Browsing by Subject "heart failure"

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Open Access
A Prospective Cohort Study of Medical Decision-Making Roles and Their Associations with Patient Characteristics and Patient-Reported Outcomes among Patients with Heart Failure.
(Medical decision making : an international journal of the Society for Medical Decision Making, 2023-09) Ozdemir, Semra; Lee, Jia Jia; Yeo, Khung Keong; Sim, Kheng Leng David; Finkelstein, Eric Andrew; Malhotra, Chetna
Objective
Among patients with heart failure (HF), we examined 1) the evolution of patient involvement in decision making over 2 y, 2) the association of patient characteristics with decision-making roles, and 3) the association of decision-making roles with distress, spiritual well-being, and quality of physician communication.
Methods
We administered the survey every 4 mo over 24 mo to patients with New York Heart Association class 3/4 symptoms recruited from inpatient clinics. The decision-making roles were categorized as no patient involvement, physician/family-led, joint (with family and/or physicians), patient-led, or patient-alone decision making. The associations between patient characteristics and decision-making roles were assessed using a mixed-effects ordered logistic regression, whereas those between patient outcomes and decision-making roles were investigated using mixed-effects linear regressions.
Results
Of the 557 patients invited, 251 participated in the study. The most common roles in decision making at baseline assessment were "no involvement" (27.53%) and "patient-alone decision making" (25.10%). The proportions of different decision-making roles did not change over 2 y (P = 0.37). Older age (odds ratio [OR] = 0.97; P = 0.003) and being married (OR = 0.63; P = 0.035) were associated with lower involvement in decision making. Chinese ethnicity (OR = 1.91; P = 0.003), higher education (OR = 1.87; P = 0.003), awareness of terminal condition (OR = 2.00; P < 0.001), and adequate self-care confidence (OR = 1.74; P < 0.001) were associated with greater involvement. Compared with no patient involvement, joint (β = -0.58; P = 0.026) and patient-led (β = -0.59; P = 0.014) decision making were associated with lower distress, while family/physician-led (β = 4.37; P = 0.001), joint (β = 3.86; P < 0.001), patient-led (β = 3.46; P < 0.001), and patient-alone (β = 3.99; P < 0.001) decision making were associated with better spiritual well-being.
Conclusion
A substantial proportion of patients was not involved in decision making. Patients should be encouraged to participate in decision making since it is associated with lower distress and better spiritual well-being.
Highlights
The level of involvement in medical decision making did not change over time among patients with heart failure. A substantial proportion of patients were not involved in decision making throughout the 24-mo study period.Patients' involvement in decision making varied by age, ethnicity, education level, marital status, awareness of the terminal condition, and confidence in self-care.Compared with no patient involvement in decision making, joint and patient-led decision making were associated with lower distress, and any level of patient involvement in decision making was associated with better spiritual well-being.
Open Access
Addressing the Menace of Enterococcal Endocarditis.
(Journal of the American College of Cardiology, 2020-02) Bashore, Thomas M; Turner, Nicholas A
Open Access
Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact.
(J Card Fail, 2015-09) Buggey, Jonathan; Mentz, Robert J; DeVore, Adam D; Velazquez, Eric J
Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity over the past decade of new pharmacotherapies that improve outcomes. However, recent data from a large randomized controlled trial compared the novel agent LCZ696, a dual-acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well established angiotensin-converting enzyme (ACE) inhibitor enalapril and found significant reduction in mortality among the chronic reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides and thereby promoting natriuresis and vasodilatation and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACE inhibition but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNi LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest that LCZ696 may improve surrogate markers of HF severity. In this paper, we review the preclinical and clinical data that led to the development of LCZ696, the understanding of the underlying mechanistic action, and the robust clinical impact that LCZ696 may have in the near future.
Open Access
Association Between Comorbidities and Outcomes in Heart Failure Patients With and Without an Implantable Cardioverter-Defibrillator for Primary Prevention.
(J Am Heart Assoc, 2015-08-06) Khazanie, Prateeti; Hellkamp, Anne S; Fonarow, Gregg C; Bhatt, Deepak L; Masoudi, Frederick A; Anstrom, Kevin J; Heidenreich, Paul A; Yancy, Clyde W; Curtis, Lesley H; Hernandez, Adrian F; Peterson, Eric D; Al-Khatib, Sana M
BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is associated with improved outcomes in patients with heart failure (HF), but whether this association holds among older patients with multiple comorbid illnesses and worse HF burden remains unclear. METHODS AND RESULTS: Using the National Cardiovascular Data Registry's ICD Registry and the Get With The Guidelines-Heart Failure (GWTG-HF) registry linked with Medicare claims, we examined outcomes associated with primary-prevention ICD versus no ICD among HF patients aged ≥65 years in clinical practice. We included patients with an ejection fraction ≤35% who received (ICD Registry) and who did not receive (GWTG-HF) an ICD. Compared with patients with an ICD, patients in the non-ICD group were older and more likely to be female and white. In matched cohorts, the 3-year adjusted mortality rate was lower in the ICD group versus the non-ICD group (46.7% versus 55.8%; adjusted hazard ratio [HR] 0.76; 95% CI 0.69 to 0.83). There was no associated difference in all-cause readmission (HR 0.99; 95% CI 0.92 to 1.08) but a lower risk of HF readmission (HR 0.88; 95% CI 0.80 to 0.97). When compared with no ICD, ICDs were also associated with better survival in patients with ≤3 comorbidities (HR 0.77; 95% CI 0.69 to 0.87) and >3 comorbidities (HR 0.77; 95% CI 0.64 to 0.93) and in patients with no hospitalization for HF (HR 0.75; 95% CI 0.65 to 0.86) and at least 1 prior HF hospitalization (HR 0.69; 95% CI 0.58 to 0.82). In subgroup analyses, there were no interactions between ICD and mortality risk for comorbidity burden (P=0.95) and for prior HF hospitalization (P=0.46). CONCLUSION: Among older HF patients, ICDs for primary prevention were associated with lower risk of mortality even among those with high comorbid illness burden and prior HF hospitalization.
Open Access
Effectiveness and Safety of Aldosterone Antagonist Therapy Use Among Older Patients With Reduced Ejection Fraction After Acute Myocardial Infarction.
(J Am Heart Assoc, 2016-01-21) Wang, Tracy Y; Vora, Amit N; Peng, S Andrew; Fonarow, Gregg C; Das, Sandeep; de Lemos, James A; Peterson, Eric D
BACKGROUND: While aldosterone antagonists have proven benefit among post-myocardial infarction (MI) patients with low ejection fraction (EF), how this treatment is used among older MI patients in routine practice is not well described. METHODS AND RESULTS: Using ACTION Registry-GWTG linked to Medicare data, we examined 12 080 MI patients ≥65 years with EF ≤40% who were indicated for aldosterone antagonist therapy per current guidelines and without documented contraindications. Of these, 11% (n=1310) were prescribed aldosterone antagonists at discharge. Notably, 10% of patients prescribed an aldosterone antagonist were eligible for, but not concurrently treated with, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Spironolactone was the predominantly prescribed aldosterone antagonist. At 2-year follow-up, aldosterone antagonist use was not associated with lower mortality (unadjusted 39% versus 38%; HR 0.99, 95% CI 0.88-1.33 using inverse probability-weighted propensity adjustment) except in symptomatic HF patients (HR 0.84, 95% CI 0.72-0.99, Pinteraction=0.009). Risks of hyperkalemia were low at 30 days, but significantly higher among patients prescribed aldosterone antagonists (unadjusted 2.3% versus 1.5%; adjusted HR 2.04, 95% CI 1.16-3.60), as was 2-year risk of acute renal failure (unadjusted 6.7% versus 4.8%; adjusted HR 1.39, 95% CI 1.01-1.92) compared with patients not prescribed aldosterone antagonists. CONCLUSIONS: Aldosterone antagonist use among eligible older MI patients in routine clinical practice was not associated with lower mortality except in patients with HF symptoms, but was associated with increased risks of hyperkalemia and acute renal failure. These results underscore the importance of close post-discharge monitoring of this patient population.
Open Access
Effectiveness of catheter ablation of atrial fibrillation according to heart failure etiology.
(Journal of arrhythmia, 2020-02) Black-Maier, Eric; Steinberg, Benjamin A; Trulock, Kevin M; Wang, Frances; Lokhnygina, Yuliya; O'Neal, Wanda; Al-Khatib, Sana; Atwater, Brett D; Daubert, James P; Frazier-Mills, Camille; Hegland, Donald D; Jackson, Kevin P; Jackson, Larry R; Koontz, Jason I; Lewis, Robert K; Sun, Albert Y; Thomas, Kevin L; Bahnson, Tristram D; Piccini, Jonathan P
Background
Catheter ablation is an important rhythm control therapy in patients with atrial fibrillation (AF) with concomitant heart failure (HF). The objective of this study was to assess the comparative efficacy of AF ablation patients with ischemic vs nonischemic heart failure.
Methods
We conducted a retrospective, observational cohort study of patients with HF who underwent AF ablation. Outcomes were compared based on HF etiology and included in-hospital events, symptoms (Mayo AF Symptom Inventory [MAFSI]), and functional status (New York Heart Association class) and freedom from atrial arrhythmias at 12 months.
Results
Among 242 patients (n = 70 [29%] ischemic, n = 172 [71%] nonischemic), patients with nonischemic cardiomyopathy were younger (mean age 64 ± 11.5 vs 69 ± 9.1, P = .002), more often female (36% vs 17%, P = .004), and had higher mean left-ventricular ejection fraction (47% vs 42%, P = .0007). There were no significant differences in periprocedural characteristics, including mean procedure time (243 ± 74.2 vs 259 ± 81.8 minutes, P = .1) and nonleft atrial ablation (17% vs 20%, P = .6). All-cause adverse events were similar in each group (15% vs 17%, P = .7). NYHA and MAFSI scores improved significantly at follow-up and did not differ according to HF etiology (P = .5; P = .10-1.00 after Bonferroni correction). There were no significant differences in freedom from recurrent atrial arrhythmia at 12-months between ischemic (74%) and nonischemic patients (78%): adjusted RR 0.63, 95% confidence interval 0.33-1.19.
Conclusions
Catheter ablation in patients with AF and concomitant heart failure leads to significant improvements in functional and symptom status without significant differences between patients with ischemic vs nonischemic HF etiology.
Open Access
Initiation, Continuation, or Withdrawal of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers and Outcomes in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction.
(J Am Heart Assoc, 2017-02-11) Gilstrap, Lauren G; Fonarow, Gregg C; Desai, Akshay S; Liang, Li; Matsouaka, Roland; DeVore, Adam D; Smith, Eric E; Heidenreich, Paul; Hernandez, Adrian F; Yancy, Clyde W; Bhatt, Deepak L
BACKGROUND: Guidelines recommend continuation or initiation of guideline-directed medical therapy, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), in hospitalized patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure Registry, we linked clinical data from 16 052 heart failure with reduced ejection fraction (ejection fraction ≤40%) patients with Medicare claims data. We divided ACEi/ARB-eligible patients into 4 categories based on admission and discharge ACEi/ARB use: continued (reference group), started, discontinued, or not started on therapy. A multivariable Cox proportional hazard model was used to determine the association between ACEi/ARB category and outcomes. Most, 90.5%, were discharged on ACEi/ARB (59.6% continued and 30.9% newly started). Of those discharged without ACEi/ARB, 1.9% were discontinued, and 7.5% were eligible but not started. Thirty-day mortality was 3.5% for patients continued and 4.1% for patients started on ACEi/ARB. In contrast, 30-day mortality was 8.8% for patients discontinued (adjusted hazard ratio [HRadj] 1.92; 95% CI 1.32-2.81; P<0.001) and 7.5% for patients not started (HRadj 1.50; 95% CI 1.12-2.00; P=0.006). The 30-day readmission rate was lowest among patients continued or started on therapy. One-year mortality was 28.2% for patients continued and 29.7% for patients started on ACEi/ARB compared to 41.6% for patients discontinued (HRadj 1.35; 95% CI 1.13-1.61; P<0.001) and 41.7% (HRadj 1.28; 95% CI 1.14-1.43; P<0.001) for patients not started on therapy. CONCLUSIONS: Compared with continuation, withdrawal of ACEi/ARB during heart failure hospitalization is associated with higher rates of postdischarge mortality and readmission, even after adjustment for severity of illness.
Open Access
Intracoronary Adenovirus-Mediated Delivery and Overexpression of the β2-Adrenergic Receptor in the Heart
(2000-02) Shah, AS; Lilly, RE; Kypson, AP; Tai, O; Hata, JA; Pippen, A; Silvestry, SC; Lefkowitz, RJ; Glower, DD; Koch, WJ
Background—Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of β2-adrenergic receptors (β2ARs) has been shown to enhance contractility in transgenic mice and reverse signaling abnormalities found in failing cardiomyocytes in culture. In this study, we sought to determine the feasibility and in vivo consequences of delivering an adenovirus containing the human β2AR cDNA to ventricular myocardium via catheter-mediated subselective intracoronary delivery. Methods and Results—Rabbits underwent percutaneous subselective catheterization of either the left or right coronary artery and infusion of adenoviral vectors containing either a marker transgene (Adeno-βGal) or the β2AR (Adeno-β2AR). Ventricular function was assessed before catheterization and 3 to 6 days after gene delivery. Both left circumflex– and right coronary artery–mediated delivery of Adeno-β2AR resulted in ≈10-fold overexpression in a chamber-specific manner. Delivery of Adeno-βGal did not alter in vivo left ventricular (LV) systolic function, whereas overexpression of β2ARs in the LV improved global LV contractility, as measured by dP/dtmax, at baseline and in response to isoproterenol at both 3 and 6 days after gene delivery. Conclusions—Percutaneous adenovirus-mediated intracoronary delivery of a potentially therapeutic transgene is feasible, and acute global LV function can be enhanced by LV-specific overexpression of the β2AR. Thus, genetic modulation to enhance the function of the heart may represent a novel therapeutic strategy for congestive heart failure and can be viewed as molecular ventricular assistance.
Open Access
Isolated Noncompaction of the Left Ventricle in Adults.
(J Am Coll Cardiol, 2015-08-04) Hussein, Ayman; Karimianpour, Ahmadreza; Collier, Patrick; Krasuski, Richard A
Isolated left ventricular noncompaction (ILVNC) is a cardiomyopathy that was first described in 1926 as a "spongy myocardium." The disorder results from intrauterine arrest of compaction of the loose interwoven meshwork of the fetal myocardial primordium and subsequent persistence of deep trabecular recesses in the myocardial wall. The classical clinical presentation is a triad of heart failure, arrhythmias, and embolic events from mural thrombi. ILVNC has been associated with several autosomal dominant, X-linked, and mitochondrial genetic mutations that are also shared among other cardiomyopathies. Over the past decade, ILVNC has been subject to intensive research, as it increases the risk for sudden cardiac death. This review focuses on the current understanding of ILVNC in adult populations and attempts to provide organized insight into the disease process, screening, diagnosis, management, role of device therapy, and prognosis.
Open Access
Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.
(J Am Heart Assoc, 2016-07-29) Hunter, Wynn G; Kelly, Jacob P; McGarrah, Robert W; Khouri, Michel G; Craig, Damian; Haynes, Carol; Ilkayeva, Olga; Stevens, Robert D; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Felker, G Michael; Hernandez, Adrian F; Velazquez, Eric J; Kraus, William E; Shah, Svati H
BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No-HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long-chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no-HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance. CONCLUSIONS: We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.
Open Access
One Small Step for a Patient, One Giant Leap for Orthostatic Hypotension.
(Cureus, 2022-11) Coniglio, Amanda C; Kittipibul, Veraprapas; Pelligra, Ralph; Richardson, Eric S; Holley, Christopher L; Fudim, Marat
A 52-year-old man with ischemic cardiomyopathy presented with progressive, severe orthostatic hypotension refractory to medical therapy. Standard abdominal and leg compression devices were used without success. A novel, inflatable abdominal compression device was created that alleviated the patient's symptoms and maintained his blood pressure.
Open Access
Predicting Outcomes Over Time in Patients With Heart Failure, Left Ventricular Systolic Dysfunction, or Both Following Acute Myocardial Infarction.
(J Am Heart Assoc, 2016-06-27) Lopes, Renato D; Pieper, Karen S; Stevens, Susanna R; Solomon, Scott D; McMurray, John JV; Pfeffer, Marc A; Leimberger, Jeffrey D; Velazquez, Eric J
BACKGROUND: Most studies of risk assessment or stratification in patients with myocardial infarction (MI) have been static and fail to account for the evolving nature of clinical events and care processes. We sought to identify predictors of mortality, cardiovascular death or nonfatal MI, and cardiovascular death or nonfatal heart failure (HF) over time in patients with HF, left ventricular systolic dysfunction, or both post-MI. METHODS AND RESULTS: Using data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial, we developed models to estimate the association between patient characteristics and the likelihood of experiencing an event from the time of a follow-up visit until the next visit. The intervals are: hospital arrival to discharge or 14 days, whichever occurs first; hospital discharge to 30 days; 30 days to 6 months; and 6 months to 3 years. Models were also developed to predict the entire 3-year follow-up period using baseline information. Multivariable Cox proportional hazards modeling was used throughout with Wald chi-squares as the comparator of strength for each predictor. For the baseline model of overall mortality, the 3 strongest predictors were age (adjusted hazard ratio [HR], 1.35; 95% CI, 1.28-1.42; P<0.0001), baseline heart rate (adjusted HR, 1.17; 95% CI, 1.14-1.21; P<0.0001), and creatinine clearance (≤100 mL/min; adjusted HR, 0.86; 95% CI, 0.84-0.89; P<0.0001). According to the integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices, the updated model had significant improvement over the model with baseline covariates only in all follow-up periods and with all outcomes. CONCLUSIONS: Patient information assessed closest to the time of the outcome was more valuable in predicting death when compared with information obtained at the time of the index hospitalization. Using updated patient information improves prognosis over using only the information available at the time of the index event.
Open Access
Pulmonary Hypertension Subtypes and Mortality in CKD.
(American journal of kidney diseases : the official journal of the National Kidney Foundation, 2019-11-12) Edmonston, Daniel L; Parikh, Kishan S; Rajagopal, Sudarshan; Shaw, Linda K; Abraham, Dennis; Grabner, Alexander; Sparks, Matthew A; Wolf, Myles
RATIONALE & OBJECTIVE:Pulmonary hypertension (PH) contributes to cardiovascular disease and mortality in patients with chronic kidney disease (CKD), but the pathophysiology is mostly unknown. This study sought to estimate the prevalence and consequences of PH subtypes in the setting of CKD. STUDY DESIGN:Observational retrospective cohort study. SETTING & PARTICIPANTS:We examined 12,618 patients with a right heart catheterization in the Duke Databank for Cardiovascular Disease from January 1, 2000, to December 31, 2014. EXPOSURES:Baseline kidney function stratified by CKD glomerular filtration rate category and PH subtype. OUTCOMES:All-cause mortality. ANALYTICAL APPROACH:Multivariable Cox proportional hazards analysis. RESULTS:In this cohort, 73.4% of patients with CKD had PH, compared with 56.9% of patients without CKD. Isolated postcapillary PH (39.0%) and combined pre- and postcapillary PH (38.3%) were the most common PH subtypes in CKD. Conversely, precapillary PH was the most common subtype in the non-CKD cohort (35.9%). The relationships between mean pulmonary artery pressure, pulmonary capillary wedge pressure, and right atrial pressure with mortality were similar in both the CKD and non-CKD cohorts. Compared with those without PH, precapillary PH conferred the highest mortality risk among patients without CKD (HR, 2.27; 95% CI, 2.00-2.57). By contrast, in those with CKD, combined pre- and postcapillary PH was associated with the highest risk for mortality in CKD in adjusted analyses (compared with no PH, HRs of 1.89 [95% CI, 1.57-2.28], 1.87 [95% CI, 1.52-2.31], 2.13 [95% CI, 1.52-2.97], and 1.63 [95% CI, 1.12-2.36] for glomerular filtration rate categories G3a, G3b, G4, and G5/G5D). LIMITATIONS:The cohort referred for right heart catheterization may not be generalizable to the general population. Serum creatinine data in the 6 months preceding catheterization may not reflect true baseline CKD. Observational design precludes assumptions of causality. CONCLUSIONS:In patients with CKD referred for right heart catheterization, PH is common and associated with poor survival. Combined pre- and postcapillary PH was common and portended the worst survival for patients with CKD.
Open Access
Race and Sex Differences in QRS Interval and Associated Outcome Among Patients with Left Ventricular Systolic Dysfunction.
(J Am Heart Assoc, 2017-03-20) Randolph, Tiffany C; Broderick, Samuel; Shaw, Linda K; Chiswell, Karen; Mentz, Robert J; Kutyifa, Valentina; Velazquez, Eric J; Gilliam, Francis R; Thomas, Kevin L
BACKGROUND: Prolonged QRS duration is associated with increased mortality among heart failure patients, but race or sex differences in QRS duration and associated effect on outcomes are unknown. METHODS AND RESULTS: We investigated QRS duration and morphology among 2463 black and white patients with heart failure and left ventricular ejection fraction ≤35% who underwent coronary angiography and 12-lead electrocardiography at Duke University Hospital from 1995 through 2011. We used multivariable Cox regression models to assess the relationship between QRS duration and all-cause mortality and investigate race-QRS and sex-QRS duration interaction. Median QRS duration was 105 ms (interquartile range [IQR], 92-132) with variation by race and sex (P<0.001). QRS duration was longest in white men (111 ms; IQR, 98-139) followed by white women (108 ms; IQR, 92-140), black men (100 ms; IQR, 91-120), and black women (94 ms; IQR, 86-118). Left bundle branch block was more common in women than men (24% vs 14%) and in white (21%) versus black individuals (12%). In black patients, there was a 16% increase in risk of mortality for every 10 ms increase in QRS duration up to 112 ms (hazard ratio, 1.16; 95% CI, 1.07, 1.25) that was not present among white patients (interaction, P=0.06). CONCLUSIONS: Black individuals with heart failure had a shorter QRS duration and more often had non-left bundle branch block morphology than white patients. Women had left bundle branch block more commonly than men. Among black patients, modest QRS prolongation was associated with increased mortality.
Open Access
Racial differences in the prevalence and outcomes of atrial fibrillation among patients hospitalized with heart failure.
(J Am Heart Assoc, 2013-09-26) Thomas, Kevin L; Piccini, Jonathan P; Liang, Li; Fonarow, Gregg C; Yancy, Clyde W; Peterson, Eric D; Hernandez, Adrian F; Get With the Guidelines Steering Committee and Hospitals
BACKGROUND: The intersection of heart failure (HF) and atrial fibrillation (AF) is common, but the burden of AF among black patients with HF is poorly characterized. We sought to determine the prevalence of AF, characteristics, in-hospital outcomes, and warfarin use associated with AF in patients hospitalized with HF as a function of race. METHODS AND RESULTS: We analyzed data on 135 494 hospitalizations from January 2006 through January 2012 at 276 hospitals participating in the American Heart Association's Get With The Guidelines HF Program. Multivariable logistic regression models using generalized estimating equations approach for risk-adjusted comparison of AF prevalence, in-hospital outcomes, and warfarin use. In this HF population, 53 389 (39.4%) had AF. Black patients had markedly less AF than white patients (20.8% versus 44.8%, P < 0.001). Adjusting for risk factors and hospital characteristics, black race was associated with significantly lower odds of AF (adjusted odds ratio 0.52, 95% CI 0.48 to 0.55, P < 0.0001). There were no racial differences in in-hospital mortality; however, black patients had a longer length of stay relative to white patients. Black patients compared with white patients with AF were less likely to be discharged on warfarin (adjusted odds ratio 0.76, 95% CI 0.69 to 0.85, P < 0.001). CONCLUSIONS: Despite having many risk factors for AF, black patients, relative to white patients hospitalized for HF, had a lower prevalence of AF and lower prescription of guideline-recommended warfarin therapy.
Open Access
Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF).
(Circ Heart Fail, 2015-07) Lala, Anuradha; McNulty, Steven E; Mentz, Robert J; Dunlay, Shannon M; Vader, Justin M; AbouEzzeddine, Omar F; DeVore, Adam D; Khazanie, Prateeti; Redfield, Margaret M; Goldsmith, Steven R; Bart, Bradley A; Anstrom, Kevin J; Felker, G Michael; Hernandez, Adrian F; Stevenson, Lynne W
BACKGROUND: Congestion is the most frequent cause for hospitalization in acute decompensated heart failure. Although decongestion is a major goal of acute therapy, it is unclear how the clinical components of congestion (eg, peripheral edema, orthopnea) contribute to outcomes after discharge or how well decongestion is maintained. METHODS AND RESULTS: A post hoc analysis was performed of 496 patients enrolled in the Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trials during hospitalization with acute decompensated heart failure and clinical congestion. A simple orthodema congestion score was generated based on symptoms of orthopnea (≥2 pillows=2 points, <2 pillows=0 points) and peripheral edema (trace=0 points, moderate=1 point, severe=2 points) at baseline, discharge, and 60-day follow-up. Orthodema scores were classified as absent (score of 0), low-grade (score of 1-2), and high-grade (score of 3-4), and the association with death, rehospitalization, or unscheduled medical visits through 60 days was assessed. At baseline, 65% of patients had high-grade orthodema and 35% had low-grade orthodema. At discharge, 52% patients were free from orthodema at discharge (score=0) and these patients had lower 60-day rates of death, rehospitalization, or unscheduled visits (50%) compared with those with low-grade or high-grade orthodema (52% and 68%, respectively; P=0.038). Of the patients without orthodema at discharge, 27% relapsed to low-grade orthodema and 38% to high-grade orthodema at 60-day follow-up. CONCLUSIONS: Increased severity of congestion by a simple orthodema assessment is associated with increased morbidity and mortality. Despite intent to relieve congestion, current therapy often fails to relieve orthodema during hospitalization or to prevent recurrence after discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00608491, NCT00577135.
Open Access
Short- and long-term rehospitalization and mortality for heart failure in 4 racial/ethnic populations.
(J Am Heart Assoc, 2014-10-16) Vivo, Rey P; Krim, Selim R; Liang, Li; Neely, Megan; Hernandez, Adrian F; Eapen, Zubin J; Peterson, Eric D; Bhatt, Deepak L; Heidenreich, Paul A; Yancy, Clyde W; Fonarow, Gregg C
BACKGROUND: The degree to which outcomes following hospitalization for acute heart failure (HF) vary by racial and ethnic groups is poorly characterized. We sought to compare 30-day and 1-year rehospitalization and mortality rates for HF among 4 race/ethnic groups. METHODS AND RESULTS: Using the Get With The Guidelines-HF registry linked with Medicare data, we compared 30-day and 1-year outcomes between racial/ethnic groups by using a multivariable Cox proportional hazards model adjusting for clinical, hospital, and socioeconomic status characteristics. We analyzed 47 149 Medicare patients aged ≥65 years who had been discharged for HF between 2005 and 2011: there were 39 213 whites (83.2%), 4946 blacks (10.5%), 2347 Hispanics (5.0%), and 643 Asians/Pacific Islanders (1.4%). Relative to whites, blacks and Hispanics had higher 30-day and 1-year unadjusted readmission rates but lower 30-day and 1-year mortality; Asians had similar 30-day readmission rates but lower 1-year mortality. After risk adjustment, blacks had higher 30-day and 1-year CV readmission than whites but modestly lower short- and long-term mortality; Hispanics had higher 30-day and 1-year readmission rates and similar 1-year mortality than whites, while Asians had similar outcomes. When socioeconomic status data were added to the model, the majority of associations persisted, but the difference in 30-day and 1-year readmission rates between white and Hispanic patients became nonsignificant. CONCLUSIONS: Among Medicare patients hospitalized with HF, short- and long-term readmission rates and mortality differed among the 4 major racial/ethnic populations and persisted even after controlling for clinical, hospital, and socioeconomic status variables.
Open Access
Variant R94C in TNNT2-Encoded Troponin T Predisposes to Pediatric Restrictive Cardiomyopathy and Sudden Death Through Impaired Thin Filament Relaxation Resulting in Myocardial Diastolic Dysfunction.
(Journal of the American Heart Association, 2020-03) Ezekian, Jordan E; Clippinger, Sarah R; Garcia, Jaquelin M; Yang, Qixin; Denfield, Susan; Jeewa, Aamir; Dreyer, William J; Zou, Wenxin; Fan, Yuxin; Allen, Hugh D; Kim, Jeffrey J; Greenberg, Michael J; Landstrom, Andrew P
Background Pediatric-onset restrictive cardiomyopathy (RCM) is associated with high mortality, but underlying mechanisms of disease are under investigated. RCM-associated diastolic dysfunction secondary to variants in TNNT2-encoded cardiac troponin T (TNNT2) is poorly described. Methods and Results Genetic analysis of a proband and kindred with RCM identified TNNT2-R94C, which cosegregated in a family with 2 generations of RCM, ventricular arrhythmias, and sudden death. TNNT2-R94C was absent among large, population-based cohorts Genome Aggregation Database (gnomAD) and predicted to be pathologic by in silico modeling. Biophysical experiments using recombinant human TNNT2-R94C demonstrated impaired cardiac regulation at the molecular level attributed to reduced calcium-dependent blocking of myosin's interaction with the thin filament. Computational modeling predicted a shift in the force-calcium curve for the R94C mutant toward submaximal calcium activation compared within the wild type, suggesting low levels of muscle activation even at resting calcium concentrations and hypercontractility following activation by calcium. Conclusions The pathogenic TNNT2-R94C variant activates thin-filament-mediated sarcomeric contraction at submaximal calcium concentrations, likely resulting in increased muscle tension during diastole and hypercontractility during systole. This describes the proximal biophysical mechanism for development of RCM in this family.
Open Access
Ventricular conduction and long-term heart failure outcomes and mortality in African Americans: insights from the Jackson Heart Study.
(Circ Heart Fail, 2015-03) Mentz, Robert J; Greiner, Melissa A; DeVore, Adam D; Dunlay, Shannon M; Choudhary, Gaurav; Ahmad, Tariq; Khazanie, Prateeti; Randolph, Tiffany C; Griswold, Michael E; Eapen, Zubin J; O'Brien, Emily C; Thomas, Kevin L; Curtis, Lesley H; Hernandez, Adrian F
BACKGROUND: QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. METHODS AND RESULTS: We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. CONCLUSIONS: QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.
Open Access
What's Harder: Seeing a Doctor or Reducing Readmissions?
(JACC Heart Fail, 2015-10) Hernandez, Adrian F; DeVore, Adam D

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