Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed.

BACKGROUND The Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial found that as compared to placebo, neither low-dose dopamine (2 ug/kg/min) nor low-dose nesiritide (0.005 µg/kg/min without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF). This post-hoc analysis examined potential interaction between treatment effect and EF group (EF ≤ 40% vs > 40%) on the ROSE AHF endpoints. METHODS AND RESULTS ROSE AHF enrolled AHF patients (n=360; any EF) with renal dysfunction. The co-primary endpoints were cumulative urine volume and the change in serum cystatin-C from over 72 hours. The effect of dopamine (interaction p=0.001) and nesiritide (interaction p=0.039) on urine volume varied by EF group. In HFrEF, urine volume was higher with active treatment versus placebo whereas in HFpEF, urine volume was lower with active treatment. The effect of dopamine and nesiritide on weight change, sodium excretion and incidence of AHF treatment failure also varied and in a similar manner by EF group (interaction p<0.05 for all). There was no interaction between either vasoactive treatment’s effect and EF group on change in cystatin-C. Compared to placebo, dopamine was associated with improved clinical outcomes in HFrEF and worse clinical outcomes in HFpEF. With nesiritide, there were no differences in clinical outcomes as compared to placebo in both HFrEF and HFpEF. CONCLUSIONS In this post-hoc analysis of ROSE AHF, the response to vasoactive therapies differed in patients with HFrEF and HFpEF. Investigation of AHF therapies should assess the potential for differential responses in AHF with preserved versus reduced EF. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01132846.

Background The cardiac intensive care unit ( CICU ) population is no longer composed of only patients with acute coronary syndromes, and includes those with acute heart failure and multiple comorbidities. We hypothesized that the GWTG ‐ HF (Get With The Guidelines–Heart Failure) risk score that predicts inpatient mortality in hospitalized patients with heart failure would predict mortality in CICU patients. Methods and Results We retrospectively analyzed CICU patients at a tertiary care hospital from 2007 to 2015. The GWTG ‐ HF risk score was calculated at CICU admission. As a secondary analysis, the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) , OPTIMIZE‐HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure), and ADHERE (Acute Decompensated Heart Failure National Registry) risk scores were calculated. Kaplan–Meier survival analysis and the area under the receiver operating characteristic curve value were determined for inpatient and 1‐year mortality. The GWTG ‐ HF risk score was calculated in 9532 (95%) patients, with a median value of 40 (interquartile range, 35–47). Inpatient mortality occurred in 824 (8.6%) patients, and 2075 (21.8%) patients died by 1 year. Patients who died in hospital had a significantly higher mean GWTG ‐ HF score (47.7 versus 40.2; P <0.001). Inpatient and 1‐year mortality increased in each GWTG ‐ HF risk score quartile ( P <0.0001). Discrimination of the GWTG ‐ HF , EFFECT, OPTIMIZE‐HF, and ADHERE risk scores was assessed using area under the receiver operating characteristic curve values for hospital mortality, and were similar for all risk scores (0.72–0.74; P >0.05). The Hosmer–Lemeshow statistic suggested poor calibration for hospital mortality by the GWTG ‐ HF risk score ( P <0.001). Conclusions The GWTG ‐ HF risk score and other heart failure prediction tools demonstrate good discrimination for inpatient and 1‐year mortality in a heterogeneous cohort of CICU patients. Our study emphasizes that prognostic variables overlap in cardiac patients, regardless of the admission diagnosis.

Objective Our objective is to determine in patients with preclinical diastolic dysfunction (PDD), if there is development of tachyphylaxis to enhancement of cardiorenal response to acute volume loading (AVL) with B-type natriuretic peptide (BNP) after 12-week, twice-daily subcutaneous BNP administration. Background PDD is characterized by normal systolic function, moderate or severe diastolic dysfunction but no symptoms of heart failure (HF). Impairment in cardiorenal endocrine response to stress by AVL exists in PDD and is corrected by acute administration of subcutaneous BNP. Methods Double-blinded, placebo controlled proof-of-concept study to compare 12 weeks of twice daily subcutaneous BNP 10 ug/kg (n=24) versus placebo (n=12) in PDD. Subjects underwent two study visits: baseline and after 12 weeks. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular AVL. Results Among those with PDD, there was a statistically significant improvement in diastolic function after 12 weeks of BNP as measured by a decrease in Doppler E/e’ ratio (p = 0.004) and improvement of diastolic dysfunction grade (p = 0.008). After 12 weeks there was a statistically significantly greater sodium excretion, urine flow, and urinary cGMP excretion to AVL (all p < 0.001), as well as a trend towards greater glomerular filtration rate (p = 0.050) in the BNP group as compared to the placebo group. Conclusion In subjects with PDD, chronic BNP administration resulted in sustained improvement in diastolic function without development of tachyphylaxis to the enhancement of cardiorenal response to volume expansion with BNP.

Transesophageal echocardiography continues to have a central role in the diagnosis of infective endocarditis and its sequelae. Recent technological advances offer the option of 3-dimensional imaging in the evaluation of patients with infective endocarditis. We present an illustrative case and review the literature regarding the potential advantages and limitations of 3-dimensional transesophageal echocardiography in the diagnosis of complicated infective endocarditis. A 51-year-old man, an intravenous drug user who had undergone bioprosthetic aortic valve replacement 5 months earlier, presented with prosthetic valve endocarditis. Preoperative transesophageal echocardiography with 3D rendition revealed a large abscess involving the mitral aortic intervalvular fibrosa, together with a mycotic aneurysm that had ruptured into the left atrium, resulting in a left ventricle-to-left atrium fistula. Three-dimensional transesophageal echocardiography enabled superior preoperative anatomic delineation and surgical planning. We conclude that 3-dimensional transesophageal echocardiography can be a useful adjunct to traditional 2-dimensional transesophageal echocardiography as a tool in the diagnosis of infective endocarditis.

With the widespread use of blood pressure medications, it has become extremely difficult to assess the effects of elevated blood pressure on physiological and pathological phenomena without the confounding effects of antihypertensives. In both observational studies and randomized clinical trials, attempts to account for the antihypertensive effects have ranged from overly simplified dichotomous measures (either on or not on treatment) to tedious formulas that, in most instances, cannot be calculated in the population studied. Here, we propose a novel yet simple measurement index that not only takes into consideration whether an individual is on treatment but also accounts for the number and doses of each antihypertensive medication taken. We are suggesting that this measure maybe superior to the dichotomous measure and can be used to prospectively assess changes in blood pressure treatment. The developed measure was used in an ongoing trial, the Antihypertensive and Vascular, Endothelial, and Cognitive Function, to evaluate the burden of antihypertensive treatment before and after the intervention. The Antihypertensive and Vascular, Endothelial, and Cognitive Function Trial is a double-blind, randomized clinical trial examining the cognitive effects of antihypertensive medications among older adults with mild cognitive impairment. As part of the research protocol, participants were tapered off their usual antihypertensive medications and started on one of the study medications (lisinopril, candesartan, or hydrochlorothiazide; step 2: nifedipine XL; and step 3: metoprolol). This new measure of the antihypertensive load was used to monitor the drug burden of the participants during different phases of the trial. We define the antihypertensive load as the sum of the ratio of the current daily dosage divided by the maximum recommended daily dosage for each medication. The maximum daily dosage of each agent as indicated for hypertension was obtained from the drug database. A similar but more complex drug burden index has been developed for other drug classes. 1(1) Antihypertensive load ϭ antihypertensive medications prescribed daily dosage maximum daily dosage Using this antihypertensive load index, we are monitoring the drug burden of the participants and evaluating whether achieving blood pressure control is associated with increased antihypertensive burden during the study period. So far we have enrolled and randomized 34 individuals, 26 of whom were receiving antihypertensives (mean age: 70 years; 65% women; 27% blacks; antihypertensive load: 0.60Ϯ0.09; controlled to below 140/ 90 mm Hg [58%]). Overall, the antihypertensive load decreased in our sample to 0.55Ϯ0.13, although we achieved a 100% control rate. Of particular interest, among the 15 participants who were controlled when they entered the study, their load significantly decreased from 0.50 to 0.25 (Mann-Whitney test Pϭ0.034), although they remained controlled. In comparison, using the dichotomous measure (treated or not) or the number of antihypertensive...

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Background:The impact of fasting plasma glucose (FPG) on survival outcomes in patients with acute heart failure (HF) is unclear, and the relationship between intensity of glycemic control of FPG in diabetes mellitus (DM) patients and HF prognosis remains uncertain. This retrospective study aimed to evaluate the prognostic impact of FPG in patients with acute HF.Methods:A total of 624 patients hospitalized with acute HF from October 2000 to April 2014 were enrolled in this study. All patients were stratified by three groups according to their admission FPG levels (i.e., DM, impaired fasting glucose [IFG], and non-DM). All-cause and cardiovascular mortality was the primary end point, and HF re-hospitalization was the secondary end point during follow-up period.Results:A total of 587 patients were included in final asnalysis. The all-cause mortality rates of patients with DM, IFG, and non-DM were 55.5%, 40.3%, and 39.2%, with significant difference (P = 0.001). Moreover, compared with those with IFG (34.3%) and non-DM (32.6%), patients with DM had significantly higher rate of cardiovascular mortality (45.1%). Multiple Cox regression analysis showed that DM as well as IFG was related to all-cause mortality (DM: hazard ratio [HR] = 1.936, P < 0.001; IFG: HR = 1.672, P = 0.019) and cardiovascular mortality (DM: HR = 1.739, P < 0.001; IFG: HR = 1.817, P = 0.013). However, they were both unrelated to HF re-hospitalization. DM patients with strictly controlled blood glucose (FPG <3.9 mmol/L) had higher all-cause mortality than patients with non-DM, IFG, and DM patients with moderately controlled glucose (3.9 mmol/L≤ FPG <7.0 mmol/L). Likewise, both the primary end point and secondary end point were found to be worse in DM patients with poorly controlled blood glucose (FPG ≥7.0 mmol/L).Conclusions:IFG and DM were associated with higher all-cause mortality and cardiovascular mortality in patients with acute HF. The association between mortality and admission FPG in DM patients with acute HF appeared U-shaped.