Heart Of Iron IV

Heart Of Iron IV

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From the heart of the battlefield to the command center, you will guide your nation to glory and wage war, negotiate or invade. You hold the power to tip the very balance of WWII. It is time to show your ability as the greatest military leader in the world. Will you relive or change history Will you change the fate of the world by achieving victory at all costs

Iron deficiency occurs in approximately 50% of heart failure (HF) patients and is associated with reductions in functional capacity, quality of life, and life expectancy, independent of the presence of anemia or left ventricular ejection fraction (LVEF).1 In addition to its impact on erythropoiesis and oxygen delivery, iron deficiency adversely affects oxidative metabolism and cellular immune mechanisms that impact myocardial function.1 Myocardial iron deficiency is correlated with reduced myocardial oxygen consumption and abnormal myocardial metabolism.1 Given these epidemiologic and pathophysiologic concerns, correction of iron deficiency has become an important target in HF management.

Treatment of iron deficiency with high dose oral iron has been studied in the IRONOUT-HF study and showed no improvement in exercise capacity at 16 weeks.2 One of the potential reasons for failure of oral iron is hepcidin-mediated inhibition of iron absorption, a problem that can be avoided by using intravenous (IV) administration of iron. Multiple studies have examined the role of IV iron in patients with chronic systolic HF and iron deficiency. The FAIR-HF study randomized 459 stable outpatients with NYHA Class II-III HF and an LVEF of

AFFIRM-AHF was a multicenter, randomized, double blind, placebo-controlled trial conducted to answer the question: do hospitalized, acute heart failure patients with iron deficiency benefit from iron replacement with IV ferric carboxymaltose (FCM)6 The investigators included patients hospitalized with acute HF with an LVEF

The primary composite outcome (HF hospitalizations, cardiovascular death) occurred at a rate of 57.2 per 100 patient years in the FCM group and 72.5 per 100 patient years in the placebo group (rate ratio 0.79, p = 0.059). There was no difference in cardiovascular death (14% in both groups) but there was a significant reduction in total HF hospitalizations (rate ratio 0.74, p = 0.013). Furthermore, in the COVID-19 sensitivity analysis, the primary outcome was significantly reduced with treatment with FCM (rate ratio 0.75, p = 0.024). The investigators concluded that treatment with ferric carboxymaltose reduced the risk of heart failure hospitalizations but did not reduce the risk of cardiovascular death.

Aptly named, the AFFIRM-AHF trial does, in fact, affirm our understanding of the benefits and limitations of IV iron replacement in patients with HF. Similar to prior experience in FAIR-HF and CONFIRM-HF, correction of iron deficiency with IV iron confers a reduction in HF hospitalizations and an improvement in patient reported symptomatology and functional status, although with no cardiovascular mortality benefit.3,4 As such, IV iron represents an important treatment option for patients with HF, but it does not currently ascend into the upper echelon of \"must use\" medications that improve survival.

Perhaps most importantly, AFFIRM-AHF demonstrates that the administration of IV iron during hospitalization for acute HF decompensation is safe and effective, thus obviating the need to delay until the patient returns for follow-up in the outpatient setting. This finding continues a recent trend of HF goal-directed medical therapy (GDMT) publications that have broken down the \"silos\" of inpatient versus outpatient initiation of key HF medications. Despite FDA approval, both sacubitril-valsartan and the SGLT-2 inhibitors were omitted from hospital formularies (resulting in missed opportunities for initiation and low overall utilization rates) due to concern that they had not been shown to be safe to initiate in a hospitalized, acutely decompensated HF patient. This led to the design and execution of studies like PIONEER-HF7 and EMPA-RESPONSE AHF8; only after these publications were the agents made available to hospital practitioners. We welcome the findings of AFFIRM-AHF, as in our experience, the prescription and initiation of IV iron in the outpatient setting is complicated by logistical challenges. If given in conjunction with a clinic visit, IV iron requires the establishment of vascular access and the designation of a dedicated infusion room where the patient can receive the medication and wait the appropriate amount of time to ensure no adverse reactions have occurred. Also, affordability of the infusion for patients has proven to be highly variable based on third-party reimbursement. As a result, many patients who would benefit from IV iron replacement go untreated or undertreated with the aforementioned oral medications. Furthermore, given the relative paucity of evidence-based pharmacotherapies for patients with acute HF, the AFFIRM-HF identifies treatment of iron deficiency as a meaningful intervention and supports the case for widespread screening for iron deficiency in all patients hospitalized with acute decompensated systolic heart failure.

Of note, the IV iron regimen utilized in AFFIRM-HF was initiated during hospitalization, but then completed in the outpatient setting over the course of weeks, with most patients in the FCM arm (80%) only requiring one or two infusions over the course of the study. In real world practice, providers must consider the risk of unfinished regimens due to loss of follow-up, affordability, and the logistical issues described above. A previous small publication showed that IV ferric gluconate can be given safely in a more accelerated fashion over the course of 2-3 days, a regimen we have used successfully to complete iron replacement during an inpatient encounter at our institution for years.9 This pragmatic strategy ensures expeditious correction of iron deficiency and can prevent the patient from shouldering the burdens of outpatient charges to complete this important therapy. However, further studies would be warranted to validate this strategy and to determine if all IV iron formulations carry the same degree of sustained clinical benefit (class effect).

In summary, AFFIRM-AHF clarifies the benefit of identifying and treating iron deficiency with IV iron in patients hospitalized with acute decompensated HF. Furthermore, we hope that this also helps to usher in an era where HF GDMT is thoughtfully prescribed at any patient encounter, whether inpatient or outpatient, as the benefits of these medications are too important to be subject to \"location restrictions\" that are increasingly proving to be arbitrary.

So, Hearts of Iron 4: By Blood Alone is a solid addition to the series. There are some high points to the DLC, and if you want to play any of the new nation trees, I heartily recommend it. Italy, Ethiopia and Switzerland all add fun new experiences to the game and are a fun run to do. However, while the small changes which affect all nations are very welcome, its price a large expense for those who just want to play nations other than Italy, Ethiopia, and Switzerland, and a couple of the mechanics need refinement and improvement (such as the aircraft designer and the peace conference mechanics). 59ce067264

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