York Heart Association Class III-IV Research Articles

Screening for heart transplantation and left ventricular assist system: results from the ScrEEning for advanced Heart Failure treatment (SEE‐HF) study

Heart transplantation (HTx) and implantable left ventricular assist systems (LVAS) improve outcomes in advanced heart failure but may be underutilized. We hypothesized that screening can identify appropriate candidates. The ScrEEning for advanced Heart Failure treatment (SEE-HF) study was a multicentre prospective study screening patients with existing cardiac resynchronization therapy (CRT) and/or implantable cardioverter-defibrillator (ICD) for ejection fraction ≤40% and New York Heart Association (NYHA) class III-IV, and subsequently for guideline-based HTx and LVAS indication. Of 1722 (mean age 64 ± 14 years, 26% women) patients screened at eight centres in seven European countries, 121 (7.0%) were eligible and 99 (5.7%; mean age 61 ± 10 years, 19% women) patients were enrolled for detailed assessment. Twenty-six of the 99 enrolled patients (26%) were eligible for either HTx or LVAD (18 eligible for HTx; 7 eligible for LVAD; and 1 eligible for both). Eleven patients were listed for HTx and three received an LVAS. Eligible patients were 61 ± 8 years and 19% women, whereas those actually receiving intervention were 56 ± 8 years and 8% women. Among patients with CRT and/or ICD, a minority have NYHA class III-IV heart failure and ejection fraction ≤40%. Among these, however, more than one-quarter have an unrecognized need for HTx or LVAS. When patients are offered intervention based on screening, many decline. Discrepancies exist between clinical and patient equipoise. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.

Factors associated with early mortality in haemodialysis patients undergoing coronary artery bypass surgery.

SummaryIntroduction:Coronary artery bypass grafting (CABG) results in higher morbidity and mortality rates in end-stage renal disease (ESRD) patient populations than in patients with normal renal function. This study aimed to identify the early results of CABG performed on ESRD patients, and the factors that affected the mortality rates of those patients.Methods:A retrospective evaluation of our hospital database revealed 84 haemodialysis-receiving patients who underwent CABG during the years 2006 to 2012. Mortality was observed in 21 patients (group 1), and this group was compared with the remaining patients (group 2) for peri-operative parameters such as age, EuroSCORE, functional capacity, myocardial infarction, use of inotropes and completeness of revascularisation.Results:The study included 60 male (71.4%) and 24 female patients (28.6%); the participants’ mean age was 59.50 ± 9.93 years. The pre-operative additive EuroSCORE was 7.96 ± 2.88 (range: 2–18). Pre-operative functional capacity was impaired in 35.7% of the patients [New York Heart Association (NYHA) classes III–IV]. Mean age and preoperative EuroSCORE values of group 1 were significantly higher than those of group 2. Impaired functional capacity (NHYA classes III–IV) was also associated with mortality (OR: 3.333; 95% CI: 1.199–9.268).Fifty-four patients (64.3%) underwent on-pump CABG procedures, and 30 (35.7%) underwent off-pump CABG procedures. The study found no statistically significant difference in mortality rates between these two techniques. Mortality occurred in 12 patients (22.2%) in the on-pump group and in nine (30%) in the off-pump group. Complete revascularisation was performed on 46 patients (85.2%) in the on-pump group and seven (23.3%) in the off-pump group (p < 0.001).ConclusionAdvanced age, impaired NYHA functional capacity and pre-operative hypertension were determinative for early-term surgical mortality. An on-pump surgical technique is recommended to ensure completeness of revascularisation.

Closure of mitral paravalvular defects without performing an arteriovenous loop: a case series of fourteen patients.

IntroductionThe arteriovenous (AV) loop is recommended when further support is needed during paravalvular leak (PVL) closure.AimWe report the feasibility and safety of mitral PVL closure without constructing an AV loop, based on a single-centre experience.Material and methodsFourteen patients with mitral valve replacement (MVR) who had New York Heart Association (NYHA) class III–IV dyspnoea or NYHA class II symptoms with significant haemolytic anaemia caused by severe or moderate-to-severe paravalvular regurgitation and who underwent transcatheter PVL closure (TPVLC) between May 2014 and February 2017 were enrolled.ResultsIn total, 15 PVL procedures and 19 device deployments were performed. The patients had one (n = 10), three (n = 1) or four (n = 1) devices for closure at the time of the procedure; one patient had two devices from two procedures at different times with different access ways. Nineteen devices (10 (66.6%) via transseptal access; 4 (26.6%), transapical access; and 1 (6.6%), retrograde access) were deployed successfully without making an AV loop.ConclusionsThe TPVLC is a less invasive and effective alternative to surgery in symptomatic patients with significant PVLs and high operational risks. The success rates are satisfactory, with improving techniques and devices. Procedural success without using an AV loop can be achieved with reduced costs, fluoroscopic times and complications.

Clinical risk profile score predicts all cause mortality but not implantable cardioverter defibrillator intervention rate in a large unselected cohort of patients with congestive heart failure.

Primary prophylactic implantable cardioverter defibrillator (ICD) therapy is indicated for patients with reduced left ventricular ejection fraction (LVEF). We aimed to determine if preoperative clinical risk profiling can predict long-term benefit, and if clinical risk scores can be applied and improved in a patient cohort outside the clinical trial setting. Using registry data, 789 patients with reduced LVEF who received ICDs for primary prevention during 2006-2011 were identified (age 64±11years, 82% men, 63% ischemic etiology, 52% cardiac resynchronization therapy with defibrillator). The patients were divided into three risk groups, based on the presence of baseline clinical risk factors (age >70, QRS duration >120ms, New York Heart Association class III-IV, atrial fibrillation history, or creatinine >106μmol/L). Endpoints were all-cause mortality and survival free of adequate ICD therapy. Mean follow-up was 39±18months. Annual mortality was 7.6%, and increased with risk group (p<.001). Rates of appropriate antitachycardia pacing and shock therapy were not statistically different between the groups, and ranged from 11%-16% and 6%-14%, respectively. By combining the previous risk score with data on diabetes, a better independent prediction of mortality was achieved; mortality rates then ranged from 11% (low-risk) to 46% (high-risk) (p<.0001). Implantable cardioverter defibrillator therapies occur across the spectrum of comorbidities in a population with systolic heart failure. However, all-cause mortality is considerably higher in the group of patients with accumulated risk factors, and using the proposed scoring system can be helpful for the evaluation and risk stratification of the patient prior to making a decision for a primary prophylactic ICD implantation.

251 - Baseline Hypokalemia and Long-Term Outcomes in Ambulatory Patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and New York Heart Association Class III-IV: A Propensity-Matched Study of Beta-Blocker Evaluation of Survival Trial (BEST)

251 - Baseline Hypokalemia and Long-Term Outcomes in Ambulatory Patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and New York Heart Association Class III-IV: A Propensity-Matched Study of Beta-Blocker Evaluation of Survival Trial (BEST)

56-63: Perfusion and metabolic scintigraphy with radiolabeled fatty acid in prognosis of cardiac resynchronization therapy in patients with dilated cardiomyopathy

Purpose: To study perfusion and metabolism of the left ventricular (LV) myocardium in patients with idiopathic dilated cardiomyopathy (DCM) and to identify the scintigraphic predictors of the efficacy of cardiac resynchronization therapy (CRT). Methods: The study comprised 63 patients with DCM and severe heart failure of New York Heart Association (NYHA) class III-IV, LV ejection fraction 29,7 ± 6.4 % by echocardiography, who underwent CRT. Before CRT, all patients received gamma-scintigraphy with 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and with 123I-β-methyl-iodophenyl pentadecanoic acid (123I-BMIPP) for evaluation of myocardial perfusion and metabolism, respectively. Before CRT and six months after, all patients underwent echocardiography study to estimate cardiac hemodynamics. Results: Patients were divided into two groups six months after CRT: (1) responders - LV end systolic volume (ESV) decreased by ≥ 15% (n = 39); (2) non-responders - LV ESV decreased by < 15% (n = 24). Prior to CRT, no statistically significant differences were found between groups in hemodynamic parameters (LV ejection Fraction, LV end-diastolic volume, LV end-systolic volume), intra- and interventricular dyssynchrony. Significant difference between groups was found on the following preoperative scintigraphic parameters: size of perfusion defect (9.22 ± 5.06% and 12.5 ± 4.22%, p < 0.01), metabolic defect size (7.35 ± 4.54% and 10.92 ± 4.15%, p < 0,01). Correlation analysis demonstrated the presence of significant association (r = 0.37, p < 0.5) between the original sizes of metabolic defect and changes in the values of LVESV after the implantation of CRT device. Metabolic scintigraphy showed higher diagnostic efficacy in determination of indications for CRT compared with perfusion scintigraphy (area under ROC-curves (AUC) = 0.722 and AUC = 0.612, respectively). The best metabolic defect size threshold value of 7.35% predicted CRT efficacy with the sensitivity and specificity of 77.8% and 66.7%, respectively. The study was supported by a grant from the Russian Science Foundation (№15-15-10016). Conclusion: Data, generated by metabolic scintigraphy, may be used for the integrated prediction of CRT efficacy.

Flecainide-metoprolol combination reduces atrial fibrillation clinical recurrences and improves tolerability at 1-year follow-up in persistent symptomatic atrial fibrillation.

Atrial fibrillation (AF) affects ∼2% of the total population. In order to prevent AF recurrences, many anti-arrhythmic drugs are currently available, but most of them are burdened by serious side effects and suboptimal efficacy. The aim of the present study was to test efficacy and safety of a combination of flecainide and metoprolol in preventing AF clinical recurrences. This study is a monocentric, prospective, randomized, open-blinded trial on 173 patients with a recent episode of paroxysmal or persistent AF. Patients were randomized into group A (flecainide + metoprolol; n = 80), group B (flecainide only; n = 72), or group C (metoprolol only; n = 21). Main exclusion criteria were recent acute coronary syndrome, heart failure New York Heart Association class III-IV, left ventricular ejection fraction <0.40, atrioventricular conduction disorders, and severe bradycardia. Primary endpoint was symptomatic recurrence over 1-year follow-up. Secondary endpoint was quality of life (QoL) over 1-year follow-up, as assessed by the SF-36 and Atrial Fibrillation Severity Scale questionnaires. Combination therapy with flecainide and metoprolol significantly reduced recurrences at 1-year follow-up when compared with flecainide alone in the whole population (66.7 vs. 46.8%; P < 0.001) and in patients with persistent AF (71.1 vs. 43.6%; P = 0.025) while adding beta-blocker therapy to paroxysmal AF showed no benefit over IC anti-arrhythmic drug-only. Patients randomized to combination therapy experienced a significant improvement of QoL when compared with those assigned to a flecainide-only regimen irrespective of AF type. Flecainide-metoprolol combination therapy improves effectiveness of rhythm control in persistent symptomatic AF and increases tolerability, with a concomitant reduction of side effects and a better compliance.

Psychometric Analysis of the Heart Failure Somatic Perception Scale as a Measure of Patient Symptom Perception.

Symptoms are known to predict survival among patients with heart failure (HF), but discrepancies exist between patients' and health providers' perceptions of HF symptom burden. The purpose of this study is to quantify the internal consistency, validity, and prognostic value of patient perception of a broad range of HF symptoms using an HF-specific physical symptom measure, the 18-item HF Somatic Perception Scale v. 3. Factor analysis of the HF Somatic Perception Scale was conducted in a convenience sample of 378 patients with chronic HF. Convergent validity was examined using the Physical Limitation subscale of the Kansas City Cardiomyopathy Questionnaire. Divergent validity was examined using the Self-care of HF Index self-care management score. One-year survival based on HF Somatic Perception Scale scores was quantified using Cox regression controlling for Seattle HF Model scores to account for clinical status, therapeutics, and lab values. The sample was 63% male, 85% white, 67% functionally compromised (New York Heart Association class III-IV) with a mean (SD) age of 63 (12.8) years. Internal consistency of the HF Somatic Perception Scale was α = .90. Convergent (r = -0.54, P < .0001) and divergent (r = 0.18, P > .05) validities were supported. Controlling for Seattle HF scores, HF Somatic Perception Scale was a significant predictor of 1-year survival, with those most symptomatic having worse survival (hazard ratio, 1.012; 95% confidence interval, 1.001-1.024; P = .038). Perception of HF symptom burden as measured by the HF Somatic Perception Scale is a significant predictor of survival, contributing additional prognostic value over and above objective Seattle HF Risk Model scores. This analysis suggests that assessment of a broad range of HF symptoms, or those related to dyspnea or early and subtle symptoms, may be useful in evaluating therapeutic outcomes and predicting event-free survival.

Does Surgical Repair of Moderate Ischemic Mitral Regurgitation Improve Survival? A Systematic Review.

Mitral regurgitation (MR) is one of the common complications in myocardial infarction (MI) patients. Almost half of the post MI patients have MR (ischemic MR)(17) which is moderate to severe (grade II-IV). Whether there is a mortality benefit of performing mitral valve repair (MVR) along with coronary artery bypass grafting (CABG) in patients with post MI moderate MR remains inconclusive. Literature search was done from PubMed, Google scholar, Ovid, and Medline databases. Studies which included post MI patients with moderate ischemic MR and reported mortality outcomes of performing CABG and MVR were chosen for the systematic review. Our preliminary literature search identified 194 studies, of which 11 studies met our inclusion criteria. Nine studies showed no survival benefit of performing simultaneous MVR and CABG. One study demonstrated survival benefit of performing CABG plus MVR only in the New York Heart Association (NYHA) class III-IV, and one study suggested survival benefit of performing CABG plus MVR as compared to CABG alone in patient with ischemic MR irrespective of preoperative NYHA functional class. Review of current literature showed mixed results in terms of improvement in functional status but failed to show any survival benefit of performing MVR along with CABG. Limitations of studies include small sample size, difference in baseline demographic variables, and short follow-up period which might influence the outcome of the study. Prospective randomized studies are required to establish clear benefit of performing MVR simultaneously with CABG.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry

The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

Should Moderate-to-Severe Tricuspid Regurgitation be Repaired During Reoperative Left-Sided Valve Procedures?

The risks vs benefits of tricuspid valve (TV) surgery in reoperative patients requiring left-sided valve surgery and moderate-to-severe tricuspid regurgitation is unclear. We compared patients with and without concomitant TV surgery. A total of 200 patients with moderate-to-severe TV regurgitation had reoperative left-sided valve procedures from January 2002 to April 2014; 75 with TV intervention (TVI) and 125 with no tricuspid intervention (TVN). Propensity-matched cohorts of 60 TVI and 60 TVN patients were compared. Outcomes included New York Heart Association class, TV regurgitation and survival. TVI patients were younger (66 ± 15 vs 72 ± 13 years, P < 0.001), had more cardiogenic shock (6 of 75, vs 0 of 125, P < 0.001) and mitral valve surgery (60 of 75 vs 69 of 125, P < 0.001). Propensity matching yielded 60 pairs of TVI cases and TVN controls. Matched groups were comparable in age (TVI = 67 ± 13 vs TVN 68 ± 14 years, P = 0.67), cardiogenic shock (2 vs 0, P = 0.50), and mitral valve surgery (15 each, P = 1.0). Operative mortality was 2 of 60 in TVI vs 10 of 60 TVN (P = 0.27). Median follow-up was 4.4 years. Follow-up rates of New York Heart Association class III-IV were similar (12 of 60 for TVI vs 16 of 60 TVN, P = 0.52). Kaplan-Meier analysis indicated improved event-free survival for TVI patients (6 years, 95% CI: 4.8-7.2 years vs 8 years, 95% CI: 6.7-9.3 years for TVN, P = 0.030). There was a trend towards increased TR at follow-up in patients with valve repair alone vs annuloplasty (P = 0.15). TV surgery was performed more often in higher-risk patients. Matched case-control analyses showed TVI was associated with improved midterm outcomes. Our data suggest that annuloplasty was preferable to TV repair alone.

Atrioventricular Node Ablation.

Cardiac resynchronization therapy (CRT) is a device-based, nonpharmacologic approach that has shown to improve the outcome in patients with heart failure in terms of mortality and morbidity reduction. Large randomized trials have virtually enrolled patients in New York Heart Association class III-IV, with reduced left ventricular ejection fraction, with evidence of electrical dyssynchrony, and receiving optimal medical therapy and who were in sinus rhythm. Guidelines remain imprecise as to defining differentiated approaches according to the forms of atrial fibrillation other than permanent. These recommendations remain unsupported by evidence derived from randomized controlled trials, which are much needed.

Safety of Noncardiac Surgery in Patients With Hypertrophic Obstructive Cardiomyopathy at a Tertiary Care Center.

This study's purpose was to review non-cardiac surgery (NCS) in patients with hypertrophic obstructive cardiomyopathy (HOCM) to examine perioperative management and quantify postoperative mortality and worsening heart failure. Retrospective review. A single tertiary care center. The study included 57 adult patients with HOCM who underwent NCS from January 1, 1996, through January 31, 2014. Noncardiac surgery. The authors identified 57 HOCM patients who underwent 96 NCS procedures. Vasoactive medications were administered to the majority of NCS patients. Three patients (3%) died within 30 days of NCS, but causes of death did not appear to be cardiac in nature. Death after NCS was not significantly associated with preoperative left ventricular ejection fraction (p = 0.2727) or peak instantaneous systolic resting gradient (0.8828), but was associated with emergency surgery (p = 0.0002). Three patients experienced worsening heart failure postoperatively, and this was significantly associated with preoperative New York Heart Association Class III-IV symptoms compared with I-II symptoms (p = 0.0008). HOCM patients safely can undergo NCS at multidisciplinary centers experienced in caring for these patients. The mortality rate in this study was less than that reported in the majority of other studies. Postoperative complications, including increasing heart failure, may occur, especially in patients with more severe preoperative cardiac symptoms.

Sub-valvular repair of ischemic mitral regurgitation in a patient with severe tethering of mitral leaflets.

A 61-year-old male presented with a six-month history of dyspnea [New York Heart Association (NYHA) Class IIIIV]. He had a myocardial infarction three years previously. His comorbidities included claudication due to a right iliac artery stenosis. His transthoracic (TTE) and transesophageal (TOE) echocardiograms diagnosed ischemic mitral regurgitation (MR): the left ventricular (LV) end-diastolic diameter was 7.1 cm and the ejection fraction (EF) was 30%. The apex was dyskinetic while the anterior and inferior midsegments were hypokinetic. A severe central jet of MR due to tethering of both leaflets (tenting height 16 mm) was identified. The ‘seagull sign’ due to anterior leaflet restriction by secondary chordae from the posterior papillary muscle (PPM) was noted. Coronary angiography showed occluded left anterior descending (LAD) and right coronary arteries. Cardiac magnetic resonance (CMR) confirmed the TOE findings and showed evidence of a transmural scar on the inferior wall.

Long-term monitoring of respiratory rate in patients with heart failure: the Multiparametric Heart Failure Evaluation in Implantable Cardioverter-Defibrillator Patients (MULTITUDE-HF) study.

Monitoring respiratory rate (RR) is recommended at the time of hospital presentation for acute decompensation in heart failure (HF). Device-based continuous monitoring of RR may be helpful for diagnostic and prognostic stratification after implantable cardioverter-defibrillator (ICD) implantation. This study was undertaken to analyze short- and long-term changes in ICD-measured RR and to relate RR with the patient's clinical status and the occurrence of HF events. One hundred twenty-four consecutive HF patients who received ICD endowed with this diagnostic capability (Boston Scientific Inc., Natick, MA, USA) were prospectively enrolled. Patients were followed up for 12 months. At the baseline, the proportion of New York Heart Association (NYHA) class III-IV was higher among patients with daily maximum RR >27 breaths/min (third tertile) than those with <24 breaths/min (first tertile) (43 vs. 23%, p < 0.05). Moreover, the ejection fraction was lower (27 ± 7 vs. 34 ± 8%, p < 0.05). In patients with HF hospitalizations (33 events) and urgent visits for HF (15 events), the weekly average of RR calculated over the 7 days preceding hospital accesses did not differ from values recorded at the baseline and before scheduled follow-up visits. However, the weekly variation in RR (i.e., the difference between maximum and minimum values collected over the week) was significantly higher prior to hospitalization (p < 0.05). A weekly variation >3 breaths/min in maximum RR predicted an impending hospital admission for HF with sensitivity of 73 % and specificity of 57%. In this study, elevated values of ICD-monitored RR identified patients with worse functional status and lower systolic function. The weekly variation in RR increased before HF exacerbation. This monitoring technology may represent a useful tool in the clinical management of patients with HF.

Abnormal serum calcium levels are associated with clinical response to maximization of heart failure therapy.

Abnormal serum calcium levels are associated with adverse cardiovascular effects. Therapy of heart failure (HF) may result in urinary calcium excretion and calcium apposition to bones, and consequently, in calcemia. The aim of the study was to assess the prevalence of abnormal calcium levels in the blood of patients receiving maximized HF therapy, to explore clinical and laboratory determinants of abnormal serum calcium levels, and to analyze the relation of abnormal calcium levels to prognosis. The study included 722 patients with HF classified as New York Heart Association (NYHA) classes III-IV at baseline (age 53 ±10 years, 13% of women), who underwent HF therapy optimization to maximum tolerated doses. After therapy maximization, the NYHA class improved in 66.7% of the patients, while it did not change in 31.0% and worsened in 2.4%. Hypocalcemia occurred in 166 patients (22.9%) and was more prevalent in patients in whom the NYHA class improved. Hypercalcemia was diagnosed in 63 patients (8.7%) and was more common in patients with no functional improvement or worsening of the NYHA class. This effect was independent of age, sex, etiology of HF, body mass index, kidney function, or the use of thiazides. Hypercalcemia was associated with increased catabolism, hemodynamic compromise, more intensive inflammation, and lower bone mineral density. Lower albumin and higher phosphorus levels, were significant predictors of hypercalcemia, independently of kidney function. Hypocalcemia was associated with reduced catabolism, higher albumin and lower phosphorus levels, use of thiazides, and smoking history. Neither hypocalcemia nor hypercalcemia was associated with poor prognosis. Our study shows that abnormal serum calcium levels are associated with a clinical response to treatment maximization in patients with HF. Mild hypocalcemia after maximization of therapy is not associated with poorer prognosis. Hypercalcemia is associated with lack of response to treatment, and its prognostic value remains unclear.

Effects of an Accelerated Intravenous Iron Regimen in Hospitalized Patients With Advanced Heart Failure and Iron Deficiency

To assess the short-term efficacy and safety of an accelerated intravenous iron regimen in hospitalized patients with heart failure and iron deficiency. Prospective, single-arm, open-label study. Large tertiary care medical center. Thirteen patients with New York Heart Association class III-IV heart failure, anemia (hemoglobin level ≤12.0g/dl), and iron deficiency (ferritin level <100ng/ml, or ferritin level of 100-300ng/ml with transferrin saturation <20%) hospitalized between April 2011 and December 2013. All patients received sodium ferric gluconate 250mg in 100ml of normal saline intravenously over 2hours twice/day until the iron deficit was corrected or the patient was discharged. Changes in hematologic parameters were assessed at 1-4weeks after therapy. Patients received a mean±standard deviation (SD) total iron dose of 1269±207mg over 3.4±1.0days. After a mean±SD follow-up of 13.1±5.6days, intravenous iron increased hemoglobin level by 1.2g/dl (95% confidence interval [CI] 0.45-1.9, p=0.005), ferritin level by 364.2ng/ml (95% CI 129.7-598.7, p=0.007), and transferrin saturation by 10.5% (95% CI 6.5-14.6%, p<0.001). Changes in hemoglobin level did not correlate with volume status, as determined by differences in body weight. No significant changes in blood pressure or heart rate were observed. Adverse events were few and minor in severity (e.g., nausea, constipation, and abdominal discomfort). An accelerated intravenous iron regimen improved hematologic parameters and was well tolerated in hospitalized patients with advanced heart failure. A randomized multicenter trial comparing this regimen with placebo is warranted.

Quality of life in cardiac resynchronization recipients: association with response and impact on outcome.

The prognostic impact of improvement in health-related quality of life (QoL) and its relation to response in cardiac resynchronization therapy (CRT) recipients remains unknown. To assess the correspondence between response to CRT and improvements in QoL and to verify if a change in QoL after pacing influences outcome in CRT patients. Ninety-seven participants of the Triple-Site Versus Standard Cardiac Resynchronization Therapy Trial (TRUST CRT) randomized trial, in New York Heart Association class III-IV, QRS width ≥ 120 ms, left ventricular ejection fraction ≤ 35%, and significant mechanical dyssynchrony were included. Subjects filled out the Minnesota-QoL questionnaire prior to and 6 months after CRT with defibrillator (CRT-D) implantation. Data on major adverse cardiac events (MACEs: death, heart failure hospitalization, heart transplant) collected within the next 2.5 years and adjudicated blindly constituted the censoring variables. Within the first 6 months of resynchronization QoL improved in 81%, while worsening in 19% of patients. Clinical response, but not the echocardiographic one, was associated with improved QoL. During subsequent 2.5 years MACEs occurred in 37% of patients (23% died). Subjects without QoL improvement were significantly (both P < 0.05) more prone to experience MACE (61% vs 32%) and die (44% vs 18%) within the follow-up. Unimproved QoL increased the probability of future MACE by 2.7 times (95% confidence intervals [CI]: 1.26-5.83; P = 0.01) and death by 3.2 times (95% CI: 1.23-8.32; P = 0.02) independently from clinical and echocardiographic response. Clinical response, but not the echocardiographic one, was associated with improved QoL in CRT recipients. These preliminary data suggest that lack of improvement in QoL after CRT was associated with a strongly unfavorable prognosis, regardless of functional or echocardiographic response. Our results merit further studies with a larger number of patients.

The clinical dilemma of quantifying mechanical left ventricular dyssynchrony for cardiac resynchronization therapy: segmental or global?

Heart failure (HF) represents a serious clinical and public cause of mortality, morbidity, as well as healthcare expenditures. Guidelines for treatment of HF join in recommending multimedical regimen at targeted doses as the best medical strategy, despite that a significant percentage of patients remain symptomatic. Studies have shown that these patients might benefit from cardiac resynchronization therapy (CRT), particularly those presenting with broad QRS duration, >135 msec. Trials have already shown that CRT results in improved morbidity and survival of these patients particularly those in New York Heart Association class III-IV HF, but almost 30% do not show any symptomatic or survival benefit, hence are classified as nonresponders. Exhaustive efforts have been made in using noninvasive methods of assessing left ventricle (LV) dyssynchrony in predicting nonresponders to CRT, including Doppler echocardiography, magnetic resonance imaging, and even single photon emission computed tomography analysis, but only with modest success. In this report, we aimed to review the available evidence for assessing markers of mechanical LV dyssynchrony by various echocardiographic modalities and their respective strength in predicting favorable response to CRT treatment, comparing global with segmental ones. While the accuracy of segmental markers of dyssynchrony in predicting satisfactory response to CRT remains controversial because of various technical limitations, global markers seem easier to measure, reproducible, and potentially accurate in reflecting overall cavity response and its clinical implications. More studies are needed to qualify this proposal.

Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease

Although the important role of fibroblast growth factor (FGF)23 on cardiac remodeling has been suggested in advanced chronic kidney disease (CKD), little is known about serum (s)FGF23 levels in patients with heart failure (HF) due to nonischemic cardiac disease (NICD) and early CKD. The present study aimed to investigate sFGF23 levels in NICD patients and identify the responsible factors for the elevation of sFGF23 levels. We prospectively measured sFGF23 levels in consecutive hospitalized NICD patients with early CKD (estimated glomerular filtration rate ≥ 40 ml·min(-1)·1.73 m(-2)) and analyzed the data of both echocardiography and right heart catheterization. Of the 156 NICD patients (estimated glomerular filtration rate range: 41-128 ml·min(-1)·1.73 m(-2)), the most severe HF symptom (New York Heart Association class III-IV, 53% vs. 33%, P = 0.015) was found in the above median sFGF23 (39.1 pg/ml) group compared with the below median sFGF23 group. sFGF23 levels were higher in patients with HF hospitalization history compared with those without HF [median: 46.8 (interquartile range: 38.8-62.7) vs. 34.7 (interquartile range: 29.6-42.4) pg/ml, P < 0.0001]. In the multivariate analysis, HF hospitalization was independently related to elevated sFGF23 levels (P = 0.022). Both systolic dysfunction and high plasma aldosterone concentration were identified as predictors of high sFGF23 levels (P < 0.05). Among the neurohormonal parameters, elevated sFGF23 levels were the only factor to predict a declining left ventricular ejection fraction (P = 0.001). These findings suggest that the progression of HF per se contributes to the elevation of sFGF23 levels even in the early stages of CKD, which leads to further myocardial dysfunction, potentially creating a vicious cycle.