Unravelling the Fate of Coronary Artery Disease in Patients Undergoing Valve Replacement for Severe Aortic Valve Stenosis.

Severe aortic valve stenosis is the most frequent valve pathology in the western world and approximately 50% of these patients have concomitant coronary artery disease (CAD). Revascularization of proximal obstructive CAD in patients undergoing surgical aortic valve replacement (SAVR) is common practice considered appropriate. However, the management of patients with CAD undergoing transcatheter aortic valve implantation (TAVI) is more controversial. Nevertheless, performing percutaneous coronary intervention (PCI) of significant ( > 70%) proximal coronary lesions is a widely adopted strategy, but robust supporting scientific evidence is missing. Some studies suggest that complex CAD with incomplete revascularization negatively impacts outcomes post-TAVI. As increasingly younger patients are undergoing TAVI, optimizing the long-term outcomes will become more important. Although PCI in TAVI patients is safe, no benefit on outcomes has been demonstrated, possibly due to an inadequate selection of prognostically important lesions for revascularization. A possible solution might be the use of coronary physiological indices, but these have their own limitations and more data is needed to support widespread adoption. In this review we provide an overview of current evidence on the outcomes after aortic valve replacement (AVR) and the evidence regarding revascularization in this population.

Heart Failure-Related Outcomes in Patients with Left Ventricular Dysfunction Undergoing Percutaneous Chronic Total Occlusion Revascularization.

Background: The presence of a chronic total occlusion (CTO) and severe left ventricular (LV) systolic dysfunction are known negative prognostic factors in patients with coronary artery disease. Several studies have examined the effect of CTO revascularization on mortality, symptoms, occurrence of myocardial infarction (MI), and cardiac function in patients with normal or reduced LV function. However, the effect of CTO revascularization on heart failure-related events in patients with LV dysfunction, such as heart failure hospitalization (HFH), the occurrence of atrial fibrillation (AF), and a worsening renal function (WRF), has not yet been evaluated. To assess the success rate and safety of CTO percutaneous coronary interventions (PCIs) in coronary patients with LV ejection fractions of ≤ 40% and evaluate the impact of successful CTO revascularization on HFH, occurrence of AF, and WRF. Methods: Prospectively, data were collected from CTO PCIs performed at three referral centers and analyzed. From a total of 1435 CTO PCIs, 132 (9.2%) patients with a left ventricular ejection fraction (LVEF) of ≤ 40% were included in this analysis. The median follow-up duration was 23.18 months (interquartile range (IQR): 11.02-46.66 months). Results: A successful CTO PCI was achieved in 109 of these patients, while the procedure was unsuccessful in 23 patients (82.5% procedural success rate). Overall, the intervention had an acceptable number of peri-procedural (or in-hospital) complications (9.1%). During the follow-up period, the rates of all-cause death, cardiovascular death, and non-fatal MI were not significantly different between the two groups. The rates of HFH were significantly lower in the successful PCI group, while WRF and AF did not differ between successful and unsuccessful PCI groups. Successful PCI and higher estimated glomerular filtration rate (eGFR) were independent predictors of a lower risk of HFH, while prior stroke and diabetes were independent predictors of a higher risk of HFH. Conclusions: In patients with reduced LV systolic function (ejection fraction, EF ≤ 40%), CTO PCI is a safe and effective procedure and successful CTO PCI is independently associated with a lower risk of HFH during follow-up. Further expansion of this cohort is necessary to confirm these results.

The coronary and microcirculatory measurements in patients with aortic valve stenosis study: rationale and design.

Although concomitant coronary artery disease (CAD) is frequent in patients with severe aortic stenosis (AS), hemodynamic assessment of CAD severity in patients undergoing valve replacement for severe AS is challenging. Myocardial hypertrophic remodeling interferes with coronary blood flow and may influence the values of fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). The aim of the current study is to investigate the effect of the AS and its treatment on current indices used for evaluation of CAD. We will compare intracoronary hemodynamics before, immediately after, and 6 mo after aortic valve replacement (AVR) when it is expected that microvascular function has improved. Furthermore, we will compare FFR and resting full-cycle ratio (RFR) with myocardial perfusion single-photon emission-computed tomography (SPECT) as indicators of myocardial ischemia in patients with AS and CAD. One-hundred consecutive patients with AS and intermediate CAD will be prospectively included. Patients will undergo pre-AVR SPECT and intracoronary hemodynamic assessment at baseline, immediately after valve replacement [if transcatheter AVR (TAVR) is chosen], and 6 mo after AVR. The primary end point is the change in FFR 6 mo after AVR. Secondary end points include the acute change of FFR after TAVR, the diagnostic accuracy of FFR versus RFR compared with SPECT for the assessment of ischemia, changes in microvascular function as assessed by the index of microcirculatory resistance (IMR), and the effect of these changes on FFR. The present study will evaluate intracoronary hemodynamic parameters before, immediately after, and 6 mo after AVR in patients with AS and intermediate coronary stenosis. The understanding of the impact of AVR on the assessment of FFR, NHPR, and microvascular function may help guide the need for revascularization in patients with AS and CAD planned for AVR.

Economical aspects of coronary angiography for diagnostic purposes: a Belgian perspective.

Coronary angiography (CA) is an increasing diagnostic procedure in Belgium. The aim of this analysis was to look at the financial aspects of CA in a large tertiary Belgium hospital to establish if current reimbursement is appropriate. For the analysis of costs we considered the use of the catheterisation laboratory, personnel costs and material costs during multiple weekly periods in the spring of 2023. We calculated that one cathlab needs to perform 8.21 CA's to equal incomes with costs. To allow for a small positive income (200€) for the hospital/cardiologist 9 procedures per cathlab day are required. Our hospital performs a 7 (mean) ± 0.75 (standard deviation) of CA's per cathlab day and therefore does not reach this financial break-even point. Our calculations are on the safe side, since coronary physiological interrogation with fractional flow reserve (FFR) was excluded from this analysis. Nevertheless, this is a cost-effective technique for which no extra reimbursement is foreseen in the current Belgium system.

Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices.

BACKGROUND: Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta-analysis was to study immediate and long-term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). METHODS AND RESULTS: Lesion-specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (-0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. CONCLUSIONS: TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut-offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

Phantom study of augmented reality framework to assist epicardial punctures.

Purpose: The objective of this study is to evaluate the accuracy of an augmented reality (AR) system in improving guidance, accuracy, and visualization during the subxiphoidal approach for epicardial ablation. Approach: An AR application was developed to project real-time needle trajectories and patient-specific 3D organs using the Hololens 2. Additionally, needle tracking was implemented to offer real-time feedback to the operator, facilitating needle navigation. The AR application was evaluated through three different experiments: examining overlay accuracy, assessing puncture accuracy, and performing pre-clinical evaluations on a phantom. Results: The results of the overlay accuracy assessment for the AR system yielded 2.36±2.04 mm. Additionally, the puncture accuracy utilizing the AR system yielded 1.02±2.41 mm. During the pre-clinical evaluation on the phantom, needle puncture with AR guidance showed 7.43±2.73 mm, whereas needle puncture without AR guidance showed 22.62±9.37 mm. Conclusions: Overall, the AR platform has the potential to enhance the accuracy of percutaneous epicardial access for mapping and ablation of cardiac arrhythmias, thereby reducing complications and improving patient outcomes. The significance of this study lies in the potential of AR guidance to enhance the accuracy and safety of percutaneous epicardial access.

Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds.

BACKGROUND: Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety. METHODS: Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion. RESULTS: Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates. CONCLUSIONS: Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions: Design and rationale of the SONAR trial.

BACKGROUND: The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction. STUDY DESIGN AND OBJECTIVES: The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events. CONCLUSIONS: The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Gender Differences in the Impact of Coronary Artery Disease and Complete Revascularization on Long-Term Outcomes After Transcatheter Aortic Valve Implantation.

In this study, we compare gender-specific clinical outcomes. We show that outcomes among women after transcatheter aortic valve implantation are significantly influenced by co-existing coronary artery disease (CAD) and its complexity, whereas in men, this is less pronounced. Moreover, we identified a subgroup of women with complex CAD who are at particularly high risk for fatal cardiovascular events, even when compared with men with similar CAD.

Clinical outcomes of coronary intravascular lithotripsy in patients with stent failure (COIL registry).

BACKGROUND: Intravascular lithotripsy (IVL) has been demonstrated to be an effective treatment of calcified de novo coronary lesions. Safety data on the use of IVL within stented segments are lacking. We sought to evaluate the safety, feasibility, and long-term outcomes of IVL in patients with stent failure. METHODS: This was a retrospective multi-centre registry that included consecutive patients with stent failure who had undergone IVL treatment. The primary efficacy endpoint was procedural success defined as residual stenosis <30% (determined by quantitative coronary angiography analysis) in patients who survived hospital admission without in-hospital adverse events. Major adverse cardiovascular events (MACE) were defined as the composite endpoints of cardiovascular death, spontaneous myocardial infarction, and target vessel revascularisation at one-year follow up. RESULTS: 102 patients were included in this study. Mean age was 73 ± 9 years and 81% were male. The duration from previous stent implantation and IVL treatment was 24 (interquartile range 7-76) months, of which 10.8% received IVL for acute under-expanded stent. IVL treatment allowed significant improvement in both minimal lumen diameter (1.14 ± 0.60 to 2.53 ± 0.59, P < 0.001) and degree of stenosis (66.8 ± 19.9 to 20.3 ± 11.3%, P < 0.001). The rate of procedural success was 78.4% (80/102 of patients). The one-year MACE was 15.7%. Ostial disease (HR 5.16; 95% CI 1.19 to 22.33; P = 0.028) and lesion length (HR 1.05; 95% CI 1.01 to 1.10; P = 0.010) were independently associated with one-year MACE. CONCLUSIONS: In patients with stent failure, IVL is a safe and feasible treatment for this high-risk group.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Coronary physiology to guide treatment of coronary artery disease in a patient with severe aortic valve stenosis: friend or foe? A case report.

Background: Severe aortic valve stenosis (AS) is the most frequent valve pathology in the developed world requiring intervention. Due to common factors in pathogenesis, patients with AS frequently have concomitant coronary artery disease (CAD). Determining the relative contribution of each component to the disease state is not easy as there is much overlap in complaints. Moreover, severe AS interferes with the haemodynamic assessment of intermediate coronary lesions. Case summary: In this case report we describe the presentation and management of an 84-year-old patient, with a severely degenerated aortic valve bioprosthesis and an intermediate coronary artery lesion, presenting with acute decompensated heart failure and chest pain. Initial invasive haemodynamic assessment of the coronary lesion provided challenging findings and a second catheterization and intervention was needed to free the patient from his chest pain. Discussion: Optimal assessment and treatment of CAD before valve replacement are controversial. Aortic valve stenosis on itself can lead to subendocardial ischaemia with subsequent angina pectoris. Simultaneously, AS can significantly affect coronary haemodynamics, hereby interfering with intra-coronary haemodynamic assessment of co-existing coronary lesions. Currently used coronary physiological indices are not validated in the AS population and valve replacement has variable effects on the fractional flow reserve and commonly used resting indices, such as the resting full-cycle ratio. Further research on this topic is needed and an overview of currently running studies that will advance this field significantly is provided.

The Effect of Coronary Lesion Complexity and Preprocedural Revascularization on 5-Year Outcomes After TAVR.

BACKGROUND: Aortic stenosis and coronary artery disease (CAD) frequently coincide. However, the management of coexisting CAD in patients undergoing transcatheter aortic valve replacement (TAVR) remains controversial. OBJECTIVES: This study sought to determine whether the presence of CAD, its complexity, and angiography-guided percutaneous coronary intervention (PCI) are associated with outcomes after TAVR. METHODS: All patients undergoing TAVR at a tertiary referral center between 2008 and 2020 were included in a prospective observational study. Baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) and, whenever applicable, a residual SS after PCI were calculated. A multivariate analysis was performed to determine the effect of CAD, stratified according to complexity, and PCI on 5-year outcomes. RESULTS: In 604 patients, the presence of CAD and its complexity were significantly associated with worse 5-year survival (SS 0: 67.9% vs SS 1-22: 56.1% vs SS >22: 53.0%; log-rank P = 0.027) and increased cardiovascular mortality (SS 0: 15.1% vs SS 1-22: 24.0% vs SS >22: 27.8%; log-rank P = 0.024) after TAVR. Having noncomplex CAD (SS 1-22) was an independent predictor for increased all-cause mortality (HR: 1.43; P = 0.046), while complex CAD (SS >22) increased cardiovascular mortality significantly (HR: 1.84; P = 0.041). Angiography-guided PCI or completeness of revascularization was not associated with different outcomes. CONCLUSIONS: The presence of CAD and its anatomical complexity in patients undergoing TAVR are associated with significantly worse 5-year outcomes. However, angiography-guided PCI did not improve outcomes, highlighting the need for further research into physiology-guided PCI.

Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops.

BACKGROUND: Shear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties. OBJECTIVES: This study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method. METHODS: In 15 pigs, conventional and high-frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury. RESULTS: Shear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant ß (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001). CONCLUSIONS: Shear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

The importance of dose optimisation in the treatment of iron deficiency in heart failure.

Background: Treatment with ferric carboxymaltose (FCM) is limited to 1 g during one administration, which is insufficient in patients with a higher body weight or low haemoglobin (Hb). As a consequence, under-dosing might be common in clinical practice, yet the consequences remain unstudied.Methods: We retrospectively assessed all HFrEF-patients with iron-deficiency (ferritin <100 µg/l or between 100 and 300 µg/l if TSAT < 20%) receiving treatment with FCM between 2015 and 2017. This time-frame was chosen as during this we used a 1-g FCM-regimen for all patients (unless Hb = 14-15 mg/dl, than 500 mg). We compared the actual given dose versus the calculated target dose (according to the SmPC, with the difference between both being the dose deficit). We assessed the impact of dose deficits on clinical and biochemical status after 12 weeks.Results: A total of 211 HFrEF patients were analysed. The actual given dose FCM was 918 ± 188 mg, while the calculated target dose was 1308 ± 470 mg. In 121(61%) patients, a standard dose of 1-g FCM resulted in a dose deficit, of whom 93 had a dose deficit of 500 mg and 35 had a dose deficit of 1000 mg. Follow-up was available in 81% of patients (median = 12 weeks). A dose deficit of 500 mg was associated with a 4.93 higher odds, while a dose deficit of 1000 mg was associated with a 7.78 higher odds of residual iron deficiency. After adjusting for baseline NYHA-class, a dose deficit was associated with less symptomatic improvement. During 442 ± 292 days of follow-up, 68 patients were readmitted with heart failure and 15 patients died. In an univariate model (but not in a multivariate model), a dose deficit was associated with adverse clinical outcome.Conclusion: A majority of HFrEF patients with iron deficiency require doses exceeding 1 g of FCM, and thus require follow-up appointments to correct a residual dose deficit. A residual dose deficit is associated with less functional and biochemical improvement.

Prevalence of underlying gastrointestinal malignancies in iron-deficient heart failure.

AIMS: Anaemia and iron deficiency (ferritin level < 100 or 100-300 µg/L with transferrin saturation < 20%) are prevalent in heart failure. Mechanistically, iron deficiency is linked to poor intestinal uptake, increased intestinal loss, and chronic inflammation. However, the prevalence of underlying gastrointestinal malignancies is not established in iron-deficient heart failure with or without anaemia. METHODS AND RESULTS: Patients followed up in a single-centre, heart failure database with baseline registration of haemoglobin and iron status were retrospectively evaluated. The proportion of patients undergoing upper and lower gastrointestinal endoscopy between inclusion and censoring was determined. Afterwards, the prevalence of biopsy that confirmed intestinal malignancies in relation to baseline iron and haemoglobin status was determined. Anaemia was defined as a haemoglobin level <12 g/dL, and iron deficiency according to the aforementioned criteria. Of the 1197 patients in the database, 699 (59%) patients underwent full endoscopic workup over a mean follow-up of 50 ± 27 months. A total of 50 intestinal malignancies were identified (n = 42, 84%, in iron-deficient vs. n = 8, 16%, non-iron-deficient patients; P < 0.001). The prevalence of intestinal malignancies was non-statistically different in iron-deficient patients with anaemia (n = 12/129, 9.3%) or without anaemia (n = 30/287, 10.5%; P = 0.551). The prevalence was much lower in patients without iron deficiency with anaemia (n = 5/83, 6%) or without anaemia (n = 3/200, 1.5%). In patients with iron deficiency but without anaemia (a group in which the role of endoscopic workup is less established), ferritin levels carried an inverse diagnostic capacity in detecting patients with an underlying malignancy (area under the curve = 0.741, P < 0.001). A ferritin level < 56 µg/L had the best acuity, detecting malignancies with a sensitivity of 80% and a specificity of 71%. CONCLUSIONS: Endoscopic evaluation is warranted in heart failure patients with iron-deficient anaemia given the high prevalence of underlying intestinal malignancies, as advised by gastroenterology guidelines. However, additional research is needed assessing the best approach to patients with iron deficiency without anaemia, given the high occurrence of intestinal malignancies in these patients. A lower ferritin level could potentially help stratify the need for an endoscopic workup in these patients.