Lung-to-Heart Nano-in-Micro Peptide Promotes Cardiac Recovery in a Pig Model of Chronic Heart Failure.

BACKGROUND: The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. OBJECTIVES: In this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. METHODS: Heart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. RESULTS: DpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. CONCLUSIONS: The overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart.

Missense Variant E1295K of Sodium Channel SCN5A Associated With Recurrent Ventricular Fibrillation and Myocardial Inflammation.

SCN5A was considered an exclusively cardiac expressed ion channel but discovered to also act as a novel innate immune sensor. We report on a young SCN5A variant carrier with recurrent ventricular fibrillation and massive myocardial inflammation whose peculiar clinical course is highly suggestive of such a dual role of SCN5A. (Level of Difficulty: Advanced.).

Benefit of a wearable cardioverter defibrillator for detection and therapy of arrhythmias in patients with myocarditis.

AIMS: Myocarditis may lead to malignant arrhythmias and sudden cardiac death. As of today, there are no reliable predictors to identify individuals at risk for these catastrophic events. The aim of this study was to evaluate if a wearable cardioverter defibrillator (WCD) may detect and treat such arrhythmias adequately in the peracute setting of myocarditis. METHODS AND RESULTS: In this observational, retrospective, single centre study, we reviewed patients presenting to the Charité Hospital from 2009 to 2017, who were provided with a WCD for the diagnosis of myocarditis with reduced ejection fraction (<50%) and/or arrhythmias. Amongst 259 patients receiving a WCD, 59 patients (23%) were diagnosed with myocarditis by histology. The mean age was 46 ± 14 years, and 11 patients were women (19%). The mean WCD wearing time was 86 ± 63 days, and the mean daily use was 20 ± 5 h. During that time, two patients (3%) had episodes of sustained ventricular tachycardia (VT; four total) corresponding to a rate of 28 sustained VT episodes per 100 patient-years. Consequently, one of these patients underwent rhythm stabilization through intravenous amiodarone, while the other patient received an implantable cardioverter defibrillator. Two patients (3.4%) were found to have non-sustained VT. CONCLUSIONS: Using a WCD after acute myocarditis led to the detection of sustained VT in 2/59 patients (3%). While a WCD may prevent sudden cardiac death after myocarditis, our data suggest that WCD may have impact on clinical management through monitoring and arrhythmia detection.

Safe procedures despite ultra low radiation doses during catheter ablations of atrial and ventricular arrhythmias-A multicenter experience.

INTRODUCTION: Despite the development of non-fluoroscopic catheter visualization options, fluoroscopy is still used in most ablation procedures. The aim of this multicenter study was to evaluate the safety and efficacy of a new ultra-low dose radiation protocol for EP procedures in a large number of patients. METHODS AND RESULTS: A total of 3462 consecutive patients (male 1926 (55.6%), age 64.4 ± 14.0 years, BMI 26.65 ± 4.70) undergoing radiofrequency ablation (left atrial (n = 2316 [66.9%], right atrial (n = 675 [19.5%], or ventricular (n = 471 [13.6%]) in three German centers were included in the analysis. Procedures were performed using a new ultra-low dose protocol operating at 8nGy for fluoroscopy and 36nGy for cine-loops. Additionally a very low framerate (2-3FPS) was used. Using the new protocol very low Air kerma-area product (KAP) values were achieved for left atrial ablations (104.25 ± 84.22 µGym2 ), right atrial ablations (70.98 ± 94.79 µGym2 ) and ablations for ventricular tachycardias or PVCs (78.62 ± 66.59 µGym2 ). Acute procedural success was achieved in 3289/3388 (97.1%) while the rate of major complications was very low compared to previously published studies not using low dose settings (n = 20, 0.6%). CONCLUSION: The ultra-low dose, low framerate protocol leads to very low radiation doses for all EP procedures while neither procedural time, fluoroscopy time nor success or complication rates were compromised. When compared to current real-world Air KAP data the new ultra-low dose fluoroscopy protocol reduces radiation exposure by more than 90%.

[Update on radiation exposure in catheter ablation of atrial fibrillation]. / Update zum Strahlenschutz bei der Katheterablation von Vorhofflimmern.

The rising number of catheter ablations of atrial fibrillation increases radiation exposure for both patients and surgeons. Fortunately, this trend is counteracted by the development of measures to reduce total fluoroscopy time using non-fluoroscopic catheter visualization. Since even low-dose radiation can cause serious injury, all options to reduce radiation burden must be utilized (ALARA, "as low as reasonably achievable"). Dose reduction protocols with low-dose settings, which include reduced framerates, pulse duration, detector entrance dose and increased beam hardening, play a decisive role in this regard. This review provides a state-of-the-art summary of non-fluoroscopic catheter visualization and dose reduction protocols for catheter ablation of atrial fibrillation.

Ventricular Tachycardia (VT) Storm After Cryoballoon-Based Pulmonary Vein Isolation.

BACKGROUND Following catheter ablation of atrial fibrillation, increased incidence of ventricular arrhythmia has been observed. We report a case of sustained ventricular arrhythmia in a patient who underwent cryoballoon-based pulmonary vein isolation for symptomatic persistent atrial fibrillation. CASE REPORT A 57-year-old patient with dilated cardiomyopathy underwent CB-based pulmonary vein isolation for symptomatic persistent AF. On the day following an uneventful procedure, the patient for the first time experienced a sustained ventricular tachycardia that exacerbated into VT storm. Each arrhythmia was terminated by the ICD that had been implanted for primary prevention. Antiarrhythmic treatment with amiodarone was initiated immediately. The patient remained free from sustained ventricular arrhythmia during follow-up. CONCLUSIONS After pulmonary vein isolation, physicians should be vigilant for ventricular arrhythmia. The influence of atrial autonomic innervation on ventricular electrophysiology is largely unknown.

Right ventricular function and mechanics in chemotherapy- and radiotherapy-naïve cancer patients.

The present research evaluated right ventricular (RV) structure, function and mechanics in the cancer patients before initiation of chemo- or radiotherapy, and the association between cancer and decreased RV longitudinal strain. This retrospective investigation included 101 chemo- and radiotherapy-naïve patients with solid cancer and 38 age- and gender-matched controls with similar cardiovascular risk profile. Echocardiographic examination and strain evaluation was performed in all participants. RV structure and RV systolic and diastolic function estimated with conventional echocardiographic parameters were similar between the cancer patients and controls. However, RV global longitudinal strain (- 22.7 ± 2.6% vs. - 21.1 ± 2.4%, p < 0.001) was significantly decreased in the cancer patients than in controls. The same was revealed for RV free wall endocardial (- 33.6 ± 4.3% vs. - 31.4 ± 4.0%, p = 0.006) and mid-myocardial (- 25.2 ± 3.6% vs. - 23.7 ± 3.8%, p = 0.035) longitudinal RV strains, whereas difference was not found in RV free wall epicardial longitudinal strain. The presence of cancer was independently of age, gender, body mass index, left ventricular hypertrophy, diabetes, hypertension and pulmonary pressure associated with reduced RV global longitudinal strain (OR 3.79; 95% CI 2.18-10.92, p < 0.001), as well as with decreased free wall RV longitudinal strain (OR 5.73; 95% CI 3.17-9.85, p < 0.001). RV strain is deteriorated in the chemo- and radiotherapy-naïve cancer patients. Endocardial and mid-myocardial layers are more affected than epicardial strain in the cancer patients. The presence of cancer is independently of other clinical parameters associated with reduced RV longitudinal strain.

Left Ventricular Strain in Chemotherapy-Naive and Radiotherapy-Naive Patients With Cancer.

BACKGROUND: We sought to investigate left ventricular (LV) function and mechanics in patients with cancer before they received chemotherapy or radiotherapy, as well as the relationship between cancer and reduced LV multidirectional strain in the whole study population. METHODS: The retrospective study involved 122 chemotherapy- and radiotherapy-naive patients with cancer and 45 age- and sex-matched controls with a cardiovascular risk profile similar to that of the patients with cancer. All the patients underwent echocardiographic examination before introduction of chemotherapy or radiotherapy. RESULTS: LV longitudinal (-19.1% ± 2.1% vs -17.8% ± 3.5%; P = 0.022), circumferential (-22.9% ± 3.5% vs -20.1% ± 4.1%; P < 0.001), and radial (40.5% ± 8.8% vs 35.2% ± 10.7%; P = 0.004) strain was significantly lower in the patients with cancer than in the control group. Endocardial and midmyocardial longitudinal LV strain was significantly reduced in the patients with cancer compared with the controls, whereas epicardial longitudinal strain was similar between these groups. Endocardial, midmyocardial, and epicardial circumferential strain was significantly lower in the chemotherapy- or radiotherapy-naive patients with cancer than in the controls. Cancer was associated with reduced longitudinal (odds ratio [OR], 9.0; 95% confidence interval [CI], 2.20-23.50; P < 0.001), reduced circumferential (OR, 7.1; 95% CI, 3.80-20.40; P < 0.001), and reduced radial strain (OR, 7.2; 95% CI, 3.41-25.10; P < 0.001) independent of age, sex, body mass index, diabetes, and hypertension. CONCLUSIONS: LV mechanics was impaired in the patients with cancer compared with the controls even before initiation of chemotherapy and radiotherapy. Cancer and hypertension were associated with reduced LV multidirectional strain independent of other clinical parameters. The present results indicate that cancer itself potentially induces cardiac remodelling independent of chemotherapy and radiotherapy.

Pushing the limits: establishing an ultra-low framerate and antiscatter grid-less radiation protocol for left atrial ablations.

Aims: Despite the use of 3D mapping systems and new developments of non-fluoroscopic options, most centres still rely at least in part on fluoroscopy for catheter visualization during catheter ablations. The purpose of this study was to assess the feasibility of using an ultra-low frame rate and antiscatter grid-less radiation protocol during complex left atrial ablations to minimize radiation exposure for the patient and staff. Methods and results: A total of 150 consecutive patients undergoing left atrial ablations in our hospital were included in the analysis. The procedures were performed between January 2015 and November 2016. Of the included patients 75 (50%) underwent ablation before and 75 (50%) after the ultra-low frame rate (reduced from 4 to 2 FPS) and antiscatter grid-less radiation protocol was established. Procedures performed after the dose reduction protocol was established showed a 64% reduction of the dose area product (630.28 ± 550.96 vs. 226.44 ± 277.44 µGym2, P < 0.001), while fluoroscopy duration (14.22 ± 4.47 vs. 13.62 ± 7.11 min, P = 0.066) and procedural duration (1:48 ± 0:28 vs. 1:53 ± 0:34 min, P = 0.525) were not prolonged. Acute procedural success was achieved in all procedures. Two complications occurred before and one complication after the protocol was established. During four procedures, operators decided to re-introduce the antiscatter grid. This was due to impaired visibility in morbidly obese patients (n = 2) or technically difficult transseptal puncture (n = 2). Conclusion: The use of an ultra low framerate and antiscatter grid-less radiation protocol effectively reduced radiation dose for complex left atrial ablation procedures and lead to very low average patient doses. Reduced image quality did not impair procedural and fluoroscopy duration or acute procedural success.

Effects of propofol on ventricular repolarization and incidence of malignant arrhythmias in adults.

BACKGROUND: Propofol is commonly used for procedural sedation in interventional electrophysiology. However, ventricular arrhythmias under Propofol have been reported. Our aim was to investigate ventricular repolarization and incidence of ventricular arrhythmias under Propofol infusion in adults with cardiac arrhythmias. METHODS: QRS, QTcB (Bazett), QTcFri (Fridericia), JTc, measurement of T peak to Tend time (Tp-e) at baseline and under Propofol infusion was performed in 235 patients. Screening for unexpected ventricular arrhythmias was performed in 1165 patients undergoing EP procedures under Propofol. RESULTS: A significant prolongation of Tp-e under Propofol infusion (79.7±17.3 vs. 86.4±22.5ms, p<0.001) and of QTcFri (429.3±35.8 vs. 435.5±36.5, p=0.033) was detected. No significant change of the QTcB interval, JTc interval or QRS duration was observed. One case (0.09%) of ventricular fibrillation during rapid ventricular pacing under Propofol occurred. CONCLUSION: Although transmural dispersion of ventricular repolarisation is increased under Propofol, incidence of malignant ventricular arrhythmias is low. For evaluation of QT interval under Propofol, Fridericia's correction formula should be used rather than Bazett's formula.

The effect of an ultra-low frame rate and antiscatter grid-less radiation protocol for cardiac device implantations.

BACKGROUND AND AIMS: Antiscatter grids improve image contrast by absorbing scattered x-ray beams, although by removing the antiscatter grid patient dose can be reduced as more x-ray beams reach the image receptor. Additionally, there is a trend toward ultra-low frame rates for radiation dose reduction during various electrophysiology procedures. As for most cardiac device implantations (CIED) image quality demands are usually modest, the purpose of this study was to assess the safety and efficacy of an ultra-low frame rate and scatter grid-less radiation protocol. METHODS/RESULTS: A total of 140 patients undergoing CIED implantation between 2014 and 2017 were included in the study. Seventy patients (50%) implanted after implementation of the antiscatter grid-less and ultra-low frame rate protocol were matched to controls before the dose-reduction protocol was established. Forty patients (28.6%) had a one-chamber pacemaker or one-chamber implantable cardioverter defibrillator (ICD) implantation/revision, 60 (42.9%) had a two-chamber pacemaker or two-chamber ICD implantation/revision, and 40 (28.6%) patients had a cardiac resynchronization therapy device implantation/revision. Removing the antiscatter-grid and lowering the frame rate led to a 73% reduction of the overall dose area product (1,206 ± 2,015 vs 324 ± 422 µGym, P < 0.001). Procedural duration (95 ± 51 minutes vs 82 ± 44 minutes, P  =  0.053) and rate of complications were not significantly different between the two groups. CONCLUSION: The use of an ultra-low frame rate and antiscatter grid-less radiation protocol significantly reduced radiation dose for implantation of CIED and led to very low average patient doses, while procedural duration and complication rates did not increase.

Cardiac device implantations in obese patients: Success rates and complications.

BACKGROUND: Obesity is associated with increased complications and potentially worse outcomes for various cardiac interventions. This study analyzed the success rate and complication rates associated with implantation of cardiac implantable electronic devices (CIEDs) in obese patients. HYPOTHESIS: Success rates are lower and complication rates higher in obese patients. METHODS: Consecutive patients undergoing CIED implantation between 2011 and 2015 in our hospital were included. Patients were categorized into obese and nonobese groups according to body mass index (BMI); cutoff was 30 kg/m2 . Patient characteristics, complication rates, procedural duration, and fluoroscopy data were compared between the 2 groups. RESULTS: A total of 965 patients (mean age, 69.0 ± 12.9 years; 67% male) were included. Of these, 249 (25.8%) patients were classified obese and 716 (74.2%) nonobese. Mean BMI was 34.7 ± 4.7 kg/m2 vs 25.1 ± 3.0 kg/m2 , respectively. There was no difference in procedural success rates between the 2 groups (97.2% vs 97.1%, respectively). Major complications were significantly lower in the obese group compared with the nonobese group (11 [4.4%] vs 62 [8.7%]; P < 0.05). Procedural duration and fluoroscopy duration were not different between the 2 groups, but the total dose-area product was significantly higher in obese patients vs nonobese patients (4012 ± 5416 cGcm2 vs 2692 ± 5277 cGcm2 ; P < 0.005). CONCLUSIONS: CIED implantation can be safely and effectively achieved in patients with BMI >30 kg/m2 . However, total radiation dose was significantly higher in the obese group, emphasizing that efforts should be made to reduce radiation exposure in these patients.

Safety and efficacy of applying a low-dose radiation fluoroscopy protocol in device implantations.

AIMS: For cardiac implantable electronic device (CIED) implantations, visualization of lead placement is necessary and fluoroscopy remains by far the most commonly used technique. With simple changes in the X-ray system settings, total radiation dose can be reduced significantly. The purpose of this study was to assess the safety and efficacy of various CIED implantations performed after implementation of a new dose reduction protocol (DRP). METHODS AND RESULTS: We conducted a retrospective chart review of 584 patients undergoing CIED implantation or revision in our hospital. Of these patients, 280 (48%) underwent the implantation prior to and 304 (52%) after the DRP introduction. The DRP included various changes for optimized image processing and exposure system settings to enable dose reduction, as well as a reduced frame rates (4 FPS for fluoroscopy and 7.5 FPS for cinematographic images). Of the 584 patients, 53 (9.1%) had a one-chamber pacemaker, 232 (39.7%) a two-chamber pacemaker, 133 (22.8%) a one-chamber ICD, 35 (6.0%) a two-chamber ICD, 82 (14.0%) a CRT (de novo) implantation, and 49 (8.3%) had an upgrade to a CRT device. DRP was associated with a 64% reduction of the dose-area product (1372 ± 2659 vs. 3792 ± 5025 cGcm2, P < 0.001), while fluoroscopy duration (13 ± 15 vs. 13 ± 15 min) and procedural duration (93 ± 52 vs. 92 ± 52 min.) did not significantly increase. Complication rates did not differ significantly between the two groups. CONCLUSION: The DRP proved to effectively reduce radiation dose for all types of CIED implantations. Fluoroscopy time, total procedure time, and the number of complications did not increase after introducing the DRP.

Pain Reactions during Pulmonary Vein Isolation under Deep Sedation: Cryothermal versus Radiofrequency Ablation.

BACKGROUND: Left atrial ablation can be accompanied by discomfort or pain. The purpose of this study was to systematically compare pain reactions during ablation of atrial fibrillation under deep sedation with cryothermal and radiofrequency energy. METHODS AND RESULTS: Circumferential ablation was performed in patients with atrial fibrillation using either radiofrequency (RF) or cryoenergy. Deep sedation was achieved with a combination of propofol and midazolam. Pain reactions were counted and painful ablation sites located. To determine the severity of the pain reactions a Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Pain Assessment Scale was used: 79 patients (53 RF- vs 26 Cryoablations) were included. A total of 92% of patients treated with RF energy showed ≥1 pain reaction during the procedure compared to only 13% in the cryoenergy group (<0.001). The total number of pain reactions was significantly higher in the RF energy group (3.6 ± 4.7 vs1.3 ± 0.6, P = 0.005). Determination of painful sites was performed in the RF group only. Pain reactions were significantly more often observed during RF application left superior pulmonary vein (LSPV) ostium compared to other left atrial ablation sites (Total FLACC Score 2.8 ± 0.6 LSPV, 1.4 ± 0.4 left inferior pulmonary vein [P = 0.009], 1.4 ± 0.3 right superior pulmonary vein [P = 0.044], 1.1 ± 0.3 right inferior pulmonary vein [P = 0.032]). CONCLUSIONS: Our results show that despite deep sedation pain reactions often occur during RF ablation. Knowledge of areas with more frequent pain reactions may help electrophysiologists to reduce pain reactions and related patient movements. Ablation with cryoenergy was significantly less painful compared to ablation with RF energy. Cryoablation therefore may be considered for patients at a higher risk for anesthesia-related complications.

[Mapping and ablation of a mechanically blocked concealed accessory pathway under repeated adenosine bolus infusions]. / Mapping und Ablation einer mechanisch blockierten akzessorischen Leitungsbahn unter wiederholten Adenosin-Bolusgaben.

During mapping and catheter ablation of an accessory pathway, a mechanically induced conduction block can occur. Adenosine is used to detect dormant conduction of incomplete ablation lesions. Presented in this article is the case of a patient with a left-sided accessory pathway, which was mechanically blocked during the mapping procedure and could only be successfully ablated after repeated adenosine bolus infusions, which resulted in intermittent restitution of conduction via the accessory pathway.

Role of iron deficiency and anemia in cardio-renal syndromes.

Chronic heart failure is a common disorder associated with unacceptably high mortality rates. Chronic renal disease and anemia are two important comorbidities that significantly influence morbidity and mortality in patients with chronic heart failure (CHF). Progress in CHF again may cause worsening of kidney function and anemia. To describe this vicious cycle, the term cardio-renal anemia syndrome has been suggested. Iron deficiency is part of the pathophysiology of anemia in both CHF and chronic kidney disease, which makes it an interesting target for treatment of anemia in cardio-renal anemia syndrome. Recently, studies have highlighted the potential clinical benefits of treating iron deficiency in patients with CHF, even if these patients are nonanemic. This article summarizes studies investigating the influence of iron deficiency with or without anemia in chronic kidney disease and CHF and gives an overview of preparations of intravenous iron currently available.

Hormonal consequences and prognosis of chronic heart failure.

PURPOSE OF REVIEW: Chronic heart failure (CHF) is a major public health problem. The failure to provide peripheral tissues with sufficient amounts of oxygen is accompanied by maladaptive responses that include pathophysiological pathways that may lead to an anabolic-catabolic imbalance with the development of cardiac cachexia. This review aims to highlight players of the catabolic-anabolic imbalance, regulators or appetite, and other mediators that are involved in the progression of CHF to cachexia. RECENT FINDINGS: Clinical research has buttressed the view that deficiencies or resistance to growth hormone and testosterone plays an important role in the pathophysiology of CHF. The role of appetite regulation in the development of cardiac cachexia is also subject of recent studies. The resistance of CHF patients to the effects of appetite-stimulating peptide ghrelin may be one of the contributing factors. These circumstances drive muscle, bone, and fat wasting. Plasma levels of the adipokines leptin and adiponectin may have a role in the detection of such wasting processes. SUMMARY: Hormonal signaling pathways play an essential role in the development of cardiac cachexia. Recent findings enhance our understanding of the complex interplay between these regulators and may serve as a hub for the development of therapeutic interventions to prevent or potentially even to treat cardiac cachexia.

Parotid carcinoma metastasis to parietal meningioma: case report and molecular biologic considerations.

INTRODUCTION: A combination of factors as the meningioma's rich vascularity, its low metabolic rate, immunologic factors and the molecular pattern explains the affinity of some cancer metastasis to seed inside meningiomas. In this context, the importance of surface adhesion molecules is of rising interest. CASE REPORT: We report the exceptional case of a parotid carcinoma metastasis within a meningioma. A 68-year old male was referred to our hospital with headache and progressive right hemiparesis. Four years before he was diagnosed with parotid gland cancer for which he had undergone parotidectomy, radiation, neck dissection and chemotherapy. MRI showed a left sided high-parietal, dural-based, extraaxial, contrast enhancing tumor which was consequently removed microsurgically. Histological examination revealed a dedifferentiated parotid carcinoma metastasis inside a microcystic meningioma WHO grade I. Mechanisms that have been suggested to be responsible for metastasis into meningioma include meningiomas' rich vascularity, slow growth, their high collagen and lipid content, immunologic factors but also the expression of certain surface adhesion molecules, in particular E-cadherin. In the presented case E-cadherin immunostaining was strongly positive in the metastatic tissue that invaded the meningioma in a droppled-like fashion. We discuss the potential role of E-cadherin, re-expression of a modified E-cadherin complex and the potential importance of mesenchymal surface proteins in the pathophysiology of carcinoma metastasis into meningioma. CONCLUSION: Surface proteins of carcinoma cells might play a key role regarding their affinity to seed inside meningiomas. This might be a leading mechanism to the multifactorial process of carcinoma-to-meningioma metastasis.

Treatment with iron of patients with heart failure with and without anemia.

Iron deficiency is a common cause of anemia in otherwise healthy individuals and plays an important role in the development of anemia within the heart failure patient population. Iron-deficient heart failure patients experience worse symptoms and are less exercise tolerant than those without iron deficiency. These symptoms may occur even before clinical anemia is evident. This article reviews studies of the benefits of the use of intravenous iron to treat iron deficiency in anemic and nonanemic heart failure patients and an overview of the physiology and pathophysiology of iron metabolism in chronic heart failure.