Long-term outcomes of phenoclusters in preclinical heart failure with preserved and mildly reduced ejection fraction.

AIMS: The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID-Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification. METHODS: The DAVID-Berg study prospectively enrolled 596 asymptomatic outpatients with EF > 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death. RESULTS: The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N-terminal pro-brain natriuretic peptide (NT-proBNP) and the largest left atrium. During a median follow-up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log-rank test: Cluster 3 vs. 1 P < 0.001; Cluster 3 vs. 2 P = 0.008). Cluster 3 was associated with a risk of HF/death 2.5 times higher than Cluster 1 [adjusted hazard ratio (HR) = 2.46, 95% confidence interval (CI) 1.24-4.90]. CONCLUSIONS: Based on phenomapping, older patients with lower kidney function and worse diastolic function might represent a subset of preclinical HF with EF > 40% who deserve more efforts to prevent clinical HF.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.

Cine-cardiac magnetic resonance to distinguish between ischemic and non-ischemic cardiomyopathies: a machine learning approach.

OBJECTIVE: This work aimed to derive a machine learning (ML) model for the differentiation between ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) on non-contrast cardiovascular magnetic resonance (CMR). METHODS: This retrospective study evaluated CMR scans of 107 consecutive patients (49 ICM, 58 NICM), including atrial and ventricular strain parameters. We used these data to compare an explainable tree-based gradient boosting additive model with four traditional ML models for the differentiation of ICM and NICM. The models were trained and internally validated with repeated cross-validation according to discrimination and calibration. Furthermore, we examined important variables for distinguishing between ICM and NICM. RESULTS: A total of 107 patients and 38 variables were available for the analysis. Of those, 49 were ICM (34 males, mean age 60 ± 9 years) and 58 patients were NICM (38 males, mean age 56 ± 19 years). After 10 repetitions of the tenfold cross-validation, the proposed model achieved the highest area under curve (0.82, 95% CI [0.47-1.00]) and lowest Brier score (0.19, 95% CI [0.13-0.27]), showing competitive diagnostic accuracy and calibration. At the Youden's index, sensitivity was 0.72 (95% CI [0.68-0.76]), the highest of all. Analysis of predictions revealed that both atrial and ventricular strain CMR parameters were important for the identification of ICM patients. CONCLUSION: The current study demonstrated that using a ML model, multi chamber myocardial strain, and function on non-contrast CMR parameters enables the discrimination between ICM and NICM with competitive diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: A machine learning model based on non-contrast cardiovascular magnetic resonance parameters may discriminate between ischemic and non-ischemic cardiomyopathy enabling wider access to cardiovascular magnetic resonance examinations with lower costs and faster imaging acquisition. KEY POINTS: • The exponential growth in cardiovascular magnetic resonance examinations may require faster and more cost-effective protocols. • Artificial intelligence models can be utilized to distinguish between ischemic and non-ischemic etiologies. • Machine learning using non-contrast CMR parameters can effectively distinguish between ischemic and non-ischemic cardiomyopathies.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Indirect Calorimetry-Based Novel Approach for Evaluating Metabolic Flexibility and Its Association with Circulating Metabolic Markers in Middle-Aged Subjects.

We propose a novel method for assessing metabolic flexibility (MF) through indirect calorimetry. A total of twenty healthy volunteers (10 females; 10 males) aged 45-65 were categorized into a Low-Intensity activity group (LI, 0-1 session of 1 h per week) and a High-Intensity activity group (HI, 5-6 sessions of 2 h per week). Volunteers underwent a stepwise exercise test on a cycle ergometer, connected to a calorimeter, to examine respiratory gas exchange to evaluate peak fatty acid Oxidation (PFO) and peak carbohydrate oxidation (PCO). Circulating peroxisome proliferator-activated receptor α (PPARα) biomarkers, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio and N-oleoylethanolamine (OEA), and the endocannabinoid- 2-arachidonoylglycerol (2-AG), were evaluated. We developed two MF parameters: the MF index (MFI), calculated by the product of PFO normalized per kg of fat-free mass (FFM) and the percentage of VO2max at PFO, and the peak energy substrates' oxidation (PESO), computed by summing the kilocalories from the PFO and PCO, normalized per kg FFM. The MFI and PESO were significantly different between the HI and LI groups, showing strong correlations with the circulating bioactive substances. Higher DHA/EPA ratio (p ≤ 0.05) and OEA (p ≤ 0.01), but lower 2-AG levels (p ≤ 0.01) were found in the HI group. These new parameters successfully established a functional link between MF and the balance of PPARα/endocannabinoid systems.

Artificial Intelligence in the Differential Diagnosis of Cardiomyopathy Phenotypes.

Artificial intelligence (AI) is rapidly being applied to the medical field, especially in the cardiovascular domain. AI approaches have demonstrated their applicability in the detection, diagnosis, and management of several cardiovascular diseases, enhancing disease stratification and typing. Cardiomyopathies are a leading cause of heart failure and life-threatening ventricular arrhythmias. Identifying the etiologies is fundamental for the management and diagnostic pathway of these heart muscle diseases, requiring the integration of various data, including personal and family history, clinical examination, electrocardiography, and laboratory investigations, as well as multimodality imaging, making the clinical diagnosis challenging. In this scenario, AI has demonstrated its capability to capture subtle connections from a multitude of multiparametric datasets, enabling the discovery of hidden relationships in data and handling more complex tasks than traditional methods. This review aims to present a comprehensive overview of the main concepts related to AI and its subset. Additionally, we review the existing literature on AI-based models in the differential diagnosis of cardiomyopathy phenotypes, and we finally examine the advantages and limitations of these AI approaches.

A case series of the twiddler syndrome.

Background: Twiddler syndrome (TS) is a complication of cardiac implantable electronic device (CIED) implantation, caused by the deliberate or unconscious manipulation of the device by the patient himself, which results in dislocation of the leads by retraction towards the subcutaneous pocket. Case summary: This report describes two clinical cases that occurred in our centre, for which two different solutions were successfully implemented. In the first case, a complete removal of the stimulation system was performed, and a leadless pacemaker (PM; Medtronic Micra VR) was implanted. In the second case, the patient underwent a revision procedure. The PM was disconnected, and the electrodes were debrided, a submuscular pocket for the PM was created, and at the end of the procedure, the PM was anchored to the pectoralis major. Discussion: Twiddler syndrome is a not so rare and serious complication of CIED implantation, leading to device malfunctioning and higher risk of infection of the pocket due to multiple re-interventions. In these two cases, different surgical solutions were performed, both resulting to be effective to solve the effects of TS.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry.

BACKGROUND AND AIMS: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. METHODS: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. RESULTS: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. CONCLUSIONS: Statin therapy after a TTS event was not associated with better prognosis at follow-up.

Smoking influence in Takotsubo syndrome: insights from an international cohort.

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.

Why is it Important to Assess and Treat Alexithymia in the Cardiologic Field? An Overview of the Literature.

Background: Alexithymia has been found to be associated with several somatic illnesses, such as cardiovascular, indicating that it might be a risk factor for early death in the long-term course of post-myocardial infarction. From the cardiology perspective, the aim was to collect current evidence about the relationship between alexithymia and somatic illness. Methods: The literature was synthesized and summarized in a narrative format. The literature search was carried out in PubMed. Pertinent studies published in the last 50 years written in English were included and organized by three main topics ("The relation between alexithymia and somatic illness from the cardiology perspective"; "How do assess alexithymia?"; "Treating alexithymia") to be discussed. Results: High alexithymia is a dimensional trait that affects around 10% of the general population and up to 55% of people with essential hypertension. Also, the link between alexithymia and cardiovascular activity has been pointed out. There are several validated tools to assess alexithymia, as well as treatment options. Conclusion: Knowledge about the main features of alexithymia, as well as its assessment and treatment, can promote a multifactorial approach to the primary, secondary, and tertiary prevention of cardiac diseases.

Syncope and Cannabis: hypervagotonia from chronic abuse? A case report and literature review.

BACKGROUND: Cannabis is the most consumed drug worldwide and number of users is increasing, particularly among youth. Moreover, cannabis potential therapeutic properties have renewed interest to make it available as a treatment for a variety of conditions. Albeit rarely, cannabis consumption has been associated with cardiovascular diseases such as arrhythmias, myocardial infarction (MI) and potentially sudden death. CASE PRESENTATION: A 24-year-old woman presented to the emergency department sent by her cardiologist because of a recent finding of a 16 seconds asystole on the implantable loop recorder (ILR) she implanted 7 months before for recurrent syncopes. She declared that she is a heavy cannabis user (at least 5 cannabis-cigarette per day, not mixed up with tobacco, for no less than 12 years) and all syncopes occurred shortly after cannabis consumption. After a collective discussion with the heart team, syncope unit, electrophysiologists and toxicologist, we decided to implant a dual chamber pacemaker with a rate response algorithm due to the high risk of trauma of the syncopal episodes. 24 months follow-up period was uneventful. CONCLUSIONS: Cannabis cardiovascular effects are not well known and, although rare, among these we find ischemic episodes, tachyarrhythmias, symptomatic sinus bradycardia, sinus arrest, ventricular asystole and possibly death. Because of cannabis growing consumption both for medical and recreational purpose, cardiovascular diseases associated with cannabis use may become more and more frequent. In the light of the poor literature, we believe that cannabis may produce opposite adverse effects depending on the duration of the habit. Acute administration increases sympathetic tone and reduces parasympathetic tone; conversely, with chronic intake an opposite effect is observed: repetitive dosing decreases sympathetic activity and increases parasympathetic activity. Clinicians should be aware of the increased risk of cardiovascular complications associated with cannabis use and should investigate its consumption especially in young patients presenting with cardiac dysrhythmias.

Base-to-apex Gradient Pattern Assessed by Cardiovascular Magnetic Resonance in Takotsubo Cardiomyopathy.

OBJECTIVES: The purpose of this study was to investigate the base-to-apex gradient strain pattern as a noncontrast cardiovascular magnetic resonance (CMR) parameter in patients with Takotsubo cardiomyopathy (TTC) and determine whether this pattern may help discriminate TTC from patients with anterior myocardial infarction (AMI). MATERIALS AND METHODS: A total of 80 patients were included in the analysis: 30 patients with apical ballooning TTC and 50 patients with AMI. Global and regional ventricular function, including longitudinal (LS), circumferential (CS), and radial strain (RS), were assessed using CMR. The base-to-apex LS, RS, and CS gradients, defined as the peak gradient difference between averaged basal and apical strain, were calculated. RESULTS: The base-to-apex RS gradient was impaired in TTC patients compared with the AMI group (14.04 ± 15.50 vs. -0.43 ± 11.59, P=0.001). Conversely, there were no significant differences in the base-to-apex LS and CS gradients between the AMI group and TTC patients (0.14 ± 2.71 vs. -1.5 ± 3.69, P=0.054: -0.99 ± 6.49 vs. ±1.4 ± 5.43, P=0.47, respectively). Beyond the presence and extension of LGE, base-to-apex RS gradient was the only independent discriminator between TTC and AMI (OR 1.28; 95% CI 1.08, 1.52, P=0.006) in multivariate logistic regression analysis. CONCLUSION: The findings of this study suggest that the pattern of regional myocardial strain impairment could serve as an additional noncontrast CMR tool to refine the diagnosis of TTC. A pronounced base-to-apex RS gradient may be a specific left ventricle strain pattern of TTC.

Sex differences in diagnostic modalities of coronary artery disease: Evidence from coronary microcirculation.

Although atherosclerosis is usually considered a disease of the large arteries, risk factors for atherosclerosis also trigger structural and functional abnormalities at a microvascular level. In cardiac disease, microvascular dysfunction is especially relevant in women, among whom the manifestation of ischemic disease due to impaired coronary microcirculation is more common than in men. This sex-specific clinical phenotype has important clinical implications and, given the higher pre-test probability of coronary microvascular dysfunction in females, different diagnostic modalities should be used in women compared to men. In this review, we summarize invasive and non-invasive diagnostic modalities to assess coronary microvascular function, ranging from catheter-based evaluation of endothelial function to Doppler echocardiography and positron emission tomography. Moreover, we discuss different clinical settings in which microvascular disease plays an important role, underlining the importance of choosing the right diagnostic modality depending on the sex of the patients.

Sex-based differences in late gadolinium enhancement among patients with acute myocarditis.

OBJECTIVE: The aims of our study were to investigate the sex differences in late gadolinium enhancement (LGE) using cardiovascular magnetic resonance (CMR) in a single-centre cohort of consecutive patients with acute myocarditis (AM). METHOD: This retrospective study performed CMR scans in 135 consecutive patients with AM that met the Lake Louise criteria. On CMR, LV ventricular strain functions were performed on conventional cine SSFP sequences. Besides myocardial strain measurements, myocardial scar location, extension, and size were assigned and quantified by LGE imaging. RESULTS: There was no difference in age (age 42.51 ± 19.64 years vs 40.92 ± 19.94 years; p = 0.74) and cardiovascular risk profile between women and men. Despite similar comorbidities, women were more like to present with dyspnea (p = 0.001). Women demonstrated higher prevalence of septal LGE (p = 0.004) and increased global circumferential strain parameters (p = 0.008) in comparison with men. In multivariate analysis, female sex remained an independent determinant of septal LGE (ß coefficient = -0.520, p = 0.001). CONCLUSION: This is the first study reporting sex differences in LGE localization in AM. Women have more septal LGE involvement independent of age, cardiovascular risk factors, and CMR parameters. These findings further emphasize the sex-based differences in cardiovascular diseases.

Does Patient Compliance Influence Wearable Cardioverter Defibrillator Effectiveness? A Single-Center Experience.

The study was designed to assess patient adherence to wearable cardioverter defibrillator as an indicator of device effectiveness. The patient training is not widely properly standardized. We enrolled 25 patients with a wearable cardioverter defibrillator to prevent sudden cardiac death between June 2020 and August 2022. Among them, 84% were male with a median age of 63.6 years. The indication was an ischemic (44%) and a non-ischemic (56%) disease. The patients were followed-up until the decision to upgrade to an implantable device was taken. We trained the patients according to our suggested protocol. The median wear time was 90 days, and the median daily wear time was 23.5 h, similar throughout sex, age, and indication groups. In total, 24% of the participants underwent cardioverter defibrillator implantation. Between the device-implanted and non-implanted groups, left ventricular ejection fraction and left ventricular indexed end-diastolic volume were significantly different (EF 35.8 ± 12 vs. 46.4 ± 8.5%, p = 0.028, iEDV 108 ± 52 vs. 70.7 ± 21.1 mL/m2, p = 0.024). We did not find any differences in cardiac magnetic resonance data, even though all patients who underwent device implantation had late gadolinium enhancement spots. Our results support standardized patient training to obtain great patient adherence to the instructions to the wearable device and therefore its effectiveness.

Trigger-Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

Background Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German-Italian-Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in-hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long-term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long-term mortality, while chest pain (P=0.035) and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long-term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long-term mortality.

Catecholamine-induced Takotsubo syndrome: a case series.

Background: Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during the acute phase, good short-term prognosis, and frequent apical sparing at echocardiogram. We present two clinical cases of cat-TS treated in our department. Case summary: Case one: 78-year-old man, admitted to Ear Nose and Throat Unit for surgical removal of oral squamous cellular carcinoma. During surgery, the occurrence of hypotensive episode was treated with catecholamines. After surgery, the occurrence of atrial fibrillation was followed by evidence of phasic increase of troponin levels and akinesia of midventricular segments. Angiography showed the absence of significant coronary stenoses, and during hospital stay, we observed rapid recovery of wall motion abnormalities. Case two: 64-year-old woman, admitted for hysteropexy surgery, during which cardiac arrest occurred, treated with epinephrine i.v.1 mg and DC shock. Two hours after resuscitation, the patient developed pulmonary oedema, troponin levels increased progressively, and the echocardiogram demonstrated hypokinesia in all midventricular segments with apical sparing. Afterwards, an urgent angiography highlighted normal coronary anatomy. Cardiac magnetic resonance imaging (MRI) revealed oedema corresponding to hypokinetic areas. On the seventh day, echocardiogram showed a complete remission of wall motion abnormalities. Discussion: These cases warn the physicians about the importance of routinely screening myocardial impairment through clinical assessment, electrocardiogram (ECG) monitoring, and serial cardiac troponin testing after catecholamine i.v. bolus administration. In case of alterations of these exams, performing a prompt echocardiogram allows early detection of cat-TS, to provide immediate suitable medical support and avoid complications.

Non-invasive coronary flow velocity reserve assessment predicts adverse outcome in women with unstable angina without obstructive coronary artery stenosis.

Background: Evaluation of coronary flow velocity reserve (CFVR) is the physiological approach to assess the severity of coronary stenosis and microvascular dysfunction. Impaired CFVR occurs frequently in women with suspected or known coronary artery disease. The aim of this study was to assess the role of CFVR to predict long-term cardiovascular event rate in women with unstable angina (UA) without obstructive coronary artery stenosis. Methods: CFVR in left anterior descending coronary artery was assessed by adenosine transthoracic echocardiograhy in 161 women admitted at our Department with UA and without obstructive coronary artery disease. Results: During a mean FU of 32.5 ± 19.6 months, 53 cardiac events occurred: 6 nonfatal acute myocardial infarction, 22 UA, 7 coronary revascularization by percutaneous transluminal coronary angioplasty, 1 coronary bypass surgery, 3 ischemic stroke, and 8 episodes of congestive heart failure with preserved ejection fraction and 6 cardiac deaths. Using a ROC curve analysis, CFVR 2.14 was the best predictor of cardiac events and was considered as abnormal CFVR. Abnormal CFVR was associated with lower cardiac event-free survival (30 vs 80%, p < 0.0001). During FU, 70% of women with reduced CFVR had cardiac events whereas only 20% with normal CFVR (p = 0.0001). At multivariate Cox analysis, smoke habitus (p = 0.003), metabolic syndrome (p = 0.01), and CFVR (p < 0.0001) were significantly associated with cardiac events at FU. Conclusion: Noninvasive CFVR provides an independent predictor of cardiovascular prognosis information in women with UA without obstructive coronary artery disease whereas, impaired CFVR seems to be associated with higher CV events at FU.