Diastolic dysfunction of the heart is correlated with cardiac mortality. Serum cystatin C (CysC) is an endogenous marker of kidney function. It is not clear whether serum CysC is associated with diastolic dysfunction in patients with varying cardiac conditions with concomitant diastolic abnormalities and preserved ejection fraction (EF). The authors measured serum CysC levels in patients with cardiac diseases and examined the relationships between serum CysC levels and diastolic function. Serum CysC was measured and echocardiography was performed in 124 consecutive patients with cardiac diseases. Transmitral flow (TMF) patterns surrogating diastolic function were categorized into two groups: a normal group and an abnormal group. Serum CysC and BNP showed a significant positive correlation. There were no significant differences in serum CysC among those cardiac diseases. Seventy-eight patients with cardiac disease and preserved EF (left ventricular EF ≥50%) and without renal dysfunction (estimated glomerular filtration rate ≥60 mL/minute/1.73 m(2)) were examined. Multivariate linear regression analysis demonstrated that left atrium diameter and abnormal TMF patterns were independent determinants of serum CysC. Furthermore, patients with elevated serum CysC levels had poor prognosis. Serum CysC is associated with diastolic dysfunction in patients with various cardiac diseases and preserved EF. Serum CysC might be a biomarker of cardiac diastolic dysfunction in patients with preserved EF.

A systematic review of the literature was performed by searching Pubmed and EMBASE databases using the terms "thiamine," "vitamin B1," "heart failure," "systolic dysfunction," "ventricular dysfunction," "cardiomyopathy," "ventricular failure," and "systolic failure." Relevant trials and articles were evaluated pertaining to thiamine deficiency in patients with heart failure (HF) and references were searched for further inclusion of articles. A total of 20 articles were reviewed and summarized in detail. While more research is needed to fully elucidate the clinical thiamine deficiency in HF patients, recent evidence has indicated that supplementing with thiamine in HF patients has the potential to improve left ventricular ejection fraction. Thiamine deficiency appears to be not uncommon in patients with HF, and supplementation with thiamine has been shown to improve cardiac function, urine output, weight loss, and signs and symptoms of HF. Therefore, this simple therapy should be tested in large-scale randomized clinical trial to further determine the effects of thiamine in HF patients.

The authors designed this prospective study to show the relationship between preload reserve and treatment effectiveness of chronic heart failure (CHF). Fifty patients, aged 77±24 years, with decompensated CHF (B-type brain natriuretic peptide [BNP] >1000 pg/mL) were included. Preload reserve was assessed by the changes in contraction indices during a passive leg raise (PLR). Contraction indices were assessed noninvasively using Bioreactance technology. After 4 days of optimized therapy, the same variables were reassessed and treatment-induced differences were calculated. Treatment effectiveness was assessed by the 4-day changes in BNP, body weight, and thoracic fluid content. The authors then compared treatment-induced changes in preload reserve with treatment effectiveness. Therapy was associated with an overall decrease in heart rate, blood pressure, and cardiac power index (CPi) and with an increase in all preload reserve indices. Treatment effectiveness correlated well with changes in preload reserve. The best correlation was found between treatment-induced changes in BNP and in PLR-induced changes of CPi (R=0.63, P<.001). The PLR-induced changes in CPi increased from 21±48 to 51±48 in BNP responders and decreased from 34±34 to 5±19 mW/m(2) in BNP nonresponders (P<.0001). Hence, effective treatment, as indexed by a decrease in BNP, restores the preload reserve in patients with decompensated CHF.

Providing effective discharge instructions, appropriate dose uptitration, education regarding heart failure (HF) monitoring, and strict follow-up have all been shown to decrease readmissions for HF but are all underutilized. The authors developed and evaluated the impact of a quality-improvement HF checklist as a tool to remind physicians to improve quality of care in HF patients. The checklist was used in randomly selected patients admitted with a primary diagnosis of acute decompensated HF. It included documentation regarding medications and dose uptitration, relevant counseling, and follow-up instructions at discharge. The checklist was used in 48 patients, and this checklist group was compared with 48 patients as a randomly selected control group. Higher proportions of patients were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in the checklist group compared with the control group (40 of 48 vs 23 of 48, P<.001). Compared with the controls, the rate of dose uptitration for β-blockers and/or ACE inhibitors/ARBs was more common in the checklist group (4 of 48 vs 21 of 48, P<.001). Both 30-day (19% to 6%) and 6-month (42% to 23%) readmissions were lower in the checklist group. The use of an HF checklist was associated with better quality of care and decreased readmission rates for patients admitted with HF.

Persistent atrial flutter (AFL) in left ventricular assist device (LVAD) recipients can result in loss of AV synchrony, impaired ventricular filling and right heart failure (RHF). The authors report the largest series of HeartMate II (HMII) patients who developed AFL with decompensated RHF, which successfully resolved with AFL ablation. Eight patients with HMII LVAD (mean age, 57±12 years) had medically refractory AFL, with 7 developing de novo AFL after LVAD implant (onset range, 2 days-22 months post-implant). Three patients developed recurrent syncope, 2 had inappropriate implantable cardioverter-defibrillator shocks, and 6 had new or escalating need for inotropes. All had features of decompensated RHF. Seven patients underwent electrophysiology testing where mapping confirmed typical counterclockwise AFL (mean AFL cycle length, 252±49 ms) and radiofrequency ablation of cavotricuspid isthmus restored sinus rhythm in all patients. Complete resolution of symptoms and signs of RHF with improved quality of life were noted in all. No procedural complications were noted. During a mean follow-up of 9±5 months, all patients remained free of atrial flutter. Catheter ablation of AFL in LVAD patients is safe and highly effective, resulting in immediate and significant improvement in symptoms of RHF, and should be considered first-line therapy for AFL in these patients.

Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m(2)), obese (30.1-40 kg/m(2)), and morbidly obese (≥40 kg/m(2)). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event-free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40-4.30; P=.002) had significantly higher risk of all-cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re-emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon.

Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD); however, the early implementation of hemodialysis may halt its progression. Nonconventional hemodialysis, such as frequent hemodialysis, appears to have an advantage over conventional hemodialysis. Kidney transplantation has been shown to reverse uremic cardiomyopathy and to confer a significant survival advantage over hemodialysis. Targeting future therapies at the underlying cellular mechanisms of uremic cardiomyopathy may finally start to reduce the burden of uremic cardiomyopathy in the CKD and ESRD population.

Resynchronization therapy has become standard of care in patients with left bundle branch block (LBBB), congestive heart failure (CHF), and low ejection fraction (EF). In order to characterize the left ventricular (LV) function evolution in patients with LBBB and baseline preserved LVEF, records of all patients who visited an academic echocardiography laboratory during a period of 4 years were retrospectively investigated. Patients were included if they had a baseline EF >50%, LBBB on surface electrocardiography, and at least one follow-up echocardiogram no earlier than 3 months after the baseline study. The endpoint was the occurrence of EF deterioration to values ≤40%. Clinical variables associated with this outcome were identified. Forty-nine patients satisfied the entry criteria. Over a mean 13±8.5 months of follow-up (range 3 to 36), 8 patients (16%) experienced EF deterioration ≤40%. History of CHF prior to baseline echocardiogram and LV mass >300 g were associated with this phenomenon (P=.004 and P=.015, respectively), with a negative predictive value of 100% and 92%, respectively. Our data profiles a risk-stratification methodology in patients with LBBB and baseline EF >50% and possibly a triage strategy toward resynchronization therapy in this population.

Anemia, a common comorbidity in older adults with heart failure and a preserved ejection fraction (HFPEF), is associated with worse outcomes. The authors quantified the effect of anemia treatment on left ventricular (LV) structure and function as measured by cardiac magnetic resonance (CMR) imaging. A prospective, randomized single-blind clinical trial (NCT NCT00286182) comparing the safety and efficacy of epoetin alfa vs placebo for 24 weeks in which a subgroup (n=22) had cardiac magnetic resonance imaging (MRI) at baseline and after 3 and 6 months to evaluate changes in cardiac structure and function. Pressure volume (PV) indices were derived from MRI measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated. Patients (75±10 years, 64% women) with HFPEF (EF=63%±15%) with an average hemoglobin of 10.3±1.1 gm/dL were treated with epoetin alfa using a dose-adjusted algorithm that increased hemoglobin compared with placebo (P<.0001). As compared with baseline, there were no significant changes in end-diastolic (-7±8 mL vs -3±8 mL, P=.81) or end-systolic (-0.4±2 mL vs -0.7±5 mL, P=.96) volumes at 6-month follow-up between epoetin alfa compared with placebo. LV function as measured based on EF (-1.5%±1.6% vs -2.6%±3.3%, P=.91) and pressure volume indices (PVAiso-EDP at 30 mm Hg, -5071±4308 vs -1662±4140, P=.58) did not differ between epoetin alfa and placebo. Administration of epoetin alfa to older adult patients with HFPEF resulted in a significant increase in hemoglobin, without evident change in LV structure, function, or pressure volume relationships as measured quantitatively using CMR imaging.

The aim of the present study was to investigate whether vitamin D supplementation could improve biochemical findings and functional capacity of patients with heart failure (HF). One hundred patients with New York Heart Association (NYHA) class I through III HF were included in this prospective study and their 25-hydroxyvitamin D levels were evaluated. Only 6% of the participants had a sufficient serum concentration of 25(OH) D >30 nmol/L. Patients with insufficient or deficient serum levels of 25(OH) D (<30 ng/mL and <20 ng/mL, respectively) received oral vitamin D3 (cholecalciferol) for a total period of 4 months. Vitamin D supplementation increased mean serum concentration of 25(OH) D from 12.63±7.60 nmol/L to 54.49±18.01 nmol/L (P<.001). After vitamin D supplementation, the serum level of pro-brain natriuretic peptide markedly decreased (P<.001). Cholecalciferol significantly decreased high-sensitivity C-reactive protein level (P<.001). Restoration of serum 25(OH) D level was also associated with substantial improvement in NYHA class (P<.001) and 6-minute walk distance (P<.001).

Cognitive impairment is common in heart failure (HF) and believed to be the result of cerebral hypoperfusion and subsequent brain changes including white matter hyperintensities (WMHs). The current study examined the association between cerebral blood flow and WMHs in patients with HF and the relationship between WMHs and cognitive impairment. Sixty-nine patients with HF completed the Mini-Mental State Examination (MMSE) and underwent echocardiography, transcranial Doppler sonography for cerebral blood flow velocity of the middle cerebral artery, and brain magnetic resonance imaging. Multivariable hierarchical regression analyses controlling for medical and demographic characteristics as well as intracranial volume showed reduced cerebral blood flow velocity of the middle cerebral artery was associated with greater WMHs (β=-0.34, P=.02). Follow-up regression analyses adjusting for the same medical and demographic factors in addition to cerebral perfusion also revealed marginal significance between increased WMHs and poorer performance on the MMSE (β=-0.26, P=.05). This study suggests that reduced cerebral perfusion is associated with greater WMHs in older adults with HF. These findings support the widely proposed mechanism of cognitive impairment in HF patients and prospective studies are needed to confirm these results.

In heart failure (HF), longitudinal changes in ventricular ejection fraction are poorly studied. The authors' objective was to document the dynamic changes in systolic function of both ventricles during acute HF and after a 3-month follow-up period, and to identify factors associated with ventricular improvement. A limited access dataset from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial provided by The National Heart, Lung, and Blood Institute was analyzed. In patients admitted to the hospital with acute HF, both ventricles were evaluated by echocardiography on admission, at discharge, and at 3 months. From baseline to 3 months, left ventricular ejection fraction (LVEF) increased in 43.4% of patients, decreased in 23.9%, and remained unchanged in 32.7%. Similarly, right ventricular systolic function improved in 40.9%, deteriorated in 25.0%, and remained stable in 34.1%. Weight loss during index admission and cardiac index/cardiac output increase were the only factors associated with LVEF improvement from baseline to month 3. There was no difference between ischemic and nonischemic etiology. In acute HF, ischemic or nonischemic, systolic function of the ventricles improved during 3 months in about 40% of patients and remained unchanged or deteriorated in the rest. Weight loss and increase in cardiac index/output during hospitalization was associated with improvement in LVEF.