Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?

BACKGROUND: We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar. CONCLUSIONS: In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.

Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator.

AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.

Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants.

BACKGROUND: Filamin C truncating variants (FLNCtv) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers. METHODS: FLNCtv carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP-related arrhythmogenic cardiomyopathies were used for prognostic comparison. RESULTS: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area - right ventricular end-systolic area)/right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD. CONCLUSIONS: Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.

Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise.

BACKGROUND: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine. PATIENTS AND METHODS: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout. RESULTS: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44). CONCLUSION: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended. CLINICAL TRIALS REGISTRATION NUMBER: CRO-2010-17.

The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

Prevalence and prognostic significance of ischemic late gadolinium enhancement pattern in non-ischemic dilated cardiomyopathy.

BACKGROUND: Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM. METHODS: A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. RESULTS: Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P = .006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P = .034 with respect to non-ischemic LGE). CONCLUSIONS: The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

The right ventricular involvement in dilated cardiomyopathy: prevalence and prognostic implications of the often-neglected child.

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by left or biventricular systolic impairment. Historically, most of the clinical attention has been devoted to the evaluation of left ventricular function and morphology, while right ventricle (RV) has been for many years the forgotten chamber. Recently, progresses in cardiac imaging gave clinicians precious tools for the evaluation of RV, raising the awareness of the importance of biventricular assessment in DCM. Indeed, RV involvement is far from being uncommon in DCM, and the presence of right ventricular dysfunction (RVD) is one of the major negative prognostic determinants in DCM patients. However, some aspects such as the possible role of specific genetic mutations in determining the biventricular phenotype in DCM, or the lack of specific treatments able to primarily counteract RVD, still need research. In this review, we summarized the current knowledge on RV involvement in DCM, giving an overview on the epidemiology and pathogenetic mechanisms implicated in determining RVD. Furthermore, we discussed the imaging techniques to evaluate RV function and the role of RV failure in advanced heart failure.

Effect of prehospital treatment in STEMI patients undergoing primary PCI.

BACKGROUND: The appropriate timing to administer antithrombotic therapies in ST-elevation myocardial infarction (STEMI) remains uncertain. This study aims to evaluate the role of antithrombotic therapy administration at first medical contact (FMC) compared with the administration in the Cathlab. METHODS: We conducted a "before-after" observational study enrolling STEMI undergoing primary percutaneous coronary intervention (PCI). Outcomes were evaluated during two successive periods, before (control group: aspirin only at FMC) and after (pretreated intervention group: heparin, aspirin plus ticagrelor at FMC) the introduction of a new regional pretreatment protocol. RESULTS: A total of 537 consecutive patients (300 in control vs. 237 in intervention group) were enrolled. The pretreated compared with no pretreated population showed better basal reperfusion, expressed as basal Thrombolysis in Myocardial Infarction (TIMI)-flow (p for trend p < 0.001). Pretreated population showed lower frequency of TIMI 0 (56.5% vs. 73.7%, odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.32-0.67, p < 0.001) and higher frequency of TIMI 2-3 (33.3% vs. 19.3% OR: 2.0, 95% CI: 1.38-2.00, p < 0.001) and TIMI 3 (14.3% vs. 9.7%, OR: 1.56, 95% CI: (0.92-2.65), p = 0.094). Pretreated compared with no pretreated population showed reduced infarct size expressed as Troponin Peak (20,286 (8726-75,027) versus 48,676 (17,229-113,900), p = 0.001), and higher left ventricular ejection fraction at discharge (53% (44-59) vs. 50% (44-56), p = 0.027). In-hospital BARC ≥ 2 bleeding were similar (2.1% vs. 2.0%, p = 0.929, in pretreated versus no pretreated population, respectively). CONCLUSION: This study provides support for an early pretreatment strategy in STEMI patients and confirmed the importance of an efficient organization of STEMI networks which allow initiation of antithrombotic treatment at FMC.

Risk Reduction and Hemodynamics with Initial Combination Therapy in Pulmonary Arterial Hypertension.

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known.Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs.Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores.Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR <25%. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography, a right/left ventricular surface area ratio of greater than 1 associated with low tricuspid annular plane systolic excursion of less than 18 mm. A low-risk status at 6 months was achieved or maintained in only 34.8% (Registry to Evaluate Early and Long-Term PAH Disease Management score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low-risk status.Conclusions: A majority of patients with PAH still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores.

Using marginal structural joint models to estimate the effect of a time-varying treatment on recurrent events and survival: An application on arrhythmogenic cardiomyopathy.

In many clinical applications to evaluate the effect of a treatment, randomized control trials are difficult to carry out. On the other hand, clinical observational registries are often available and they contain longitudinal data regarding clinical parameters, drug therapies, and outcomes. In the past, much research has addressed causal methods to estimate treatment effects from observational studies. In the context of time-varying treatments, marginal structural models are often used. However, most analyses have focused on binary outcomes or time-to-the-first event analyses. The novelty of our approach is to combine the marginal structural methodology with the case where correlated recurrent events and survival are the outcomes of interest. Our work focuses on solving the nontrivial problem of defining the measures of effect, specifying the model for the time-dependent weights and the model to estimate the outcome, implementing them, and finally estimating the final treatment effects in this life-history setting. Our approach provides a strategy that allows obtaining treatment effect estimates both on the recurrent events and the survival with a clear causal and clinical interpretation. At the same time, the strategy we propose is based on flexible modeling choices such as the use of joint models to capture the correlation within events from the same subject and the specification of time-dependent treatment effects. The clinical problem which motivated our work is the evaluation of the treatment effect of beta-blockers in arrhythmogenic right ventricular cardiomyopathy (ARVC/D), and the dataset comes from the Trieste Heart Muscle Disease Registry.

The Arrhythmic Phenotype in Cardiomyopathy.

In the wide phenotypic spectrum of cardiomyopathies, sudden cardiac death (SCD) has always been the most visible and devastating disease complication. The introduction of implantable cardioverter-defibrillators for SCD prevention by the late 1980s has moved the question from how to whom we should protect from SCD, leaving clinicians with a measure of uncertainty regarding the most reliable option to guide identification of the highest-risk patients. In this review, we will go through all the available evidence in the field of arrhythmic expression and arrhythmic risk stratification in the different phenotypes of cardiomyopathies to provide practical suggestions in daily clinical management.

STEMI and Multivessel Disease: Medical Therapy Amplifies the Benefit of Complete Myocardial Revascularisation.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) with multivessel disease (MVD) may be treated with different revascularisation strategies. However, the potential predictors of outcomes on top of different revascularisation strategies are poorly studied. This study aimed to evaluate the prognostic impact of two different revascularisation strategies and the potential impact of medical therapy. METHODS: Using a propensity score approach, the impact of two treatment strategies was analysed -staged non-culprit revascularisation group vs culprit-lesion-only percutaneous coronary intervention (PCI) group -- on a composite outcome of cardiovascular death (CVD), myocardial infarction, and repeated revascularisation. Moreover, models were further adjusted for medication at discharge. RESULTS: Among 1,385 STEMI patients treated with primary PCI, a subgroup of 433 with MVD was analysed. At the median follow-up of 41 (IQR, 21-65) months, after propensity-score adjustment, the multivariable Cox proportional hazard analysis showed that the staged non-culprit revascularisation group was associated with a lower composite endpoint (HR, 0.44; 95% CI, 0.24-0.82; p=0.01), lower CVD (HR, 0.34; 95% CI, 0.14-0.82; p=0.02), and lower all-cause death (HR, 0.46; 95% CI, 0.24-0.86; p=0.02). Use of renin-angiotensin inhibitors was associated with lower CVD (HR, 0.51; 95% CI, 0.27-0.95; p=0.03), and both renin-angiotensin inhibitors (HR, 0.52; 95% CI, 0.32-0.86; p=0.01) and beta blockers (HR, 0.48; 95% CI, 0.29-0.79; p=0.01) were associated with lower all-cause death. CONCLUSIONS: In a real-word STEMI population with multivessel disease, staged non-culprit revascularisation was associated with lower cardiovascular mortality compared with a culprit-only PCI strategy. However, both revascularisation and medical therapy played a role in the improvement of mortality outcomes. Medical therapy amplified the benefit of myocardial revascularisation.

Advanced Heart Failure in Special Population: Cardiomyopathies and Myocarditis.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF) in young populations. The variety of causes, multiple underlying pathophysiological mechanisms, and different phenotypic expressions influence their presentation and response to treatment. Dilated cardiomyopathy is the most prevalent cause of HF. Advanced HF in hypertrophic, restrictive, and arrhythmogenic cardiomyopathies is rare, but its development portends a poor prognosis. The active phase of fulminant myocarditis may result in acute HF requiring advanced strategies to support the systemic circulation or may determine an irreversible persisting left ventricular failure with end-stage HF.

Association Between Use of Primary-Prevention Implantable Cardioverter-Defibrillators and Mortality in Patients With Heart Failure: A Prospective Propensity Score-Matched Analysis From the Swedish Heart Failure Registry.

BACKGROUND: Most randomized trials on implantable cardioverter-defibrillator (ICD) use for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction enrolled patients >20 years ago. We investigated the association between ICD use and all-cause mortality in a contemporary heart failure with reduced ejection fraction cohort and examined relevant subgroups. METHODS: Patients from the Swedish Heart Failure Registry fulfilling the European Society of Cardiology criteria for primary-prevention ICD were included. The association between ICD use and 1-year and 5-year all-cause and cardiovascular (CV) mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort and in prespecified subgroups. RESULTS: Of 16 702 eligible patients, only 1599 (10%) had an ICD. After matching, 1305 ICD recipients were compared with 1305 nonrecipients. ICD use was associated with a reduction in all-cause mortality risk within 1 year (hazard ratio, 0.73 [95% CI, 0.60-0.90]) and 5 years (hazard ratio, 0.88 [95% CI, 0.78-0.99]). Results were consistent in all subgroups including patients with versus without ischemic heart disease, men versus women, those aged <75 versus ≥75 years, those with earlier versus later enrollment in the Swedish heart failure registry, and patients with versus without cardiac resynchronization therapy. CONCLUSIONS: In a contemporary heart failure with reduced ejection fraction population, ICD for primary prevention was underused, although it was associated with reduced short- and long-term all-cause mortality. This association was consistent across all the investigated subgroups. These results call for better implementation of ICD therapy.

Impact of patient delay in a modern real world STEMI network.

BACKGROUND: The impact of patient delay on left ventricular ejection fraction (LVEF), when system delay has performance that meets the current recommended guidelines, is poorly investigated. METHODS: We evaluated a cohort of STEMI patients treated with primary percutaneous coronary intervention (pPCI) and with an ECG STEMI diagnosis to wire crossing time (ETW) ≤120 min. Independent predictors of pre-discharge decreased LVEF (≤45%) were analyzed. RESULTS: 490 STEMI patients with both ETW time ≤120 min and available pre-discharge LVEF were evaluated. Mean age was 64.2 ± 12 years, 76.2% were male, 19.5% were diabetics, 42.7% had and anterior myocardial infarction (MI), and 9.8% were in Killip class III-IV. Median time of patient's response to initial symptoms (patient delay) was 58,5 (IQR 30;157) minutes and median ETW time was 78 (IQR 62-95) minutes. 115 patients (23.4%) had pre-discharge LVEF ≤45%. At multivariable analysis independent predictors of decreased LVEF (≤45%) were anterior MI (OR 4,659, 95% CI 2,618-8,289, p < 0,001), Killip class (OR 1,449, 95% CI 1,090-1,928, p = 0,011) and patients delay above the median (OR 2,030, 95% CI 1,151-3.578, p = 0,014). These independent predictors were confirmed in patients with ETW time ≤90 min. CONCLUSIONS: When system delay meets the recommended criteria for pPCI, patient delay becomes an independent predictor of pre-discharge LVEF. These findings provide further insights into the potential optimization of STEMI management and identify a target that needs to be improved, considering that still a significant proportion of patients continue to delay seeking medical care.

Treatment of Functional Mitral Regurgitation in Heart Failure.

PURPOSE OF REVIEW: To analyze the current state of the art of functional mitral regurgitation (FMR) treatment. RECENT FINDINGS: The first-line treatment of severe FMR consists of guideline medical therapy (GMT) and resynchronization therapy when indicated; the impact of new medical therapies like sacubitril/valsartan needs further assessment. Valvular intervention may be considered in FMR symptomatic patients despite GMT, and can be performed surgically or percutaneously. MitraClip is a safe percutaneous procedure associated with symptoms improvement. Recently, the COAPT trial showed superior outcomes for MitraClip versus GMT contrasting the MITRA-FR trial which showed no benefit of MitraClip compared with GMT. These results should be interpreted as complementary rather than opposite. The COAPT trial provided a "proof of concept" that percutaneous treatment of severe FMR in patients without too advanced left ventricular disease translates into a prognostic benefit. Careful patient selection will play a critical role in defining the clinical niche for successful interventions.

Lifelong arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy: distribution of events and impact of periodical reassessment.

Aims: The arrhythmic risk stratification of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains controversial. We evaluated the long-term distribution of life-threatening arrhythmic events assessing the impact of periodical risk reassessment. Methods and results: Ninety-eight ARVC patients with no previous major ventricular arrhythmias were retrospectively analysed. Patients were assessed at baseline, at 22 [inter-quartile range (IQR) 16-26], 49 (IQR 41-55) and 97 months (IQR 90-108). The primary endpoint was a composite of sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or appropriate implanted cardioverter-defibrillator intervention. During a median follow-up of 91 months (IQR 34-222) 28 patients (29%) experienced the composite endpoint. The median time for the primary event was 35 months (IQR 18-86 months), and 39% of events occurred beyond 49 months of follow-up. History of syncope (HR 4.034; 95% CI, 1.488 to 10.932; P-value = 0.006), non-sustained ventricular tachycardia (NSVT; HR 3.534; 95% CI 1.265-9.877; P-value = 0.016), premature ventricular contractions (PVC) >1000/24h (HR 2.761; 95% CI 1.120-6.807; P-value = 0.027), and right ventricular fractional area change (RVFAC; HR 0.945; 95% CI 0.906-0.985; P-value = 0.008) were found as independent predictors at baseline multivariate analysis. Nevertheless, when the prognostic impact of each variable was reassessed overtime only NSVT (HR 3.282; 95% CI, 1.122 to 9.598, P-value = 0.023) and RVFAC (HR 0.351, 95% CI, 0.157 to 0.780; P-value = 0.010) remained independent predictors throughout the whole follow-up. Conclusion: In our cohort of ARVC patients only NSVT and RVFAC maintained their independent prognostic impact in predicting arrhythmic events during the long-term follow-up. Periodical re-assessment of risk in these patients is strongly recommended.

Cardiac fluid dynamics meets deformation imaging.

Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.