Federico Guerra

Comorbidities Frequency in Takotsubo Syndrome: An International Collaborative Systematic Review Including 1109 Patients

BACKGROUND To identify predisposing factors that can result in the onset of takotsubo syndrome, we performed an international, collaborative systematic review focusing on clinical characteristics and comorbidities of patients with takotsubo syndrome. METHODS We searched and reviewed cited references up to August 2013 to identify relevant studies. Corresponding authors of selected studies were contacted and asked to provide additional quantitative details. Data from each study were extracted by 2 independent reviewers. The cumulative prevalence of presenting features and comorbidities was assessed. Nineteen studies whose authors sent the requested information were included in the systematic review, with a total of 1109 patients (951 women; mean age, 59-76 years). Evaluation of risk factors showed that obesity was present in 17% of patients (range, 2%-48%), hypertension in 54% (range, 27%-83%), dyslipidemia in 32% (range, 7%-59%), diabetes in 17% (range, 4%-34%), and smoking in 22% (range, 6%-49%). Emotional stressors preceded takotsubo syndrome in 39% of patients and physical stressors in 35%. The most common comorbidities were psychological disorders (24%; range, 0-49%), pulmonary diseases (15%; range, 0-22%), and malignancies (10%; range, 4%-29%). Other common associated disorders were neurologic diseases (7%; range, 0-22%), chronic kidney disease (7%; range, 2%-27%), and thyroid diseases (6%; range, 0-37%). CONCLUSIONS Patients with takotsubo syndrome have a relevant prevalence of cardiovascular risk factors and associated comorbidities. Such of associations needs to be evaluated in further studies.

A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I

BACKGROUND Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS). OBJECTIVES This study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS. METHODS This study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up. RESULTS During the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p < 0.0001), a family history of SCD (p = 0.03), and AF (p < 0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract. CONCLUSIONS The presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects.

Role of electrical storm as a mortality and morbidity risk factor and its clinical predictors: a meta-analysis

AIMS Electrical storm (ES) is a devastating and life-threatening event in clinical practice, but its real weight as a risk factor and its clinical predictors remain unclear. Our objective was to evaluate ES as a mortality and morbidity risk factor and to define the clinical variables associated with ES. METHODS AND RESULTS The meta-analysis was performed according to the PRISMA guidelines. At the end of the selection process, 13 studies were collected and included in the quantitative analysis. Mortality and morbidity due to ES were assessed. The most acknowledged ES predictors were taken into account in separate sub-analyses. The whole cohort included 5912 patients (857 with ES). Risk of death was increased in the ES group [risk ratio (RR) 3.15; 95% confidence interval (CI) 2.22-4.48]. Electrical storm was also associated with increased composite risk of all-cause death, cardiac transplantation, and hospitalization for acute heart failure (RR 3.39; 95% CI 2.31-4.97). These results were confirmed by comparing the ES group with patients with or without previous unclustered episodes of ventricular arrhythmias. Moreover, implantable cardioverter-defibrillator (ICD) for secondary prevention, lower ejection fraction, monomorphic ventricular tachycardia as triggering arrhythmia, and class I anti-arrhythmic drugs therapy were all associated with ES. CONCLUSION Electrical storm is a strong mortality risk factor and it is associated with an increased combined risk of death, heart transplantation, and hospitalization for heart failure. Implantable cardioverter-defibrillator for secondary prevention, monomorphic ventricular tachycardia as triggering arrhythmia, lower ejection fraction, and class I anti-arrhythmic drugs therapy are all associated with ES and could be used to define specific populations with higher risk to develop ES.

Summer does not always mean lower: seasonality of 24 h, daytime, and night-time blood pressure.

Objective: Evaluation of seasonal influences on ambulatory blood pressure monitoring (ABPM) values in a very large population living in a mild-climate geographic area. Methods: Among patients referred to our Hypertension Center between September 2002 and January 2011 with a reliable ABPM, we considered those in the two hottest (July and August) vs. those in the two coldest (January and February) months. Results: Seven hundred and forty-two men (53.2%) and 653 women (46.8%) were studied; 1245 (89.3%) were hypertensive patients of which 795 (63.9%) were drug-treated. In winter, mean daytime SBP and DBP were higher (P = 0.001 and P < 0.001, respectively), but only 24-h DBP was significantly higher (P = 0.012). On the contrary, higher night-time SBP and pulse pressure were recorded in summer (P = 0.005 and P = 0.023, respectively). Uncontrolled hypertensive patients had the highest mean difference between winter and summer night-time SBP (127.1 ± 13.4 vs. 131.0 ± 12.6 mmHg; P = 0.001). In winter a dipping pattern was prevalent (58.2%), whereas in summer a nondipping pattern prevailed (61.9%; P < 0.001). Isolated nocturnal hypertension (INH) was present in 9.8% in winter vs. 15.2% in summer (P = 0.003). Conclusion: Our data on a very large ABPM sample confirmed that hottest summer months are associated with lower daytime BP and also lower 24-h DBP. However, we found an inverse relationship regarding night-time BP, dipping pattern, and INH that were higher or more common in summer. These findings were even more evident in treated patients, especially when not at target. Different sleeping behaviors or improper dose reduction of drug therapy in summer may explain the findings.

Transient QRS amplitude attenuation is associated with clinical recovery in patients with takotsubo cardiomyopathy

BACKGROUND/OBJECTIVES Low voltage QRS complexes (LQRSV) and amplitude attenuation of QRS voltage (AAQRS) have been described in takotsubo (TC) patients, and postulated as valuable pre-angiographic markers. The aim of this observational study is to evaluate potential diagnostic and prognostic features of QRS amplitude in TC and acute coronary syndrome (ACS) patients. METHODS Fifty-eight patients with TC were matched with 58 patients with ACS according to age, gender, and presence or absence of ST elevation at hospital admission. A 12-lead ECG was recorded within 12h after symptoms onset, the day after coronary angiography (CA) and before hospital discharge. When available, ECGs prior and subsequent to the acute event were also collected. RESULTS QRS amplitude showed a time related trend, with a first phase characterized by an initial decrease in amplitude in both groups and a second phase, with a progressive recovery of QRS amplitude in TC patients up to pre-event levels, while QRS amplitude in ACS patients remained substantially unchanged from admission onwards. Rise in AAQRS during hospitalization showed a positive linear association with systolic function recovery and both troponin I and CK-MB decrease (all p<0.01) in TC patients. A 20% increase of mean AAQRS from admission is able to predict LVEF recovery and troponin I and CK-MB normalization in TC patients with good sensitivity and specificity. CONCLUSIONS LQRSV and AAQRS are not reliable in differentiating ACS from TC. However, QRS amplitude attenuation in TC is transient, and is linearly associated with systolic function recovery and cardiac biomarkers normalization.

Electrical storm and heart failure worsening in implantable cardiac defibrillator patients

AIMS In patients with an implantable cardiac defibrillator (ICD), electrical storm (ES) is associated with increased sudden and non-sudden cardiac mortality, the latter largely due to worsening heart failure (HF). Aim of this study is to test the association between ES and impending pump failure in patients with known chronic HF and ICD. METHODS AND RESULTS Inclusion criteria were a previous history of chronic HF, former ICD implant, and hospital admission for HF worsening, or ES, or unclustered ventricular tachyarrhythmias (VTs/VFs). Patients with concomitant stable HF or HF worsening due to another specific cause were excluded. Primary endpoint was all cause mortality. Main secondary endpoint was time to first rehospitalization. Prospective, observational study on 146 patients: 34 with ES, 30 with unclustered VTs/VFs, and 82 with HF worsening. During the 5 years of follow-up, there was no significant difference between survival estimates between ES and HF worsening (P = 0.7), while both were significantly lower than survival of unclustered VT/VF patients (all log rank P < 0.05). Hospitalization-free time was significantly lower in both the ES group and in the HF worsening group when compared with unclustered VT/VF patients (all log rank P < 0.05). There was no significant difference between hospitalization estimates between ES and HF worsening. CONCLUSION Heart failure patients admitted for ES have major similarities with patients admitted for HF clinical decompensation such as similar survival, cause of death and time to first rehospitalization. There is evidence suggesting that, in this population, ES could be considered as a clinical manifestation of HF worsening.

Cardiac resynchronization therapy improves ejection fraction and cardiac remodelling regardless of patients' age

AIMS Cardiac resynchronization therapy (CRT) improves symptoms and reduces mortality in heart failure (HF) patients, but little data exist on the efficacy of CRT in the elderly. The aim of our study is to define CRT-related benefits in terms of left ventricular ejection fraction (LVEF) improvement in two subgroups of patients (<75 and ≥75 years old) and test possible differences between these two groups. METHODS AND RESULTS Single-centre prospective observational study including 65 patients with optimally treated, advanced HF and indication to CRT. All patients were investigated with clinical evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 12-lead electrocardiogram, and full echocardiographical study before CRT implant and 3 and 12 months after. Left ventricular ejection fraction showed a time-related improvement in the whole population (+10.6% over 12 months) as well as in each subgroup. The magnitude of LVEF improvement was similar in elderly and non-elderly patients (+13.6 vs. +7.9%; P = ns). Left ventricular diameters, pulmonary artery systolic pressure, New York Heart Association class, MLHFQ score, and QRS width all showed a time-related improvement in the whole population as well as in each subgroup. End-diastolic left ventricular diameter remodelling and QRS width reduction were significantly more pronounced in the elderly, whereas other clinical and instrumental secondary endpoints showed a similar improvement between ≥75 and <75 years old patients. There was no significant difference regarding mortality between elderly and non-elderly patients. CONCLUSION Cardiac resynchronization therapy is as effective in improving LVEF in elderly as in non-elderly patients. Age alone should not be a determinant to restrict resynchronization therapy in HF patients.

Implantable cardioverter-defibrillator programming and electrical storm: Results of the OBSERVational registry On long-term outcome of ICD patients (OBSERVO-ICD).

BACKGROUND Electrical storm (ES) is defined as 3 or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 hours and is associated with increased cardiac and all-cause mortality. OBJECTIVE The purpose of this study was to test whether aggressive implantable cardioverter-defibrillator (ICD) programming can be associated with ES. METHODS The OBSERVational registry On long-term outcome of ICD patients (OBSERVO-ICD) is a multicenter, retrospective registry enrolling all consecutive patients undergoing ICD implantation from 2010 to 2012 in 5 Italian high-volume arrhythmia centers. Clinical history and risk factors were collected for all patients, as were ICD therapy-related variables such as detection zones and delays. The total number of arrhythmic episodes and therapies delivered by the ICD were collected through out-of-hospital visits and remote monitoring. RESULTS The registry enrolled 1319 consecutive patients, of whom 62 (4.7%) experienced at least 1 ES during follow-up (median 39 months). Patients who experienced ES had a significantly lower VF detection zone (P = .002), more frequently had antitachycardia pacing therapies programmed off during capacitor charge (P = .001), and less frequently had an ICD set with delayed therapies for VT zones (P = .042) and VF zone (P = .036). Patients who experienced ES had a significantly higher incidence of death and heart failure-related death compared to patients with no ventricular arrhythmias and patients with unclustered VTs/VFs (P = .025 and P <.001, respectively). CONCLUSION Patients with ES had a more aggressive ICD programming setup, including lower VF detection rates, shorter detection times, and no antitachycardia pacing therapies during capacitor charge. This kind of ICD programming potentially could increase the likelihood of ES and the related risk of death.

Antiplatelet Treatment Reduces All-Cause Mortality in COPD Patients: A Systematic Review and Meta-Analysis

ABSTRACT Previous studies clearly showed that patients with chronic obstructive pulmonary disease (COPD) are at high risk for cardiovascular events. Platelet activation is significantly heightened in these patients, probably because of a chronic inflammatory status. Nevertheless, it is unclear whether antiplatelet treatment may contribute to reduce all-cause mortality in COPD patients. To clarify this issue, we performed a systematic review and meta-analysis including patients with COPD (outpatients or admitted to hospital for acute exacerbation). The primary endpoint was all-cause mortality. We considered studies stratifying the study population according the administration or not of antiplatelet therapy and reporting its relationship with the primary endpoint. Overall, 5 studies including 11117 COPD patients were considered (of those 3069 patients were with acute exacerbation of COPD). IHD was present in 33% of COPD patients [95%CI 31%–35%). Antiplatelet therapy administration was common (47%, 95%CI 46%–48%), ranging from 26% to 61%. Of note, IHD was considered as confounding factor at multivariable analysis in all studies. All-cause mortality was significantly lower in COPD patients receiving antiplatelet treatment (OR 0.81; 95%CI 0.75–0.88). The data was consistent both in outpatients and in those with acute exacerbation of COPD. The pooled studies analysis showed a very low heterogeneity (I2 : 8%). Additional analyses (meta-regression) showed that antiplatelet therapy administration was effective independently (to potential confounding factors as IHD, cardiovascular drugs and cardiovascular risk factors. In conclusion, our meta-analysis suggested that antiplatelet therapy might significantly contribute to reduce all-cause mortality in COPD patients.

Incidence and risk of cardiotoxicity in cancer patients treated with targeted therapies

BACKGROUND Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. RESULTS Our search yielded a total of 4998 clinical studies; of them, 31 trials were finally considered for this meta-analysis. A total of 28,538 patients were included; 7995 of these patients had breast cancer (28%), 6151 (22%) prostate cancer and 14,392 (50%) were treated for other malignancies. The highest RR of high-grade events was observed with Vandetanib (RR=7.71, 95% CI 1.04-56.99), followed by Ramucirumab (RR=5.0) and Aflibercept (RR=4.1). Grouping by drug category, the highest incidence of high-grade cardiotoxicity was shown by anti-VEGFR-TKIs (RR 5.62, 95% CI 1.49-21.24) and anti-VEGF mAbs/VEGF-trap (RR 1.82, 95% CI 1.24-2.69). Grouping by tumor type, the highest incidence of cardiotoxicity was observed in thyroid cancer (8%), followed by gastric cancer (4%). CONCLUSIONS Treatment with targeted agents in cancer patients is correlated with a significant increase in the risk of cardiotoxicity. Frequent clinical monitoring should be emphasized when using these and newer biological agents.