Right atrial strain and cardiovascular outcome in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty infiltration of the myocardium and associated with adverse cardiovascular (CV) events. This study aims to examine right atrial (RA) deformation in ARVC and understand its association with CV outcomes. METHODS AND RESULTS: RA strain was determined in 50 patients with definite ARVC, compared with a matched control group of 50 healthy individuals, and analysed for outcome association over a median follow-up duration of 5 years. A subgroup of 30 ARVC patients with normal RA volume (ARVC-N group) was compared with 30 matched controls (Control-N), and the outcome was analysed separately. RA reservoir, conduit, and pump strain were significantly impaired in ARVC vs. control. Similar observations were made in the N-ARVC subgroup. Reservoir strain was associated with an increased risk of atrial arrhythmia (AA) [hazard ratio (HR) 0.88, P < 0.01] and CV events (HR 0.92, P < 0.01). Conduit strain also predicted AA (HR 1.02, P < 0.01), while pump strain predicted CV events (HR 1.09, P = 0.02). Reservoir strain improved the fitness of bivariable models for the association of RV end-diastolic area index, RV fractional area change, and RV global longitudinal strain with CV events. CONCLUSION: ARVC patients display impaired RA strain even when RA volume is normal. Reservoir and pump strain are associated with an increased risk of CV events. Reservoir strain improved model fitness for the association of RVGLS and other echocardiographic parameters with CV events.

Incidence and Clinical Impact of Right Ventricular Involvement (Biventricular Ballooning) in Takotsubo Syndrome: Results From the GEIST Registry.

BACKGROUND: The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood. RESEARCH QUESTION: What is the incidence and clinical outcome of RV involvement in TTS? STUDY DESIGN AND METHODS: This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias. RESULTS: The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P < .01), whereas emotional stressors were less prevalent (P < .01). Patients with RV involvement had a higher incidence of in-hospital cardiogenic shock (P = .02). The primary outcome (in- and out-of-hospital all-cause mortality) was observed in 12.8% of patients without RV involvement compared with 29% of patients with RV involvement. Although the in-hospital mortality rate was similar in both groups, a higher out-of-hospital all-cause mortality rate (log-rank test, P = .008) was observed in the RV involvement group. The Cox multivariable regression analysis showed that physical triggers were independent predictors of RV involvement. INTERPRETATION: RV involvement defines a high-risk cohort of patients with TTS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04361994; URL: www.clinicaltrials.gov.

Concealed structural heart disease discovered at cardiac magnetic resonance in patients with ventricular extrasystoles from ventricular outflow tract and apparently normal hearts.

BACKGROUND: Outflow tract (OT) premature ventricular contractions (PVCs) are commonly found in clinical practice; in most cases, PVCs are benign and observed in structurally normal hearts, not requiring any therapeutic intervention. In this study, we therefore sought to evaluate with cardiac magnetic resonance (CMR) patients with PVC and apparently normal heart at echocardiographic examination, in order to identify possible substrates linked with higher prevalence of arrhythmias or structural heart disease. METHODS: Thirty-three consecutive patients with frequent PVCs originating from the ventricular OT (right and left) were enrolled in the study and assessed by echocardiography and CMR. All patients had normal baseline electrocardiogram. RESULTS: CMR showed structural changes in 5 patients out of 33; in 3 cases, areas of fibrosis limited in one case to the middle basal segments of the interventricular septum and in two patients to the middle basal segments of the inferior-lateral wall were found. In 2 other cases, however, late gadolinium enhancement showed significant anomalies characterized in one patient by extensive areas of subepicardial fibrosis of the left ventricle, suitable with arrhythmogenic left dominant dysplasia; in another patient, a marked trabeculation of left ventricular medium apical segments suitable with non-compaction myocardium was present. CONCLUSIONS: CMR may identify cases of structural heart disease in subjects with OT PVCs and apparently normal electrocardiogram and echocardiogram examinations. A preliminary screening with CMR may be considered before any further invasive electrophysiology assessment and therapeutic planning.

Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

Malignancies and outcome in Takotsubo syndrome: a meta-analysis study on cancer and stress cardiomyopathy.

Takotsubo syndrome (TTS) can be induced by a large variety of physical/emotional triggers; several cases, however, are related to either an overt or occult malignancy, as shown in retrospective studies and case reports. The aim of this study was therefore to evaluate the clinical outcome of patients with TTS and cancer in a meta-analysis study. In June 2018, a Pubmed systematic research was conducted for studies assessing outcome in patients with TTS and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for adverse events at follow-up. After paper retrieval, four studies were included in the meta-analysis, with a total of 123,563 patients. The prevalence of current or previous malignancy among patients admitted with TTS was 6.7% (8258 patients). When compared to control patients, patients with cancer showed an increased risk of clinical events (RR 3.24, 95% CI 3.04-3.45, p < 0.01). The risk of in-hospital events was significantly higher in the cancer group (RR 2.08 95% CI, 1.50-2.87, p < 0.01) and was mainly due to higher need for respiratory support (RR 1.67, 95% CI, 1.58-1.77, p < 0.01). The risk of adverse events at follow-up was also higher in the cancer group (RR 3.30, 95% CI 3.09-3.51, p < 0.01). Cancer, either history or active, is associated with an increased risk of adverse events in TTS.

Serum interleukin 6 and 10 levels in Takotsubo cardiomyopathy: Increased admission levels may predict adverse events at follow-up.

BACKGROUND AND AIMS: Systemic inflammation has been hypothesized as a possible mechanism of Takotsubo cardiomyopathy (TTC). Aim of the study was to assess the role of interleukin (IL)-6 and IL-10 in subjects with an episode of TTC. METHODS: Fifty-six consecutive subjects with TTC were prospectively enrolled in the study and followed for a mean of 178 days. Circulating levels of IL-6, IL-10, clinical condition and left ventricular ejection fraction were evaluated at admission. Incidence of death, re-hospitalization and recurrence of TTC during follow-up was also recorded. RESULTS: 23% of patients experienced in-hospital complications while 20% of patients had adverse events at follow-up. IL-6 and IL-10 serum levels at admission were higher in subjects with adverse events at follow-up (120 ± 294 vs. 22 ± 40 pg/ml, p<0.05; 13 ± 35 vs. 2 ± 3 pg/ml, p=0.05, respectively). Increased serum levels of IL-6 and IL-10 were associated with higher adverse events rates at follow-up (Log-Rank p<0.001, <0.05, hazard ratio 8.6, 5.1, respectively) and mortality rates (Log-Rank p<0.001, p<0.05, hazard ratio 20.8, 7.1, respectively). Subjects with both increased IL-6 and IL-10 levels were characterized by an increased risk of adverse events when compared to subjects with only IL-6 or IL-10 increased levels or with values below cutoff values (Log-Rank p<0.01 for any event, <0.001 for death; hazard ratio 1.20 for any event, 1.31 for death), even after correction for age, LVEF and NTproBNP levels in multivariable Cox analysis. CONCLUSIONS: Serum IL-6 and IL-10 admission levels are associated with higher risk of adverse events during follow-up.