Journal: J Card Fail

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Abstract

Prevention of Chemotherapy-Induced Left Ventricular Dysfunction With Enalapril and Carvedilol: Rationale and Design of the OVERCOME Trial.

Bosch X, Esteve J, Sitges M, de Caralt TM, ... Perea RJ, Rovira M
Background: The current treatment of hematologic malignancies includes diverse potentially cardiotoxic chemotherapy agents, including high-dose myeloablative regimens used in autologous hematopoietic stem cell transplantation (HSCT). Many of these treatments could induce left ventricular dysfunction (LVD), and limit their efficacy. Angiotensin-converting enzime inhibitors and beta-blockers prevent LVD and prolong survival after infarction, and recent animal and pilot clinical studies suggest that they can prevent the development of chemotherapy-induced cardiac toxicity. Methods: This is a prevention, parallel-assignment, randomized, controlled, clinical efficacy study. Ninety patients recently diagnosed of acute leukemia or undergoing autologous HSCT and with normal LV ejection fraction will be randomized to enalapril and carvedilol or to the control group. Echocardiogram and a cardiac magnetic resonance imaging studies will be performed at baseline and 6-9 months after randomization. The primary efficacy endpoint is the change from baseline in LV ejection fraction. Secondary endpoints include the assessment of LV volumes and diastolic function, and the incidence of death, heart failure, or LVD. Conclusions: The OVERCOME study will be the first clinical trial to test the preventive efficacy on LVD of combined treatment with enalapril and carvedilol administered to patients with hematologic malignancies submitted to current treatment with intensive chemotherapy.

J Card Fail: 02 Aug 2011; 17:643-648
Bosch X, Esteve J, Sitges M, de Caralt TM, ... Perea RJ, Rovira M
J Card Fail: 02 Aug 2011; 17:643-648 | PMID: 21807325
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Abstract

Diabetic cardiomyopathy.

Murarka S, Movahed MR
Individuals with diabetes are at a significantly greater risk of developing cardioymyopathy and heart failure despite adjusting for concomitant risks such as coronary artery disease or hypertension. This has led to the increased recognition of a distinct disease process termed as "diabetic cardiomyopathy." In this article, we perform an extensive review of the pathogenesis and treatment of this disease. From a clinical perspective, physicians should be aware of this entity, and early screening should be considered because physical evidence of early diabetic cardiomyopathy could be difficult to detect. Early detection of the disease should prompt intensification of glycemic control, concomitant risk factors, use of pharmacologic agents such as β-blockers and renin-angiotensin-aldosterone system antagosists. From a research perspective, more studies on myocardial tissue from diabetic patients are needed. Clinical trials to evaluate the development of diabetic cardiomyopathy and fibrosis in early stages of the disease, as well as clinical trials of pharmacologic intervention in patients specifically with diabetic cardiomyopathy, need to be conducted.

J Card Fail: 29 Nov 2010; 16:971-9
Murarka S, Movahed MR
J Card Fail: 29 Nov 2010; 16:971-9 | PMID: 21111987
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Abstract

Transthyretin Cardiac Amyloidosis in Older Americans.

Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS
Wild type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase making it the most common form of cardiac amyloidosis. An important precondition to reduce under-diagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiogram and non-invasive imaging techniques. Nuclear scintigraphy agents using (99m)Tc-phosphate derivatives combined with assessment for monoclonal proteins are eliminating the need for tissue confirmation in ATTR cardiac amyloid. Morbidity and mortality from ATTRwt cardiac amyloid is high and the emergence of numerous therapies based on a biologic understanding of the pathophysiology of this condition including drugs to inhibit the synthesis of TTR, stabilize TTR, and degrade or extract amyloid provides new hope for those afflicted. This review will briefly cover the epidemiology, pathophysiology and clinical manifestations, as well as diagnostic strategies and treatment of older adults with ATTR cardiac amyloid.

J Card Fail: 21 Oct 2016; epub ahead of print
Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS
J Card Fail: 21 Oct 2016; epub ahead of print | PMID: 27769906
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Abstract

Predictors of Hospital Length of Stay in Heart Failure: Findings from Get With the Guidelines.

Whellan DJ, Zhao X, Hernandez AF, Liang L, ... Schwamm LH, Fonarow GC
Background: This study was undertaken to identify predictors of hospital length of stay (LOS) for heart failure (HF) patients using clinical variables available at the time of admission and hospital characteristics. Methods and results: A cohort of 70,094 HF patients discharged to home from 246 hospitals participating in the Get With The Guidelines-Heart Failure was analyzed for admission predictors for LOS. The analysis incorporated patient characteristics (PC) first, then added hospital characteristics (HC) followed by standard laboratory evaluations (SL), including troponin and brain natriuretic peptide (BNP). There were 31,995 patients (45.6%) with LOS < 4 days, 26,750 (38.2%) with LOS 4 to 7 days, and 11,349 (16.2%) with LOS > 7 days. Patients with longer LOS had more comorbidities and a higher severity of disease on admission. Overall models explained a modest amount of LOS variation, with an r(2) of 4.8%, with PC responsible for 1.3% of variation and together with SL explained 2.2% of variation. HC did not change the variation. Conclusions: Based on admission vital signs and BNP levels, patients with longer LOS have more comorbidities and a higher disease severity. The ability to risk stratify for LOS based on patient admission and hospital characteristics is limited.

J Card Fail: 02 Aug 2011; 17:649-656
Whellan DJ, Zhao X, Hernandez AF, Liang L, ... Schwamm LH, Fonarow GC
J Card Fail: 02 Aug 2011; 17:649-656 | PMID: 21807326
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Abstract

Heart Failure Patients Monitored With Telemedicine: Patient Satisfaction, a Review of the Literature.

Kraai IH, Luttik ML, de Jong RM, Jaarsma T, Hillege HL
Background: Remote monitoring of the clinical status of heart failure patients has developed rapidly and is the subject of several trials. Patient satisfaction is an important outcome, as recommended by the U.S. Food and Drug Administration to use in clinical research, and should be included in studies concerning remote monitoring. The objective of this review is to describe the current state of the literature on patient satisfaction with noninvasive telemedicine, regarding definition, measurement, and overall level of patient satisfaction with telemedicine. Methods and results: The Pubmed, Embase, Cochrane, and Cinahl databases were searched using heart failure-, satisfaction-, and telemedicine-related search terms. The literature search identified 193 publications, which were reviewed by 2 independent reviewers. Fourteen articles were included. None of the articles described a clear definition or concept of patient satisfaction with telemedicine. Patient satisfaction with telemedicine was measured with self-developed questionnaires or face-to-face or telephonic interviews. None of the articles used the same questionnaire or telephonic survey to measure patient satisfaction. Only one questionnaire was assessed for validity and reliability. In general, patients seemed to be satisfied or very satisfied with the use of telemedicine. Conclusions: Measurement of patient satisfaction is still underexposed in telemedicine research and the measurement of patient satisfaction with telemedicine underappreciated with poorly constructed questionnaires.

J Card Fail: 02 Aug 2011; 17:684-690
Kraai IH, Luttik ML, de Jong RM, Jaarsma T, Hillege HL
J Card Fail: 02 Aug 2011; 17:684-690 | PMID: 21807331
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Abstract

A Pharmacokinetic Analysis of Molecular Cardiac Surgery With Recirculation Mediated Delivery of βARKct Gene Therapy: Developing a Quantitative Definition of the Therapeutic Window.

Fargnoli AS, Katz MG, Yarnall C, Sumaroka MV, ... Koch WJ, Bridges CR
Background: Two major problems for translating gene therapy for heart failure therapy are: safe and efficient delivery and the inability to establish a relationship between vector exposure and in vivo effects. We present a pharmacokinetics (PK) analysis of molecular cardiac surgery with recirculating delivery (MCARD) of scAAV6-βARKct. MCARD\'s stable cardiac specific delivery profile was exploited to determine vector exposure, half-life, and systemic clearance. Methods and results: Five naive sheep underwent MCARD with 10(14) genome copies of scAAV6-βARKct. Blood samples were collected over the recirculation interval time of 20 minutes and evaluated with quantitative polymerase chain reaction (qPCR). C(t) curves were generated and expressed on a log scale. The exposure, half-life, and clearance curves were generated for analysis. qPCR and Western blots were used to determine biodistribution. Finally, all in vivo transduction data was plotted against MCARD\'s PK to determine if a relationship existed. Vector concentrations at each time point were (cardiac and systemic, respectively): 5 minutes: 9.16 ± 0.15 and 3.21 ± 0.38; 10 minutes: 8.81 ± 0.19 and 3.62 ± 0.37; 15 minutes: 8.75 ± 0.12 and 3.69 ± 0.31; and 20 minutes: 8.66 ± 0.22 and 3.95 ± 0.26; P < .00001. The half life of the vector was 2.66 ± 0.24 minutes. PK model data revealed that only 0.61 ± 0.43% of the original dose remained in the blood after delivery, and complete clearance from the system was achieved at 1 week. A PK transfer function revealed a positive correlation between exposure and in vivo transduction. Robust βARKct expression was found in all cardiac regions with none in the liver. Conclusion: MCARD may offer a viable method to establish a relationship between vector exposure and in vivo transduction. Using this methodology, it may be possible to address a critical need for establishing an effective therapeutic window.

J Card Fail: 02 Aug 2011; 17:691-699
Fargnoli AS, Katz MG, Yarnall C, Sumaroka MV, ... Koch WJ, Bridges CR
J Card Fail: 02 Aug 2011; 17:691-699 | PMID: 21807332
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Abstract

Growing Relevance of Cardiac Rehabilitation for an Older Population with Heart Failure.

Schopfer DW, Forman DE
Cardiac rehabilitation (CR) is a comprehensive lifestyle program that can have particular benefit for older patients with heart failure (HF). Prevalence of HF is increasingly common among older adults. Mounting effects of cardiovascular risk factors in older age as well as the added effects of geriatric syndromes such as multimorbidity, frailty, and sedentariness contribute to the high incidence of HF as well as to management difficulty. Cardiac rehabilitation can play a decisive role in improving function, quality of life, symptoms, morbidity, and mortality, and also address the idiosyncratic complexities of care that often arise in old age. Unfortunately, the current policies and practices regarding CR for patients with HF are limited to heart failure with reduced ejection fraction (HFrEF), and do not extend to heart failure with preserved ejection fraction (HFpEF), which is likely undercutting its full potential to improve care for today\'s aging population. Despite the strong rationale for CR on important clinical outcomes it remains underused, particularly among older patients with HF. In this review we discuss both the potential and the limitations of contemporary CR for older adults with HF.

J Card Fail: 21 Oct 2016; epub ahead of print
Schopfer DW, Forman DE
J Card Fail: 21 Oct 2016; epub ahead of print | PMID: 27769907
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Abstract

Results of the Randomized Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction Trial (RAAM-PEF).

Deswal A, Richardson P, Bozkurt B, Mann DL
Background: Cardiac fibrosis is a major determinant of myocardial stiffness, diastolic dysfunction, and heart failure (HF). By reducing cardiac fibrosis, aldosterone antagonists have the potential to be beneficial in heart failure with preserved ejection fraction (HFpEF). Methods and results: In a randomized, double-blind, placebo-controlled trial of 44 patients with HFpEF, we examined the effects of eplerenone, an aldosterone antagonist, on changes in 6-minute walk distance (primary end point), diastolic function, and biomarkers of collagen turnover (secondary end points). All patients had a history of hypertension, 61% were diabetic, and 52% had prior HF hospitalization. After 6 months of treatment, similar improvements in 6 minute walk distance were noted in the eplerenone and placebo groups (P = .91). However, compared with placebo, eplerenone was associated with a significant reduction in serum markers of collagen turnover (procollagen type I aminoterminal peptide, P = .009 and carboxy-terminal telopeptide of collagen type I, P = .026) and improvement in echocardiographic measures of diastolic function (E/E\', P = .01). Conclusions: Although eplerenone was not associated with an improvement in exercise capacity compared to placebo, it was associated with significant reduction in markers of collagen turnover and improvement in diastolic function. Whether these favorable effects will translate into morbidity and mortality benefit in HFpEF remains to be determined.

J Card Fail: 02 Aug 2011; 17:634-642
Deswal A, Richardson P, Bozkurt B, Mann DL
J Card Fail: 02 Aug 2011; 17:634-642 | PMID: 21807324
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Abstract

Skilled Nursing Facility Care for Patients with Heart Failure: Can We Make It "Heart Failure Ready?"

Orr NM, Boxer RS, Dolansky MA, Allen LA, Forman DE
Skilled nursing facilities (SNF) have emerged as an integral component of care for older adults with heart failure (HF). Despite their prominent role, poor clinical outcomes for the medically complex patients with HF managed in SNFs are common. Barriers to providing quality care include poor transitional care during hospital-to-SNF and SNF-to-community discharges, lack of HF training among SNF staff, and a lack of a standardized care process among SNF facilities. While no evidence-based practice standards have been established, various measures and tools designed to improve HF management in SNFs are being investigated. In this review we discuss the challenges of HF care in SNFs as well as potential targets and recommendations that can help improve care with respect to transitions, HF management within SNFs, and modifiable factors within facilities. Policy considerations that might help catalyze improvements in SNF-based HF management are also discussed.

J Card Fail: 21 Oct 2016; epub ahead of print
Orr NM, Boxer RS, Dolansky MA, Allen LA, Forman DE
J Card Fail: 21 Oct 2016; epub ahead of print | PMID: 27769909
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Abstract

Prediction of ACC/AHA Stage B Heart Failure by Clinical and Neurohormonal Profiling Among Patients in the Community.

Poppe KK, Whalley GA, Richards AM, Wright SP, Triggs CM, Doughty RN
AIM: N-Terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful test to "rule out" heart failure (HF) in patients presenting with dyspnea in primary care. However, many false positive diagnoses may occur. Early identification of abnormal left ventricular (LV) function would allow early intervention. The aim of this study was to predict LV dysfunction in these patients using a combination of neurohormones and other clinical factors. Methods and results: A total of 190 people with dyspnea and/or peripheral edema were assessed. In those with NT-proBNP <100 pmol/L (n = 125), two models were constructed to predict LV dysfunction and so differentiate stage B HF from stage A and no HF. Model 1 included clinical factors and a range of neurohormones, whereas NT-proBNP was the only neurohormone in model 2. A model containing NT-proBNP, A-type NP, NT C-type NP, adrenomedullin, endothelin, creatinine, age, gender, body surface area, cardiothoracic ratio, and hypertension gave the lowest false negative rate (FNR) of 8.2%. The FNR of the model restricted to NT-proBNP as the only neurohormone was 13.7%. Conclusions: This study demonstrated that by combining a neurohormonal profile with clinical variables, it is possible to differentiate stage B from stage A or no HF in patients presenting to primary care, enabling early intervention which can reduce the progression to stage C HF.

J Card Fail: 29 Nov 2010; 16:957-63
Poppe KK, Whalley GA, Richards AM, Wright SP, Triggs CM, Doughty RN
J Card Fail: 29 Nov 2010; 16:957-63 | PMID: 21111985
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Abstract

Impact of Medication Nonadherence on Hospitalizations and Mortality in Heart Failure.

Fitzgerald AA, Powers JD, Ho PM, Maddox TM, ... Magid DJ, Havranek EP
Background: Limited literature exists on the association between medication adherence and outcomes among patients with heart failure. Methods and results: We conducted a retrospective longitudinal cohort study of 557 patients with heart failure with reduced ejection fraction (HFrEF) (defined by EF <50%) in a large health maintenance organization. We used multivariable Cox proportional hazards models to assess the relationship between adherence (with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, and aldosterone antagonists) and the primary outcome of all-cause mortality plus cardiovascular hospitalizations. Mean follow-up time was 1.1 years. Nonadherence (defined as <80% adherence) was associated with a statistically significant increase in the primary outcome in the cohort overall (hazard ratio 2.07, 95% confidence interval 1.62-2.64; P < .0001). This association remained significant when all 3 classes of heart failure medications and the components of the composite end point were considered separately and when the adherence threshold was varied to 70% or 90%. Conclusions: Medication nonadherence was associated with an increased risk of all-cause mortality and cardiovascular hospitalizations in a community heart failure population. Further research is needed to define systems of care that optimize adherence among patients with heart failure.

J Card Fail: 02 Aug 2011; 17:664-669
Fitzgerald AA, Powers JD, Ho PM, Maddox TM, ... Magid DJ, Havranek EP
J Card Fail: 02 Aug 2011; 17:664-669 | PMID: 21807328
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Abstract

Serum levels of high-sensitivity troponin T: a novel marker for cardiac remodeling in hypertrophic cardiomyopathy.

Moreno V, Hernández-Romero D, Vilchez JA, García-Honrubia A, ... Valdés M, Marín F
Background: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, small-vessel coronary artery disease, myocyte disarray, and increased interstitial fibrosis. High-sensitivity troponin T (hs-TnT) could be a reliable indicator of myocardial remodeling, a proposed prognostic marker in HCM. Therefore we hypothesized that increased hs-TnT levels are related to different variables associated with myocardial remodeling, such as the presence of fibrosis assessed with cardiac magnetic resonance imaging (MRI). Methods and results: We included 95 hemodynamically stable HCM patients, 72 male, aged 45.7 ± 14.2 years, and 45 healthy control subjects with similar age and gender. A complete history and clinical examination was performed, including 12-lead electrocardiogram (ECG), echocardiography, 24-hour ECG-Holter monitoring, symptom-limited treadmill exercise test, and late gadolinium enhancement in cardiac MRI. Risk factors for sudden death were evaluated. A blinded cardiac MRI was performed with late gadolinium enhancement study. Serum hs-TnT levels were assayed. A high proportion (42%) of hemodynamically stable patients studied showed increased levels of hs-TnT. The hs-TnT levels were raised in patients with severe dyspnea: New York Heart Association (NYHA) functional class ≥3 (P = .020), outflow obstruction (P = .013), systolic dysfunction (P = .037), abnormal blood pressure response (P = .036), and presence of gadolinium enhancement (P = .021). The hs-TnT levels correlated positively with the maximum left ventricular wall thickness (r = 0.47; P < .001), left atrial diameter (r = 0.36, P = .014), and outflow gradient (r = 0.28; P = .008). Conclusions: A high proportion of hemodynamically stable patients show increased levels of hs-TnT. We observed that raised hs-TnT serum levels are associated with different conditions related to the severity of the disease.

J Card Fail: 29 Nov 2010; 16:950-6
Moreno V, Hernández-Romero D, Vilchez JA, García-Honrubia A, ... Valdés M, Marín F
J Card Fail: 29 Nov 2010; 16:950-6 | PMID: 21111984
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Abstract

Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions.

Giamouzis G, Kalogeropoulos A, Georgiopoulou V, Laskar S, ... Triposkiadis F, Butler J
Patients with heart failure (HF) are hospitalized over a million times annually in the United States. Hospitalization marks a fundamental change in the natural history of HF, leading to frequent subsequent rehospitalizations and a significantly higher mortality compared with nonhospitalized patients. Three-fourths of all HF hospitalizations are due to exacerbation of symptoms in patients with known HF. One-half of hospitalized HF patients experience readmission within 6 months. Preventing HF hospitalization and rehospitalization is important to improve patient outcomes and curb health care costs. To implement cost-effective strategies to contain the HF hospitalization epidemic, optimal schemes to identify high-risk individuals are needed. In this review, we describe the risk factors that have been associated with hospitalization risk in HF and the various multimarker risk prediction schemes developed to predict HF rehospitalization. We comment on areas that represent gaps in our knowledge or difficulties in interpretation of the current literature, representing opportunities for future research. We also discuss issues with using HF readmission rate as a quality indicator.

J Card Fail: 28 Dec 2010; 17:54-75
Giamouzis G, Kalogeropoulos A, Georgiopoulou V, Laskar S, ... Triposkiadis F, Butler J
J Card Fail: 28 Dec 2010; 17:54-75 | PMID: 21187265
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Abstract

Myocardial Function With Reduced Expression of the Sodium-Calcium Exchanger.

Jordan MC, Henderson SA, Han T, Fishbein MC, Philipson KD, Roos KP
Background: The complete removal of the cardiac sodium-calcium exchanger (NCX1) is associated with embryonic lethality, whereas its overexpression is linked to heart failure. To determine whether or not a reduced expression of NCX1 is compatible with normal heart structure and function, we studied 2 knockout (KO) mouse models with reduced levels of NCX1: a heterozygous global KO (HG-KO) with a 50% level of NCX1 expression in all myocytes, and a ventricular-specific KO (V-KO) with NCX1 expression in only 10% to 20% of the myocytes. Methods and results: Both groups of mice were evaluated at baseline, after transaortic constriction (TAC), and after acute or chronic beta-adrenergic stimulation. At baseline, the HG-KO mice had smaller hearts and the V-KO mice had larger hearts than their wild-type (WT) controls (P < .05). The HG-KO and their control WT mice had normal responses to TAC and beta-adrenergic stimulation. However, the V-KO group was intolerant to TAC and had a significantly (P < .05) blunted response to beta-adrenergic stimulation as compared with the HG-KO mice and WT controls. Unlike the HG-KO mice, the V-KO mice did not tolerate chronic isoproterenol infusion. Telemetric analysis of the electrocardiogram, body temperature, and activity revealed a normal diurnal rhythm in all groups of mice, but confirmed shorter QT intervals along with increased arrhythmias and reduced R wave to P wave amplitude ratios in the V-KO mice. Conclusions: Though NCX1 can be reduced by half in all myocytes without significant functional alterations, it must be expressed in more than 20% of the myocytes to prevent severe remodeling and heart failure in mouse heart.

J Card Fail: 27 Aug 2010; 16:786-796
Jordan MC, Henderson SA, Han T, Fishbein MC, Philipson KD, Roos KP
J Card Fail: 27 Aug 2010; 16:786-796 | PMID: 20797603
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Peripheral Adaptation Mechanisms in Physical Training and Cardiac Rehabilitation: The Case of a Patient Supported by a Cardiowest Total Artificial Heart.

Bellotto F, Compostella L, Agostoni P, Torregrossa G, ... Tarzia V, Gerosa G
Background: The benefits of exercise training in patients with chronic heart failure (CHF) are due to a combination of cardiac and peripheral adaptations. Separating these 2 components is normally impossible, except for patients implanted with total artificial heart (TAH), where cardiac adaptation cannot occur. Methods and results: We report the case of a patient implanted with a CardioWest-TAH who underwent a comprehensive strength and endurance training program and was evaluated by repeated peak cardiopulmonary exercise tests. The patient experienced a 24% increase of peak oxygen consumption and an improvement in recovery kinetics during the training period of 29 months. Conclusion: This unique situation of a patient with a TAH, and therefore a fixed peak cardiac output, allows us to isolate training-induced changes in the periphery, that suggest greater oxygen extraction and more efficient metabolic gas kinetics during the exercise and recovery phases.

J Card Fail: 02 Aug 2011; 17:670-675
Bellotto F, Compostella L, Agostoni P, Torregrossa G, ... Tarzia V, Gerosa G
J Card Fail: 02 Aug 2011; 17:670-675 | PMID: 21807329
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Thrombomodulin is Upregulated in Cardiomyocytes During Cardiac Hypertrophy and Prevents the Progression of Contractile Dysfunction.

Li YH, Chung HC, Luo CY, Chao TH, ... Shi GY, Wu HL
Background: Cardiac hypertrophy is a common response to pressure overload and leads to left ventricular (LV) dysfunction. Thrombomodulin (TM), an endothelial anticoagulant protein, was found to have direct effects on cellular proliferation and inflammation. We examined the TM expression in cardiomyocytes during cardiac hypertrophy and investigated its physiological significance. Methods and results: TM expression was evaluated in cardiomyocytes from hearts of mice that underwent transverse aortic constriction (TAC). The effects of recombinant TM protein on cardiomyocytes apoptosis and related signaling pathways were examined. Recombinant TM protein was administered continuously in mice that underwent TAC, and serial LV function was determined. There was significant TM expression in cardiomyocytes during cardiac hypertrophy elicited by TAC in mice. TM treatment decreased doxorubicin-induced apoptosis of cardiomyocytes and increased the Bcl-2/Bax ratio. It also increased cardiomyocytes hypertrophy, expression of atrial natriuretic peptide, and significantly activated the extracellular signal-regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (Akt) signaling pathways in cardiomyocytes. Continuous TM supply after TAC prevented the progression of LV contractile dysfunction in mice. Conclusions: TM treatment decreased cardiomyocyte apoptosis and maintained LV contractile function in response to pressure overload.

J Card Fail: 29 Nov 2010; 16:980-90
Li YH, Chung HC, Luo CY, Chao TH, ... Shi GY, Wu HL
J Card Fail: 29 Nov 2010; 16:980-90 | PMID: 21111988
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Evidence-based heart failure performance measures and clinical outcomes: a systematic review.

Maeda JL
Background: Evidence-based performance measures for heart failure are increasingly being used to stimulate quality improvement efforts. Methods and results: A literature search was performed using MEDLINE, EMBASE, Cochrane Review, and a citation review. Research studies that assessed the association between the American College of Cardiology (ACC)/American Heart Association (AHA) heart failure performance measures from the inpatient setting and patient outcomes were examined. Studies were restricted to those conducted within the United States from 2001 until the present and included at least 1 of the ACC/AHA performance measures for chronic heart failure and a clinical outcome as an endpoint. Eleven original studies and 1 literature review met the study inclusion criteria. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker use at discharge had the strongest association with improved patient outcomes, whereas discharge instructions had a weaker but positive effect. Conclusions: The findings from this systematic review suggest that an increase in compliance with the heart failure performance measures leads to a consistent positive impact on patient outcomes although the strength, magnitude, and significance of this effect is variable across the individual performance indicators. Further longitudinal studies and additional measure sets may yield deeper insights into the causal relationship between heart failure processes of care and clinical outcomes.

J Card Fail: 07 May 2010; 16:411-8
Maeda JL
J Card Fail: 07 May 2010; 16:411-8 | PMID: 20447578
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The STARBRITE Trial: A Randomized, Pilot Study of B-Type Natriuretic Peptide-Guided Therapy in Patients With Advanced Heart Failure.

Shah MR, Califf RM, Nohria A, Bhapkar M, ... Stevenson LW, O\'Connor CM
Background: STARBRITE, a multicenter randomized pilot trial, tested whether outpatient diuretic management guided by B-type natriuretic peptide (BNP) and clinical assessment resulted in more days alive and not hospitalized over 90 days compared with clinical assessment alone. Methods and results: A total of 130 patients from 3 sites with left ventricular ejection fraction ≤35% were enrolled during hospitalization for heart failure (HF) and randomly assigned to therapy guided by BNP and clinical assessment (BNP strategy) or clinical assessment alone. The clinical goal was resolution of congestion without hypotension or renal dysfunction. In the BNP arm, therapy was adjusted to achieve optimal fluid status, defined as the BNP level and congestion score obtained at the time of discharge. In the clinical assessment arm, therapy was titrated to achieve optimal fluid status, represented by the patient\'s signs and symptoms at the time of discharge. Exclusion criteria were serum creatinine >3.5 mg/dL and acute coronary syndrome. Follow-up was done in HF clinics. BNP was measured with the use of a rapid assay test. There was no significant difference in number of days alive and not hospitalized (hazard ratio 0.72, 95% confidence interval 0.41-1.27; P = .25), change in serum creatinine, or change in systolic blood pressure (SBP). BNP strategy was associated with a trend toward a lower blood urea nitrogen (24 mg/dL vs 29 mg/dL; P = .07); BNP strategy patients received significantly more angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and the combination of ACE inhibitor or angiotensin receptor blocker plus beta-blockers. Conclusions: BNP strategy was not associated with more days alive and not hospitalized, but the strategy appeared to be safe and was associated with increased use of evidence-based medications.

J Card Fail: 02 Aug 2011; 17:613-621
Shah MR, Califf RM, Nohria A, Bhapkar M, ... Stevenson LW, O'Connor CM
J Card Fail: 02 Aug 2011; 17:613-621 | PMID: 21807321
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Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.

Rigol M, Solanes N, Farré J, Roura S, ... Bayés-Genís A, Heras M
Background: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. Methods and results: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks\' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. Conclusions: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

J Card Fail: 30 Mar 2010; 16:357-366
Rigol M, Solanes N, Farré J, Roura S, ... Bayés-Genís A, Heras M
J Card Fail: 30 Mar 2010; 16:357-366 | PMID: 20350704
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Elevated Plasma Renin Activity Predicts Adverse Outcome in Chronic Heart Failure, Independently of Pharmacologic Therapy: Data From the Valsartan Heart Failure Trial (Val-HeFT).

Masson S, Solomon S, Angelici L, Latini R, ... Cohn JN, The Val-Heft Investigators
Background: The prognostic value of plasma renin activity (PRA) in chronic heart failure (HF) has been assessed before the widespread use of angiotensin-converting enzyme inhibitors (ACEi) and beta-blockers, which exert opposite effects on renin secretion. We evaluated the association between PRA and outcome in patients with chronic HF treated with ACEi and beta-blockers. Methods and results: PRA was measured in 4,291 patients from the Valsartan Heart Failure Trial (Val-HeFT). The prognostic performance of PRA in patients who were or were not taking ACEi or beta-blockers was evaluated by multivariable Cox models. PRA was elevated in patients on ACEi (median 5.85 [interquartile range (IQR) 1.82-17.83] ng/mL/h) compared with those not on ACEi (1.57 [0.74-4.15] ng/mL/h), and lower in those on beta-blockers (3.89 [1.17-12.61] ng/mL/h) than in those not on beta-blockers (6.21 [1.97-19.24] ng/mL/h). Lower systolic blood pressure, higher plasma aldosterone, and ACEi were associated with high PRA. Higher PRA was a strong and independent predictor of mortality in the whole population and in patients who were or were not treated with ACEi or beta-blockers. Conclusions: PRA is a powerful prognostic marker of death over a wide range of concentrations in patients with chronic HF. Prescription of ACEi and/or beta-blockers does not influence the relation between PRA and outcome.

J Card Fail: 29 Nov 2010; 16:964-970
Masson S, Solomon S, Angelici L, Latini R, ... Cohn JN, The Val-Heft Investigators
J Card Fail: 29 Nov 2010; 16:964-970 | PMID: 21111986
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Abstract

Patient perspectives on decision making in heart failure.

Matlock DD, Nowels CT, Bekelman DB
Background: Patients with heart failure (HF) face an array of challenging decisions involving medications, devices, and transplants. The goal of this qualitative study was to describe patients\' perceptions surrounding difficult decisions along with factors that influenced their decisions. Methods and results: We studied 22 patients with symptomatic HF from the University of Colorado Hospital using in-depth, semistructured interviews. We used descriptive theme analysis in an iterative process to analyze responses to the question: "Can you tell me about any important or difficult decisions you have had to make about your heart condition?" Two distinct decision-making styles emerged: active (55%) and passive (45%). Active decision makers identified interventions such as implantable cardioverter-defibrillators, medications, and transplants to be the most difficult decisions and weighed concerns for side effects, family, and quality of life. Passive decision makers generally did not identify a difficult decision and described factors such as trust in God, trust in the physician, and power of the physician as reasons for their passivity. Conclusions: Patients with HF use active and passive decision styles in their approach to medical decision making. Future work should investigate communication techniques to assure that passive decision makers receive health care that is concordant with their values.

J Card Fail: 11 Oct 2010; 16:823-6
Matlock DD, Nowels CT, Bekelman DB
J Card Fail: 11 Oct 2010; 16:823-6 | PMID: 20932464
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Abstract

Role of cardiac resynchronization in end-stage heart failure patients requiring inotrope therapy.

Bhattacharya S, Abebe K, Simon M, Saba S, Adelstein E
Background: Outcomes among inotrope-treated heart failure (HF) patients receiving cardiac resynchronization therapy (CRT) have not been well characterized, particularly in those requiring intravenous inotropes at the time of implant. Methods: We analyzed 759 consecutive CRT-defibrillator recipients who were categorized as never on inotropes (NI; n = 585), weaned from inotropes before implant (PI; n = 124), or on inotropes at implant (II; n = 50). Survival free from heart transplant or ventricular assist device and overall survival were compared using the Social Security Death Index. A patient cohort who underwent unsuccessful CRT implantation and received a standard defibrillator (SD; n = 94) comprised a comparison group. Propensity score analysis was used to control for intergroup baseline differences. Results: Compared with the other cohorts, II patients had more comorbidities. Both survival endpoints differed significantly (P < .001) among the 4 cohorts; II patients demonstrated shorter survival than NI patients, with the PI and SD groups having intermediate survival. After adjusting for propensity scores, overall differences and patterns in survival endpoints persisted (P < .01), but the only statistically significant pairwise difference was overall survival between the NI and II groups at 12 months (hazard ratio 2.95, 95% confidence interval 1.05-8.35). CRT recipients ever on inotropes (PI and II) and SD patients ever requiring inotropes (n = 17) experienced similar survival endpoints. Among II patients, predictors of hospital discharge free from inotropes after CRT included male gender, older age, and ability to tolerate β-blockade. Conclusions: Inotrope-dependent HF patients show significantly worse survival despite CRT than inotrope-naïve patients, in part because of more comorbid conditions at baseline. CRT may not provide a survival advantage over a standard defibrillator among patients who have received inotropes before CRT. Weaning from inotropes and initiating neurohormonal antagonists before CRT should be an important goal among inotrope-dependent HF patients.

J Card Fail: 29 Nov 2010; 16:931-7
Bhattacharya S, Abebe K, Simon M, Saba S, Adelstein E
J Card Fail: 29 Nov 2010; 16:931-7 | PMID: 21111981
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Abstract

Factors Associated With Patient Delay in Seeking Care After Worsening Symptoms in Heart Failure Patients.

Nieuwenhuis MM, Jaarsma T, van Veldhuisen DJ, van der Wal MH
Background: To receive optimal treatment and care, it is essential that heart failure (HF) patients react adequately to worsening symptoms and contact a health care provider early. This specific "patient delay" is an important part of the total delay time. The purpose of this study was to assess patient delay and its associated variables in HF patients. Methods and results: In this cross-sectional study, data of 911 hospitalized HF patients from 17 Dutch hospitals (mean age 71 ± 12 years; 62% male; left ventricular ejection fraction 34 ± 15%) were analyzed. During the index hospitalization, patient delay and HF symptoms were assessed by interview. Patients completed questionnaires on depressive symptoms, knowledge and compliance. Clinical and demographic data were collected from medical charts and interviews by an independent data collector. Logistic regression analysis was performed to examine independent associations with patient delay. Median patient delay was 48 hours; 296 patients reported short delay (<12 h) and 341 long delay (≥168 h). A history of myocardial infarction (MI) (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.34-0.71) or stroke (OR 0.43, 95% CI 0.24-0.76) was independently associated with short patient delay. Male gender, more HF knowledge, and more HF symptoms were associated with long patient delay. No differences were found between patients with and without a history of HF. Conclusions: Patients with a history of a life-threatening event (MI or stroke) had a shorter delay than patients without such an event. Patients without a life-threatening event might need to be educated on the recognition and need for appropriate action in a different way then those with an acute threatening previous experience.

J Card Fail: 02 Aug 2011; 17:657-663
Nieuwenhuis MM, Jaarsma T, van Veldhuisen DJ, van der Wal MH
J Card Fail: 02 Aug 2011; 17:657-663 | PMID: 21807327
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Abstract

The Death of Balzac (1799-1850) and the Treatment of Heart Failure during the Nineteenth Century.

Perciaccante A, Riva MA, Coralli A, Charlier P, Bianucci R
Overweight, workaholic and caffeine abuser, Honoré de Balzac lived a life of excess. He prematurely died aged 51 due to a gangrene associated with congestive heart failure. Textual sources allowed us to take a glimpse into his last three months of life. Due to ventricular hypertrophy, Balzac\'s respiratory conditions were appalling and he developed severe leg edemas and possibly stasis dermatitis. Here we report on Balzac\'s demise and provide first evidence of a pioneering medical treatment applied to save his life: the use of trocar to drain leg edema. Based on the empirical observation of the benefits derived from an accidental leg drainage, Balzac\'s physicians anticipated the invention of the "Southey\'s tubes", whose use evolved in the following century to treat obstinate edema in heart failure patients. Unfortunately, following the daily manoeuvres for trocar insertion and in the absence of adequate disinfection measures and antibiotics, bacteria infected the open wound and gave rise to the gangrene, which led the writer to death within 24 hours from its onset.

J Card Fail: 16 Sep 2016; epub ahead of print
Perciaccante A, Riva MA, Coralli A, Charlier P, Bianucci R
J Card Fail: 16 Sep 2016; epub ahead of print | PMID: 27638234
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Abstract

Both High and Low Body Mass Indexes are Prognostic Risks in Japanese Patients With Chronic Heart Failure: Implications From the CHART Study.

Nochioka K, Shiba N, Kohno H, Miura M, Shimokawa H
Background: Prognostic impact of body mass index (BMI) in Japanese patients with chronic heart failure (HF) remains unclear. Methods and results: We examined the relationship between BMI and the prognosis of Japanese HF patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART) study. The study sample was 972 Japanese chronic HF patients (mean age, 68.2 ± 13.5; male 65.2%). We categorized them into 5 groups; BMI <18.5, 18.5 to 22.9, 23.0 to 24.9 (reference), 25.0 to 29.9, and ≥30.0. Using a Cox hazards model, the relationships between BMI and deaths or admission for worsening HF were studied in detail. Mean follow-up period was 3.4 ± 1.7 years. Multivariate analysis showed that, as compared with reference group (BMI 23.0 to 24.9), hazard ratios (HR) for all-cause death showed a U-shaped association with 1.70 (95% confidence interval; 1.04-2.76), 1.23 (0.85-1.78), 1.26 (0.84-1.90), and 2.75 (1.51-5.00) among those with BMI<18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥30.0, respectively. There were significant and suggestive U-shaped associations between BMI and cardiac-cause death or admission for worsening HF. Conclusions: Both high and low BMIs were associated with increased outcomes, suggesting that extreme obesity is not beneficial in improving the prognosis of Japanese chronic HF patients.

J Card Fail: 08 Nov 2010; 16:880-7
Nochioka K, Shiba N, Kohno H, Miura M, Shimokawa H
J Card Fail: 08 Nov 2010; 16:880-7 | PMID: 21055652
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Abstract

Chronic baroreflex activation: a potential therapeutic approach to heart failure with preserved ejection fraction.

Georgakopoulos D, Little WC, Abraham WT, Weaver FA, Zile MR
Heart failure with preserved ejection fraction (HFpEF) is a substantial public health issue, equal in magnitude to heart failure with reduced ejection fraction. Clinical outcomes of HFpEF patients are generally poor, related annual accrual of health care expenses amount to billions of dollars, and no therapy has been shown to be effective in randomized clinical trials. Baroreflex activation therapy (BAT) produced by stimulating the carotid sinuses using an implanted device (Rheos) is being studied for the treatment of hypertension, the primary comorbidity of HFpEF. Other potential benefits include regression of left ventricular hypertrophy, normalization of the sympathovagal balance, inhibition of the renin-angiotensin-aldosterone system, arterio- and venodilation, and preservation of renal function. This paper reviews the evidence suggesting that BAT may be a promising therapy for HFpEF and introduces the HOPE4HF trial (ClinicalTrials.gov Identifier: NCT00957073), a randomized outcomes trial designed to evaluate the clinical safety and efficacy of BAT in the HFpEF population.

J Card Fail: 08 Feb 2011; 17:167-78
Georgakopoulos D, Little WC, Abraham WT, Weaver FA, Zile MR
J Card Fail: 08 Feb 2011; 17:167-78 | PMID: 21300307
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Abstract

Chronic alternate-day fasting results in reduced diastolic compliance and diminished systolic reserve in rats.

Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan MI
Background: Based on animal experiments and limited data from the few human trials, alternate-day fasting (ADF) resulted in weight loss, prolonged life, reduced metabolic risk factors for diabetes and cardiovascular diseases, and reduced prevalence of age-related diseases. The present study is the first comprehensive examination of the long-term effects of ADF on general cardiovascular fitness in rats. Methods and results: Four-month-old male Sprague-Dawley rats were started on ADF or continued on ad libitum diets and followed for 6 months with serial echocardiography. A comprehensive hemodynamic evaluation including a combined dobutamine-volume stress test was performed at the end of the study, and hearts were harvested for histological assessment. The 6-month-long ADF diet resulted in a 9% reduction (P < .01) of cardiomyocyte diameter and 3-fold increase in interstitial myocardial fibrosis. Left ventricular chamber size was not affected by ADF and ejection fraction was not reduced, but left atrial diameter was increased 16%, and the ratio of early (E) and late atrial (A) waves, in Doppler-measured mitral flow was reduced (P < .01). Pressure-volume loop analyses revealed a "stiff" heart during diastole in ADF rats, whereas combined dobutamine and volume loading showed a significant reduction in left ventricular diastolic compliance and a lack of increase in systolic pump function, indicating a diminished cardiac reserve. Conclusion: Chronic ADF in rats results in development of diastolic dysfunction with diminished cardiac reserve. ADF is a novel and unique experimental model of diet-induced diastolic dysfunction. The deleterious effect of ADF in rats suggests that additional studies of ADF effects on cardiovascular functions in humans are warranted.

J Card Fail: 11 Oct 2010; 16:843-53
Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan MI
J Card Fail: 11 Oct 2010; 16:843-53 | PMID: 20932467
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Abstract

Right Ventricular Heart Failure From Pulmonary Embolism: Key Distinctions From Chronic Pulmonary Hypertension.

Watts JA, Marchick MR, Kline JA
Background: The right ventricle normally operates as a low pressure, high-flow pump connected to a high-capacitance pulmonary vascular circuit. Morbidity and mortality in humans with pulmonary hypertension (PH) from any cause is increased in the presence of right ventricular (RV) dysfunction, but the differences in pathology of RV dysfunction in chronic versus acute occlusive PH are not widely recognized. Methods and results: Chronic PH that develops over weeks to months leads to RV concentric hypertrophy without inflammation that may progress slowly to RV failure. In contrast, pulmonary embolism (PE) results in an abrupt vascular occlusion leading to increased pulmonary artery pressure within minutes to hours that causes immediate deformation of the RV. RV injury is secondary to mechanical stretch, shear force, and ischemia that together provoke a cytokine and chemokine-mediated inflammatory phenotype that amplifies injury. Conclusions: This review will briefly describe causes of pulmonary embolism and chronic PH, models of experimental study, and pulmonary vascular changes, and will focus on mechanisms of right ventricular dysfunction, contrasting mechanisms of RV adaptation and injury in these 2 settings.

J Card Fail: 08 Mar 2010; 16:250-259
Watts JA, Marchick MR, Kline JA
J Card Fail: 08 Mar 2010; 16:250-259 | PMID: 20206901
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Abstract

What are the Thromboembolic Risks of Heart Failure Combined With Chronic or Paroxysmal AF?

Caldwell JC, Mamas MA, Neyses L, Garratt CJ
Background: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks. Methods and results: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF. Conclusions: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF.

J Card Fail: 30 Mar 2010; 16:340-347
Caldwell JC, Mamas MA, Neyses L, Garratt CJ
J Card Fail: 30 Mar 2010; 16:340-347 | PMID: 20350702
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Abstract

Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure.

Chiarantini D, Volpato S, Sioulis F, Bartalucci F, ... Marchionni N, Di Bari M
Background: In older heart failure (HF) patients, survival depends on the severity of their cardiac condition and on their functional status. Lower extremity performance, assessed with the Short Physical Performance Battery (SPPB), predicts survival in older persons, both in epidemiologic and clinical settings. We evaluated whether SPPB predicts long-term survival in older subjects hospitalized for HF, independent of traditional measures of HF severity. Methods and results: Subjects aged 65+ years were enrolled on discharge after hospitalization for decompensated HF. Participants underwent echocardiography, comprehensive geriatric assessment, and SPPB. Cox proportional hazards regression models were used to predict survival over a 30-month follow-up. Of 157 participants (mean age 80 years, range 65-101; 50% men), 61 died. After adjustment for potential confounders, including demographics, ejection fraction, New York Heart Association classification, and comorbidity, we found a graded independent association between SBBP score and mortality risk: compared with an SPPB score of 9-12, scores of 0, 1-4, and 5-8 were associated with hazard ratios (HR) and 95% confidence interval (CI) of death of 6.06 (2.19-16.76), 4.78 (1.63-14.02), and 1.95 (0.67-5.70), respectively. Conclusions: SPPB is an independent predictor of long-term survival of older subjects hospitalized for decompensated HF.

J Card Fail: 07 May 2010; 16:390-5
Chiarantini D, Volpato S, Sioulis F, Bartalucci F, ... Marchionni N, Di Bari M
J Card Fail: 07 May 2010; 16:390-5 | PMID: 20447574
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Abstract

Relationship Between High Circulating Adiponectin With Bone Mineral Density and Bone Metabolism in Elderly Males With Chronic Heart Failure.

Bozic B, Loncar G, Prodanovic N, Radojicic Z, ... Dimkovic S, Popovic-Brkic V
Background: The aim of the study was to investigate the associations of adiponectin and leptin to bone mass and bone specific surrogates in elderly males with chronic heart failure (CHF). Methods and results: Seventy-three males (mean age 68 +/- 7 years) with stable mild to moderate CHF and 20 healthy individuals age- and body mass index-matching underwent dual energy x-ray absorptiometry measurements (bone mineral density (BMD) at hip and lumbar spine, total bone mineral content, and body composition); echocardiography; 6-minute walk test; grip strength; and biochemical assessment including adiponectin, leptin, bone specific surrogates (osteocalcin, beta-CrossLaps, osteoprotegerin [OPG], receptor activator of nuclear factor kappaB ligand [RANKL]), parathyroid hormone, 25-hydroxy vitamin D, testosterone, sex hormone-binding globulin, and NT-pro-BNP. Serum adiponectin, osteocalcin, beta-CrossLaps, OPG, RANKL, and parathyroid hormone were significantly increased in CHF patients, whereas 25-hydroxy vitamin D was significantly lower compared to healthy controls. The significant positive association was found between adiponectin level with osteocalcin, beta-CrossLaps, OPG, and RANKL among CHF patients. In multivariate regression analysis, adiponectin was a significant determinant of total hip BMD, although the variance was small (r(2) = 0.239), whereas leptin was determinant for total bone mineral content (r(2) = 0.469) in patients with CHF. Conclusions: Serum adiponectin is an independent predictor of BMD in elderly males with mild to moderate CHF, and showed a positive correlation to bone specific surrogates. Adiponectin, as cardioprotective hormone, seems to be able to exert a negative effect on bone mass in chronic heart failure. Further research is needed to confirm the potential for adipokines in the crosstalk between bone and energy metabolism in CHF patients.

J Card Fail: 30 Mar 2010; 16:301-307
Bozic B, Loncar G, Prodanovic N, Radojicic Z, ... Dimkovic S, Popovic-Brkic V
J Card Fail: 30 Mar 2010; 16:301-307 | PMID: 20350696
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Abstract

Relevance of Water Gymnastics in Rehabilitation Programs in Patients With Chronic Heart Failure or Coronary Artery Disease With Normal Left Ventricular Function.

Teffaha D, Mourot L, Vernochet P, Ounissi F, ... Monpère C, Dugué B
Background: Exercise training is included in cardiac rehabilitation programs to enhance physical capacity and cardiovascular function. Among the existing rehabilitation programs, exercises in water are increasingly prescribed. However, it has been questioned whether exercises in water are safe and relevant in patients with stable chronic heart failure (CHF), coronary artery disease (CAD) with normal systolic left ventricular function. The goal was to assess whether a rehabilitation program, including water-based gymnastic exercises, is safe and induces at least similar benefits as a traditional land-based training. Methods and results: Twenty-four male CAD patients and 24 male CHF patients with stable clinical status participated in a 3-week rehabilitation. They were randomized to either a group performing the training program totally on land (CADl, CHFl; endurance + callisthenic exercises) or partly in water (CADw, CHFw; land endurance + water callisthenic exercises). Before and after rehabilitation, left ventricular systolic and cardiorespiratory functions, hemodynamic variables and autonomic nervous activities were measured. No particular complications were associated with both of our programs. At rest, significant improvements were seen in CHF patients after both types of rehabilitation (increases in stroke volume and left ventricular ejection fraction [LVEF]) as well as a decrease in heart rate (HR) and in diastolic arterial pressure. Significant increases in peaks V˙O(2), HR, and power output were observed in all patients after rehabilitation in exercise test. The increase in LVEF at rest, in HR and power output at the exercise peak were slightly higher in CHFw than in CHFl. Conclusions: Altogether, both land and water-based programs were well tolerated and triggered improvements in cardiorespiratory function.

J Card Fail: 02 Aug 2011; 17:676-683
Teffaha D, Mourot L, Vernochet P, Ounissi F, ... Monpère C, Dugué B
J Card Fail: 02 Aug 2011; 17:676-683 | PMID: 21807330
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Abstract

Gender differences in cardiac dysfunction and remodeling due to volume overload.

Dent MR, Tappia PS, Dhalla NS
Background: This study examined the sex differences for hemodynamic and echocardiographic changes in hypertrophied and failing hearts induced by arteriovenous (AV) shunt. Methods and results: Echocardiographic and hemodynamic alterations were determined in male and female rats at 4 and 16 weeks after AV shunt. Ovariectomized females treated with estrogen for 16 weeks post-AV shunt were also used. Both genders developed cardiac hypertrophy at 4 and 16 weeks post-AV shunt; however, the increase in cardiac muscle mass was greater in females than males at 16 weeks. At 4 weeks post-AV shunt, increases in ventricular dimensions and left ventricular end-diastolic pressure (LVEDP) as well as a decrease in fractional shortening occurred in males only. Unlike the females, the rates of pressure development (+dP/dt) and decay (-dP/dt) were depressed and LVEDP increased in male rats at 16 weeks post-AV shunt. An increase in cardiac output was seen in both genders, but this was more marked in the males at 4 and 16 weeks post-AV shunt. Although mRNA levels for ACE were increased in both male and female rats at 4 and 16 weeks, mRNA levels for angiotensin II type 1 receptor were increased in males at 16 weeks only. Furthermore, increases in plasma catecholamines were elevated in males but were decreased or unchanged in females at 16 weeks of AV shunt. LV internal diameters as well as depressed fractional shortening occurred in males whereas increases in posterior wall thickness were seen in the female rats at 16 weeks of AV shunt. Ovariectomy resulted in depressed +dP/dt, -dP/dt, and fractional shortening, whereas a marked increase in cardiac output as well as increased LVEDP and LV internal diameters were observed at 16 weeks post-AV shunt. Although treatment with 17-beta estradiol normalized +/-dP/dt, LVEDP remained elevated. Conclusion: Gender differences in cardiac function may be due to differences in the type of cardiac remodeling as a consequence of AV shunt. Furthermore, estrogen appears to play an important role in preventing cardiac dysfunction and adverse ventricular remodeling in female rats.

J Card Fail: 07 May 2010; 16:439-49
Dent MR, Tappia PS, Dhalla NS
J Card Fail: 07 May 2010; 16:439-49 | PMID: 20447581
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Abstract

The critical link of hypervolemia and hyponatremia in heart failure and the potential role of arginine vasopressin antagonists.

Ghali JK, Tam SW
Background: Hypervolemia and hyponatremia resulting from activation of the neurohormonal system and impairment of renal function are prominent features of decompensated heart failure. Both conditions share many pathophysiologic and prognostic features and each has been associated with increased morbidity and mortality. When both conditions coexist, therapeutic options are limited. Methods and results: This review presents a concise digest of the pathophysiology, clinical significance, and pharmacological therapy of hyponatremia complicating heart failure with a special emphasis on vasopressin antagonists and their aquaretic effects in the absence of neurohormonal activation along with their ability to correct hyponatremia. Conclusions: Hypervolemia and hyponatremia share many pathophysiologic and prognostic features in heart failure. Vasopressin antagonists provide a viable option for their management and a potentially unique role when both conditions coexists.

J Card Fail: 07 May 2010; 16:419-31
Ghali JK, Tam SW
J Card Fail: 07 May 2010; 16:419-31 | PMID: 20447579
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Abstract

Cost of medical services in older patients with heart failure: those receiving enhanced monitoring using a computer-based telephonic monitoring system compared with those in usual care: the heart failure home care trial.

Soran OZ, Feldman AM, Piña IL, Lamas GA, ... Pilotte J, Lave JR
Background: Prior studies suggest that disease management programs may be effective in improving clinical and economic outcomes in patients with heart failure. Whether these types of programs can lower health care cost and be adapted to the primary care setting is unknown. This study was designed to assess the impact of a home-based disease management program, the Alere DayLink HF Monitoring System (HFMS), on the clinical and economic outcomes of Medicare beneficiaries recently hospitalized for heart failure who received the care from a community-based primary care practitioner. Methods and results: The Heart Failure Home Care trial was a multicenter, randomized, controlled trial of sophisticated, monitoring of heart failure patients with an interactive program versus standard heart failure care with enhanced patient education and follow-up (SC) in Medicare-eligible patients. The study endpoints included cardiovascular death or rehospitalization for heart failure, length of hospital stay, total patient cost, and cost to Medicare at 6 months of enrollment. A total of 315 patients age ≥65 years old were randomized: 160 to the HFMS and 155 to SC. There were no significant statistical differences between the groups in regards to 6-month cardiac mortality, rehospitalizations for heart failure, or length of hospital stay. Of those, 304 patients had their Medicare data available. The information from the Medicare claims data was used to determine the cost. Information from the trial was used to determine costs of out-patient drugs and the interventions. The 6-month mean Medicare costs were estimated to be $17,837 and $13,886 for the HFMS and the SC groups, respectively. We found that overall medical costs of medicare patients were significantly higher for patients who were randomized to the HFMS arm than they were for the patients randomized to the SC arm. Conclusions: Our study results suggest that enhanced patient education and follow-up is as successful as a sophisticated home monitoring device with an interactive program and less costly in patients who are elderly and receive the care from a community-based primary care practitioner.

J Card Fail: 08 Nov 2010; 16:859-66
Soran OZ, Feldman AM, Piña IL, Lamas GA, ... Pilotte J, Lave JR
J Card Fail: 08 Nov 2010; 16:859-66 | PMID: 21055649
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Abstract

The Effects of Depression on the Course of Functional Limitations in Patients With Chronic Heart Failure.

Shimizu Y, Yamada S, Miyake F, Izumi T, On Behalf of the PTMaTCH Collaborators
Background: This study examined whether depressive symptoms are associated with persistent functional limitations and severity classified according to the course of functional limitations in chronic heart failure (CHF) patients after discharge. Methods and results: The Performance Measure for Activities of Daily Living 8 (PMADL-8) was used to measure the course of functional limitations at 1, 3, and 5 months after discharge in a cohort of 148 patients. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale at 1 month after discharge. Repeated-measures logistic regression adjusting for potential confounders demonstrated that the depression groups had different persistent functional limitations (PMADL-8 scores ≥20 at 1, 3, and 5 months after discharge [χ(2) = 5.3; P < .05]). Using cluster analysis, we identified 4 distinctive courses of functional limitations, and there was a graded relationship between the severity of the course and depressive symptoms (χ(2) = 26.1; P < .001). Conclusions: In this prospective study, depression was associated with poorer functional limitations in CHF patients after discharge. The findings of this study suggest that depression may be a treatment target for improving functional limitations in CHF patients during the recovery phase.

J Card Fail: 31 May 2011; 17:503-510
Shimizu Y, Yamada S, Miyake F, Izumi T, On Behalf of the PTMaTCH Collaborators
J Card Fail: 31 May 2011; 17:503-510 | PMID: 21624739
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Abstract

Determinants of Red Cell Distribution Width (RDW) in Cardiorenal Patients: RDW is Not Related to Erythropoietin Resistance.

Emans ME, van der Putten K, van Rooijen KL, Kraaijenhagen RJ, ... Braam B, Gaillard CA
Background: Studies have shown that red cell distribution width (RDW) is related to outcome in chronic heart failure (CHF). The pathophysiological process is unknown. We studied the relationship between RDW and erythropoietin (EPO) resistance, and related factors such as erythropoietic activity, functional iron availability and hepcidin. Methods and results: In the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome (EPOCARES) study, which investigates the role of EPO in 54 iron-supplemented anemic patients with CHF and chronic kidney disease (CKD) (n = 35 treated with 50 IU/kg/wk Epopoetin beta, n = 19 control), RDW was not associated with EPO resistance. We defined EPO resistance by EPO levels (r = 0.12, P = .42), the observed/predicted log EPO ratio (r = 0.12, P = .42), the increase in reticulocytes after 2 weeks of EPO treatment (r = -0.18, P = .31), and the increase of hemoglobin after 6 months of EPO treatment (r = 0.26, P = .35). However, RDW was negatively correlated with functional iron availability (reticulocyte hemoglobin content, r = -0.48, P < .001, and transferrin saturation, r = -0.39, P = .005) and positively with erythropoietic activity (soluble transferrin receptor, r = 0.48, P < .001, immature reticulocyte fraction, r = 0.36, P = .01) and positively with interleukin-6 (r = 0.48, P < .001). No correlation existed between hepcidin-25 and RDW. Conclusions: EPO resistance was not associated with RDW. RDW was associated with functional iron availability, erythropoietic activity, and interleukin-6 in anemic patients with CHF and CKD.

J Card Fail: 02 Aug 2011; 17:626-633
Emans ME, van der Putten K, van Rooijen KL, Kraaijenhagen RJ, ... Braam B, Gaillard CA
J Card Fail: 02 Aug 2011; 17:626-633 | PMID: 21807323
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Abstract

Equitable Improvement for Women and Men in the Use of Guideline-Recommended Therapies for Heart Failure: Findings From IMPROVE HF.

Walsh MN, Yancy CW, Albert NM, Curtis AB, ... Reynolds D, Fonarow GC
Background: Although sex-based disparities in use of guideline-recommended heart failure (HF) therapies have been described, little is known about whether performance improvement (PI) initiatives produce equitable improvements in guideline-recommended therapies. Methods and results: IMPROVE HF is a prospective study of a practice-based PI intervention in patients with systolic HF or post-myocardial infarction left ventricular dysfunction. Mean changes from baseline to 24 months after intervention were compared between women and men for treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, aldosterone antagonists, anticoagulation for atrial fibrillation, cardiac resynchronization therapy (CRT), implantable cardioverter-defibrillator (ICD), and HF education. This analysis included 15,170 patients at 167 cardiology practices (4,383 [28.9%] women, 10,787 [71.1%] men). At baseline, women were less likely than men to be treated with anticoagulation and ICD. Significant improvements in 6 of 7 quality measures were evident at 24 months for both sexes. The absolute magnitude of improvement was similar for 5 measures and significantly better in women for CRT, ICD, and composite care. Conclusions: This PI intervention was associated with similar or greater increases in use of guideline-recommended HF therapies for eligible women compared with men. Clinical decision support and performance feedback may help to ensure improved, equitable care for men and women with HF. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov unique identifier: NCT00303979.

J Card Fail: 29 Nov 2010; 16:940-9
Walsh MN, Yancy CW, Albert NM, Curtis AB, ... Reynolds D, Fonarow GC
J Card Fail: 29 Nov 2010; 16:940-9 | PMID: 21111983
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Abstract

Critical role for death-receptor mediated apoptotic signaling in viral myocarditis.

Debiasi RL, Robinson BA, Leser JS, Brown RD, Long CS, Clarke P
Background: Apoptosis of cardiac myocytes plays a key role in the pathogenesis of many cardiac diseases, including viral myocarditis. The apoptotic signaling pathways that are activated during viral myocarditis and the role that these pathways play in disease pathogenesis have not been clearly delineated. Methods and results: We investigated the role of apoptotic signaling pathways after virus infection of primary cardiac myocytes. The death receptor-associated initiator caspase, caspase 8, and the effector caspase, caspase 3, were significantly activated after infection of primary cardiac myocytes with myocarditic, but not non-myocarditic, reovirus strains. Furthermore, reovirus-induced cardiac myocyte apoptosis was significantly inhibited by soluble death receptors. In contrast, the mitochondrial membrane potential remained unaltered and caspase 9, the initiator caspase associated with mitochondrial apoptotic signaling, was only weakly activated in cardiac myocytes after infection with myocarditic reovirus strains. Inhibition of mitochondrial apoptotic signaling had no effect on reovirus-induced cardiac myocyte apoptosis. In accordance with our in vitro data, caspase 8, but not caspase 9, was significantly activated in the hearts of reovirus-infected mice. Conclusions: Death receptor, but not mitochondrial, apoptotic signaling plays a key role in apoptosis after infection of cardiac myocytes with myocarditic reovirus strains.

J Card Fail: 08 Nov 2010; 16:901-10
Debiasi RL, Robinson BA, Leser JS, Brown RD, Long CS, Clarke P
J Card Fail: 08 Nov 2010; 16:901-10 | PMID: 21055654
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Abstract

Clinical Effectiveness of Tolvaptan in Patients with Acute Heart Failure and Renal Dysfunction - AQUAMARINE Study.

Matsue Y, Suzuki M, Torii S, Yamaguchi S, ... Yoshida K, Goldsmith SR
Background More efficacious and/or safer decongestive therapy is clearly needed in acute heart failure (AHF) patients complicated by renal dysfunction. We tested the hypothesis that adding tolvaptan, an oral vasopressin-2 receptor antagonist, to conventional therapy with loop diuretics would be more effective treatment in this population. Methods and Results A multicenter, open-label, randomized control trial was performed, and 217 AHF patients with renal dysfunction (estimated glomerular filtration rate 15 - 60 mL/min/1.73 m(2)) were randomized 1:1 to treatment with tolvaptan (n = 108) or conventional treatment (n = 109). The primary endpoint was 48-hour urine volume. The tolvaptan group showed more diuresis than the conventional treatment group (6464.4 vs. 4999.2 mL, P < 0.001) despite significantly lower amounts of loop diuretic use (80 mg vs. 120 mg, P < 0.001). Dyspnea relief was achieved significantly more frequently in the tolvaptan group at all time points within 48 hours except 6 hours from enrollment. The rate of worsening of renal function (≥ 0.3 mg/dL increase from baseline) was comparable between tolvaptan and conventional groups (24.1% vs. 27.8%, respectively; P = 0.642). Conclusions Adding tolvaptan to conventional treatment achieved more diuresis and relieved dyspnea symptoms in AHF patients with renal dysfunction. Clinical Trial registration URL: http://www.umin.ac.jp/ctr/index/htm/ Unique identifier: UMIN000007109.

J Card Fail: 25 Feb 2016; epub ahead of print
Matsue Y, Suzuki M, Torii S, Yamaguchi S, ... Yoshida K, Goldsmith SR
J Card Fail: 25 Feb 2016; epub ahead of print | PMID: 26915749
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Abstract

Presence and Implication of Temporal Non-Uniformity of Early Diastolic Left Ventricular Wall Expansion in Patients with Heart Failure.

Iwano H, Kamimura D, Fox ER, Hall ME, Vlachos P, Little WC
Background Early-diastolic left ventricular (LV) longitudinal expansion is delayed with diastolic dysfunction. We hypothesized that, in patients with heart failure (HF) regardless of LV ejection fraction (EF), there is diastolic temporal non-uniformity with a delay of longitudinal relative to circumferential expansion. Methods and Results Echocardiography was performed in 143 HF patients: 50 with preserved EF (HFpEF) and 93 with reduced EF (HFrEF) and 31 normal controls. The delay of early-diastolic mitral annular velocity from the mitral Doppler E (TE-e\') was measured as a parameter of the longitudinal-expansion delay. The delay of the longitudinal early-diastolic global strain rate (SRE) relative to circumferential SRE (DelayC-L) was calculated as a parameter of temporal non-uniformity. Intra LV pressure difference (IVPD) was estimated by using color M-mode Doppler data as a parameter of LV diastolic suction. Although normal controls had symmetrical LV expansion in early diastole, TE-e\' and DelayC-L were significantly prolonged in HF regardless of EF (P<0.01 vs controls for all). Multivariate analysis revealed that DelayC-L was the independent determinant of IVPD among the parameters of LV geometry and contraction (β=-0.21, P<0.05). Conclusion An abnormal temporal non-uniformity of early-diastolic expansion is present in HF regardless of EF, which was associated with reduced LV suction.

J Card Fail: 19 Apr 2016; epub ahead of print
Iwano H, Kamimura D, Fox ER, Hall ME, Vlachos P, Little WC
J Card Fail: 19 Apr 2016; epub ahead of print | PMID: 27095528
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Abstract

Right Ventricular Dysfunction During Intensive Pharmacologic Unloading Persists After Mechanical Unloading.

Palardy M, Nohria A, Rivero J, Lakdawala N, ... Stevenson LW, Givertz MM
Background: Right ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support. Methods and results: We studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 +/- 5 mm Hg, mean pulmonary artery pressure 36 +/- 11 mm Hg, pulmonary capillary wedge pressure 23 +/- 9 mm Hg, and cardiac index 2.0 +/- 0.6 L.min.m(2). Preoperatively, RV dysfunction was moderate (2.6 +/- 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 +/- 0.6 cm, and mid-RV was 3.5 +/- 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 +/- 0.9) failed to improve, despite reduced RV afterload. Conclusions: RV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.

J Card Fail: 08 Mar 2010; 16:218-224
Palardy M, Nohria A, Rivero J, Lakdawala N, ... Stevenson LW, Givertz MM
J Card Fail: 08 Mar 2010; 16:218-224 | PMID: 20206896
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Abstract

Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.

MacIver DH, Clark AL
The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalises wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the haemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation.

J Card Fail: 18 Apr 2016; epub ahead of print
MacIver DH, Clark AL
J Card Fail: 18 Apr 2016; epub ahead of print | PMID: 27090746
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Abstract

The Room Where It Happens: a Skeptic\'s Analysis of the New Heart Failure Guidelines.

Packer M
New heart failure guidelines have been issued during the past several months, both in the US and in Europe, in response to recent advances in and the approval of new drugs for the treatment of heart failure. Although guidelines documents are often viewed as authoritative and purely evidence-based, there are replete with meaningful (and inexplicable) inconsistencies, which derive from a review of the same body of scientific data by different groups. This satirical review highlights several examples of the entertaining foolishness of recent guideline documents in the good-natured hope that physicians will understand what the guidelines are, and more importantly, what they are not. Specifically, this paper describes the emergence of a new non-existent disease; the strange battle between two bradycardic drugs (digoxin and ivabradine); the confusion that reigns over the positioning and dosing of inhibitors of the renin-angiotensin system; and the special recommendations that have been issued for certain special populations. As Otto von Bismarck remarked, guideline deliberations are like sausages; it is better not to see them being made. Yet, even after they are ready for public view, we should be cautious. Practitioners who rely on them for clinical decision-making engage in an unnecessary form of self-deception; those who read them literally and adhere to them strictly do not practice evidence-based medicine; and those who delve into them in a search for the truth are destined to be disappointed.

J Card Fail: 30 Jul 2016; epub ahead of print
Packer M
J Card Fail: 30 Jul 2016; epub ahead of print | PMID: 27475878
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Abstract

Heart rate predicts mortality in patients with heart failure and preserved systolic function.

Kapoor JR, Heidenreich PA
Background: Elevated resting heart rates have been associated with increased mortality and morbidity in patients with heart failure and decreased left ventricular ejection fraction (EF). It is unclear, though, if this association applies to those with heart failure and preserved EF. Methods and results: We determined outcome for 685 consecutive patients with a prior diagnosis of heart failure and a preserved EF (>50%) documented on echocardiography at 1 of 3 laboratories. Patients with non-sinus rhythm were excluded from the analysis. We determined adjusted mortality rates at 1 year after the echocardiogram. The mean age of the cohort was 70 ± 11 years. Of the 685 included patients, 87% had a history of hypertension, 50% had diabetes, and the mean EF was 60% ± 6%. All-cause mortality at 1 year was significantly lower in the group with heart rate below 60 beats/min (10%) when compared with the group with heart rates between 60 and 70 beats/min (18%), 71-90 beats/min (20%), and >90 beats/min (35%) (P < .0001). After adjustment for patient history, demographics, laboratory values, and echocardiographic findings, the hazard ratios for total mortality (relative to a heart rate of <60) were 1.26 (95% CI, 0.88-1.80) for HR 60-69, 1.47 (95% CI, 1.02-2.07) for HR 70-90, and 2.00 (95% CI, 1.31-3.04) for HR>90 (P = .01 across all groups). Conclusions: These data suggest that an elevated resting heart rate is a marker for increased mortality in patients with heart failure and preserved systolic function. Heart rate may be useful in these patients for improved cardiovascular risk assessment.

J Card Fail: 11 Oct 2010; 16:806-11
Kapoor JR, Heidenreich PA
J Card Fail: 11 Oct 2010; 16:806-11 | PMID: 20932462
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Abstract

Extending the boundaries of cardiac resynchronization therapy: efficacy in atrial fibrillation, New York heart association class II, and narrow QRS heart failure patients.

Wein S, Voskoboinik A, Wein L, Billah B, Krum H
Background: Large-scale clinical trials have demonstrated the benefits of cardiac resynchronization therapy (CRT) in patients with New York Heart Association (NYHA) Class III/IV heart failure, systolic left ventricular dysfunction, and a wide QRS. However, additional patient groups may also benefit from CRT. Methods and results: We meta-analyzed clinical benefits of CRT in heart failure patients with narrow QRS, atrial fibrillation (AF) and NYHA Class II symptoms. Thirteen trials of 2882 patients contributed to this meta-analysis. In the narrow versus wide QRS group comparison, no difference in benefit was observed for change in left ventricular ejection fraction (standardized mean difference [SMD] 0.30, 95% confidence interval [CI] -0.37 to 0.97) or left ventricular end systolic volume (SMD 0.30, 95% CI -1.14 to 1.74). The benefit was greater in the wide QRS group for the 6-minute walk test (SMD 1.27, 95% CI 0.59 to 1.96) and NYHA class improvement (SMD 1.24, 95% CI 0.72 to 1.75). In the atrial fibrillation (AF) versus sinus rhythm (SR) group comparison, no difference in benefit was observed for change in left ventricular ejection fraction (SMD -0.38, 95% CI -1.28 to 0.53) or NYHA improvement (SMD 0.32, 95% CI -0.77 to 1.40). In the NYHA II versus NYHA III/IV group comparison, no difference in benefit was observed for change in left ventricular end diastolic diameter (SMD 0.05, 95% CI -0.94 to 1.05) or left ventricular end systolic diameter (SMD 0.74, 95% CI -1.98 to 3.46). Conclusions: Large-scale clinical outcome trials of CRT are warranted in heart failure patients with narrow QRS, AF, and NYHA II, given the similar benefits observed to those with wide QRS, SR, and NYHA III/IV for many parameters.

J Card Fail: 07 May 2010; 16:432-8
Wein S, Voskoboinik A, Wein L, Billah B, Krum H
J Card Fail: 07 May 2010; 16:432-8 | PMID: 20447580
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Abstract

Pharmacological and Endovascular Reversal of Left Ventricular Remodeling.

Jaiswal A, Nguyen VQ, Carry BJ, Le Jemtel TH
Pathological left ventricular (LV) remodeling as described by adverse changes in LV mass, volume, geometry, and composition in response to mechanical and systemic neurohormonal activation portends a poor prognosis in patients with underlying LV systolic dysfunction. Conversely reversal of LV remodeling is associated with improved morbidity and mortality. Improvement in LV function and size may result from either change in loading conditions or from reversal of remodeling (RR). When complete normalization of LV function and geometry occurs (ejection fraction >50% and indexed LV end diastolic dimension <33mm/m(2)), true reversal of LV alteration is likely to have occurred. Sustained improvement in function and dimensions after therapy withdrawal further supports LVRR. In the absence of complete LVRR one cannot readily differentiate incomplete RR from changes in loading conditions. In this review, we evaluate the role of renin-angiotensin-aldosterone system inhibition, beta adrenergic receptor blockade, cardiac resynchronization therapy and endovascular mitral repair on LVRR and improvement in LV geometry and function.

J Card Fail: 24 Apr 2016; epub ahead of print
Jaiswal A, Nguyen VQ, Carry BJ, Le Jemtel TH
J Card Fail: 24 Apr 2016; epub ahead of print | PMID: 27109620
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Abstract

Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment.

Murphy CJ, Oudit GY
Background: The prevalence of primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis) is reaching epidemic levels worldwide. Iron-overload leads to excessive iron deposition in a wide variety of tissues, including the heart and endocrine tissues. Methods and results: Iron-overload cardiomyopathy is the primary determinant of survival in patients with secondary iron overload, while also being a leading cause of morbidity and mortality in patients with primary hemochromatosis. Iron-induced cardiovascular injury also occurs in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, cardiomyopathy associated with Friedreich ataxia, and vascular dysfunction. The mainstay therapies for iron overload associated with primary hemochromatosis and secondary iron overload is phlebotomy and iron chelation therapy, respectively. L-type Ca(2+) channels provide a high-capacity pathway for ferrous (Fe(2+)) uptake into cardiomyocytes in iron-overload conditions; calcium channel blockers may represent a new therapeutic tool to reduce the toxic effects of excess iron. Conclusions: Iron-overload cardiomyopathy is a an important and potentially reversible cause of heart failure at an international scale and involves diastolic dysfunction, increased susceptibility to arrhythmias and a late-stage dilated cardiomyopathy. The early diagnosis of iron-overload cardiomyopathy is critical since the cardiac dysfunction is reversible if effective therapy is introduced before the onset of overt heart failure.

J Card Fail: 08 Nov 2010; 16:888-900
Murphy CJ, Oudit GY
J Card Fail: 08 Nov 2010; 16:888-900 | PMID: 21055653
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Abstract

Serum YKL-40 Predicts Adverse Clinical Outcomes in Patients With Chronic Heart Failure.

Bilim O, Takeishi Y, Kitahara T, Ishino M, ... Shishido T, Kubota I
Background: Human cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression. Methods and results: We examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048). Conclusions: Serum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF.

J Card Fail: 08 Nov 2010; 16:873-9
Bilim O, Takeishi Y, Kitahara T, Ishino M, ... Shishido T, Kubota I
J Card Fail: 08 Nov 2010; 16:873-9 | PMID: 21055651
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Abstract

IIIB or Not IIIB: A Previously Unanswered Question.

Thibodeau JT, Mishkin JD, Patel PC, Mammen PP, Markham DW, Drazner MH
The term New York Heart Association (NYHA) class IIIB has been used increasingly in clinical medicine, including as an inclusion criteria for many clinical trials assessing left ventricular assist devices (LVADs). Indeed, NYHA class IIIB is incorporated in the Food and Drug Administration\'s approved indication for the Heartmate II. However, on review of the medical literature, we found that there is no consensus definition of NYHA class IIIB. Until the ambiguity is resolved, we suggest that this designation not be used in clinical practice or by investigators leading clinical trials assessing therapies which convey substantial risk to patients and therefore require clarity in describing the enrolled patient population. With ongoing improvements in LVADs, this therapy will increasingly be considered in patients less sick than those who require inotropic support, providing urgency to establish a consensus system of classifying such patients who nevertheless fall within the spectrum of advanced heart failure. Herein we propose a modification of the standard NYHA classification system which can be used to fill this void.

J Card Fail: 03 May 2012; 18:367-72
Thibodeau JT, Mishkin JD, Patel PC, Mammen PP, Markham DW, Drazner MH
J Card Fail: 03 May 2012; 18:367-72 | PMID: 22555265
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Abstract

The sympathorenal axis in hypertension and heart failure.

Goldsmith SR, Sobotka PA, Bart BA
Excessive sympathetic drive is undoubtedly a major contributing factor to the pathophysiology of hypertension and heart failure. Much of the excessive sympathetic drive in these conditions is directed to the kidney, where it leads to inappropriate sodium retention, renin stimulation, and diminished renal function. Less well appreciated is the role the kidney itself plays in the generation of increased sympathetic activity by way of the renal somatic afferent nerves. The kidney therefore is both target and contributor to increased sympathetic activity in these conditions. Although some current pharmacotherapy indirectly targets this "sympathorenal axis," resistant hypertension remains a common problem, and the prognosis in heart failure remains poor, especially in more severe cases. It is now possible to directly target this axis via procedures, which directly interrupt renal sympathetic efferent and afferent signaling. Other procedures involving chronic carotid nerve stimulation may indirectly influence renal sympathetic tone and so improve renal sodium handling. These techniques have demonstrated early promise in hypertension and offer significant potential in heart failure as well. Should their early promise be borne out in controlled studies, the "sympathorenal axis" will have been proven to be a key element in the pathophysiology of these 2 very common, and dangerous, conditions.

J Card Fail: 07 May 2010; 16:369-73
Goldsmith SR, Sobotka PA, Bart BA
J Card Fail: 07 May 2010; 16:369-73 | PMID: 20447571
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Abstract

Native and Paced QRS Duration in Right Ventricular Apex Paced Patients.

Pan W, Su Y, Sun A, Gong X, Ge J
Background: The value between paced QRS duration (pQRSd) and native QRS duration (nQRSd) in paced population has not been compared. The relation between nQRSd and pQRSd remains undefined now. Methods and results: A total of 310 right ventricular apex (RVA) paced patients were enrolled. The correlation coefficients between nQRSd and pQRSd to left ventricular (LV) dimensions and ejection fraction (LVEF) were calculated and then compared. The association between pQRSd and nQRSd was examined. pQRSd was better correlated with LVDD, LVDS, and LVEF than nQRSd in all patients or patients with no intraventricular conduction block (NIVCB, n = 136) or complete right bundle-branch block (CRBB, n = 86) (all P < .01). pQRSd was positively correlated with nQRSd in NIVCB, CRBB, and complete left bundle-branch block (CLBB, n = 45) patients (r = 0.408, 0.465, and 0.766, respectively; all P < .001). However, pQRSd was not different between NIVCB, CRBB, and CLBB patients (P > .05) after adjusting for LVEF and LV dimensions. Conclusions: pQRSd is superior to nQRSd in terms of reflecting LV structures and function in RVA-paced patients. Bundle branch block (BBB) has no significant effect on pQRSd and thus further studies are needed to clarify whether BBB is an independent risk factor for the development of heart failure after RVA pacing.

J Card Fail: 08 Mar 2010; 16:239-243
Pan W, Su Y, Sun A, Gong X, Ge J
J Card Fail: 08 Mar 2010; 16:239-243 | PMID: 20206899
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Abstract

Development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE) study.

Guazzi M, Boracchi P, Arena R, Myers J, ... Chase P, Reina G
Background: Cardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers--peak oxygen consumption (VO₂), minute ventilation/carbon dioxide production (VE/VCO₂) slope, and exercise periodic breathing (EPB)-to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients. Methods and results: A total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO₂ slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO₂ slope and lower peak VO₂. This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO₂ slope, whereas peak VO₂ added minimal prognostic power. Conclusions: EPB with an elevated VE/VCO₂ slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO₂ ≤10 mL O₂·kg⁻¹·min⁻¹. PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition.

J Card Fail: 11 Oct 2010; 16:799-805
Guazzi M, Boracchi P, Arena R, Myers J, ... Chase P, Reina G
J Card Fail: 11 Oct 2010; 16:799-805 | PMID: 20932461
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Abstract

The Effects of Race on Peak Oxygen Consumption and Survival in Patients With Systolic Dysfunction.

Elmariah S, Goldberg LR, Allen MT, Kao A
Background: The relationship of peak exercise oxygen consumption (VO(2)) to survival in black heart failure (HF) patients is not well established. We examined the effects of race on peak VO(2) values and survival in HF patients with systolic dysfunction. Methods and results: This study evaluated consecutive ambulatory HF patients who underwent symptom-limited stress tests with breath-by-breath expired gas analyses using ramped treadmill protocols. The relationship between cardiopulmonary exercise parameters and patient transplant-free survival was assessed by race. This study included 580 HF patients (mean age 52 +/- 12 years; 28% females; 22% blacks; mean left ventricular ejection fraction 26 +/- 12%; mean body mass index 28.7 +/- 5.4; 73% on beta-blocker). Black patients had a significantly lower peak VO(2) than white patients (14.2 +/- 5.2 versus 16.4 +/- 7.0; P < .0001), despite adjusting for identified covariates. However, there was no significant difference in the 1-year transplant-free survival between black and white HF patients (87% versus 85%; P = NS). Peak VO(2) was significantly associated with survival in both racial groups. Conclusions: Black HF patients had significantly lower peak VO(2), but yet had equivalent survival rates at 1 year. Further study is warranted to clarify the impact of these racial differences on the timing of cardiac transplantation black HF patients.

J Card Fail: 30 Mar 2010; 16:332-339
Elmariah S, Goldberg LR, Allen MT, Kao A
J Card Fail: 30 Mar 2010; 16:332-339 | PMID: 20350701
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Abstract

Family caregiving for patients with heart failure: types of care provided and gender differences.

Hwang B, Luttik ML, Dracup K, Jaarsma T
Background: Knowledge about the potential burden for family caregivers related to the care of patients with heart failure (HF) is limited. The aims of the study were to compare the kind and amount of care provided by partners of HF patients and partners of healthy individuals and to examine the associations between gender and the performance of caregiving tasks. Methods and results: Caregiving tasks performed by 338 partners of HF patients were compared with those performed by 1202 partners of healthy individuals. Partners (age 70 +/- 9, 76% female) of HF patients were more likely to provide personal care compared with partners (age 65 +/- 7, 66% female) of healthy individuals after controlling for their age. However, the magnitude of the odds ratios (OR) differed by gender of partners (OR for male 6.7; 95% confidence interval [CI] 3.9-11.4; OR for female 3.7; 95% CI 2.7-5.1). Partners of HF patients were more likely to provide emotional care than partners of healthy individuals, controlling for age and gender (OR 2.4; 95% CI 1.5-3.6). Male partners of HF patients were more likely to provide personal care compared to female partners of HF patients (OR 1.9; 95% CI 1.1-3.2). Conclusions: The care performed by partners of HF patients is above and beyond normal spousal assistance. The study underscores the crucial role of family caregivers in the care of HF patients and encourages health care providers to address the needs of both HF patients and their caregivers.

J Card Fail: 07 May 2010; 16:398-403
Hwang B, Luttik ML, Dracup K, Jaarsma T
J Card Fail: 07 May 2010; 16:398-403 | PMID: 20447576
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Abstract

Bronchodilators in Heart Failure Patients With COPD: Is It Time for a Clinical Trial?

Mentz RJ, Fiuzat M, Kraft M, Lindenfeld J, O\'Connor CM
Chronic heart failure (HF) and chronic obstructive pulmonary disease (COPD) commonly coexist, and patients with both diseases fare worse than those with either disease alone. Several factors may contribute to worse outcomes, including an increased burden of care related to greater disease complexity, an overlap of symptoms resulting in misapplication of therapy, and the adverse effects of treatment for one disease on the symptoms and outcomes related to the other. For example, there are conflicting data about the cardiovascular risks of bronchodilators in HF patients who may experience worse outcomes with inhaled beta-2 agonists via arrhythmogenesis, ischemia, and/or attenuation of beta-blocker benefits. In contrast, the long-acting anticholinergic class of bronchodilators has a more reassuring safety profile. Anticholinergic bronchodilators may be the preferred first-line agents for COPD patients with comorbid HF, yet data supporting these recommendations are limited. Therapeutic trials in COPD patients have generally excluded patients with significant HF and vice-versa. This paper reviews bronchodilator therapy in HF and proposes a randomized trial designed to enroll patients with significant COPD and HF to determine the risks and/or benefits of adding a long-acting beta-2 agonist to patients currently taking a long-acting anticholinergic agent.

J Card Fail: 03 May 2012; 18:413-22
Mentz RJ, Fiuzat M, Kraft M, Lindenfeld J, O'Connor CM
J Card Fail: 03 May 2012; 18:413-22 | PMID: 22555273
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Abstract

Carvedilol for the treatment of benign prostatic hypertrophy in patients with heart failure?

Rohrer CK, Page RL, Shakar SF, Lindenfeld J
Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only β-adrenergic blocker approved for HF that also has additional α1-adrenergic blockade. As α1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient\'s symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an α1-adrenergic blockers.

J Card Fail: 03 Oct 2011; 17:875-7
Rohrer CK, Page RL, Shakar SF, Lindenfeld J
J Card Fail: 03 Oct 2011; 17:875-7 | PMID: 21962427
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Abstract

Indications for cardiac resynchronization therapy: 2011 update from the heart failure society of america guideline committee.

Stevenson WG, Hernandez AF, Carson PE, Fang JC, ... Stough WG, Starling RC
Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of ≥120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials.

J Card Fail: 03 Feb 2012; 18:94-106
Stevenson WG, Hernandez AF, Carson PE, Fang JC, ... Stough WG, Starling RC
J Card Fail: 03 Feb 2012; 18:94-106 | PMID: 22300776
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Abstract

Human serum albumin in the clinical syndrome of heart failure.

Arques S, Ambrosi P
Hypoalbuminemia is common in patients with heart failure, and this condition becomes more prevalent with increasing age and illness. Hypoalbuminemia is thought to result mainly from malnutrition, inflammation and cachexia. Other causal factors include hemodilution, liver dysfunction, protein-losing enteropathy, increased transcapillary escape rate, and nephrotic syndrome. According to Starling\'s law, low plasma oncotic pressure related to hypoalbuminemia induces a fluid shift from the intravascular to the interstitial space, and there is now clinical evidence that hypoalbuminemia facilitates the onset of cardiogenic pulmonary edema. Hypoalbuminemia has emerged as an independent predictor of incident heart failure in end-stage renal disease and elderly patients. Recent data also suggest that hypoalbuminemia provides prognostic information incremental to the usual clinical and biochemical variables in patients with heart failure regardless of clinical presentation. The presence of hypoalbuminemia in patients with heart failure may have potential therapeutic consequence in clinical practice. If present, subclinical excess of fluid must be removed. A dietary survey should also be performed, and renutrition may be indicated. It is unknown whether targeted nutritional intervention and albumin administration confer benefits to hypoalbuminemic patients with heart failure, and further research is warranted in this setting.

J Card Fail: 31 May 2011; 17:451-8
Arques S, Ambrosi P
J Card Fail: 31 May 2011; 17:451-8 | PMID: 21624732
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Abstract

Effects of ACE2 Inhibition in the Post-Myocardial Infarction Heart.

Kim MA, Yang D, Kida K, Molotkova N, ... Kjekshus J, Greenberg B
Background: There is evidence that angiotensin-converting enzyme 2 (ACE2) is cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a selective ACE2 inhibitor, after permanent coronary artery ligation or sham operation. Methods and results: Coronary artery ligation resulting in MI between 25% to 50% of the left ventricular (LV) circumference caused substantial cardiac remodeling. Daily C16 administration from postoperative days 2 to 28 at a dose that inhibited myocardial ACE2 activity was associated with a significant increase in MI size and reduction in LV % fractional shortening. Treatment with C16 did not significantly affect post-MI increases in LV end-diastolic dimension but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On postoperative day 7, C16 had no significant effect on the increased level of apoptosis in the infarct and border zones nor did it significantly affect capillary density surrounding the MI. It did, however, significantly reduce the number of c-kit(+) cells in the border region. Conclusions: These findings support the notion that ACE2 exerts cardioprotective effects by preserving jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and fibrosis with C16, however, suggests that ACE2 activity has diverse effects on post-MI remodeling.

J Card Fail: 27 Aug 2010; 16:777-785
Kim MA, Yang D, Kida K, Molotkova N, ... Kjekshus J, Greenberg B
J Card Fail: 27 Aug 2010; 16:777-785 | PMID: 20797602
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Abstract

Echocardiographic evaluation of left ventricular structure and function: new modalities and potential applications in clinical trials.

Kalogeropoulos AP, Georgiopoulou VV, Gheorghiade M, Butler J
Advances in modern echocardiography for quantification of cardiac structure and function have not been translated in clinical trial or practice applications to date. Imaging endpoints are especially well-suited for early trials with investigational therapies for heart failure as most drugs and devices approved for heart failure have shown favorable effects on cardiac structure and function also. Echocardiography is versatile and can be performed in most clinical settings. The modest interobserver and test-retest reproducibility of specific structural and functional parameters with conventional echocardiography can be improved on by using contemporary modalities, including 3-dimensional (3D) echocardiography for assessment of volumes and ejection fraction and speckle tracking for detailed functional assessment of the ventricles with mechanics-based parameters (strain and strain rate). The appropriate imaging endpoints (global vs. regional, systolic vs. diastolic) should be tailored to the specific research question and the mode of action of the therapy under investigation. The newer echocardiographic modalities, namely 3D echocardiography and speckle tracking, are more demanding in terms of equipment and personnel and therefore are better suited for implementation in experienced research centers with central interpretation. However, these modalities provide the best opportunity currently available to demonstrate treatment effects on the myocardium with investigational therapies and provide mechanistic insights for future directions.

J Card Fail: 03 Feb 2012; 18:159-72
Kalogeropoulos AP, Georgiopoulou VV, Gheorghiade M, Butler J
J Card Fail: 03 Feb 2012; 18:159-72 | PMID: 22300785
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Abstract

Functional Electrical Stimulation is More Effective in Severe Symptomatic Heart Failure Patients and Improves Their Adherence to Rehabilitation Programs.

Karavidas A, Parissis JT, Matzaraki V, Arapi S, ... Filippatos G, Kremastinos DT
Background: Functional electrical stimulation (FES) improves exercise capacity and quality of life in chronic heart failure (CHF) patients. However, there is no evidence regarding the effectiveness of this treatment modality according to the severity of CHF. This study compares the effectiveness of FES on exercise capacity, endothelial function, neurohormonal status, and emotional stress in New York Heart Association (NYHA) III-IV versus NYHA II patients. Methods and results: Eighteen NYHA II and 13 age- and sex-matched NYHA III-IV patients with stable CHF (left ventricular ejection fraction <35%) underwent a 6-week FES training program. Questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire, functional and overall), and emotional stress (Zung self-rating depression scale, Beck Depression Inventory), as well as plasma B-type natriuretic peptide (BNP), 6-minute walking distance test (6MWT), and endothelial function (flow-mediated dilatation [FMD]) were assessed at baseline and after completion of training protocol. 6MWT and plasma BNP improved significantly in 2 patient groups (both P < .001) after training program. The improvement of BNP was statistically greater in NYHA III-IV patients posttreatment than in those with NYHA II class (F=315.342, P < .001). Similarly, the improvement of 6MWT was statistically greater in NYHA III-IV group than in NYHA II patients (F=79.818, P < .001). Finally, an FES-induced greater improvement of FMD (F=9.517, P=.004) and emotional stress scores was observed in NYHA III-IV patients in comparison to NYHA II patients. There was a higher proportion of NYHA III-IV patients adhering to the FES training program for additional 3 months compared with the NYHA II group of patients (76.9% vs. 55.6%, P < .001). Conclusion: FES might exert a greater beneficial effect on clinical and neurohormonal status of NYHA III-IV patients in comparison to NYHA II patients. This effect may have important clinical relevance leading to increased adherence of severe CHF patients to exercise rehabilitation programs.

J Card Fail: 08 Mar 2010; 16:244-249
Karavidas A, Parissis JT, Matzaraki V, Arapi S, ... Filippatos G, Kremastinos DT
J Card Fail: 08 Mar 2010; 16:244-249 | PMID: 20206900
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Abstract

Mast Cell Stabilization Decreases Cardiomyocyte and LV Function in Dogs With Isolated Mitral Regurgitation.

Pat B, Killingsworth C, Chen Y, Gladden JD, ... Dillon AR, Dell\'italia LJ
Background: Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog. Methods and results: MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end-diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3-dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum time-varying elastance was significantly depressed in MR and MR + MCS dogs. Furthermore, cardiomyocyte fractional shortening was decreased in MR versus normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro administration of ketotifen to normal cardiomyocytes also significantly decreased fractional shortening and calcium transients. Conclusions: Chronic mast cell stabilization did not attenuate eccentric LV remodeling or collagen loss in MR. However, MCS therapy had a detrimental effect on LV function because of a direct negative inotropic effect on cardiomyocyte function.

J Card Fail: 27 Aug 2010; 16:769-76
Pat B, Killingsworth C, Chen Y, Gladden JD, ... Dillon AR, Dell'italia LJ
J Card Fail: 27 Aug 2010; 16:769-76 | PMID: 20797601
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Abstract

Interferon beta-1b Therapy in Chronic Viral Dilated Cardiomyopathy-Is There a Role for Specific Therapy?

Zimmermann O, Rodewald C, Radermacher M, Vetter M, ... Hombach V, Torzewski J
Background: Myocardial biopsy can be used for the detection of viral genome in dilated cardiomyopathy (DCM). Pilot studies have previously reported beneficial effects on clinical outcome and safety of an antiviral therapy using interferon beta-1b in chronic viral DCM. Methods and results: Myocardial biopsies were taken from patients with DCM. Using polymerase chain reaction and Southern Blot analysis, viral genome could be detected in 49% of patients. In 42 patients with viral infection, off-label use with interferon beta-1b was initiated. A further 68 patients formed the control group. The outcome was evaluated after follow-up with echocardiography, exercise electrocardiogram, and New York Heart Association class. A total of 81 men and 29 women with a median left ventricular ejection fraction of 34% were included. The follow-up period was 36 months. In 33 (79%) patients with interferon beta-1b treatment, minor adverse reactions occurred, but no major adverse events were reported. No significant benefit for interferon beta-1b treatment on clinical outcome could be detected during follow-up. Conclusions: Off-label use with interferon beta-1b in patients with viral DCM is feasible and safe under routine clinical practice. Concerning the herein evaluated clinical outcome parameters, promising results from pilot studies could not be confirmed. High prevalence of parvovirus B19 (92%) might influence the results.

J Card Fail: 30 Mar 2010; 16:348-356
Zimmermann O, Rodewald C, Radermacher M, Vetter M, ... Hombach V, Torzewski J
J Card Fail: 30 Mar 2010; 16:348-356 | PMID: 20350703
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Abstract

Conventional Versus Biventricular Pacing in Heart Failure and Bradyarrhythmia: The COMBAT Study.

Filho MM, de Siqueira SF, Costa R, Greco OT, ... D\'avila A, Heist EK
Background: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. Methods and results: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2max) were not significantly different. Death occurred more frequently with RVP. Conclusion: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode.

J Card Fail: 30 Mar 2010; 16:293-300
Filho MM, de Siqueira SF, Costa R, Greco OT, ... D'avila A, Heist EK
J Card Fail: 30 Mar 2010; 16:293-300 | PMID: 20350695
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Abstract

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure.

Allen LA, Felker GM, Mehra MR, Chiong JR, ... Schwartz TA, Adams KF
Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.

J Card Fail: 08 Mar 2010; 16:230-238
Allen LA, Felker GM, Mehra MR, Chiong JR, ... Schwartz TA, Adams KF
J Card Fail: 08 Mar 2010; 16:230-238 | PMID: 20206898
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Abstract

Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure.

Masutani S, Senzaki H
Despite advances in device closure for atrial septal defect (ASD), post-closure heart failure observed in adult patients remains a clinical problem. Although right heart volume overload is the fundamental pathophysiology in ASD, the post-closure heart failure characterized by acute pulmonary congestion is likely because of age-related left ventricular diastolic dysfunction, which is manifested by acute volume loading with ASD closure. Aging also appears to play important roles in the pathophysiology of heart failure through several mechanisms other than diastolic dysfunction, including ventricular systolic and vascular stiffening and increased incidence of comorbidities that significantly affect cardiovascular function. Recent studies suggested that accurate assessment of preclosure diastolic function, such as test ASD occlusion, may help identify high-risk patients for post-closure heart failure. Anti-heart failure therapy before device closure or the use of fenestrated device appears to be effective in preventing post-closure heart failure in the high-risk patients. However, the long-term outcome of such patients remains to be elucidated. Future studies are warranted to construct an algorithm to identify and treat patients at high risk for heart failure after device closure of ASD.

J Card Fail: 01 Nov 2011; 17:957-63
Masutani S, Senzaki H
J Card Fail: 01 Nov 2011; 17:957-63 | PMID: 22041334
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Abstract

Clinical features of myocardial triglyceride in different types of cardiomyopathy assessed by proton magnetic resonance spectroscopy: comparison with myocardial creatine.

Nakae I, Mitsunami K, Yoshino T, Omura T, ... Inubushi T, Horie M
Background: Myocardial lipid overstorage may produce cardiomyopathy, leading to dysfunction, but advanced heart failure may cause lipolysis via sympathetic nerve activation. In the failing heart, the creatine kinase system may also be impaired. The aims of this study were to assess myocardial triglyceride (TG) and creatine (CR) in different types of cardiomyopathy and to investigate whether they are related to the severity of cardiac dysfunction. Methods and results: In patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 12) or ischemic cardiomyopathy (ICM, n = 10), and normal subjects (NML, n = 22), myocardial TG and CR were evaluated using proton magnetic resonance spectroscopy. To assess cardiac sympathetic nerve activity, myocardial MIBG (a radioactive guanethidine analog) uptake was measured in DCM. Myocardial TG was significantly lower in hypertrophic cardiomyopathy (HCM) (1.92 ± 0.99 μmol/g), but higher in ICM (7.59 ± 4.36 μmol/g) than in NML hearts (4.05 ± 1.94 μmol/g). There was no significant difference in TG between DCM (4.84 ± 6.45 μmol/g) and NML. Myocardial CR in HCM (20.4 ± 8.4 μmol/g), DCM (14.8 ± 4.8 μmol/g), and ICM (19.4 ± 6.3 μmol/g) was significantly lower than that in NML hearts (27.1 ± 4.3 μmol/g). Overall, myocardial CR correlated positively with the severity of heart failure estimated by ejection fraction or myocardial BMIPP (a radioactive fatty acid analog) uptake, but TG did not. In DCM, myocardial TG correlated with body mass index, but not with MIBG uptake. Conclusions: Myocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. In contrast, myocardial CR reflects the severity of heart failure despite different pathoetiologic mechanisms of dysfunction. In DCM, myocardial TG may be affected by an overweight state rather than cardiac sympathetic nerve dysfunction. Thus, myocardial CR has a closer relationship to heart failure severity than does myocardial TG.

J Card Fail: 11 Oct 2010; 16:812-22
Nakae I, Mitsunami K, Yoshino T, Omura T, ... Inubushi T, Horie M
J Card Fail: 11 Oct 2010; 16:812-22 | PMID: 20932463
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Abstract

Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction heart failure society of america guidelines committee.

Butler J, Ezekowitz JA, Collins SP, Givertz MM, ... Stough WG, Starling RC
Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.

J Card Fail: 01 Apr 2012; 18:265-81
Butler J, Ezekowitz JA, Collins SP, Givertz MM, ... Stough WG, Starling RC
J Card Fail: 01 Apr 2012; 18:265-81 | PMID: 22464767
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Abstract

Renal function in outpatients with chronic heart failure.

Waldum B, Westheim AS, Sandvik L, Flønaes B, ... Hole T, Os I
Background: Impaired renal function confers an adverse prognosis in patients with heart failure (HF). The aims of the present study were to identify factors associated with and predictive of impaired renal function and to assess the relationship between estimated glomerular filtration rate (eGFR) and all-cause mortality in outpatients with HF. Methods and results: Baseline data on 3605 patients (median age 73 years, 70.1% men) from 24 outpatient HF clinics in Norway were analyzed. Median follow-up time was 9 months. Renal dysfunction (eGFR < 60 mL/min) was present in 44.9%. The population was randomized into equal-sized model-building and validation samples to enhance model stability. eGFR was an independent predictor of all-cause mortality (HR 0.94 per 5 mL/min increase, P = .001). Use of spironolactone (P = .002), higher blood pressure (P < .001), and lower hemoglobin levels (P = .002) were predictors of impaired renal function. Increasing doses of loop diuretics were strongly associated with eGFR at baseline (P < .001), but only tended to predict worsening renal function during follow-up (P = .08). Conclusions: Clinically significant reduction in renal function was prevalent in outpatients with HF, and was a strong predictor of all-cause mortality. Use of loop diuretics and spironolactone should be carefully evaluated as these agents may adversely affect renal function.

J Card Fail: 07 May 2010; 16:374-80
Waldum B, Westheim AS, Sandvik L, Flønaes B, ... Hole T, Os I
J Card Fail: 07 May 2010; 16:374-80 | PMID: 20447572
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Abstract

Congestive renal failure: the pathophysiology and treatment of renal venous hypertension.

Ross EA
Longstanding experimental evidence supports the role of renal venous hypertension in causing kidney dysfunction and "congestive renal failure." A focus has been heart failure, in which the cardiorenal syndrome may partly be due to high venous pressure, rather than traditional mechanisms involving low cardiac output. Analogous diseases are intra-abdominal hypertension and renal vein thrombosis. Proposed pathophysiologic mechanisms include reduced transglomerular pressure, elevated renal interstitial pressure, myogenic and neural reflexes, baroreceptor stimulation, activation of sympathetic nervous and renin angiotensin aldosterone systems, and enhanced proinflammatory pathways. Most clinical trials have addressed the underlying condition rather than venous hypertension per se. Interpreting the effects of therapeutic interventions on renal venous congestion are therefore problematic because of such confounders as changes in left ventricular function, cardiac output, and blood pressure. Nevertheless, there is preliminary evidence from small studies of intense medical therapy or extracorporeal ultrafiltration for heart failure that there can be changes to central venous pressure that correlate inversely with renal function, independently from the cardiac index. Larger more rigorous trials are needed to definitively establish under what circumstances conventional pharmacologic or ultrafiltration goals might best be directed toward central venous pressures rather than left ventricular or cardiac output parameters.

J Card Fail: 03 Dec 2012; 18:930-8
Ross EA
J Card Fail: 03 Dec 2012; 18:930-8 | PMID: 23207082
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Abstract

Functional Status in Left Ventricular Assist Device-Supported Patients: A Literature Review.

Abshire M, Dennison Himmelfarb CR, Russell SD
The prevalence of advanced heart failure (HF) is increasing due to the aging population and improvements in HF management strategies. Left Ventricular Assist Device (LVAD) technology and management continue to advance rapidly and it is anticipated that the number of LVAD implants will increase. LVADs have been demonstrated to extend life and improve outcomes in patients with advanced HF. The purpose of this article is to review and synthesize the evidence on impact of LVAD therapy on functional status. Significant functional gains were demonstrated in patients supported by LVAD throughout the first year with most improvement in distance walked and peak oxygen consumption demonstrated in the first 6 months. Interventions to enhance exercise performance have had inconsistent effects on functional status. Poor exercise performance was associated with increased risk of adverse events. Functional status improved with LVAD therapy, though performance remained substantially reduced compared to age adjusted norms. There is tremendous need to enhance our understanding of factors influencing functional outcomes in this high-risk population.

J Card Fail: 31 Aug 2014; epub ahead of print
Abshire M, Dennison Himmelfarb CR, Russell SD
J Card Fail: 31 Aug 2014; epub ahead of print | PMID: 25175694
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Abstract

Patients with acute heart failure in the emergency department: do they all need to be admitted?

Pang PS, Jesse R, Collins SP, Maisel A
Hospitalization for acute heart failure (AHF) is associated with a high rate of postdischarge mortality and readmissions, as well as high financial costs. Reducing 30-day readmissions after AHF hospitalization is a major national quality goal intended to both improve patient outcomes and reduce costs. Although the decision threshold for the vast majority of hospitalized AHF patients lies in the emergency department (ED), the role of the ED in reducing preventable admissions has largely been ignored. While admissions for AHF also originate from outpatient clinics, the greatest opportunity to reduce inpatient admissions lies with the cohort of patients who present to the ED with AHF. Safe discharge mandates interdisciplinary collaboration, close follow-up, careful scrutiny of psychosocial and socioeconomic factors, and a shared definition of risk stratification. Although additional research is needed, strategies for lower risk patients can and should be initiated to safely discharge AHF patients from the ED.

J Card Fail: 03 Dec 2012; 18:900-3
Pang PS, Jesse R, Collins SP, Maisel A
J Card Fail: 03 Dec 2012; 18:900-3 | PMID: 23207077
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Abstract

Cardiorenal Interactions in Acute Decompensated Heart Failure: Contemporary Concepts Facing Emerging Controversies.

Kazory A, Elkayam U
Simultaneous dysfunction of the heart and the kidney represents a distinct spectrum of disease states composed of complex clinical scenarios with adverse outcomes. Worsening renal function (WRF) in the setting of acute decompensated heart failure (ADHF) is one such clinical setup for which the underlying mechanisms are poorly understood. Apparent discrepancies exist between the emerging data on the cardiorenal interactions of patients with ADHF and contemporary concepts such as the low forward flow or the high backward pressure hypotheses. The findings of the recent retrospective studies also suggest that apparent "improvement in renal function" might be yet another risk factor for untoward outcomes in this patient population, further challenging our current understanding of the cardiorenal interactions. Besides, these data do not seem to fully support our conventional thinking about other aspects of these interactions such as the independent adverse impact of WRF on the outcomes of patients with ADHF, pointing to congestion as a possibly overlooked factor. In this article we provide an overview of these emerging controversial issues with the goal of identifying the areas where clinical research could be most helpful as it is of paramount importance to characterize the pathways leading to WRF in ADHF in order to develop a mechanistically-relevant management strategy. While the paucity of data coupled with the complexity of this field precludes any firm conclusion, these discussions are meant to prompt clinicians and researchers to revisit a number of long-believed concepts surrounding the cardiorenal interactions in ADHF.

J Card Fail: 16 Sep 2014; epub ahead of print
Kazory A, Elkayam U
J Card Fail: 16 Sep 2014; epub ahead of print | PMID: 25230240
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Abstract

Yoga in Heart Failure Patients: A Pilot Study.

Howie-Esquivel J, Lee J, Collier G, Mehling W, Fleischmann K
Background: Complementary therapies such as yoga practice have become commonplace, yet the safety, physical, and psychological effects on patients with heart failure (HF) are unknown. The purpose of this study was to determine whether an 8-week yoga program was safe and would positively influence physical and psychological function in HF patients. Methods and results: Stable HF patients were recruited (n = 15) and completed (n = 12) 8 weeks of yoga classes. Data collected were: safety (cardiac and orthopedic adverse events); physical function (strength, balance, endurance, flexibility); and psychological function (quality of life [QOL], depression scores, mindfulness) before and after 8 weeks of yoga classes. Results: Mean age was 52.4 +/- 11.6 with three-fourths (n = 9) being male and Caucasian. No participant had any adverse events. Endurance (P < .02) and strength (upper P = .04 and lower body P = .01) significantly improved. Balance improved by 13.6 seconds (26.9 +/- 19.7 to 40.0 +/- 18.5; P = .05). Symptom stability, a subscale of QOL, improved significantly (P = .02). Although no subject was depressed, overall mood was improved. Subjects subjectively reported improvements in overall well-being. Conclusions: Yoga practice was safe, with participants experiencing improved physical function and symptom stability. Larger studies are warranted to provide more nonpharmacological options for improved outcomes in patients with HF.

J Card Fail: 27 Aug 2010; 16:742-749
Howie-Esquivel J, Lee J, Collier G, Mehling W, Fleischmann K
J Card Fail: 27 Aug 2010; 16:742-749 | PMID: 20797598
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Abstract

Ventricular ectopy in patients with left ventricular dysfunction: should it be treated?

Chen T, Koene R, Benditt DG, Lü F
Ventricular premature complexes (VPCs) are commonly encountered in patients with congestive heart failure (CHF). Frequent ventricular ectopy can be associated with deterioration of cardiac function and may lead to VPC-induced cardiomyopathy. VPC-induced inter- and/or intraventricular dyssynchrony has been postulated as the main mechanism underlying VPC-induced left ventricular dysfunction. For risk stratification, VPCs in the setting of CHF can not be regarded to be a benign arrhythmia as in an apparently healthy subject. However, any potential survival benefits to be derived from suppression of VPCs or nonsustained ventricular tachycardia in CHF may be offset by the negative inotropic and proarrhythmic effects of antiarrhythmic drugs and may be masked by the risk of death that is already high in this subgroup of patients. β-Blockers are currently considered to be the first-line therapy, with amiodarone as a back-up. Catheter ablation, although invasive and not without procedural risk, avoids the common adverse effects of currently available antiarrhythmic medications. From a standpoint of preventing or reversing left ventricular dysfunction, frequent VPCs should be treated earlier regardless of their site of origin or the presence of associated symptoms, such as palpitations. Catheter ablation may be the preferable approach in selected patients, particularly when β-blocker therapy has been ineffective or not tolerated.

J Card Fail: 30 Dec 2012; 19:40-9
Chen T, Koene R, Benditt DG, Lü F
J Card Fail: 30 Dec 2012; 19:40-9 | PMID: 23273593
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Abstract

Review of vasodilators in acute decompensated heart failure: the old and the new.

Carlson MD, Eckman PM
Despite substantial improvements in treatment for chronic heart failure, morbidity and mortality for acute decompensated heart failure (ADHF) remain high. Treatment of ADHF is focused on controlling symptoms rather than improving long-term outcomes. The vasodilators nitroglycerin (NTG) and sodium nitroprusside (SNP) have been used in ADHF for decades, but, since the development of nesiritide 10 years ago, interest in new vasodilators has grown. Therapies that improve not only hemodynamics and symptoms but also long-term outcomes are in high demand, and numerous new vasodilatory agents have been investigated, including various natriuretic peptides, soluble guanylyl cyclase agents, renin-angiotensin-aldosterone system-modifying agents, and others. A review of the literature shows that few of them rise to the challenge set by NTG and SNP.

J Card Fail: 08 Jul 2013; 19:478-93
Carlson MD, Eckman PM
J Card Fail: 08 Jul 2013; 19:478-93 | PMID: 23834924
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Abstract

Memory Dysfunction, Psychomotor Slowing, and Decreased Executive Function Predict Mortality in Patients With Heart Failure and Low Ejection Fraction.

Pressler SJ, Kim J, Riley P, Ronis DL, Gradus-Pizlo I
Background: The purpose of this study was to evaluate whether dysfunction of specific cognitive abilities is a predictor of impending mortality in adults with systolic heart failure (HF). Methods: A total of 166 stable outpatients with HF completed cognitive function evaluation in language, working memory, memory, visuospatial ability, psychomotor speed, and executive function using a neuropsychological test battery. Demographic and clinical variables, comorbidity, depressive symptoms, and health-related quality of life were also measured. Patients were followed for 12 months to determine all-cause mortality. Results: There were 145 survivors and 21 deaths. In logistic regression analyses, significant predictors of mortality were lower left ventricular ejection fraction (LVEF) and poorer scores on measures of global congnitive function Mini-Mental State Examination [MMSE], working memory, memory, psychomotor speed, and executive function. Memory loss was the most predictive cognitive function variable (overall chi(2) = 17.97, df = 2, P < .001; Nagelkerke R(2) = 0.20). Gender was a significant covariate in 2 models, with men more likely to die. Age, comorbidity, depressive symptoms, and health-related quality of life were not significant predictors. In further analyses, significant predictors of mortality were lower systolic blood pressure and poorer global cognitive function, working memory, memory, psychomotor speed, and executive function, with memory being the most predictive. Conclusions: As hypothesized, lower LVEF and memory dysfunction predicted mortality. Poorer global cognitive score as determined by the MMSE, working memory, psychomotor speed, and executive function were also significant predictors. LVEF or systolic blood pressure had similar predictive values. Interventions are urgently needed to prevent and manage memory loss in HF.

J Card Fail: 27 Aug 2010; 16:750-760
Pressler SJ, Kim J, Riley P, Ronis DL, Gradus-Pizlo I
J Card Fail: 27 Aug 2010; 16:750-760 | PMID: 20797599
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Abstract

Causes of breathing inefficiency during exercise in heart failure.

Woods PR, Olson TP, Frantz RP, Johnson BD
Background: Patients with heart failure (HF) develop abnormal pulmonary gas exchange; specifically, they have abnormal ventilation relative to metabolic demand (ventilatory efficiency/minute ventilation in relation to carbon dioxide production [V(E)/VCO₂]) during exercise. The purpose of this investigation was to examine the factors that underlie the abnormal breathing efficiency in this population. Methods and results: Fourteen controls and 33 moderate-severe HF patients, ages 52 ± 12 and 54 ± 8 years, respectively, performed submaximal exercise (∼65% of maximum) on a cycle ergometer. Gas exchange and blood gas measurements were made at rest and during exercise. Submaximal exercise data were used to quantify the influence of hyperventilation (PaCO₂) and dead space ventilation (V(D)) on V(E)/VCO₂. The V(E)/VCO₂ relationship was lower in controls (30 ± 4) than HF (45 ± 9, P < .01). This was the result of hyperventilation (lower PaCO₂) and higher V(D)/V(T) that contributed 40% and 47%, respectively, to the increased V(E)/VCO₂ (P < .01). The elevated V(D)/V(T) in the HF patients was the result of a tachypneic breathing pattern (lower V(T), 1086 ± 366 versus 2003 ± 504 mL, P < .01) in the presence of a normal V(D) (11.5 ± 4.0 versus 11.9 ± 5.7 L/min, P = .095). Conclusions: The abnormal ventilation in relation to metabolic demand in HF patients during exercise was due primarily to alterations in breathing pattern (reduced V(T)) and excessive hyperventilation.

J Card Fail: 11 Oct 2010; 16:835-42
Woods PR, Olson TP, Frantz RP, Johnson BD
J Card Fail: 11 Oct 2010; 16:835-42 | PMID: 20932466
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Abstract

Right Ventricular Afterload and the Role of Nitric Oxide Metabolism in Left-Sided Heart Failure.

Dupont M, Tang WH
Awareness has grown in recent years that right ventricular (RV) function is equally important as left ventricular (LV) function in the setting of left-sided heart disease. RV dysfunction can be the consequence of an increased afterload imposed by the failing LV. The concept of "afterload" is physically most correctly described by vascular input impedance. However, for clinical purposes, afterload is most often modeled to consist of 3 components; pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), and characteristic impedance. Whereas PVR is historically most described, PAC (which represents the distensibility of the vasculature) has rapidly gained recognition for its prognostic ability in both pulmonary arterial hypertension and left-sided heart disease. Owing to the specific anatomy of the pulmonary circulation, PVR and PAC have an inverse hyperbolic relationship, which position can be shifted by varying wedge pressures. Knowledge of the afterload components helps one to understand how elevated left-sided filling pressures increase pulsatile load on the RV. An increase in resistive load (known as "reactive" or "out-of-proportion" pulmonary hypertension) ultimately complements the increase in pulsatile load. Perturbations in nitric oxide metabolism are thought to be crucial in this evolution and have therefore been sought as a major therapeutic target.

J Card Fail: 14 Oct 2013; 19:712-721
Dupont M, Tang WH
J Card Fail: 14 Oct 2013; 19:712-721 | PMID: 24125109
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Abstract

Circadian Body Temperature Variability is an Indicator of Poor Prognosis in Cardiomyopathic Hamsters.

Ahmed A, Gondi S, Cox C, Wang S, ... Casscells SW, Wilson JM
Background: Low body temperature is an independent predictor of poor prognosis in patients with congestive heart failure. The cardiomyopathic hamster develops progressive biventricular dysfunction, resulting in heart failure death at 9 months to 1 year of life. Our goal was to use cardiomyopathic hamsters to examine the relationship between body temperature and heart failure decompensation and death. Methods and results: To this end, we implanted temperature and activity transducers with telemetry into the peritoneal space of 46 male Bio-TO-2 Syrian cardiomyopathic hamsters. Multiple techniques, including computing mean temperature, frequency domain analysis, and nonlinear analysis, were used to determine the most useful method for predicting poor prognosis. Data from 44 hamsters were included in our final analysis. We detected a decline in core body temperature in 98% of the hamsters 8+/-4 days before death (P < .001). We examined the dominant frequency of temperature variation (ie, the circadian rhythm) by using cosinor analysis, which revealed a significant decrease in the amplitude of the body temperature circadian rhythm 8 weeks before death (0.28 degrees C; 95% CI, 0.26-0.31) compared to baseline (0.36 degrees C; 95% CI, 0.34-0.39; P=.005). The decline in the circadian temperature variation preceded all other evidence of decompensation. Conclusions: We conclude that a decrease in the amplitude of the body temperature circadian rhythm precedes fatal decompensation in cardiomyopathic hamsters. Continuous temperature monitoring may be useful in predicting preclinical decompensation in patients with heart failure and in identifying opportunities for therapeutic intervention.

J Card Fail: 08 Mar 2010; 16:268-274
Ahmed A, Gondi S, Cox C, Wang S, ... Casscells SW, Wilson JM
J Card Fail: 08 Mar 2010; 16:268-274 | PMID: 20206903
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Abstract

NHLBI\'s Program for VAD Therapy for Moderately Advanced Heart Failure: The REVIVE-IT Pilot Trial.

Baldwin JT, Mann DL
Background: Ventricular assist devices (VADs) are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent ("destination") therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, a National Heart, Lung, and Blood Institute (NHLBI) working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Methods and results: Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Conclusion: Based on the group\'s recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail, which will serve to test the hypothesis and inform the pivotal trial.

J Card Fail: 08 Nov 2010; 16:855-8
Baldwin JT, Mann DL
J Card Fail: 08 Nov 2010; 16:855-8 | PMID: 21055648
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Abstract

Cognitive and Psycholological Considerations in Pediatric Heart Failure.

Hollander SA, Callus E
As children with heart failure live longer, both before and after cardiac transplantation, there is renewed focus on the quality and preservation of their intellectual functioning and psychosocial health. Children with chronic heart failure are at risk for delays in both cognitive development and psychological functioning, though the extent and permanence of impairment is not well understood. Children with medically managed heart failure have been shown to be at increased for anxiety and depression, with a prevalence of emotional disorders similar to that of other children with congenital heart disease. The use of ventricular assist devices as a bridge to transplantation offers both risks and benefits for the preservation of intellectual and emotional function, with an increased risk for ischemic injury to the brain, but offers the advantage of allowing for cognitive stimulation and improved social interactions. A new population of children with heart failure, those outfitted with permanent ventricular assist devices in lieu of cardiac transplantation, may represent a particular at-risk group with regard to social and cognitive function, but as of yet are not well studied. Early intervention and school accommodations are recommended for those with cognitive, social, or emotional deficits, and brain imaging should be considered for those with persistent difficulties. Whenever possible, patients should be referred to psychologists and developmental specialists with experience treating this patient population.

J Card Fail: 18 Jul 2014; epub ahead of print
Hollander SA, Callus E
J Card Fail: 18 Jul 2014; epub ahead of print | PMID: 25038263
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Abstract

Vitamin D in Heart Failure.

Meredith AJ, McManus BM
Evidence linking vitamin D to cardiovascular (CV) health has accumulated in recent years: numerous epidemiologic studies report deficiency as a significant CV risk factor, and rodent models suggest that active vitamin D can modulate critical remodeling processes, including cardiac hypertrophy and extracellular matrix remodeling. The presence of vitamin D signaling machinery within the human heart implies a direct role for this hormone in cardiac physiology and may explain associations between vitamin D status and CV outcomes. Heart failure (HF) represents a growing social and economic burden worldwide. Myocardial remodeling is central to HF development, and in the context of emerging evidence supporting mechanistic involvement of vitamin D, this review provides critical appraisal of scientific literature related to the role of vitamin D in CV disease, including data from epidemiologic and supplementation studies, as well as novel findings from animal models and in vitro work. Although associative data linking vitamin D and CV outcomes and evidence supporting a role for vitamin D in relevant pathogenic processes are both substantial, there are limited mechanistic data to indicate vitamin D supplementation as a viable therapeutic adjunct for the prevention of HF development following myocardial injury.

J Card Fail: 14 Oct 2013; 19:692-711
Meredith AJ, McManus BM
J Card Fail: 14 Oct 2013; 19:692-711 | PMID: 24125108
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Abstract

Biomarker-guided therapies in heart failure: a forum for unified strategies.

Fiuzat M, O\'Connor CM, Gueyffier F, Mascette AM, ... Zannad F, Bristow MR
The complexity of standard medical treatment for heart failure is growing, and such therapy typically involves 5 or more different medications. Given these pressures, there is increasing interest in harnessing cardiovascular biomarkers for clinical application to more effectively guide diagnosis, risk stratification, and therapy. It may be possible to realize an era of personalized medicine for heart failure treatment in which therapy is optimized and costs are controlled. The direct mechanistic coupling of biologic processes and therapies achieved in cancer treatment remains elusive in heart failure. Recent clinical trials and meta-analyses of biomarkers in heart failure have produced conflicting evidence. In this article, which comprises a summary of discussions from the Global Cardiovascular Clinical Trialists Forum held in Paris, France, we offer a brief overview of the background and rationale for biomarker testing in heart failure, describe opportunities and challenges from a regulatory perspective, and summarize current positions from government agencies in the United States and European Union.

J Card Fail: 04 Aug 2013; 19:592-9
Fiuzat M, O'Connor CM, Gueyffier F, Mascette AM, ... Zannad F, Bristow MR
J Card Fail: 04 Aug 2013; 19:592-9 | PMID: 23910590
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Abstract

End-of-Life Care in Patients With Heart Failure.

Whellan DJ, Goodlin SJ, Dickinson MG, Heidenreich PA, ... Quality of Care Committee, Heart Failure Society of America
Stage D heart failure (HF) is associated with poor prognosis, yet little consensus exists on the care of patients with HF approaching the end of life. Treatment options for end-stage HF range from continuation of guideline-directed medical therapy to device interventions and cardiac transplantation. However, patients approaching the end of life may elect to forego therapies or procedures perceived as burdensome, or to deactivate devices that were implanted earlier in the disease course. Although discussing end-of-life issues such as advance directives, palliative care, or hospice can be difficult, such conversations are critical to understanding patient and family expectations and to developing mutually agreed-on goals of care. Because patients with HF are at risk for rapid clinical deterioration or sudden cardiac death, end-of-life issues should be discussed early in the course of management. As patients progress to advanced HF, the need for such discussions increases, especially among patients who have declined, failed, or been deemed to be ineligible for advanced HF therapies. Communication to define goals of care for the individual patient and then to design therapy concordant with these goals is fundamental to patient-centered care. The objectives of this white paper are to highlight key end-of-life considerations in patients with HF, to provide direction for clinicians on strategies for addressing end-of-life issues and providing optimal patient care, and to draw attention to the need for more research focusing on end-of-life care for the HF population.

J Card Fail: 20 Feb 2014; 20:121-34
Whellan DJ, Goodlin SJ, Dickinson MG, Heidenreich PA, ... Quality of Care Committee, Heart Failure Society of America
J Card Fail: 20 Feb 2014; 20:121-34 | PMID: 24556532
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Abstract

Prognostic significance of acute kidney injury after reperfused ST-elevation myocardial infarction: synergistic acceleration of renal dysfunction and left ventricular remodeling.

Anzai A, Anzai T, Naito K, Kaneko H, ... Yoshikawa T, Ogawa S
Background: Acute kidney injury (AKI) after myocardial infarction is associated with poor clinical outcome. However, mechanisms of the adverse effect of AKI on clinical outcome after reperfused ST-elevation myocardial infarction (STEMI) have not been fully elucidated. Methods and results: We examined 141 consecutive patients with reperfused first anterior STEMI. AKI was defined as an increase in serum creatinine of >or=0.3mg/dL within 48hours after admission. Patients with AKI had higher incidence of in-hospital cardiac death (P=.0004) and major adverse cardiac events (MACE, P=.020) during a mean of 39+/-40 (range, 1 to 96) months than those without, in association with adverse left ventricular (LV) remodeling. White blood cell count on admission and peak C-reactive protein were higher in patients with than those without AKI. Plasma norepinephrine on admission, interleukin-6, brain natriuretic peptide, and malondialdehyde-modified low-density lipoprotein 2 weeks after STEMI were higher in patients with AKI than those without AKI. Cox proportional hazards model analysis revealed AKI was an independent predictor of MACE (hazard ratio=2.38, P=.019). Conclusions: AKI was a strong predictor of MACE in association with adverse LV remodeling. Enhanced inflammatory response, oxidative stress, and neurohormonal activation may synergistically accelerate renal dysfunction and LV remodeling after STEMI.

J Card Fail: 07 May 2010; 16:381-9
Anzai A, Anzai T, Naito K, Kaneko H, ... Yoshikawa T, Ogawa S
J Card Fail: 07 May 2010; 16:381-9 | PMID: 20447573
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Abstract

Effects Of Glucocorticoids in Potentiating Diuresis in Heart Failure Patients With Diuretic Resistance.

Liu C, Liu K
Diuretic resistance in heart failure is defined as a state in which diuretic response is diminished or lost before the therapeutic goal of relief from congestion has been reached. Diuretic resistance is very common and is associated with poor outcomes. Over the past decade, several new drugs and devices targeting decongestion and improvement in renal function in patients with heart failure have failed to show benefit in randomized clinical trials. Glucocorticoids had been used to manage diuretic resistance before the advent of loop diuretics. More recent evidence appears to confirm that glucocorticoids may also help to overcome resistance to loop diuretics. This review tries to summarize the available evidence and potential mechanisms related to glucocorticoid therapy in patients with heart failure and its effect on diuretic resistance.

J Card Fail: 26 Jun 2014; epub ahead of print
Liu C, Liu K
J Card Fail: 26 Jun 2014; epub ahead of print | PMID: 24969700
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Abstract

COPD Predicts Mortality in HF: The Norwegian Heart Failure Registry.

De Blois J, Simard S, Atar D, Agewall S, For the Norwegian Heart Failure Registry
Background: Chronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients. Methods and results: The Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on beta-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. beta-blockers at baseline were associated with improved survival in patients with LVEF </=40% independently of COPD. Conclusion: COPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients.

J Card Fail: 08 Mar 2010; 16:225-229
De Blois J, Simard S, Atar D, Agewall S, For the Norwegian Heart Failure Registry
J Card Fail: 08 Mar 2010; 16:225-229 | PMID: 20206897
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Abstract

Intersections between Microbiome and Heart Failure: Revisiting the Gut Hypothesis.

Nagatomo Y, Tang WH
Microbes play an important role in human health and disease. In the setting of heart failure (HF), substantial hemodynamic changes such as hypoperfusion and congestion in the intestines can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota. These changes can disrupt the barrier function of the intestines, and exacerbate systemic inflammation through microbial or endotoxin translocation into systemic circulation. Furthermore, cardio-renal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine N-oxide (TMAO) has emerged as a key mediator which provides mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF. Potential intervention strategies which may target this microbiota-driven pathology include dietary modification, prebiotics or probiotics, and selective binders of microbial enzymes or molecules - yet further investigations into their safety and efficacy are warranted.

J Card Fail: 04 Oct 2015; epub ahead of print
Nagatomo Y, Tang WH
J Card Fail: 04 Oct 2015; epub ahead of print | PMID: 26435097
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This program is still in alpha version.