Life-Threatening Arrhythmias in Patients With Takotsubo Syndrome: Insights Into Pathophysiology and Treatment Innovations.

Takotsubo syndrome (TTS) is a reversible form of acute myocardial injury due to a neurocardiogenic mechanism associated with a relevant risk for life-threatening ventricular arrhythmias, occurring in up to 25% of all patients and including both ventricular arrhythmias (especially) in the context of QT prolongation and atrial tachy- or bradyarrhythmias. The pathogenetic mechanisms of TTS-related arrhythmic complications are not completely understood, and there are no randomized clinical trials addressing the pharmacologic and nonpharmacologic management in this specific setting. In this narrative review, the authors provide an overview of the pathogenesis and the therapeutic management of arrhythmic complications in patients with TTS, along with the future perspectives and the remaining knowledge gaps in this field.

Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer.

BACKGROUND: Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy. METHODS: Ten patients (69 [61-76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured. RESULTS: The VO2peak was reduced at baseline (1.245 [0.882-1.605] L·min- 1; 70 [62-86] %-predicted) and significantly declined (1.095 [0.810-1.448] L·min- 1, P = 0.047; 62 [56-76] %-predicted, P = 0.005) at 6.0 [3.0-6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27-1.88] to 1.57 [1.12-1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56-65]% to 66 [57-68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7-41.6] vs. 12.8 [3.1-35.9]). The hsCRP increased significantly from 4.4 [1.4-5.8] to 6.1 [3.7-20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49-125] to 121 [88-191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8-25] to 15.5 [11.5-20]; P = 0.021) post-radiotherapy. CONCLUSIONS: Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Innate and adaptive immunity in acute myocarditis.

Acute myocarditis is an acute inflammatory cardiomyopathy associated with cardiac damage triggered by a virus or a pathological immune activation. It may present with a wide range of clinical presentations, ranging from mild symptoms to severe forms like fulminant myocarditis, characterized by hemodynamic compromise and cardiogenic shock. The immune system plays a central role in the pathogenesis of myocarditis. In fact, while its function is primarily protective, aberrant responses can be detrimental. In this context, both innate and adaptive immunity play pivotal roles; notably, the innate system offers a non-specific and immediate defense, while the adaptive provides specialized protection with immunological memory. However, dysregulation in these systems can misidentify cardiac tissue, triggering autoimmune reactions and possibly leading to significant cardiac tissue damage. This review highlights the importance of innate and adaptive immune responses in the progression and treatment of acute myocarditis.

The role and application of current pharmacological management in patients with advanced heart failure.

In the last decades, several classifications and definitions have been proposed for advanced heart failure (ADVHF) patients, including clinical, functional, hemodynamic, imaging, and electrocardiographic features. Despite different inclusion criteria, ADVHF is characterized by some common items, such as drug intolerance, low arterial pressure, multiple organ dysfunction, chronic kidney disease, and diuretic use dependency. Additional features include fatigue, hypotension, hyponatremia, and unintentional weight loss associated with a specific laboratory profile reflecting systemic multiorgan dysfunction. Notably, studies evaluating guideline-directed medical therapy recently endorsed by guidelines in stable HF, including the 4 drug classes all together (i.e., betablocker, mineral corticoid antagonist, renin angiotensin inhibitors/neprilysin inhibitors, and sodium glucose transporter inhibitors), remain scarcely analyzed in ADVHF and New York Heart Association (NYHA) Class IV. Additionally, due to the common conditions associated with advanced stages, the balance between drug tolerance and potential benefits of the contemporary use of all agents is questioned. Therefore, less hard endpoints, such as exercise tolerance, quality of life (QoL) and self-competency, are not clearly demonstrated. Specific analyses evaluating outcome and rehospitalization of each drug provided conflicting results and are often limited to subjects with stable conditions and less advanced NYHA class. Current European Society of Cardiology/American Heart Association (ESC/AHA) Guidelines do not indicate the type of treatment, dosage, and administration modalities, and they do not suggest specific indications for ADVHF patients. Due to these concerns, there is an impelling need to understand what drugs may be used as the first line, what management leads to the better outcome, and what is the best treatment algorithm in this setting. In this paper, we summarize the most common pitfalls and limitations for the use of the traditional agents, and we propose a personalized approach aiming at preserve drug tolerance and maintaining adverse event protection and satisfactory QoL.

Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1.

BACKGROUND: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). METHODS: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment." RESULTS: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1ß, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. CONCLUSION: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed. METHODS: We analyzed 139 patients from three Virginia Commonwealth University Anakinra Response Trial randomized clinical trials to assess whether CRP levels predicted HF hospitalization or death in patients with STEMI, and if CRP levels influenced the effects of treatment with anakinra. RESULTS: CRP cut-off levels for prediction of the composite of death or HF hospitalization for CRP at admission, 3 and 14 days were, respectively 6.45 mg/L (100% of sensitivity and 66.1% specificity), 26 mg/L (100% of sensitivity and 78% specificity) and 9.56 mg/L (100% of sensitivity and 80% specificity). More patients with elevated CRP levels died or had a HF hospitalization (5/47 [11%] vs 0/82 [0%], p = 0.004 for CRP at admission; 5/32 [15.6%] vs 0/92 [0%], p < 0.001 for day 3 and 5/26 [19%] vs 0/89 [0%], p < 0.001 for day 14). A greater number of patients treated with anakinra had low CRP levels at 3 and 14 days compared to placebo (Odds Ratio 0.11 [95% IC 0.04-0.28], p < 0.0001 and OR 0.35 [95% CI 0.14-0.86], p = 0.02, respectively). Anakinra significantly prevented death or HF hospitalization in patients with high inflammatory burden (p = 0.04 for admission, p = 0.24 for day 3, and p = 0.05 for day 14). CONCLUSION: Patients with elevated CRP had higher incidence of HF hospitalization or death. Anakinra reduced the number of patients with elevated CRP levels and prevented death or HF hospitalization in patients with elevated CRP levels.

Skeletal muscle quality, measured via phase angle, and cardiorespiratory fitness in patients with obesity and heart failure with preserved ejection fraction.

OBJECTIVES: Cardiorespiratory fitness (CRF) is influenced by body composition quantity and quality in heart failure with preserved ejection fraction (HFpEF) and obesity. Bioelectrical impedance analysis (BIA) provides a noninvasive quantitative and qualitative body composition assessment. The aim of this study was to determine the role of phase angle (PhA), a BIA-measure of skeletal muscle quality and body cell mass, on CRF in patients with obesity and HFpEF. METHODS: Fifty-nine consecutive outpatients with HFpEF underwent cardiopulmonary exercise testing to measure CRF. Single-frequency segmental BIA was used to measure PhA and body composition quantity. Resting Doppler echocardiography and biomarkers were measured to assess cardiac function and systemic inflammation. RESULTS: Compared with patients with lower PhA, patients with higher PhA (above mean 5.8°) presented a greater absolute peak oxygen consumption (VO2; 1.83 [1.3-2.1] versus 1.39 [1.1-1.6] L/min, P = 0.003), VO2 peak adjusted for body weight (17.5 [12.3-18.1] versus 13.3 [12.7-15.2] mL/kg/min, P = 0.040), and a lower edema index (48.7 [2.9] versus 51.4% [2.7], P < 0.001) and N-terminal pro-B-type natriuretic peptide (NT-proBNP; 64 [50-121] versus 183 [68-343.5] pg/dL, P < 0.001). In the overall sample, PhA was correlated with absolute VO2 peak (r = 0.468, P < 0.001), VO2 peak adjusted for body weight (r = 0.368, P = 0.004), VO2 peak adjusted for fat-free mass (r = 0.315, P = 0.015), edema index (r = -0.508, P < 0.001), and NT-proBNP (r = -0.579, P < 0.001). PhA remained a significant predictor for CRF even after adjustment for potential confounders and HFpEF severity. CONCLUSION: In patients with obesity and HFpEF, a greater PhA is an independent predictor for favorable CRF.

Interleukin-1 blockade in heart failure: an on-treatment and off-treatment cardiorespiratory fitness analysis.

AIMS: Interleukin-1 (IL-1) blockade may improve exercise capacity in patients with heart failure (HF) patients. The extent of the improvement and its persistence beyond discontinuation of IL-1 blockade is unknown. METHODS AND RESULTS: The primary objective was to determine changes in cardiorespiratory fitness and cardiac function on-treatment with IL-1 blocker, anakinra, and off-treatment, after treatment cessation. We performed cardiopulmonary exercise testing, Doppler echocardiography, and biomarkers in 73 patients with HF, 37 (51%) females, 52 (71%) Black-African-American, before and after treatment with anakinra 100 mg daily. In a subset of 46 patients, testing was also repeated after treatment cessation. Quality of life was assessed in each patient using standardized questionnaires. Data are presented as median and interquartile range. Treatment with anakinra for 4 [2-12] weeks was associated with a significant improvement in high-sensitivity C-reactive protein (from 6.2 [3.3-15.4] to 1.4 [0.8-3.4] mg/L, P < 0.001), peak oxygen consumption (VO2peak , from 13.9 [11.6-16.6] to 15.2 [12.9-17.4] mL/kg/min, P < 0.001). Ventilatory efficiency, exercise time, Doppler-derived signs and biomarkers of elevated intracardiac pressures, and quality-of-life measures also improved with anakinra. In the 46 patients in whom off-treatment data were available 12 [4-12] weeks later, many of the favourable changes seen with anakinra were largely reversed (from 1.5 [1.0-3.4] to 5.9 [1.8-13.1], P = 0.001 for C-reactive protein, and from 16.2 [14.0-18.4] to 14.9 [11.5-17.8] mL/kg/min, P = 0.017, for VO2peak ). CONCLUSIONS: These data validate IL-1 as an active and dynamic modulator of cardiac function and cardiorespiratory fitness in HF.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.

Left atrial strain analysis improves left ventricular filling pressures non-invasive estimation in the acute phase of Takotsubo syndrome.

AIMS: The aim of our study is to assess the ability of left atrial (LA) strain values to improve left ventricular and diastolic pressure (LVEDP) non-invasive estimation as compared with traditional echocardiographic indexes in the acute phase of Takotsubo syndrome (TTS) and to predict adverse in-hospital outcomes in this population. METHODS AND RESULTS: Consecutive TTS patients were prospectively enrolled. Left ventricular and diastolic pressure was measured at the time of catheterization. Transthoracic echocardiography was performed within 48 h from hospital admission. In-hospital complications (acute heart failure, death from any cause, and life-threatening arrhythmias) were collected. A total of 62 patients were analysed (72.2 ± 10.1 years, female 80%) and in-hospital complications occurred in 25 (40.3%). Left ventricular and diastolic pressure mean value was 24.53 ± 7.92 mmHg. Left atrial reservoir and pump strain values presented higher correlation with LVEDP (r -0.859, P < 0.001 and r -0.848, P < 0.001, respectively) in comparison with E/e ' ratio, left atrial volume index (LAVi), and tricuspid regurgitation (TR) peak velocity. In addition, at receiver-operating characteristic curve analysis, LA reservoir and pump strain resulted to be better predictors of LVEDP above the mean of our population [0.909 (95% CI 0.818-0.999, P < 0.001) and 0.889 (95% CI 0.789-0.988, P < 0.001)], respectively] as compared with E/e' ratio, LAVi, and TR peak velocity.Finally, LA reservoir strain resulted to be an independent predictor of worse in-hospital outcomes, together with LVEDP and left ventricular ejection fraction (all P < 0.001). CONCLUSION: In our study, lower LA reservoir and pump strain values were better predictors of LVEDP as compared with traditional echocardiographic indexes in the acute phase of TTS syndrome. Moreover, LA reservoir strain was an independent predictor of adverse in-hospital outcomes.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction.

PURPOSE: - Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique. METHODS: - Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range. RESULTS: - Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56-72] years. Global stress MBF was 2.43 ml/min/g [2.16-2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07-2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81-0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e' and E/e' respectively). CONCLUSION: - Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

Cancer incidence and mortality in patients diagnosed with heart failure: results from an updated systematic review and meta-analysis.

BACKGROUND: Several cohort studies aimed at demonstrating an increased risk of cancer incidence and mortality in patients with a pre-existing diagnosis of heart failure (HF); however, conflicting results have been reported that call for systematic review and meta-analysis. METHODS: We conducted a systematic search of multiple databases from their inception through July 2022 and retrieved only papers reporting hazard ratios (HR). Random and fixed-effects models were fit for the study duration. RESULTS: The analysis included nine cohort studies for a total of 515'041 HF cases and 1'365'452 controls without HF. Although high heterogeneity among studies was observed, the HR for incident cancer in HF patients was statistically significant (1.45, 95% CI 1.31-1.61, p < 0.0001), which was confirmed by sensitivity analyses; however, by analyzing the few papers reporting HRs for cancer mortality, no significant difference between HF and non-HF patients could be detected (HR 2.03, 95% CI [0.93-4.43], p = 0.0736). Further scrutiny of studies with adjusted HRs, when available, confirmed that cancer incidence was significantly increased in patients with HF, as was cancer mortality as well. CONCLUSIONS: This meta-analysis shows that HF patients are at an increased risk of incident cancer. Increased mortality could not be firmly demonstrated by the available data. Our results call for inclusion of cancer-related endpoints in HF trials to adequately address this important clinical issue.

Heart Failure After ST-Elevation Myocardial Infarction: Beyond Left Ventricular Adverse Remodeling.

ST-segment elevation myocardial infarction (STEMI) remains a significant source of morbidity and mortality worldwide. Despite advances in treatment leading to a significant reduction in the early complications and in-hospital mortality, a significant proportion of STEMI survivors develop heart failure (HF) at follow-up. The classic paradigm of HF after STEMI is one characterized by left ventricular adverse remodeling (LVAR) and encompasses the process of regional and global structural and functional changes that occur in the heart as a consequence of loss of viable myocardium, increased wall stress and neurohormonal activation, and results in HF with reduced ejection fraction (HFrEF). More recently, however, with further improvements in the treatment of STEMI the incidence and entity of LVAR appear to be largely reduced, yet the risk for HF following STEMI is not abolished and remains substantial, identifying a new paradigm by which patients with STEMI present with HF and preserved EF (HFpEF) characterized by reduction of diastolic or systolic reserve independent of LVAR.

Cardiac Imaging in Childhood Cancer Survivors: A State-of-the-Art Review.

Childhood cancer survival has improved significantly in the past few decades, reaching rates of 80% or more at 5 years. However, with improved survival, early- and late-occurring complications of chemotherapy and radiotherapy exposure are becoming progressively more evident. Cardiovascular diseases represent the leading cause of non-oncological morbidity and mortality in this highly vulnerable population. Therefore, the necessity of reliable, noninvasive screening tools able to early identify cardiac complications early is now pre-eminent in order to implement prevention strategies and mitigate disease progression. Echocardiography, may allow identification of myocardial dysfunction, pericardial complications, and valvular heart diseases. However, additional imaging modalities may be necessary in selected cases. This manuscript provides an in-depth review of noninvasive imaging parameters studied in childhood cancer survivors. Furthermore, we will illustrate brief surveillance recommendations according to available evidence and future perspectives in this expanding field.

QT Prolongation and In-Hospital Ventricular Arrhythmic Complications in Patients With Apical Ballooning Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly high-risk of arrhythmias. OBJECTIVES: The aim of the study was to determine the association of QT interval on electrocardiogram for ventricular arrhythmic complications in patients with apical ballooning Takotsubo syndrome in a diverse population at a large urban hospital in the U.S. METHODS: We reviewed 105 cases of apical ballooning Takotsubo syndrome in patients admitted between 2011 and 2017. Two cardiologists reviewed the electrocardiograms to measure QT interval, adjusted for rate using the Fridericia formula (QTCF), and ventricular arrhythmic complications during the hospitalization. Data are reported as median and interquartile range or number and percentage. RESULTS: Of the 105 patients, 86 (82%) were female, and 34 (32%) were self-reported Black or African American. The mean age was 65 years (range: 58-72 years). Left ventricular ejection fraction was 25% (range: 25%-35%). Heart rate was 101 beats/min (range: 83-121 beats/min). Ten (11%) patients experienced a ventricular arrhythmic complication and had significantly longer QTCF (470 [range: 422-543] milliseconds) than did those without complications (417 [range: 383-456] milliseconds, P = 0.031). The area under the curve for QTCF was 0.708 (95% CI: 0.536-0.880; P = 0.031). Twenty-eight (27%) patients had a QTCF ≥460 milliseconds and significantly more arrhythmic complications (21% vs 5%, odds ratio 4.997 [95% CI: 1.288-19.237], P = 0.021). QTCF was an independent predictor of ventricular arrhythmias: odds ratio 1.090 for each 10-millisecond increase in QTCF (95% CI: 1.004-1.183; P = 0.040, corrected for sex). CONCLUSIONS: In a diverse population of patients with apical ballooning Takotsubo syndrome admitted to a large urban hospital in the United States, QTCF at admission ≥460 milliseconds identifies patients at high risk for in-hospital arrhythmic complications. Further studies are needed to determine strategies aimed at shortening QT interval to potentially prevent life-threatening arrhythmic events.

Microvascular complications identify a specific coronary atherosclerotic phenotype in patients with type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. METHODS: We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. RESULTS: We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). CONCLUSIONS: The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.