Iron deficiency and supplementation in patients with heart failure: Results from the IRON-HF international survey.

AIMS: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, regardless of anaemia status. Iron supplementation has been demonstrated to improve exercise capacity and quality of life in patients with HF with an ejection fraction <50% and ID. This survey aimed to provide data on real-world practices related to ID screening and management. METHODS AND RESULTS: We designed and distributed an online survey (23 questions) regarding ID screening and management in the HF setting. Overall, 256 cardiologists completed the survey (59.8% male, mostly between 30 and 50 years). The majority of physicians defined ID according to the most recent HF recommendations (98.4%) and reported screening for ID in more than half of their patients (68.4%). However, only 54.3% of the respondents performed periodic screening (every 6 months to 1 year). A total of 93.0% of participants prescribed and/or administered iron supplementation, using intravenous iron as the preferred method of administration (86.3%). After iron supplementation, 96.1% of the respondents reassessed ID, most frequently at 3-6 months (67.6%). Most physicians (93.8%) perceived ID as an underestimated comorbidity in HF. Cardiologists' age, training status, subspecialty and work setting (academic vs. non-academic hospitals) were associated with heterogeneity in the answers. CONCLUSIONS: The results of this survey highlight the need for more consistent strategies of ID screening and treatment for patients with HF.

Biomarkers in Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Updated Review of the Literature.

Myocarditis is a disease caused by cardiac inflammation that can progress to dilated cardiomyopathy, heart failure, and eventually death. Several etiologies, including autoimmune, drug-induced, and infectious, lead to inflammation, which causes damage to the myocardium, followed by remodeling and fibrosis. Although there has been an increasing understanding of pathophysiology, early and accurate diagnosis, and effective treatment remain challenging due to the high heterogeneity. As a result, many patients have poor prognosis, with those surviving at risk of long-term sequelae. Current diagnostic methods, including imaging and endomyocardial biopsy, are, at times, expensive, invasive, and not always performed early enough to affect disease progression. Therefore, the identification of accurate, cost-effective, and prognostically informative biomarkers is critical for screening and treatment. The review then focuses on the biomarkers currently associated with these conditions, which have been extensively studied via blood tests and imaging techniques. The information within this review was retrieved through extensive literature research conducted on major publicly accessible databases and has been collated and revised by an international panel of experts. The biomarkers discussed in the article have shown great promise in clinical research studies and provide clinicians with essential tools for early diagnosis and improved outcomes.

Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.

OBJECTIVE: There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS. METHODS: We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS. RESULTS: Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. CONCLUSIONS: PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.

Immune checkpoint inhibitor-associated myocarditis: from pathophysiology to rechallenge of therapy - a narrative review.

Even if immune checkpoint inhibitors have revolutionized the landscape of cancer therapy, their use may be complicated by immune-related adverse events. Among these, myocarditis is the most severe complication. The clinical suspicion often arises after clinical symptoms onset and increase in cardiac biomarkers or electrocardiographic manifestations. Echocardiography and cardiac magnetic resonance imaging are recommended for each patient. However, since they may be misleadingly normal, endomyocardial biopsy remains the gold standard for establishing the diagnosis. Until now, treatment has been based on glucocorticoids even if increasing interest has risen in other immunosuppressive agents. Although myocarditis currently imposes immunotherapy discontinuation, case reports have suggested a safety rechallenge in low-grade myocarditis paving the way for further studies to respond to this unmet clinical need.

Cardiac magnetic resonance abnormalities in patients with acute myocarditis proven by septal endomyocardial biopsy.

BACKGROUND: Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB). METHODS: From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM. RESULTS: Among 74 patients [mean age 38 ± 15 years, 65% males, left ventricular ejection fraction (LVEF) 40 ± 18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p < 0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p = 0.006). CONCLUSION: In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.

[Ten questions on cardiac magnetic resonance in patients with heart failure: from etiological diagnosis to prognostic stratification]. / Dieci quesiti in tema di risonanza magnetica cardiaca nel paziente con scompenso cardiaco: dalla diagnosi eziologica alla stratificazione prognostica.

Cardiac magnetic resonance (CMR) imaging has progressively become part of the imaging methods recommended in patients with heart failure. CMR represents the gold standard for assessing volumes, function, biventricular kinetics and providing tissue characterization through scans with and without contrast medium. In patients with heart failure with reduced ejection fraction (HFrEF) and ischemic dilated cardiomyopathy, CMR allows to search for viability, accurately estimate volumes and ejection fraction. It can assess scar extent for predicting response to cardiac resynchronization therapy and for establishing an indication for implanting a defibrillator in borderline cases. In patients with HFrEF and non-ischemic dilated cardiomyopathy, CMR helps to identify specific etiological subgroups and to estimate the arrhythmic risk beyond ejection fraction. In patients with heart failure with preserved ejection fraction, CMR offers the possibility of diagnosing specific phenotypes, including sarcomeric hypertrophic cardiomyopathy, amyloidosis or Fabry disease, and adds prognostic information. Both clinical and scientific interest in this imaging method is constantly expanding; the clinicians dealing with heart failure cannot fail to know the technique, the indications and all the potential that CMR can offer.

Viral presence-guided immunomodulation in lymphocytic myocarditis: an update.

Latest statements from European and American societies recommend to rule out viral presence in endomyocardial biopsy (EMB) via polymerase chain reaction (PCR) analysis before starting immunosuppression or immunomodulation in acute lymphocytic myocarditis presenting with life-threatening scenarios. However, recommendations in myocarditis are mostly based on heterogeneous studies enrolling patients with inflammatory cardiomyopathies and established heart failure rather than acute myocarditis. Thus, definitive evidence of a survival benefit from immunomodulation guided by viral presence is currently lacking. Finally, distinguishing innocent bystanders from causative agents among EMB-detected viruses remain challenging and a major goal to achieve in the near future. Therefore, considerable divergence remains between official recommendations and clinical practice, including the possibility of starting immunosuppressive therapy empirically, without knowing viral PCR results. This review systematically discusses the unsolved issues of immunomodulation guided by viral presence in acute lymphocytic myocarditis, namely (i) virus epidemiology and prognosis, (ii) variability of viral presence rates, (iii) the role of potential viral bystander findings, and (iv) the main results of immunosuppression controlled trials in lymphocytic myocarditis. Furthermore, a practical approach for the critical use of viral presence analysis in guiding immunomodulation is provided, highlighting its importance before starting immunosuppression or immunomodulation. Future, multicentre studies are needed to address specific scenarios such as fulminant lymphocytic myocarditis and a virus-tailored management as for parvovirus B19.

Sex Differences in the Long-term Prognosis of Dilated Cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) represents a specific phenotype of heart failure. Sex differences in the long-term prognosis of patients with DCM are unknown. The aim of this study is to investigate the long-term prognostic role of gender in a large cohort of patients with DCM. METHODS: A total of 1113 patients with DCM were prospectively enrolled. To investigate the impact of sex, a propensity score-matching analysis was performed on a sample of 586 patients. Univariable and multivariable Cox models and competing-risk analyses were estimated on both cohorts for the following outcome measures: (1) all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD); (2) cardiovascular mortality/HTx/VAD; and (3) sudden cardiac death or malignant ventricular arrhythmias. RESULTS: Women were older than men (50 ± 15 years vs 47 ± 15 years, respectively, P = 0.004) and more frequently had moderate to severe left ventricular dilation (P < 0.001) and left bundle branch block (P = 0.019). At multivariable analyses, male sex was independently associated with all considered outcome measures in the total cohort. At propensity score-matching analysis, over a median follow-up of 126 months (interquartile range, 62-201), 96 men (33%) vs 66 women (22%) experienced all-cause mortality/HTx/VAD (P = 0.03), 95 men (32%) vs 57 women (20%) experienced cardiovascular mortality/HTx/VAD (P = 0.025), and 46 men (16%) vs 28 women (10%) experienced sudden cardiac death/malignant ventricular arrhythmias (P = 0.07). CONCLUSION: The long-term outcomes of women affected by DCM are more favourable than those of men, and sex emerged as an important independent factor, particularly for cardiovascular outcomes.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.

BACKGROUND: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. RESULTS: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). CONCLUSIONS: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Arrhythmic risk stratification in patients with dilated cardiomyopathy and intermediate left ventricular dysfunction.

AIMS: Arrhythmic risk stratification is a challenging issue in patients with dilated cardiomyopathy (DCM), particularly when left ventricular ejection fraction (LVEF) is more than 35%. We studied the prevalence and predictors of sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs) in DCM patients categorized at low arrhythmic risk because of intermediate left ventricular dysfunction under optimal medical treatment (OMT). METHODS: DCM patients considered at low arrhythmic risk (LVEF >35% and New York Heart Association class I-III after 6 ±â€Š3 months of OMT) were analysed. An arrhythmogenic profile was defined as the presence of at least one among a history of syncope, nonsustained ventricular tachycardia, at least 1000 premature ventricular contractions/24 h, at least 50 ventricular couplets/24 h at Holter ECG monitoring. SCD/MVAs was considered as the study end-point. RESULTS: During a median follow-up of 152 months (interquartile range 100-234), 30 out of 360 (8.3%) patients at low arrhythmic risk (LVEF 47 ±â€Š7%) experienced the study end-point [14 (3.9%) SCD and 16 (4.4%) MVA]. Compared with survivors, patients who experienced SCD/MVAs had more frequently an arrhythmogenic profile and a larger left atrium. Their LVEF at the last available evaluation before the arrhythmic event was 36 ±â€Š12%. At multivariable analysis, left atrial end-systolic area [hazard ratio 1.107; 95% confidence interval (95% CI) 1.039-1.179, P = 0.002 for 1 mm increase] and arrhythmogenic profile (hazard ratio 3.667; 95% CI 1.762-7.632, P = 0.001) emerged as predictors of SCD/MVAs during follow-up. CONCLUSION: A consistent quota of DCM patients with intermediate left ventricular dysfunction receiving OMT experienced SCD/MVA during follow-up. Left atrial dilatation and arrhythmogenic pattern were associated with a higher risk of SCD/MVA.

Current diagnostic strategies for dilated cardiomyopathy: a comparison of imaging techniques.

INTRODUCTION: Dilated cardiomyopathy (DCM) is generally thought as a final common pathway of several conditions leading to the same clinical phenotype. Multiple imaging modalities play a fundamental role in recognizing the underlying pathological substrate in DCM. Areas covered: Echocardiography represents the first reliable and easily accessible diagnostic tool, allowing the identification of associated cardiac abnormalities, such as valve disease and highlighting features associated with an adverse prognosis. Recent advances in technology such as strain analysis and 3D-echocardiography have improved the diagnostic and prognostic capabilities of this technique. Cardiac magnetic resonance (CMR) is considered the gold standard for an accurate and reproducible assessment of ventricular volumes and ejection fraction. In addition, CMR allows us to perform tissue characterization that, through new sophisticated sequences, could be obtained even without gadolinium. Nuclear images could be useful to identify specific causes of left ventricular dysfunction, such as cardiac sarcoidosis and amyloidosis. Finally, endomyocardial biopsy is generally performed if acute myocarditis is suspected in high-risk patients. Expert commentary: Strengths and limitations are different for every method, but multiparametric evaluation of patients and family members could progressively improve current understanding of the disease. This is fundamental to specifically target therapy, allowing us to improve patients' prognosis.