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Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints.

ObjectivesFamily caregiver burden among older adults with advanced cancer remains poorly understood. We sought to (1) identify patient factors associated with caregiver burden and (2) examine how amount of time caregiving modifies these relationships.MethodsCross-sectional analysis of baseline data from a cluster-randomized palliative care intervention trial including patients with advanced cancer and their family caregivers, recruited from 17 oncology practices in Pennsylvania. Caregiver burden was measured using Zarit Burden Interview (ZBI-12; range 0-48). Patient factors included functional status (Eastern Cooperative Oncology Group), symptom burden (Edmonton Symptom Assessment Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (Functional Assessment of Chronic Illness Therapy - Palliative Care). Using adjusted multivariable regression, we analyzed (1) independent associations between patient factors and caregiver burden and (2) how weekly caregiving hours modified these relationships.ResultsAmong 441 patient-caregiver dyads, mean patient age was 70±10 and caregiver age was 62±13years. Most caregivers (59%) were patients' partners. Caregivers reported 44.5±53.5 average hours spent caregiving weekly; mean ZBI-12 scores were 10.3±7.3. Worse patient functional status (β=4.20, p&nbsp

BACKGROUND: Recent work suggests that dysregulated cellular metabolism may play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The TAME-PKD clinical trial is testing the safety, tolerability, and efficacy of metformin, a regulator of cell metabolism, in patients with ADPKD. This study investigates the cross-sectional association of urinary metabolic biomarkers with ADPKD severity among TAME-PKD trial participants at baseline. METHODS: Concentrations of total protein, targeted metabolites (lactate, pyruvate, succinate, and cAMP), and key glycolytic enzymes (pyruvate kinase M2 [PKM2], lactate dehydrogenase A [LDHA], and pyruvate dehydrogenase kinase 1 [PDK1]) were measured by ELISA, enzymatic assays, and immunoblotting in baseline urine specimens of 95 TAME-PKD participants. These analytes, normalized by urinary creatinine or osmolality to estimate excretion, were correlated with patients’ baseline height-adjusted total kidney volumes (htTKVs) by MRI and eGFR. Additional analyses were performed, adjusting for participants’ age and sex, using multivariable linear regression. RESULTS: Greater htTKV correlated with lower eGFR (r=−0.39; P=0.0001). Urinary protein excretion modestly correlated with eGFR (negatively) and htTKV (positively). Urinary cAMP normalized to creatinine positively correlated with eGFR. Among glycolytic enzymes, PKM2 and LDHA excretion positively correlated with htTKV, whereas PKM2 excretion negatively correlated with eGFR. These associations remained significant after adjustments for age and sex. Moreover, in adjusted models, succinate excretion was positively associated with eGFR, and protein excretion was more strongly associated with both eGFR and htTKV in patients

OBJECTIVE: Patient–oncologist therapeutic alliance is a foundation of quality cancer care, although there is limited research demonstrating its relationship with patient outcomes. We investigated the relationship between therapeutic alliance and patient quality of life with a secondary goal of determining whether the association varied by patients’ baseline level of psychological distress. METHODS: Cross-sectional analysis of baseline data from a randomized clinical trial of 672 patients with advanced cancer participating in a primary palliative care intervention trial. Patients completed baseline self-reported measures of therapeutic alliance (The Human Connection Scale, range: 16–64), overall quality of life (Functional Assessment of Cancer Therapy—Palliative Care, range: 0–184), and psychological distress (Hospital Anxiety and Depression Scale, range: 0–42). First, we determined the relationship between therapeutic alliance and quality of life using multivariable regression adjusting for confounders. We then examined if psychological distress was an effect modifier in this relationship by adding interaction effects of depression and anxiety symptoms on therapeutic alliance into the regression model. RESULTS: Patients reported high levels of therapeutic alliance (56.4 ± 7.4) and moderate quality of life (130.3 ± 25.5). Stronger therapeutic alliance was associated with better quality of life after adjusting for other confounding factors (β = 3.7, 95% confidence interval = 2.1, 5.3, p < 0.01). The relationship between therapeutic alliance and quality of life was generally consistent regardless of psychological distress. CONCLUSIONS: Collaborative, trusting relationships between patients with advanced cancer and their oncologists are associated with better patient quality of life. Future research should investigate the causal, longitudinal nature of these relationships.

Introduction Caregiver burden is high among caregivers of PD patients (CPD). Neuropsychiatric symptoms are leading contributors to CPD burden, but whether different symptoms differentially impact domains of caregiver burden is not known. Our objective was to examine which neuropsychiatric symptoms and demographic factors contribute to different domains of caregiver burden in PD. Methods This was a cross-sectional online survey study. Participants were recruited from the Fox Insight (FI) study and were eligible if they identified themselves as a CPD. The primary outcome was the Caregiver Burden Inventory (CBI) total score and its 5 sub-domain scores. The Neuropsychiatric Inventory Questionnaire (NPI-Q) assessed caregiver-reported neuropsychiatric symptoms in the care recipient. Multivariable linear regression models were used to characterize the associations between NPI-Q symptom severity scores and CBI scores. Covariates were caregiver age, sex, education, and caregiving duration. Results The sample consisted of 450 CPD, mean age 65.87 (SD 10.39) years, 74% females. After adjusting for covariates, CBI total score was predicted by NPI-Q total score (β = 1.96, p R2 = 39.2%. Anxiety severity had the largest effect size [standardized β (sβ) = 0.224] on the time-dependency domain, which was also associated with female sex (sβ = − 0.133) and age (sβ = 0.088). Severity of disinhibition (sβ = 0.218), agitation (sβ = 0.199), and female sex (sβ = 0.104) were associated with greater emotional burden. Conclusion Our findings indicate that demographic characteristics and specific neuropsychiatric symptoms contribute differentially to domains of caregiver burden. Tailored interventions to support CPD are needed.

PURPOSE: Providers have cited fear of taking away hope from patients as one of the principal reasons for deferring advance care planning (ACP). However, research is lacking on the relationship between ACP and hope. We sought to investigate the potential association between ACP and hope in advanced cancer. METHODS: This is a cross-sectional analysis of baseline data from a primary palliative care intervention trial. All patients had advanced solid cancers. Three domains of ACP were measured using validated questions to assess discussion with oncologists about end-of-life (EOL) planning, selection of a surrogate decision maker, and completion of an advance directive. Hope was measured using the Hearth Hope Index (HHI). Multivariable regression was performed, adjusting for variables associated with hope or ACP. RESULTS: A total of 672 patients were included in this analysis. The mean age was 69.3 ± 10.2 years; 54% were female, and 94% were White. Twenty percent of patients (132 of 661) reported having a discussion about EOL planning, 51% (342 of 668) reported completing an advance directive, and 85% (565 of 666) had chosen a surrogate. There was no difference in hope between patients who had and had not had an EOL discussion (adjusted mean difference in HHI, 0.55; P = .181 for adjusted regression), chosen a surrogate (adjusted HHI difference, 0.31; P = .512), or completed an advance directive (adjusted HHI difference, 0.11; P = .752). CONCLUSION: In this study, hope was equivalent among patients who had or had not completed 3 important domains of ACP. These findings do not support concerns that ACP is associated with decreased hope for patients with advanced cancer.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) has been associated with metabolic disturbances characterized by downregulation of AMP-activated protein kinase (AMPK), a critical sensor of the cellular energy status. Therapeutic activation of AMPK by metformin could inhibit cyst enlargement by inhibition of both the mammalian target of rapamycin pathway and fluid secretion via the CFTR chloride channel. METHODS: We designed a phase-2, randomized, placebo-controlled, clinical trial to assess the safety, tolerability, and efficacy of metformin on total kidney volume in adults without diabetes (age 18–60 years) with ADPKD and eGFR of ≥50 ml/min per 1.73 m(2). There were no eligibility criteria relating to kidney volume. In addition to demographics and clinical/family history, baseline parameters included eGFR, total kidney and liver volumes measured by MRI, and patient-reported outcomes were ascertained by the Medical Outcomes Study Short Form-36, the Gastrointestinal Safety Rating Scale, and the HALT-PKD pain questionnaire. RESULTS: We successfully randomized 97 participants recruited from two university-based clinical sites in Baltimore and Boston. The mean age of participants was 41.9 years, 72% were female, and 94% of participants were White. The majority of study participants had early stage disease, with a mean eGFR of 86.8±19.0 ml/min per 1.73 m(2). Approximately half of the study participants (48%) were classified as high risk for progression (Mayo imaging classes 1C, 1D, or 1E). There was no correlation between kidney and/or liver size and health-related quality of life (HRQoL) or gastrointestinal symptom severity. CONCLUSIONS: We report successful recruitment in this ongoing, novel, clinical trial of metformin in ADPKD, with a study sample comprising patients with early stage disease and nearly a half of participants considered at high estimated risk for progression. Participants reported a low gastrointestinal symptom burden at baseline, and HRQoL similar to that of the general population, with no differences in symptoms or HRQoL related to organomegaly. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Metformin as a Novel Therapy for Autosomal Dominant Polycystic Kidney Disease (TAME), NCT02656017

Background: We evaluated subclinical cardiovascular disease in relation to lactation history among women with normotensive pregnancies and women with hypertensive pregnancies, a distinction not previously examined. Materials and Methods: The POUCHmoms study included 678 women from a pregnancy cohort who were followed 7–15 years after delivery. We measured blood pressure, lipid levels, carotid intima-media thickness (CIMT), and lactation duration for each live birth (LB) at follow-up. We categorized lactation as never

Background Patient success with atrial fibrillation (AF) requires adequate health literacy to understand the disease and rationale for treatment. We hypothesized that individuals receiving treatment for AF would have increased knowledge about AF and that such knowledge would be modified by education and income. Methods We enrolled adults with AF receiving anticoagulation at ambulatory clinic sites. Participants responded to survey items encompassing the definitions of AF and stroke, the rationale for anticoagulation, and an estimation of their annual stroke risk. We examined responses in relation to household income and education in multivariable-adjusted models. Results We enrolled 339 individuals (age 72.0 ± 10.1; 43% women) with predominantly lower annual income ($20–49,999, n = 99, 29.2%) and a range of educational attainment (high school or vocational, n = 117, 34.5%). Participants demonstrated moderate AF knowledge (1.7 ± 0.6; range 0–2) but limited knowledge about anticoagulation (1.3 ± 0.7; range 0–3) or stroke (1.5 ± 0.8; range 0–3). Income was not associated with improvement in AF (P = 0.32 for trend), anticoagulation (P = 0.27) or stroke knowledge (P = 0.26). Individuals with bachelor or graduate degree had greater AF (1.8 ± 0.5) and stroke (1.6 ± 0.8) knowledge relative to those with high school or vocational training (1.4 ± 0.7 and 1.2 ± 0.9; P ≪ 0.01, both estimates). Education was not associated with understanding the rationale for anticoagulation. Most participants (230, 68%) estimated their annual stroke risk as ≥15%. Conclusions We identified consistent, fundamental gaps in disease-specific knowledge in a cohort of adults receiving treatment for non-valvular AF. Improved patient understanding of this complex and chronic disease may enhance shared decision making, patient engagement, anticoagulation adherence, and clinical outcomes in AF.

BACKGROUND/OBJECTIVE: Smoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation. METHOD: Data on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Smoking history was assessed for each phase of life from the onset of smoking to study enrollment. Data on second-hand smoke and drinking history were also collected. We compared demographic factors, drinking history, pain level and pancreas morphology by smoking status at age 25 (non-smoking

BACKGROUND Some literature exists potentially linking proliferation signal inhibitors (PSIs) to venous thromboembolism (VTE). We sought to determine the impact of PSIs on development of VTE in heart transplant (HT) patients while controlling for other risk factors. METHODS The incidence and predisposing factors of VTE were analyzed in this retrospective review of patients >18 years who underwent HT January 2000 to October 2016. Re-transplants, multiorgan transplants, or patients that expired within 30 days post-HT were excluded. VTE incidence rates are reported as number of events per 100 person-years. Cox proportional hazards models were used to assess the relationship between PSI exposure (time-varying covariate) and VTE. RESULTS Of 561 HT recipients, 112 received PSIs, started a median of 1.5 years post-HT. There were 102 total VTE events: 78 in PSI-naive patients during 2,547 patient-years (3.0 events per 100 person-years) vs 24 in PSI-exposed patients during 544 patient-years (4.4 events per 100 person-years). Cox proportional hazards models with PSI exposure as a time-varying covariate indicated the increased risk was statistically significant (unadjusted hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.31 to 3.49, p = 0.002). A VTE history was significantly associated with increased risk of VTE post-HT (HR 1.58, 95% CI 1.07 to 2.35, p = 0.022); however, the risk remained significant when adjusting for potential confounders, including previous VTE (HR 2.0, 95% CI 1.18 to 3.38, p = 0.010). CONCLUSIONS Exposure to PSIs is associated with a significant increase in risk for VTE even when controlling for other risk factors. When considering the use of PSI-based immunosuppression after HT, the risk of VTE over time should be weighed against the potential benefit.

Patients with nonspecific intraventricular conduction delay (IVCD) benefit less from cardiac resynchronization therapy (CRT) than patients with left bundle branch block (LBBB).The purpose of this study was to determine whether post-CRT outcome differences in patients with ischemic cardiomyopathy (ICM) relate to intrinsic QRS pattern and/or scar burden.We analyzed 393 consecutive ICM patients with left ventricular ejection fraction (LVEF) ≤35%, QRS duration120 ms, and LBBB or nonspecific IVCD who underwent single-photon emission computed tomography myocardial perfusion imaging and CRT-defibrillator implant. We compared scar burden; QRS duration; LVEF change; risk of death, transplant, or ventricular assist device; and risk of appropriate device shocks between LBBB and IVCD patients, using multivariable analyses to determine relative associations between QRS pattern vs scar burden and outcomes.Nonspecific IVCD is associated with greater scar burden and narrower baseline QRS duration than LBBB. IVCD patients demonstrated less QRS narrowing with CRT than LBBB patients, even when excluding IVCD patients with QRS duration150 ms. LVEF improved less in patients with IVCD vs LBBB, but only scar burden not QRS morphology or duration was associated with LVEF increase ≥5%. During 39-month follow-up, IVCD was associated with shorter survival free from transplant/ventricular assist device and shorter time to first appropriate device shock. Scar burden but not QRS morphology was independently associated with these outcomes on multivariate analysis.IVCD is associated with greater scar burden than LBBB in ICM CRT-defibrillator recipients. Scar burden, not QRS pattern, is independently associated with adverse clinical outcomes.

Driveline infection (DLI) is a cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that an alternate dressing protocol would decrease the rate of DLIs.A retrospective review of CF-LVAD implants at a single institution from January 2010 to October 2015 was conducted. Patients were divided into implants before (group 1) and after (group 2) the introduction of the new protocol on September 1, 2012. Patients were followed until death, transplantation, change in dressing type, or 2 years. 153 patients were included: 61 in group 1 and 92 in group 2. Group 1 had fewer HVADs than group 2 (27.9% vs 71.7%; P.001) and more destination therapy, although the latter was not statistically significant (50.8% vs 34.8%; P = .118). At 24 months, the freedom from DLI was 53% in group 1 and 89% in group 2 (P = .01). Group 1 had a significantly greater risk of DLI than group 2 (incident rate ratio 3.18, 95% confidence interval 1.23-8.18; P = .016).Dramatic improvement in freedom from DLI at 2 years was achieved with a new driveline dressing protocol. This demonstrates that DLI rates can be improved with alternate percutaneous site care techniques in CF-LVAD patients.

Background Thoracic endovascular aortic repair is increasingly used in acute complicated type B aortic dissection. The objective of this study was to demonstrate evidence of aortic remodeling by using a Proximal ExTension to Induce COmplete ATtachment (PETTICOAT) system in patients with acute complicated type B aortic dissections. Methods From 2013 to 2016, 213 patients with type B aortic dissection were seen at our institution. A total of 33 of those patients underwent thoracic endografting for complicated acute type B aortic dissection. Of these patients, 12 underwent standard thoracic endovascular aortic repair (standard group), and 21 had an additional bare metal stent distal to the covered endograft (PETTICOAT group). Aortic dimensions were measured on the basis of on three-dimensional computed tomographic scans on discharge and at 6 months. Results There were no differences in baseline characteristics between the standard group and the PETTICOAT group. At 6 months, both the PETTICOAT and standard groups had significant change in aortic diameter, true lumen diameter, and true lumen ratio throughout the thoracoabdominal aorta demonstrating positive remodeling. The change in true lumen ratio was significantly greater at the level of the celiac artery with the PETTICOAT system when compared with the standard group. Conclusions The use of a PETTICOAT concept with an addition of a bare metal stent distal to the proximal thoracic endograft offers positive aortic remodeling in the thoracoabdominal aorta at 6 months.

Author(s): Basir, Mir B; Pinto, Duane S; Ziaeian, Boback; Khandelwal, Akshay; Cowger, Jennifer; Suh, William; Althouse, Andrew | Abstract: BackgroundAcute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is associated with significant morbidity and mortality.MethodsWe provide an overview of previously conducted studies on the use of mechanical circulatory support (MCS) devices in the treatment of AMI-CS and difficulties which may be encountered in conducting such trials in the United States.ResultsWell powered randomized control trials are difficult to conduct in a critically ill patient population due to physician preferences, perceived lack of equipoise and challenges obtaining informed consent.ConclusionsWith growth in utilization of MCS devices in patients with AMI-CS, efforts to perform well-powered, randomized control trials must be undertaken.

The randomised controlled trial (RCT) is a powerful approach for testing the effectiveness of various clinical interventions. Cardiology often benefits from large RCTs, which may be used to inform practice decisions ranging from primary prevention to advanced cardiac disease and/or acute cardiac care. RCTs in cardiology often need to be quite large to test for meaningful effects on clinical outcomes, because effect sizes are typically modest and clinical outcomes may take several years to occur after treatment initiation. However, a variety of small clinical trials are also carried out in the biomedical research enterprise; these are often difficult to design and interpret, because the objectives and needs of small clinical trials are quite variable. Some are pilot trials that may be used to refine processes or as part of the planning in advance of a larger trial designed to test therapeutic efficacy. Some are first-in-human or proof-of-concept studies that, also, will eventually be followed by one or more larger trials to test therapeutic efficacy. Some are intended to be stand-alone trials that are small for other reasons. In this paper, we explore some key issues related to design and interpretation of small clinical trials in cardiology. We broadly classify small trials into 4 types: 1) pilot trials, 2) early-stage or proof-of-concept trials, 3) rare diseases or difficult-to-recruit populations, and 4) underpowered trials. For each, we describe the appropriate objectives, analysis, and interpretation.

INTRODUCTION: Although coexistence of alcohol-related liver disease (ALD) and pancreatitis (ALP) is seen in clinical practice, a clear understanding of the overlap between these diseases is lacking. Moreover, the relative risks for certain population groups have not been studied. We determined the prevalence and coexistence of ALD and ALP in patients with an alcohol use disorder using retrospective analysis of a large patient cohort from Western Pennsylvania. We specifically emphasized the analysis of underrepresented populations, including women and blacks. METHODS: We identified all unique patients who received care in UPMC health system during 2006–2017 with at least one International Classification of Diseases versions 9 and/or 10 codes for alcohol misuse, ALD and pancreatitis. We noted their sex, race and age of first diagnosis and duration of contact. RESULTS: Among 89,774 patients that fit our criteria, the prevalence of ALD, ALP and coexistent ALD and ALP in patients with alcohol misuse was 11.7%, 7.4% and 2.5%, respectively. Prevalence of ALP in ALD was 16.4%, and ALD in ALP was 33.1%. Prevalence of ALP in ALD was slightly more prevalent in women (18.6% vs. 15.6%, p < 0.001). Prevalence of ALP in ALD was 2–4 folds greater in blacks than other races. DISCUSSION: A sizeable fraction of patients with ALD or ALP has coexistent disease. This is the first study to identify that blacks are at a higher risk for ALP in the presence of ALD. Future studies should define the clinical impact of coexistent disease on clinical presentation and short- and long-term outcomes.

Background Cyclic vomiting syndrome (CVS) is an idiopathic disorder of gut-brain interaction characterized by recurrent bouts of nausea and vomiting. Although CVS negatively impacts quality of life (QOL), the determinants of impaired QOL among adult CVS sufferers are not fully understood. The unpredictability of CVS attacks may generate anticipatory anxiety and worsen quality of life in a substantial proportion of patients with CVS. Intolerance to uncertainty (IU) is a cognitive trait in which individuals experience distress when faced with unpredictable situations, particularly those with potentially negative consequences. Higher trait IU is a well-established vulnerability factor linked to the development of multiple psychiatric conditions, including anxiety. However, the extent to which higher IU is associated with impaired QOL in adults with CVS is not known. Methods To explore this issue, we surveyed 118 adult CVS patients and obtained demographic information, clinical features, reported healthcare utilization, and standardized assessments of IU, anxiety and panic, and QOL. Key results Adult CVS patients with higher IU did not report a greater frequency of CVS attacks or overall CVS-related healthcare utilization than those with lower IU. Yet, this group demonstrated substantially poorer physical and mental health-related QOL and higher rates of anxiety-spectrum disorders. Conclusions & inferences Higher degrees of IU are associated with increased anxiety and reduced QOL in patients with CVS. IU is a malleable cognitive trait that can be targeted by cognitive behavioral therapy (CBT). Our results suggest that some CVS patients may benefit from non-pharmacologic therapies such as CBT.

Pain burn-out during the course of chronic pancreatitis (CP), proposed in the 1980s, remains controversial, and has clinical implications. We aimed to describe the natural course of pain in a well-characterized cohort.We constructed the clinical course of 279 C P patients enrolled from 2000 to 2014 in the North American Pancreatitis Studies from UPMC by retrospectively reviewing their medical records (median observation period, 12.4 years). We assessed abdominal pain at different time points, characterized pain pattern (Type A [short-lived pain episodes] or B [persistent pain and/or clusters of recurrent severe pain]) and recorded information on relevant covariates.Pain at any time, at the end of follow-up, Type A pain pattern or B pain pattern was reported by 89.6%, 46.6%, 34% and 66% patients, respectively. In multivariable analyses, disease duration (time from first diagnosis of pancreatitis to end of observation) did not associate with pain - at last clinical contact (OR, 1.0, 95% CI 0.96-1.03), at NAPS2 enrollment (OR 1.02, 95% CI 0.96-1.07) or Type B pain pattern (OR 1.01, 95% CI 0.97-1.04). Patients needing endoscopic or surgical therapy (97.8 vs. 75.2%, p 0.001) and those with alcohol etiology (94.7 vs. 84.9%, p = 0.007) had a higher prevalence of pain. In multivariable analyses, invasive therapy associated with Type B pain and pain at last clinical contact.Only a subset of CP patients achieve durable pain relief. There is urgent need to develop new strategies to evaluate and manage pain, and to identify predictors of response to pain therapies for CP.

Purpose Most older adults eligible for cardiac rehabilitation (CR) do not participate or participate with low frequency, although it is a standard of care for patients with cardiovascular disease (CVD). Identifying the barriers to older adult participation is key in improving CR efficacy. Methods A range of patient characteristics was analyzed in relation to on-site frequency of participation in a CR program by older adult patients. These characteristics included demographics and indications for referral, as well as CVD and non-CVD diagnoses. The prevalence of these characteristics was compared among three patient cohorts, ranging from high contact frequency to minimal contact frequency of on-site participation in CR. Results Among the three participation frequency cohorts, no differences were noted in demographic factors, indications for referral, or CVD diagnoses. However, patients with hearing impairment (OR = 4.15: 95% CI, 1.32-13.08) or visual impairment (OR = 4.11: 95% CI, 1.46-11.59) at time of enrollment were more likely to be found in the minimal contact cohorts than the moderate or high contact frequency cohorts. Conclusions Whereas differences in CVD had little bearing on frequency of CR participation in older patients, differences in hearing and visual impairment varied significantly. Patients with hearing and vision impairments attended less frequently. Sensory impairment has previously been demonstrated to impact health care utilization by older adults, but is rarely considered in the treatment of CVD or CR. As sensory impairments are extremely prevalent among geriatric patients, further study of these potential barriers to care might open possibilities for older adult participation in CR.

Purpose Current American Association of Cardiovascular and Pulmonary Rehabilitation guidelines rely primarily on cardiovascular disease (CVD)-centered metrics to stratify risk and guide care. Yet, contemporary CVD patients are often older and are more likely to have risks attributable to rudimentary functional impairments that can have disproportionate bearing on management and prognosis. In this study, we stratified risk using novel indices of physical function as well as traditional indices of CVD in patients enrolling in phase II cardiac rehabilitation (CR). We hypothesized that risk stratification (RS) using functional criteria would be nonconcordant with CVD RS in a significant number of patients, thus inferring the conceptual value of CR management priorities that are better tailored for distinctive functional risks in many patients. Methods This was a retrospective analysis of a comprehensive quality improvement database with 489 patients. Risk stratification using novel functional indices (ie, gait speed, Timed Up and Go, hand grip, sit to stand, tandem stand, and a 6-min walk test) was compared with RS using traditional CVD criteria. Results Using functional RS, 97 patients were determined to be high risk versus 235 at low risk. Using CVD RS in the same cohort, 227 patients had high risk versus 161 who had low risk. Functional RS was consistent with CVD RS only 42.9% of the time. Conclusion Functional RS and CVD RS varied in the same patients. Enhanced assessment of functional risks adds important prognostic refinement and greater potential to tailor exercise therapy, nutrition, and other CR caregiving priorities.

Background Available estimates of coexistent alcohol-related pancreatitis (ALP) and alcohol-related liver disease (ALD) vary widely, and factors that determine coexistent disease are largely unknown. We performed a systematic review of published literature with the primary aim to generate robust estimates for coexistent alcohol-related chronic pancreatitis (ACP) and alcohol-related cirrhosis (ALC). Methods We searched PubMed, EMBASE, and Web of Science databases from inception until February 2018. Studies included were those in English-language, sample size ≥25 and allowed calculation of the coexistent disease. Pooled estimates were calculated using a random-effects model approach. Results Twenty-nine (including 5 autopsy studies) of 2000 eligible studies met inclusion criteria. Only 6.9% included patients were female. Fifteen studies enabled calculation of ACP in ALC, and 11 for ALC in ACP. Pooled prevalence of ACP in ALC was 16.2% (95% CI 10.4–24.5) overall, and 15.5% (95% CI 8.0–27.7) when data were limited to clinical studies. Corresponding prevalence for ALC in ACP was 21.5% (95% CI 12.0–35.6) and 16.9% (95% CI 11.5–24.3), respectively. There was significant heterogeneity among studies (I2 – 65–92%). Pooled prevalence for ALP in ALD or ALD in ALP in clinical studies were 15.2% and 39%, respectively. None of the studies reported outcomes in patients with coexistent disease. Conclusion A sizeable fraction of patients with ACP or ALC have coexistent disease. Future studies should define the prevalence of coexistent disease in women and minority populations, and the consequences of coexistent disease on clinical presentation and short- and long-term outcomes.

Background & aims The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. Methods Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. Results Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. Conclusions Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

Background Robotic mitral valve surgery has potential advantages in patient satisfaction and 30-day outcome. Cost concerns and repair durability limit wider adoption of robotic technology. This study examined detailed cost differences between robotic and sternotomy techniques in relation to outcomes and durability following robotic mitral program initiation. Methods Between April 2013 and October 2015, 30-day and 1-year outcomes of 328 consecutive patients undergoing robotic or sternotomy mitral valve repair or replacement by experienced surgeons were examined. Multivariable logistic regression informed propensity matching to derive a cohort of 182 patients. Echocardiographic follow-up was completed at 1 year in all robotic patients. Detailed activity-based cost accounting was applied to include direct, semidirect, and indirect costs with special respect to robotic depreciation, maintenance, and supplies. A quantitative analysis of all hospital costs was applied directly to each patient encounter for comparative financial analyses. Results Mean predicted risk of mortality was similar in both the robotic (n = 91) and sternotomy (n = 91) groups (0.9% vs 0.8%; P > .431). The total costs of robotic mitral operations were similar to those of sternotomy ($27,662 vs $28,241; P = .273). Early direct costs were higher in the robotic group. There was a marked increase in late indirect cost with the sternotomy cohort related to increased length of stay, transfusion requirements, and readmission rates. Robotic repair technique was associated with no echocardiographic recurrence greater than trace to only mild regurgitation at 1 year. Conclusions Experienced mitral surgeons can initiate a robotic program in a cost-neutral manner that maintains clinical outcome integrity as well as repair durability.

Background Deep hypothermic circulatory arrest (DHCA) is often avoided in patients with concomitant ascending aortic pathology when treating another cardiac disease to avoid increased risk of morbidity and mortality. We hypothesized that the use of DHCA with retrograde cerebral perfusion (RCP) does not add incremental risk to ascending aortic replacement alone in the setting of concomitant cardiac surgery. Methods A total of 408 ascending aortic ± hemiarch replacements and aortic (root), mitral, or tricuspid valve(s); coronary artery bypass grafting; or MAZE procedures were performed for concomitant cardiac disease. DHCA with RCP was used for all hemiarch replacements or the ascending aorta was replaced with an aortic cross-clamp proximal to the innominate artery. Propensity score matching was used to match similar ascending aorta patients versus hemiarch patients; the final propensity score–matched patients on age, sex, body mass index, previous heart surgery, preoperative aortic insufficiency, preoperative aortic stenosis, preoperative ejection fraction, and operative variables. Results Propensity score matching yielded 116 pairs of non-hemiarch patients versus 116 hemiarch patients. Within the propensity score–matched cohort, there were no differences in postoperative stroke (1.7% versus 3.4%; p = 0.41), new postoperative dialysis (6.0% versus 5.2%; p = 0.78), postoperative renal insufficiency (27.6% versus 19.8%; p = 0.16), 30-day mortality (2.6% versus 3.4%; p = 0.701), or 1-year mortality (4.3% versus 4.3%; p = 1.00) Conclusions Hemiarch replacement using DHCA with RCP does not increase the risk of operative complications compared with a normothermic, clamped-distal aortic anastomosis, and therefore its use should not be limited when planning complex multiprocedural reconstructions during elective ascending thoracic aortic replacement with concomitant cardiac surgery.

When properly executed, the randomized controlled trial is one of the best vehicles for assessing the effectiveness of one or more interventions. However, numerous challenges may emerge in the areas of study startup, recruitment, data quality, cost, and reporting of results. The use of well-run coordinating centers could help prevent these issues, but very little exists in the literature describing their creation or the guiding principles behind their inception.The Center for Clinical Trials & Data Coordination (CCDC) was established in 2015 through institutional funds with the intent of 1) providing relevant expertise in clinical trial design, conduct, coordination, and analysis; 2) advancing the careers of clinical investigators and CCDC-affiliated faculty; and 3) obtaining large data coordinating center (DCC) grants. We describe the organizational structure of the CCDC as well as the homegrown clinical trial management system integrating nine crucial elements: electronic data capture, eligibility and randomization, drug and external data tracking, safety reporting, outcome adjudication, data and safety monitoring, statistical analysis and reporting, data sharing, and regulatory compliance.Lastly, we share numerous lessons that can be taken from our experience. Specifically, we focus on 1) funding for DCCs, 2) the importance of DCCs to clinical researchers, 3) the expertise of DCC personnel, and 4) continually striving to improve.In conclusion, the CCDC strives to provide high-quality support for the design, conduct, coordination, and analyses of clinical trials, and we hope this paper will serve as a blueprint for future clinical trialists involved in DCCs. Keywords: Data coordinating center, Clinical trial management

Background The aim of this study was to evaluate hospital readmission rates and clinical outcomes between bioprosthetic (bAVR) and mechanical (mAVR) aortic valve replacements (AVR). Methods Adults aged 50 years or older undergoing isolated or concomitant AVR between 2011 and 2017 were included. The primary outcome was 5-year hospital readmission. Multivariable logistic regression analysis was used to evaluate the risk-adjusted impact of bAVR versus mAVR on outcomes. Results A total of 2981 patients were included: 406 (14%) mAVR and 2575 (86%) bAVR. Mean follow-up was 2.9 ± 1.9 years. Operative mortality was comparable (4% bAVR vs 3% mAVR; P = 0.30). There was no risk-adjusted difference in 30-day (hazard ratio [HR] 1.32, P = 0.46), 1-year (HR 1.17, P = 0.52), or 5-year mortality (HR 0.99, P = 0.93). Aortic valve 5-year reoperation rates were comparable (1%, P = 0.32). Risk-adjusted hospital readmissions were similar at 30 days (14% vs 15%; P = 0.63), 1 year (30% vs 27%; P = 0.43), and 5 years (55% vs 53%; P = 0.83) in the bAVR and mAVR groups, respectively. Similar findings were demonstrated when evaluating readmissions for bleeding (5-year readmission: 8% bAVR vs 10% mAVR; P = 0.36). Conclusions In this analysis of over 2900 AVRs, readmissions within 5 years were comparable between groups at approximately 50%, with patients being at highest risk in the early postdischarge period. Readmissions for bleeding constituted a minority of all readmissions for both cohorts.

Objective Drowsy driving is a significant cause of traffic accidents and fatalities. Although previous reports have shown an association between race and drowsy driving, the reasons for this disparity remain unclear. Study design A cross-sectional analysis of responses from 193,776 White, Black, and Hispanic adults participating in the US Behavioral Risk Factor Surveillance System from 2009 to 2012 who answered a question about drowsy driving. Measurements Drowsy driving was defined as self-reporting an episode of falling asleep while driving in the past 30 days. All analyses were adjusted for age, sex, and medical comorbidities. Subsequent modeling evaluated the impact of accounting for differences in health care access, alcohol consumption, risk-taking behaviors, and sleep quality on the race–drowsy driving relationship. Results After adjusting for age, sex, and medical comorbidities, the odds ratio (OR) for drowsy driving was 2.07 (95% confidence interval [CI] 1.69-2.53) in Blacks and 1.80 (95% CI 1.51-2.15) in Hispanics relative to Whites. Accounting for health care access, alcohol use, and risk-taking behaviors had little effect on these associations. Accounting for differences in sleep quality resulted in a modest reduction in the OR for drowsy driving in Blacks (OR = 1.55, 95% CI 1.27-1.89) but not Hispanics (OR = 1.74, 95% CI 1.45-2.08). Conclusion US Blacks and Hispanics have approximately twice the risk of drowsy driving compared to whites. Differences in sleep quality explained some of this disparity in Blacks but not in Hispanics. Further research to understand the root causes of these disparities is needed.

BACKGROUND Clinical guidelines recommend cardioverter defibrillator implantation for patients with heart failure and reduced ejection fraction. Despite this, women and minorities have been less likely to receive implantable cardioverter-defibrillator (ICD) therapy than white men. We examined race and sex differences in ICD implantation in a recent cohort. METHODS Using cross-sectional, retrospective analyses, we mined our health system's outpatient electronic medical records to assess age, race, sex, medications, and comorbidities for patients aged ≥18 years with ejection fraction ≤ 35% during 2014. While adjusting for confounding variables such as medications, age, and comorbidities, we conducted a multivariable logistic regression assessing whether racial and sex differences in ICD therapy persist. RESULTS Among 5,156 outpatients with ejection fraction ≤35%, 1,681 (32.6%) patients had an ICD present at the time of their index outpatient visit in 2014. Women were less likely to have an ICD than men (25.0% vs 36.3%, P

Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with births between 1985 and 2010 (n=272 ever preterm [P P interaction=0.04). Women with preterm delivery and a moderate-increasing SBP had a 2.17-fold higher hazards of CAC (95% confidence interval, 1.14–4.12) compared with women with term births and a lower SBP pattern, adjusted for cardiovascular disease risk factors and other pregnancy features. There was no excess CAC in women with moderate-increasing SBP and term births (adjusted hazard ratio, 1.02; 95% confidence interval, 0.49–2.14). Associations were stronger in women with hypertensive disorders of pregnancy but also detected in those with normotensive preterm deliveries. Women who deliver preterm infants are more likely to follow a high-risk blood pressure pattern throughout the childbearing years that is associated with CAC at midlife.

Pulmonary arterial hypertension (PAH) is a deadly vascular disease, characterized by increased pulmonary arterial pressures and right heart failure. Considering prior non-US studies of atrial arrhythmias in PAH, this retrospective, regional multi-center US study sought to define more completely the risk factors and impact of paroxysmal and non-paroxysmal forms of atrial fibrillation and flutter (AF/AFL) on mortality in this disease. We identified patients seen between 2010 and 2014 at UPMC (Pittsburgh) hospitals with hemodynamic and clinical criteria for PAH or chronic thromboembolic pulmonary hypertension (CTEPH) and determined those meeting electrocardiographic criteria for AF/AFL. We used Cox proportional hazards regression with time-varying covariates to analyze the association between AF/AFL occurrence and survival with adjustments for potential cofounders and hemodynamic severity. Of 297 patients with PAH/CTEPH, 79 (26.5%) suffered from AF/AFL at some point. AF/AFL was first identified after PAH diagnosis in 42 (53.2%), identified prior to PAH diagnosis in 27 (34.2%), and had unclear timing in the remainder. AF/AFL patients were older, more often male, had lower left ventricular ejection fractions, and greater left atrial volume indices and right atrial areas than patients without AF/AFL. AF/AFL (whether diagnosed before or after PAH) was associated with a 3.81-fold increase in the hazard of death (95% CI 2.64–5.52, p

Introduction Patient-reported outcomes are routinely assessed in atrial fibrillation (AF) to evaluate efficacy of treatment and as clinical trial outcomes. The relation of depression to such measures has had limited study in AF. Methods In a cohort receiving treatment for AF, we assessed depression with the Patient Health Questionniare-9 (PHQ; 0–4, normal range; 5–9, mild depression; ≥10 moderate depression). We related depression to disease-specific quality of life with the AF Effect on QualiTy of life (AFEQT, range 0–100) and the Global Perceived Stress Scale (GPPS, range 0–24) in multivariable-adjusted models. Results In 260 individuals (age 71.7 ± 10.1, 44.6% women) with AF, 51 (26.1%) had PHQ scores ≥5 and 17 (6.5%) ≥10. AFEQT scores decreased progressively with depression severity (normal range PHQ, 81.4 ± 14.1; mild depression, 65.8 ± 17.1; moderate depression, 50.6 ± 19.3). Individuals without depression had lower GPPS scores (3.0 ± 2.6) than those with mild (4.9 ± 2.5) or moderate (8.9 ± 4.0) depression. In multivariable-adjusted models mild depression was associated with a 12.1-point (95% confidence interval [CI], −17.2 to −6.9) decrease in AFEQT and 1.9-point (95% CI, 1.1 to 2.7) increase in GPSS, while moderate depression a 27.7-point (95% CI, −35.5 to −19.8) decrease in AFEQT and 5.5-point (95% CI, 4.2 to 6.8) increase in GPSS, relative to normal range PHQ. Regression analyses confirmed significant correlations between depression and AFEQT and GPPS scores in multivariable-adjusted models. Conclusions We determined that depression is associated with a step-wise, progressively adverse change in patient-centered outcomes in individuals with AF. Our findings suggest the importance of assessing depression in the evaluation of AF. Subject term list: health services, atrial fibrillation, risk factors

BACKGROUND Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. METHODS Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3 weeks and

Background The optimal timing for cardiac resynchronization therapy (CRT) after diagnosis of new-onset left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) and treatment with guideline-directed medical therapy (GDMT) is unknown. The purpose of this study was to describe relationships between time from diagnosis to CRT and outcomes in new-onset LBBB-associated idiopathic NICM with left ventricular ejection fraction (LVEF) ≤35%. Methods A retrospective cohort study examined associations between time from diagnosis to CRT (≤9 months vs >9 months) and clinical and echocardiographic outcomes. Results In 123 subjects with LBBB-associated idiopathic NICM, time from diagnosis to CRT was ≤9 months in 60 (49%) subjects and 9 months in 63 (51%) subjects. Clinical outcomes were similar for those implanted ≤9 months versus >9 months for adverse clinical events (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.41–1.78; P = 0.67) and all-cause mortality (HR, 0.57; 95% CI, 0.19–1.70; P = 0.31). Multivariable analyses demonstrated similar results. In 105 subjects with post-CRT echocardiograms, LVEF improvement to >35% was more likely in those implanted ≤9 months when compared to >9 months (odds ratio [OR], 3.53; 95% CI, 1.32–9.46; P = 0.01). This association persisted in the final multivariable model adjusted for age at diagnosis, sex, QRS duration, post-GDMT LVEF, and time from CRT to post-CRT echocardiogram (OR, 5.10; 95% CI, 1.71–15.22; P = 0.004). Conclusion In LBBB-associated idiopathic NICM, earlier CRT implantation was associated with more favorable cardiac remodeling. Delaying CRT may miss a critical period to halt and reverse progressive myocardial damage.

Objectives: Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the treatment of refractory cardiac arrest (extracorporeal cardiopulmonary resuscitation [ECPR]) and postarrest cardiogenic shock (PACS). Our primary objective was to determine the 1-year survival of patients who were treated with ECMO for PACS or in ECPR. Methods: We conducted a retrospective analysis of hospitalized patients in a tertiary care facility who underwent treatment with ECMO for ECPR or PACS. Between January 2004 and December 2013, patients were prospectively entered into an institutional registry. One-year follow-up was assessed by electronic medical record or social security death index if clinical follow-up was unavailable. Results: Fifty-one patients were treated with ECMO during the study period. The mean age was 54.0 ± 10.9 years; the majority of patients were men (80.4%). The most common etiology of arrest was acute myocardial infarction (51.0%). Overall, 13 (25.4%) patients survived for at least 1 year. Preexisting coronary artery disease, hypertension, and hyperlipidemia were associated with reduced likelihood of survival. We observed a significant improvement in 1-year mortality in patients treated for PACS when compared to ECPR, 46.7% versus 16.7%, respectively. Conclusion: The use of ECMO for treatment of refractory cardiac arrest or cardiogenic shock may be a suitable treatment in a very select cohort of patients. Our results support a significantly higher 1-year survival in patients with PACS compared to refractory cardiac arrest.

Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Patients presenting with AF are often admitted to hospital for rhythm or rate control, symptom management, and/or anticoagulation. We investigated temporal trends in AF hospitalizations in United States from 1996 to 2010. Methods: Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by National Center for Health Statistics. Because of the survey design, sampling weights were applied to the raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of AF were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 427.31. Weighted least squares regression was used to test for linear trends in the number of AF admissions, length of stay, and inpatient mortality. We further stratified AF admissions based on patients' age, gender, and race. Results: Admissions for a primary diagnosis of AF increased from approximately 286,000 in 1996 to about 410,000 in 2010 with a significant linear trend (β = 9470 additional admissions per year, p

Introduction: With the recent publication of the negative DANISH trial, the mortality benefit of the implantable cardioverter-defibrillator (ICD) has been put in question in patients with non-ischemic cardiomyopathy (NICM). Because a majority of patients in DANISH receive cardiac resynchronization therapy (CRT) devices, we investigated in the present study the survival of recipients of CRT pacemakers (CRT-P) versus CRT ICDs (CRT-D) in a cohort of older (≥75 years) NICM patients at our institution. Methods: A total of 135 NICM patients with CRT device were identified (42 with CRT-P and 93 with CRT-D) and were followed to the endpoint of all-cause mortality. Overall survival was compared between the CRT-P and CRT-D groups with adjustment for differences in baseline characteristics. Results: Over a median follow-up of 46 months from the time of CRT device implantation, there were 54 total deaths (40%): 14 in the CRT-P (33%) and 40 in the CRT-D (43%) groups. Overall, CRT-P recipients had similar unadjusted mortality compared to CRT-D recipients (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.56–1.93), and this remained unchanged after adjusting for unbalanced covariates (HR 0.95, 95% CI 0.47–1.89) including left ventricular ejection fraction, used of angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and the Charlson comorbidity index. Conclusion: Our data support that in older NICM patients with CRT devices, the addition of ICD therapy does not improve survival. Keywords: Cardiac resynchronization therapy, Non-ischemic cardiomyopathy, Pacemaker, Defibrillator, Mortality

INTRODUCTION Readmissions are a burden on health care resources and have negative impact on patients. Cardiovascular implantable electronic devices (CIEDs) are frequently used in the management of rhythm disorders and advanced heart failure. We assessed 30-day readmissions in patients admitted for CIED implantation in a sample of United States patients. METHODS Data were extracted from Nationwide Readmissions Database for calendar year 2013. Patients admitted for CIED implantation were identified using ICD-9 codes. Patients

Background: Reports of left ventricular assist device (LVAD) malfunction have focused on pump thrombosis. However, the device consists of the pump, driveline, and peripherals, all of which are potentially subject to failure. Methods: Prospectively collected data were reviewed for all LVAD device malfunctions (DMs) occurring in rotary LVADs implanted at a single center between April 2004 and May 2016. Durable LVADs included 108 Heartmate II (HM II) and 105 HeartWare VAD (HVAD). DM data were categorized according to device type and into categories related to the component that failed: (1) controller, (2) peripheral components, and (3) implantable blood pump or its integral electric driveline. Pump-related events were analyzed as pump-specific (suspected or confirmed thrombosis) or nonpump-specific (driveline failure). DM rates were reported as events per 1000 patient-days, and Cox proportional hazard models were used for time-to-event analyses. Cumulative rates of malfunction were examined for the main components of each type of LVAD. Results: Types of DM included controller failure (30%), battery failure (19%), or patient cable failure (14%), whereas only 13% were because of pump failure. DMs were more common in the HM II device (3.73 per 1000 patient-days versus 3.06 per 1000 patient-days for the HVAD, P P P P P Conclusions: Device malfunction is much broader than pump failure alone and occurs for different components at different rates based on the type of LVAD.

Background There are important differences in medical cannabis laws across the U.S.. However, prior studies investigating the effect of medical cannabis laws on outcomes disregard this heterogeneity. Findings from the body of literature using a simple dichotomous assessment of whether a particular state has enacted a medical cannabis law are equivocal or conflicting. To advance the science, a national advisory group of experts in medical cannabis developed and utilized a systematic methodology, the “medicalization of cannabis laws standardized scale” (MCLaSS), to characterize and quantify state laws’ degree of medicalization, the extent to which medical cannabis is treated similarly to pharmaceutical medications. Methods We conducted a systematic review of state-level medical cannabis laws in the U.S. Using the novel MCLaSS, we calculated seven domain scores (patient-clinician relationship, manufacturing and testing, product labeling, types of products, supply and dose limit, prescription drug monitoring program, and dispensing practices) and a summary score for each state which had enacted medical cannabis laws as of July 2019. Results There is substantial heterogeneity in the degree of medicalization of states’ medical cannabis laws, as demonstrated by the MCLaSS summary score, which ranged from 23 (least medicalized) to 86 (most medicalized). Conclusion This methodology will advance the evidence base about the impact of medical cannabis laws on patient and public health outcomes, which is urgently needed to ensure the development of policies that minimize the risks and maximize the benefits of medical cannabis.

Context Patients with advanced cancer often worry about dying. Less is known about the role of worry in decision making regarding future care. Objectives To explore relationships between patients' worry about dying and their illness understanding, treatment preferences, and advance care planning (ACP). Methods This cross-sectional study used baseline data from a primary palliative care intervention trial. All participants had metastatic solid tumors. Using patients' response to I worry about dying from the Functional Assessment of Chronic Illness—Palliative Care survey instrument, univariate and multivariate analyses assessed associations with illness understanding, treatment preferences, and ACP. Results Of 672 patients, 47% reported worrying about dying not at all, whereas 9.7% worried quite a bit or very much. In regression analysis, compared with patients who reported not worrying about dying, those who reported high levels of worry were more likely to describe themselves as terminally ill (adjusted odds ratio [AOR] = 1.98; 95% CI = 1.10–3.54; P = 0.021) and prefer life-extending therapy over symptom-focused care (AOR = 2.61; 95% CI = 1.30–5.22; P = 0.007). They were less likely to have completed an advance directive (AOR = 0.49; 95% CI = 0.25–0.94; P = 0.032). The same relationships were seen using patients' response to I feel scared about my future from the Herth Hope Index. Conclusion Patients with advanced cancer who worry about dying are more likely to identify as terminally ill and desire life-extending treatment and are less likely to engage in ACP. Understanding how patients cope with worry and make medical decisions is important in providing quality care to these patients.

We have previously reported that long-tone-burst, high-mechanical-index ultrasound (US) and microbubble (MB) therapy can restore perfusion in both in vitro and in vivo models of microvascular obstruction (MVO). Addition of MBs to US has been found to potentiate the efficacy of thrombolytics on large venous thrombi; however, the optimal US parameters for achieving microvascular reperfusion of MVO caused by microthrombi, when combined with tissue plasminogen activator (tPA), are unknown. We sought to elucidate the specific effects of US, with and without tPA, for effective reperfusion of MVO in an in vitro model using both venous and arterial microthrombi. Venous- and arterial-type microthrombi were infused onto a mesh with 40-μm pores to simulate MVO. Pulsed US (1 MHz) was delivered with inertial cavitation (IC) (1.0 MPa, 1000 cycles, 0.33 Hz) and stable cavitation (SC) US (0.23 MPa, 20% duty cycle, 0.33 Hz) regimes while MB suspension (2 × 10 6 MBs/mL) was infused. The efficacy of sonoreperfusion with these parameters was tested with and without tPA. Sonoreperfusion efficacy was significantly greater for IC + tPA compared with tPA alone, IC, SC and SC + tPA, suggesting lytic synergism between tPA and US for both venous- and arterial-type microthrombi. In contrast to our previous in vitro studies using 1.5 MPa at 5000 US cycles without tPA, the IC regime employed herein used 90% less US energy. These findings suggest an IC regime can be used with tPA synergistically to achieve a high degree of fibrinolysis for both thrombus types.

Background Heart failure (HF) readmission rates have become an increasingly important quality metric since the advent of the Hospital Readmissions Reduction Program. Despite many well-intentioned efforts to reduce readmissions, clinicians continue to struggle with the problem of high HF readmission rates. Hypothesis HF patients with obstructive sleep apnea (OSA) will have higher burden of rehospitalization and mortality than HF patients without OSA. Methods Our study included 344 patient encounters (among 271 unique patients) with a diagnosis of HF from September 2014 through September 2015. Our primary endpoints were all-cause readmission within 30 and 90 days. Multivariate logistic regression was used to assess the relationship between OSA and readmission when accounting for potential confounders. Results The patients’ were 72 ± 10 years old, and predominantly white (76.2%) and male (99.4%). Among the 344 patient encounters, 247 (71.8%) had diagnosed coronary artery disease, 159 (46.2%) had atrial fibrillation, and 99 (28%) had obstructive sleep apnea (OSA). Notably, patients with OSA had an elevated rate of readmission within 30 days (OSA: 30.3% vs no OSA: 19.6%, P = 0.037) and within 90 days (OSA: 57.6% vs no OSA: 36.3P < 0.01). Patients with OSA had increased risk of readmission within 90 days (odds ratio: 2.38, 95% confidence interval: 1.47-3.83, P < 0.01) even after adjustment for potential confounders of age, race, obesity, diabetes, and chronic obstructive pulmonary disease. Conclusions HF patients with OSA have an elevated rate of readmission compared to the general HF population, particularly within the first 90 days after discharge.

Clinical heart failure (HF) occurs frequently after ST-segment elevation myocardial infarction (STEMI), and is associated with increased mortality. We assessed the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of STEMI patients on clinical HF following primary percutaneous coronary intervention (pPCI).Data from Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With the Guidelines™ (ACTION Registry-GWTG) from two PCI-hospitals that are utilizing RIPC during inter-facility helicopter transport of STEMI patients for pPCI between March, 2013 and September, 2015 were used for this study. The analyses were limited to inter-facility STEMI patients transported by helicopter with LVEF55% after pPCI. The outcome measures were occurrence of clinical HF and serum level of brain-type natriuretic peptide (BNP).Out of the 150 STEMI patients in this analysis, 92 patients received RIPC and 58 did not. The RIPC and non-RIPC groups were generally similar in demographic and clinical characteristics except for lower incidence of cardiac arrest in the RIPC group (3/92 [3.3%] versus 13/58 [22.4%], p=0.002). STEMI patients who received RIPC were less likely to have in-hospital clinical HF compared to patients who did not receive RIPC (3/92 [3.3%] versus 7/58 [12.1%]; adjusted OR=0.22, 95% CI 0.05-0.92, p=0.038) after adjusting for baseline differences. In subgroup analysis, RIPC was associated with lower BNP (123 [interquartile range, 17.0-310] versus 319 [interquartile range, 106-552], p=0.029).RIPC applied during inter-facility air transport of STEMI patients for pPCI is associated with reduced incidence of clinical HF and serum BNP.

Spermatogonial stem cells (SSC) are essential for spermatogenesis and male fertility. In addition, these adult tissue stem cells can be used as vehicles for germline modification in animal models and may have application for treating male infertility. To facilitate the investigation of SSCs and germ lineage development in rats, we generated a DEAD-box helicase 4 (DDX4) (VASA) promoter-enhanced green fluorescent protein (EGFP) reporter transgenic rat. Quantitative real-time polymerase chain reaction and immunofluorescence confirmed that EGFP was expressed in the germ cells of the ovaries and testes and was absent in somatic cells and tissues. Germ cell transplantation demonstrated that the EGFP-positive germ cell population from DDX4-EGFP rat testes contained SSCs capable of establishing spermatogenesis in experimentally infertile mouse recipient testes. EGFP-positive germ cells could be easily isolated by fluorescence-activated cells sorting, while simultaneously removing testicular somatic cells from DDX4-EGFP rat pup testes. The EGFP-positive fraction provided an optimal cell suspension to establish rat SSC cultures that maintained long-term expression of zinc finger and BTB domain containing 16 (ZBTB16) and spalt-like transcription factor 4 (SALL4), two markers of mouse SSCs that are conserved in rats. The novel DDX4-EGFP germ cell reporter rat described here combined with previously described GCS-EGFP rats, rat SSC culture and gene editing tools will improve the utility of the rat model for studying stem cells and germ lineage development.

Background Characteristics and outcomes of concurrently diagnosed new rapid atrial fibrillation (AF) or atrial flutter (AFL) and new heart failure with reduced left ventricular ejection fraction (LVEF) are not well described. Methods A retrospective cohort study of subjects referred for expedited transesophageal echocardiography-guided rhythm-control strategies for concurrent new rapid AF/AFL and new LVEF ≤ 40% diagnosed during the same admission was analyzed. Results Twenty-five subjects (median age 57 years; 96% male; 96% Caucasian; median CHA2DS2-VASc = 2) presented with new AF (n = 18) or AFL (n = 7) with rapid ventricular rate (median 135 beats/min) and new reduced LVEF (median 27%; range, 10–37.5%). Seven (28%) subjects had left atrial appendage thrombi (LAAT) and five (20%) subjects had heavy or binge alcohol use. Baseline characteristics were similar between those with and without LAAT. Thirteen subjects with AF and without LAAT underwent direct-current cardioversion (DCCV) and 10 (77%) had AF recurrence within 90 days. Improvement of long-term LVEF to >40% was comparable for subjects with and without initial LAAT (83% vs 94%; P = 0.46). Three of four subjects who received primary prophylaxis implantable cardioverter-defibrillators improved their LVEF to >35% after sinus rhythm maintenance. The median long-term follow-up time was 3.0 years. Conclusions Subjects with concurrently diagnosed new rapid AF/AFL and new reduced LVEF are characterized by a high prevalence of LAAT and significant alcohol use. AF subjects without initial LAAT who underwent DCCV had a high 90-day AF recurrence rate. The presence of LAAT did not have a prognosticative effect on eventual LVEF improvement, which was observed in almost all subjects.

Background Although heart failure (HF) is a common cause of hospital admissions, few data describe temporal trends in HF hospitalization. We present data on number of HF admissions, length of stay (LOS), and inpatient mortality in the United States, 1996–2009. Hypothesis To assess HF hospitalizations in a national sample of United States population. Methods Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by the National Center for Health Statistics. Sampling weights are applied to raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of HF were identified using ICD-9-CM codes. We excluded hospitalizations where HF was a secondary diagnosis. Weighted least squares regression was used to test for linear trends in HF hospitalizations. Results Approximately 15.5 million weighted primary HF hospitalizations were included. The number of total primary HF hospitalizations increased from 1 000 766 in 1996 to about 1 173 832 in 2009 (β = 7371 hospitalizations per year; 95% confidence interval (CI): 552 to 14 190, P = 0.036). Mean LOS per hospitalization decreased from 6.07 days in 1996 to about 5.26 days in 2009 (β = −0.059 days per year; 95% CI: −0.079 to −0.039, P < 0.001). Inpatient mortality rates declined from 4.92% in 1996 to 3.41% in 2009 (β = −0.17% per year; 95% CI: −0.23 to −0.10, P < 0.001). Conclusions In a nationally representative sample of HF hospitalizations, mean LOS and inpatient mortality rates declined over the past 2 decades. HF management cost is most likely to be reduced by decreasing the number of HF admissions.

Objective To assess the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of ST-segment elevation myocardial infarction (STEMI) patients on the incidence of acute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI). Background STEMI patients who receive pPCI have an increased risk of AKI for which there is no well-defined prophylactic therapy in the setting of emergent pPCI. Methods Using the ACTION Registry-GWTG, we evaluated the impact of RIPC applied during inter-facility helicopter transport of STEMI patients from non-PCI capable hospitals to 2 PCI-hospitals in the United States between March, 2013 and September, 2015 on the incidence of AKI following pPCI. AKI was defined as ≥0.3 mg/dL increase in creatinine within 48–72 hours after pPCI. Results Patients who received RIPC (n = 127), compared to those who did not (n = 92), were less likely to have AKI (11 of 127 patients [8.7%] vs. 17 of 92 patients [18.5%]; adjusted odds ratio = 0.32, 95% CI 0.12–0.85, P = 0.023) and all-cause in-hospital mortality (2 of 127 patients [1.6%] vs. 7 of 92 patients [7.6%]; adjusted odds ratio = 0.14, 95% CI 0.02–0.86, P = 0.034) after adjusting for socio-demographic and clinical characteristics. There was no difference in hospital length of stay (3 days [interquartile range, 2–4] vs. 3 days [interquartile range, 2–5], P = 0.357) between the 2 groups. Conclusion RIPC applied during inter-facility helicopter transport of STEMI patients for pPCI is associated with lower incidence of AKI and in-hospital mortality. The use of RIPC for renal protection in STEMI patients warrants further in depth investigation.

Background Dual antiplatelet therapy is recommended for patients with acute coronary syndrome (ACS) that undergo percutaneous coronary intervention (PCI). However, the effect of switching P2Y12 inhibitors between the loading dose and therapy after discharge is not well described. Methods This post-hoc analysis of a prospectively collected registry included 3219 consecutive ACS patients who underwent PCI. Patients were categorized into four groups: clopidogrel at load and discharge (C–C), loading dose of clopidogrel and discharged on prasugrel/ticagrelor (C–PT), loading dose of prasugrel/ticagrelor and discharged on clopidogrel (PT–C), and prasugrel/ticagrelor at load and discharge (PT–PT). Results While 77.6% of patients received the C–C treatment regimen and 13.6% received the PT–PT strategy, the strategy of P2Y12 switching was fairly common with 6.2% in the PT–C group and 2.6% in the C–PT group. While C–C was the most common treatment regimen, PT–C and PT–PT were more commonly used in STEMI patients than in NSTEMI or unstable angina patients. A significantly lower unadjusted incidence of the composite outcome (death, MI, and repeat revascularization) was appreciated in both the PT–C (1.0%) and PT–PT (2.3%) groups than the C–C group (4.0%). Propensity-score matched analysis still showed significantly reduced risk (HR=0.22, 95% CI 0.05–0.93, p=0.04) in the PT–C group vs. a matched group of C–C controls. Conclusions The strategy of utilizing a newer P2Y12 inhibitor and then switching to clopidogrel in ACS patients following PCI is used with some frequency in routine clinical practice and further studies should evaluate the safety and efficacy of such a strategy.

Background Sex differences in clinical outcomes for left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) after cardiac resynchronization therapy (CRT) are not well described. Methods A retrospective cohort study at an academic medical center included subjects with LBBB-associated idiopathic NICM who received CRT. Cox regression analyses estimated the hazard ratios (HRs) between sex and clinical outcomes. Results In 123 total subjects (mean age 62 years, mean initial left ventricular ejection fraction 22.8%, 76% New York Heart Association class III, and 98% CRT-defibrillators), 55 (45%) were men and 68 (55%) were women. The median follow-up time after CRT was 72.4 months. Similar risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate antitachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) was observed between men and women (HR, 1.20; 95% confidence interval [CI] 0.57-2.51; p = 0.63). This persisted in multivariable analyses. Men and women had similar risk for all-cause mortality in univariable analysis, but men had higher risk in the final multivariable model that adjusted for age at diagnosis, QRS duration, and left ventricular end-diastolic dimension index (HR, 4.55; 95% CI, 1.26-16.39; p = 0.02). The estimated 5-year mortality was 9.5% for men and 6.9% for women. Conclusions In LBBB-associated idiopathic NICM, men have higher risk for all-cause mortality after CRT when compared to women.