Dual antiplatelet therapy is a Class I recommendation for patients with an acute coronary syndrome (ACS). However, whether patients should be loaded with a P2Y12 antagonist at the time of hospital admission remains controversial. Following angiography, about 10% of ACS patients are found to have

Case Presentation: Cardiorenal syndrome (CRS) is prevalent in patients requiring heart transplantation (HT) and is often reversed prior to HT through hemodynamic optimization with inotropes. The use of calcineurin inhibitors is known to induce and worsen renal failure post-HT. In this study we evaluated whether pre HT renal dysfunction, as determined by prior diagnosis of CRS, was associated with worse renal function, progression to ESRD, and mortality post HT. In this single center retrospective study, 75 patients who underwent HT were followed for 5 years. Patients were stratified by history of pre-existing CRS based on history of chronic kidney disease (CKD) prior to transplant. Patients who progressed to hemodialysis (HD) (10 patients) were censored in order to not confound laboratory markers of renal dysfunction. In addition to baseline demographics, outcome data for 5 years post HT including renal function, initiation of chronic hemodialysis (HD), stroke, infection, arrhythmia, mortality and graft failure was assessed. Data was analyzed using Mann-Whitney U and X2 analysis. Our final cohort was comprised of 66 patients (No CKD, N = 44 and CKD N = 31). Index labs measured after hemodynamic optimization for HT showed no significant difference in renal function between patients with and without a diagnosis of CRS. As time progressed, patients with pre-HT CRS were noted to have significantly worse renal function compared to patients without a pre-HT diagnosis of CRS (Fig. 1). There was no difference between the number of patients with and without a pre-HT diagnosis of CRS who progressed to end stage renal disease necessitating hemodialysis (12.9% vs 11.4% P = .840). Overall mortality was greater in patients with pre-HT CRS compared to those without, however this did not reach statistical significance (25.8% vs 18.2%, P = .427). A pre-HT diagnosis of CRS was associated with increased progression of renal failure despite similar pre-HT renal function. This suggests that patients with CRS prior to HT require closer follow up and more aggressive management of modifiable risk factors for progression of CRS such as hypertension and diabetes. Additionally, dose reduction of calcineurin inhibitors or transitioning to alternative therapy with proliferation signal inhibitors may be preferable in this subset of patients in order to reduce the progression of renal dysfunction post HT, however further research is necessary.

The benefits of stem cell therapy for patients with chronic symptomatic systolic heart failure due to ischemic and nonischemic cardiomyopathy (ICM and NICM, respectively) are unclear. We performed a systematic review of major published and ongoing trials of stem cell therapy for systolic heart failure and compared measured clinical outcomes for both types of cardiomyopathy. The majority of the 29 published studies demonstrated clinical benefits of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). Left ventricular ejection fraction (LVEF) was improved in the majority of trials after therapy. Cell delivery combined with coronary artery bypass grafting was associated with the greatest improvement in LVEF. Left ventricular end-systolic volume (or diameter), New York Heart Association functional classification, quality of life, and exercise capacity were also improved in most studies after cell therapy. Most ICM trials demonstrated a significant improvement in perfusion defects, infarct size, and myocardial viability. Several larger clinical trials that are in progress employ alternative delivery modes, cell types, and longer follow-up periods. Stem cells are a promising therapeutic modality for patients with heart failure due to ICM or NICM. More data are required from larger blinded trials to determine which combination of cell type and delivery mode will yield the most benefit with avoidance of harm in these patient populations.

Background/objectives: Cystatin-C and beta-2-microglobulin may be superior to serum creatinine, blood urea nitrogen (BUN), or estimated glomerular filtration rate (eGFR) in patients hospitalized with heart failure (HF). We compared these renal markers in ambulatory HF patients.Methods: We prospectively evaluated the association of baseline renal markers and eGFR (by 4 different formulas) with (1) the composite of death or HF-related hospitalization and (2) rates of hospitalizations and emergency department (ED) visits in 166 outpatients with HF (57.3 +/- 11.6 years; 57.2% white, 38.6% black, median left ventricular ejection fraction 27.5% [17.5, 40.0]).Results: After a median of 3.9 years, 63 (38.0%) patients met the composite endpoint. There were 458 hospitalizations (177 [38.6%] for HF) and 209 ED visits (51 [24.4%] for HF). Cystatin-based eGFR most consistently predicted (1) the composite endpoint (highest-to-lowest tertile adjusted hazard ratio [HR] 4.92 [95% CI 2.07-11.7; P < 0.001]); and (2) hospitalization rates, including HF hospitalizations (highest-to-lowest tertile, adjusted relative rate 5.24 [95% CI 1.61-17.01; P = 0.006]). Serum creatinine alone was a strong predictor of the composite endpoint (highest-to-lowest tertile, adjusted HR 3.20 [95% CI, 1.51-6.78; P = 0.002]). Only the highest tertile of BUN was associated with rates of ED visits.Conclusions: In outpatients with HF, cystatin-based eGFR provides consistent prognostication across outcomes, except ED visits. Serum creatinine is an adequate prognosticator of death or HF hospitalization. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Introduction: Left ventricular assist devices (LVAD) are being used increasingly as lifesaving bridge-to-transplant therapy. However, the understanding of the impact of such devices on post cardiac transplant outcomes is evolving. This study investigates the effect of LVAD implantation on patient outcomes after heart transplantation. Methods: In this single center retrospective cohort study, 76 heart transplant patients were followed for 5 years post transplantation. These patients were stratified based on the presence or absence of LVAD prior to transplantation. In addition to baseline demographic information, post-transplant outcomes including transplant rejection, infection, arrhythmia, renal failure, stroke, graft failure and mortality were assessed. Data was analyzed using student's t-test and X2 analysis. Our cohort was comprised of 17 (22.4%) patients with prior LVAD and 59 (77.6%) controls. Results: Analysis of baseline demographic information did not reveal any significant differences between the two cohorts. Our outcomes data showed a statistically significant difference in graft failure, defined as impaired graft function on echocardiography, during the first year post-transplant in patients with prior LVAD (29.4% vs 10.2% P = .047) compared to those without. This difference was maintained at 5-year follow up (41% vs 11.9%, P = .006). Overall mortality was increased in patients with prior LVAD (41.2% vs 13.6%, P = .012) compared to those without. Conclusion: Our results suggest that prior LVAD implantation is associated with increased incidence of graft failure, particularly in the first year, and increased mortality post-heart transplantation. This may be due to increased allosensitization and suggests that aggressive management of former LVAD recipients undergoing heart transplantation is needed. Further research is warranted to determine the precise mechanism underlying this increase graft in failure.

BACKGROUND: Impaired spirometric parameters have been reported in patients with stage C heart failure and portend worse outcomes in these patients. The impact of spirometric parameters on outcomes in patients with stage D heart failure listed for heart transplantation is unknown. METHODS: We collected data on consecutive subjects listed for heart transplantation and examined the association of FEV1, FVC, and FEV1/FVC with (1) death or left ventricular assist device implantation (primary end point) and (2) death, left ventricular assist device implantation, or urgent transplantation (secondary end point). In a secondary analysis, we examined the association of baseline spirometry with post-transplant outcomes. RESULTS: Among 187 subjects (53 +/- 10 y old, 17.1% women, 69.5% white subjects, 28.9% black subjects), there were 19 deaths, 28 left ventricular assist device implantations, and 74 urgent transplantations (primary end point of 25.1%, secondary end point of 64.7%) after a median of 5.5 months (interquartile range of 2.3-15.2). For FEV1, the hazard ratios for the primary and secondary end points were 0.93 (95% CI 0.61-1.41, P = .72) and 0.94 (95% CI 0.72-1.21, P = .62) per L, respectively. The hazard ratios of FVC were 0.90 (95% CI 0.65-1.25, P = .52) and 0.92 (95% CI 0.76-1.13, P = .43) per L, respectively. Impairment patterns (obstructive, restrictive, mixed) were not associated with risk for events. There was no interaction of spirometric parameters with smoking or lung disease for outcomes. Baseline spirometry was not associated with perioperative 30-d mortality (1.4%) and 1-y post-transplant survival (97.1%). CONCLUSIONS: In contrast to stage C subjects with heart failure, spirometric parameters were not associated with outcomes in this homogeneous stage D heart failure population. (C) 2015 Daedalus Enterprises

Introduction: Arrhythmias after orthotopic heart transplantation (OHT) are common. However the influence of pre-transplant atrial arrhythmia on post-OHT atrial arrhythmia has not been established. In this study we analyzed the occurrence of post-OHT atrial arrhythmias in patients with prior atrial fibrillation or flutter (afib/flutter). Methods: In this retrospective single center study, 56 patients who underwent OHT from 2003-14 were enrolled. Patients were stratified based on history of pre-OHT afib/flutter. Baseline demographics, and post-transplant outcomes including atrial arrythmias were recorded. Post-OHT atrial arrhythmias were defined as afib/flutter, atrial tachycardia, multifocal atrial tachycardia, and wandering atrial pacemaker Data was analyzed using student’s t-test and X2 analysis. Results: The cohort comprised of 20 patients with pre-transplant history of afib/flutter and 36 patients without such diagnosis. There was no statistical difference in age, gender or BMI in patients between the two groups. Our analysis revealed that patients with afib/flutter prior to OHT had significantly more atrial arrhythmias at one year compared to those without afib/flutter (31.6% vs 8.8%, p=0.034), and this difference was maintained at five years follow-up (50% vs 11.1%, p=0.001). Additionally, there was a strong trend toward increased overall mortality in in this group (35% vs 13.9%, p=0.065). Discussion: Our results suggest a novel finding of a link between pre and post-OHT atrial arrhythmias, particularly in the first year after transplantation. This surprising finding may be related to residual recipient pulmonary vein activity, recipient atrial anastomotic tissue, or patient related factors. Further prospective research is indicated to confirm our findings.

Background Pulmonary hypertension (PH) in patients with heart failure (HF) is associated with worse outcomes and is rapidly being recognized as a therapeutic target. To facilitate pragmatic research efforts, data regarding the prognostic importance of noninvasively assessed pulmonary artery systolic pressure (PASP) in stable ambulatory patients with HF are needed. Methods and Results We examined the association between echocardiographic PASP and outcomes in 417 outpatients with HF (age, 54±13 years; 60.7% men; 50.4% whites; 24.9% with preserved ejection fraction). Median PASP was 36 mm Hg (interquartile range [IQR]: 29, 46). After a median follow‐up of 2.6 years (IQR: 1.7, 3.9) there were 72 major events (57 deaths; 9 urgent heart transplants; and 6 ventricular assist device implantations) and 431 hospitalizations for HF. In models adjusting for clinical risk factors and therapy, a 10‐mm Hg higher PASP was associated with 37% higher risk (95% CI: 18, 59; P<0.001) for major events, and 11% higher risk (95% CI: 1, 23; P=0.039) for major events or HF hospitalization. The threshold that maximized the likelihood ratio for both endpoints was 48 mm Hg; those with PASP ≥48 mm Hg (N=84; 20.1%) had an adjusted hazard ratio of 3.33 (95% CI: 1.96, 5.65; P<0.001) for major events and 1.47 (95% CI: 1.02, 2.11; P=0.037) for major events or HF hospitalization. Reduced right ventricular systolic function had independent prognostic utility over PASP for adverse outcomes. Right atrial pressure and transtricuspid gradient both contributed to risk. Conclusions Elevated PASP, determined by echocardiography, identifies ambulatory patients with HF at increased risk for adverse events.

IntroductionSpirometric parameters are impaired in patients with heart failure (HF); however, their prognostic value in patients listed for heart transplantation is not well known.HypothesisSpirometric variables predict prognosis among HF patients listed for heart transplantation.MethodsWe studied 187 consecutive heart transplant candidates listed between January 2000 and December 2012. We examined the association of FEV1, FVC, FEV1/FVC and ventilatory patterns (obstructive, restrictive, mixed) with (1) death or left ventricular assist device (LVAD) implantation (primary endpoint) and (2) death, LVAD implantation, or urgent transplantation (secondary endpoint). We also assessed for correlation of spirometric parameters with clinical characteristics, medications, and central hemodynamics.ResultsThe mean age of patients was 53 ± 10 years; 17.1% were women; 69.5% were whites and 28.9% blacks. After a median of 5.5 months (2.3-15.2) there were 19 deaths, 28 LVAD implantations, and 74 urgent trans¬plantations (primary endpoint: 25.1%; secondary endpoint: 64.7%). For FEV1, the hazard ratio (HR) for the primary and secondary endpoint was 0.93 (95%CI 0.61, 1.41; P=0.72) and 0.94 (95%CI 0.72, 1.21; P=0.62) per L, respectively. The HR of FVC was 0.90 (95%CI, 0.65, 1.25; P=0.52) and 0.92 (95%CI, 0.76, 1.13; P=0.43) per L, respectively (Table). Similarly, neither % predicted FEV1 and FVC and FEV1/FVC ratio nor ventilatory patterns were associated with the primary or secondary endpoint (Table & Figure). There was no interaction of spirometric parameters with smoking or lung disease for outcomes. Right-sided pressures were negatively correlated and cardiac output was positively correlated with absolute and %predicted FEV1 and FVC.ConclusionTableAssociation between spirometric parameters and outcomes in patients listed for heart transplant.Spirometric ParameterHR95% CIP ValuePrimary AnalysisFEV1, L0.930.61, 1.410.72FEV1 predicted, %1.000.98, 1.020.80FVC,L0.900.65, 1.250.52FVC predicted, %0.990.98, 1.010.53FEV1/FVC1.010.98, 1.030.65Secondary AnalysisFEV1, L0.940.72, 1.210.62FEV1 predicted, %1.000.99, 1.010.75FVC, L0.920.76, 1.130.43FVC predicted, %1.000.99, 1.010.58FEV1/FVC1.010.99, 1.020.45CI, confidence interval; FEV1; forced expiratory volume at 1st sec; FVC, forced vital capacity; HR, hazard ratio Open table in a new tab IntroductionSpirometric parameters are impaired in patients with heart failure (HF); however, their prognostic value in patients listed for heart transplantation is not well known.

The largest published study of renal denervation (RDN), SYMPLICITY HTN–2, demonstrated significant blood pressure (BP) reduction in eligible patients with resistant hypertension. Given the strict inclusion and exclusion criteria of SYMPLICITY HTN–2, we sought to determine its generalizability

BACKGROUND:Studies of endovascular renal denervation (RDN) have demonstrated significant blood pressure reduction in eligible patients with resistant hypertension. These trials have used stringent inclusion and exclusion criteria in patient enrollment, potentially selecting for a small subset of patients with resistant hypertension. In this study, we examined the changes in estimated prevalence of resistant hypertension when using increasingly stringent definitions of resistant hypertension in a fixed population and assessed the generalizability of RDN when applying study criteria to a community-based hypertensive population.METHODS:A retrospective chart review was done of hypertensive outpatients. Four increasingly stringent interpretations of the American Heart Association definition of resistant hypertension were used to calculate prevalence estimates. Patients eligible for RDN were identified using criteria from SYMPLICITY HTN-3. Demographic and clinical characteristics were compared.RESULTS:We identified 1,756 hypertensive outpatients; 55.0% were male, 53.9% were white, and subjects had a mean age of 66.6 ± 12.5 years and a body mass index (BMI) of 30.1 ± 10.7 kg/m(2). Only 14 (0.8%) were eligible for RDN. Among these patients, 10 (71.4%) were female and all were black, with a mean age of 69.9 ± 8.8 and BMI of 35.7 ± 6.6. Congestive heart failure was more common in patients eligible for RDN.CONCLUSIONS:Patients eligible for RDN based on published studies represent an exceedingly small proportion of the total hypertensive population. Further studies are necessary to determine if the benefits of RDN can be generalized to a broader range of hypertensive patients than those included in previous trials.

Background: Handgrip strength test quantifies the amount of static force that the hand can squeeze around a dynamometer and is associated with increased mortality in middle-aged and older adults, and in patients with chronic diseases. The prognostic role of handgrip strength in heart failure (HF) has not been fully investigated. Methods: A hydraulic hand dynamometer was used to measure handgrip strength in 317 outpatients with HF enrolled in The Atlanta Cardiomyopathy Consortium (TACC) cohort study. Patients repeated the test 3 times in each hand and the average from both hands was used. We defined poor handgrip strength based on age- and gender-specific normative data. We evaluated the association between poor handgrip strength and major clinical event (death, heart transplant, left ventricular assist device) and healthcare resource utilization. Results: Baseline patient characteristics are presented in Table 1; 228 patients (71.9%) had poor handgrip strength. Total follow-up was 911 patient-years; 55 patients (17.4%) experienced a major clinical event. There was a total of 836 all-cause hospitalizations with an average length of stay of 4.7 days. Poor handgrip strength was not significantly associated with major clinical events (hazard ratio (HR) 1,19; 95% CI: 0.64 to 2,21; P=0.59). However, patients with poor strength had 42% higher hospitalization rate (95% CI: 1.3% to 98%; P=0.042) and spent 85% (95% CI: 10% to 210%; P=0.020) more days in the hospital. Average length of stay among patients with poor handgrip strength was 4.9 days vs. 4.2 days in those with preserved strength. Conclusion: Poor handgrip strength is highly prevalent among HF patients and is associated with higher healthcare resource utilization and length of stay.

Simultaneous adherence with multiple self-care instructions among heart failure (HF) patients is not well described. Patient-reported adherence to 8 recommendations related to exercise, alcohol, medications, smoking, diet, weight, and symptoms was assessed among 308 HF patients using the Medical Outcomes Study Specific Adherence Scale questionnaire (0="never" to 5="always," maximum score=40). A baseline cumulative score of ≥32/40 (average ≥80%) defined good adherence. Clinical events (death/transplantation/ventricular assist device), resource utilization, functional capacity (6-minute walk distance), and health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were compared among patients with and without good adherence. The mean follow-up was 2.0±1.0 years, and adherence ranged from 26.3% (exercise) to 89.9% (medications). A cumulative score indicating good adherence was reported by 35.7%, whereas good adherence with every behavior was reported by 9.1% of patients. Good adherence was associated with fewer hospitalizations (all-cause 87.8 vs 107.6; P=.018; HF 29.6 vs 43.8; P=.007) and hospitalized days (all-cause 422 vs 465; P=.015; HF 228 vs 282; P<.001) per 100-person-years and better health status (KCCQ overall score 70.1±24.6 vs 63.8±22.8; P=.011). Adherence was not associated with clinical events or functional capacity. Patient-reported adherence with HF self-care recommendations is alarmingly low and selective. Good adherence was associated with lower resource utilization and better health status.

Background: Resistant hypertension (RH) is defined as BP above goal despite the use of 3 antihypertensive agents of different classes, or BP controlled on 4 agents, ideally maximally dosed and including a diuretic. RH studies have used varying interpretations of this definition, with prevalence estimates ranging from 3% to 30%. This study characterizes RH when different definitions are used in the same population. METHODS: We calculated the prevalence of RH among consecutive hypertensive outpatients presenting to an academic cardiology clinic over 6 months using 4 increasingly stringent definitions of RH. These included 1) SBP>140 (130 if DM or CKD) on three medications or controlled on four medications regardless of dosage; 2) Definition 1 including a diuretic; 3) SBP>140 (130 if DM or CKD) on three maximally-dosed medications (per JNC-7) or controlled on four medications, at least three which are maximally dosed; and 4) Definition 3 including a diuretic. We compared demographic and clinical characteristics of patients with and without RH using chi-square and t tests. Results: Among 1761 hypertensive outpatients, 46 (2.6%), 374 (21.2%), 602 (34.2%), and 739 (42.6%) were using 0, 1, 2, and ≥3 medications, respectively; 856 (47.6%) were using a diuretic-containing regimen. Overall, 500 patients (28.4%) had RH by Definition 1, which decreased to 402 patients (22.8%) using Definition 2 which required a diuretic. However, with inclusion of medication dosage, the number of patients with RH decreased to 29 (1.7%) using Definition 3, and 24 (1.4%) using Definition 4. RH using Definition 1 was associated with African-American race, female sex, coronary disease, diabetes, congestive heart failure, stroke, and end-stage renal disease (p<0.05). Conclusion: RH represents a small proportion of the overall hypertensive population when a strict definition of RH including maximal medication dosing and/or the presence of a diuretic is applied. These findings suggest that some patients with RH by more inclusive definitions may benefit from optimization of antihypertensive therapy. Consistent definitions of RH should be applied in the future to ensure that RH is adequately identified and so RH treatment interventions and pathophysiology may be consistently compared.