by the Seattle Angina Questionnaire [SAQ] and Short Form [SF]-12. Secondary outcomes included 1-year rehospitalization and 4-year mortality. Hierarchical regression models accounted for patient socio-demographic, clinical, and quality of care characteristics, and access and barriers to care. RESULTS: Among 2344 AMI patients, 1241 (52.9%) reported no financial stress, 735 (31.4%) reported low financial stress, and 368 (15.7%) reported high financial stress. When comparing individuals reporting low financial stress to no financial stress, there were no significant differences in post-AMI outcomes. In contrast, individuals reporting high financial stress were more likely to have worse physical health (SF-12 PCS mean difference -3.24, 95% Confidence Interval [CI]: -4.82, -1.66), mental health (SF-12 MCS mean difference: -2.44, 95% CI: -3.83, -1.05), disease-specific QoL (SAQ QoL mean difference: -6.99, 95% CI: -9.59, -4.40), and be experiencing angina (SAQ Angina Relative Risk = 1.66, 95%CI: 1.19, 2.32) at 1 year post-AMI. While 1-year readmission rates were increased (Hazard Ratio = 1.50; 95%CI: 1.20, 1.86), 4-year mortality was no different. CONCLUSIONS: High financial stress is common and an important risk factor for worse long-term outcomes post-AMI, independent of access and barriers to care.

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.

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.

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.