Additional value of T1 and T2 mapping techniques for early detection of myocardial involvement in scleroderma.

BACKGROUND: We evaluated the prevalence of myocardial involvement by native T1 and T2 mapping, the diagnostic performance of mapping in addition to conventional Lake Louise Criteria (LLC), as well as correlations between mapping findings and clinical or conventional cardiovascular magnetic resonance (CMR) parameters in systemic sclerosis (SSc) patients. METHODS: Fifty-five SSc patients (52.31 ± 13.24 years, 81.8% female) and 55 age- and sex-matched healthy subjects underwent clinical, bio-humoral assessment, and CMR. The imaging protocol included: T2-weighted, early post-contrast cine sequences, native T1 and T2 mapping by a segmental approach, and late gadolinium enhancement (LGE) technique. RESULTS: Global myocardial T1 and T2 values were significantly higher in SSc patients than in healthy subjects. An increase in native T1 and/or T2 was present in the 62.1% of patients with normal conventional CMR techniques (negative LGE and T2-weighted images). Respectively, 13.5% and 59.6% of patients fulfilled original and updated LLC (overall agreement = 53.9%). Compared with patients with normal native T1, patients with increased T1 (40.0%) featured significantly higher left ventricular end-diastolic volume index and cardiac index, biventricular stroke volume indexes, and global heart T2 values, and more frequently had a history of digital ulcers. Biochemical and functional CMR parameters were comparable between patients with normal and increased T2 (61.8%). CONCLUSION: T1 and T2 mapping are sensitive parameters that should be included in the routine clinical assessment of SSc patients for detecting early/subclinical myocardial involvement.

Prognostic significance of longitudinal strain in dilated cardiomyopathy with recovered ejection fraction.

OBJECTIVE: Patients with non-ischaemic dilated cardiomyopathy (NICM) may experience a normalisation in left ventricular ejection fraction (LVEF). Although this correlates with improved prognosis, it does not correspond to a normalisation in the risk of death during follow-up. Currently, there are no tools to risk stratify this population. We tested the hypothesis that absolute global longitudinal strain (aGLS) is associated with mortality in patients with NICM and recovered ejection fraction (LVEF). METHODS: We designed a retrospective, international, longitudinal cohort study enrolling patients with NICM with LVEF <40% improved to the normal range (>50%). We studied the relationship between aGLS measured at the time of the first recording of a normalised LVEF and all-cause mortality during follow-up. We considered aGLS >18% as normal and aGLS ≥16% as of potential prognostic value. RESULTS: 206 patients met inclusion criteria. Median age was 53.5 years (IQR 44.3-62.8) and 56.6% were males. LVEF at diagnosis was 32.0% (IQR 24.0-38.8). LVEF at the time of recovery was 55.0% (IQR 51.7-60.0). aGLS at the time of LVEF recovery was 13.6%±3.9%. 166 (80%) and 141 (68%) patients had aGLS ≤18% and <16%, respectively. During a follow-up of 5.5±2.8 years, 35 patients (17%) died. aGLS at the time of first recording of a recovered LVEF correlated with mortality during follow-up (HR 0.90, 95% CI 0.91 to 0.99, p=0.048 in adjusted Cox model). No deaths were observed in patients with normal aGLS (>18%). In unadjusted Kaplan-Meier survival analysis, aGLS <16% was associated with higher mortality during follow-up (31 deaths (22%) in patients with GLS <16% vs 4 deaths (6.2%) in patients with GLS ≥16%, HR 3.2, 95% CI 1.1 to 9, p=0.03). CONCLUSIONS: In patients with NICM and normalised LVEF, an impaired aGLS at the time of LVEF recovery is frequent and associated with worse outcomes.

Dilated Cardiomyopathy With Mid-Range Ejection Fraction at Diagnosis: Characterization and Natural History.

Background Limited data are available on mid-range ejection fraction (mrEF) patients with dilated cardiomyopathy. We sought to define the characteristics, evolution, and long-term prognosis of dilated cardiomyopathy patients with mrEF at diagnosis. Methods and Results We analyzed all dilated cardiomyopathy patients consecutively evaluated in the Trieste Heart Muscle Disease Registry from 1988 to 2013. mrEF and reduced ejection fraction (rEF) were defined as baseline left ventricular (LV) ejection fraction values between 40% and 49% and <40%, respectively. All-cause mortality or heart transplantation, sudden cardiac death, or major ventricular arrhythmias were considered as outcome measures. Worsening LV ejection fraction (reduction to <40%) during follow-up was also considered to identify possible predictors of adverse remodeling. Among 812 enrolled patients, 175 (22%) presented with mrEF at presentation. At baseline, as compared with the rEF group, mrEF patients had lower rates of moderate-severe mitral regurgitation and restrictive LV filling pattern. During a median follow-up period of 120 (60-204) months, the mrEF group presented a lower rate of death/heart transplantation (9% versus 36%, P<0.001) and sudden cardiac death or major ventricular arrhythmias (4.5% versus 15%, P<0.001) than rEF patients. Moreover, 29 out of 175 mrEF patients (17%) evolved to rEF. Restrictive LV filling pattern emerged as the strongest predictor of rEF development following multivariable analysis. Conclusions mrEF identified a consistent subgroup of dilated cardiomyopathy patients diagnosed in an earlier stage with subsequent apparent better long-term evolution. However, 17% of these patients evolved into rEF despite the use of medical therapy. A baseline restrictive LV filling pattern was independently associated with subsequent evolution to rEF.

Usefulness of Addition of Magnetic Resonance Imaging to Echocardiographic Imaging to Predict Left Ventricular Reverse Remodeling in Patients With Nonischemic Cardiomyopathy.

Defining short-term prognosis in nonischemic cardiomyopathy (NICM) is challenging in clinical practice. Although left ventricular reverse remodeling (LVRR) is a key prognostic marker in NICM there are few parameters able to predict it. We investigated whether a complete structural and functional cardiac magnetic resonance imaging (cMRI) evaluation was incremental to the classic clinical-echocardiographic approach in predicting LVRR in a large cohort of NICM patients receiving evidence-based treatment. Patients with a recent diagnosis of NICM (<3 months) who underwent complete clinical, echocardiographic and cMRI assessment were consecutively enrolled from 2008 to 2016. LVRR was defined as an increase in ≥10 points or normalization of left ventricular ejection fraction, associated with a ≥10% reduction or normalization of left ventricular end-diastolic diameter at midterm (median time 20 months) echocardiographic follow-up. Among 80 NICM patients included in the study, LVRR was observed in 43 (54%). At multivariate analysis, the clinical-echocardiographic evaluation failed to identify independent predictors of LVRR. However, absence of late gadolinium enhancement (odds ratio [OR] 9.07; confidence interval [CI] 2.7 to 13.1; p value 0.0003), left ventricular mass (OR 1.018; CI 1.001 to 1.036; p value 0.045) and peak circumferential strain (OR 1.213; CI 1.011 to 1.470; p value 0.049) assessed by cMRI were independently associated with LVRR. A model for LVRR prediction based on cMRI and clinical-echocardiographic parameters performed significantly better than the clinical-echocardiographic model alone (area under curve 0.84 vs 0.72; p value 0.023). In conclusion, an integrated imaging approach with the addition of a structural and functional cMRI study to the standard-of-care evaluation improves the prediction of LVRR in a large cohort of patients with recently diagnosed NICM receiving evidence-based treatment.

Arrhythmic Risk Stratification in Patients With Idiopathic Dilated Cardiomyopathy.

Arrhythmic risk stratification in idiopathic dilated cardiomyopathy (IDC) remains a major concern. As the ventricles remodel in time, risk factors for arrhythmic death may change. A cohort of 710 patients with idiopathic dilated cardiomyopathy, without previous ventricular arrhythmias, was retrospectively studied to understand how risks vary in time. The primary end point was a composite of sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator interventions. The prediction of the arrhythmic outcome was assessed dynamically through landmark analysis. Patients were assessed at baseline, short term (12 months, interquartile range 6 to 18), and long-term (72 months, interquartile range 60 to 84). The strongest risk predictors at each evaluation were combined in 3 multivariate models. During a median follow-up of 102 months, 80 patients (11%) experienced the primary end point. At baseline, QRS duration (p = 0.008), disease duration (p <0.001), and mitral regurgitation (p = 0.010) were significantly associated with the primary end point. The 12 months' landmark model included disease duration (p = 0.049), syncope (p = 0.005), New York Heart Association classes III and IV (p = 0.02), and indexed left ventricular end-diastolic volume (p = 0.001). Finally, the 72 months' landmark model combined the indexed left ventricular end-diastolic volume (p = 0.048), the left ventricular ejection fraction (p = 0.008), and the left atrial area (p = 0.001). All the 3 models provided a satisfactory accuracy (area under the curve ranging from 0.76 to 0.82, p <0.001). With an implantable cardioverter-defibrillator, the natural course of the disease influences the effect of arrhythmic risk factors overtime. Different predictors should be considered for the risk stratification according to the timing of assessment. Impaired left ventricular ejection fraction was significantly associated with major arrhythmias only in the long term.

Evolving concepts in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co-morbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red-flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non-pharmacological evidence-based treatments. However, some important issues in clinical management remain unresolved, including the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review offers a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.

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.

The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.

OBJECTIVES: In this study, the authors analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). BACKGROUND: RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. METHODS: From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of ≥72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. RESULTS: At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). CONCLUSIONS: Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF throughout regular follow-up conferred additive long-term prognostic value to the baseline evaluation.

Early Arrhythmic Events in Idiopathic Dilated Cardiomyopathy.

OBJECTIVES: The study sought to provide an insight into the prevalence, characterization and possible reliable indicators of early sudden cardiac death/malignant ventricular arrhythmias (SCD/MVAs) in a large cohort of dilated cardiomyopathy (DCM). BACKGROUND: DCM generally affects young individuals and is characterized by an unpredictable prognosis with a non-negligible risk of SCD/MVAs, particularly in early stages of disease. METHODS: From 1988 to 2014, 952 patients with DCM were consecutively included in the Heart Muscle Disease Registry of Trieste. RESULTS: Globally, 20 patients (2.1% of the overall population) experienced SCD/MVAs within the first 6 months after enrollment (primary endpoint). At baseline they showed a worse functional class (New York Heart Association functional class III to IV 42% vs. 22%, p = 0.038), a longer QRS complex duration (127 ± 41 ms vs. 108 ± 33 ms; p = 0.013) and a larger indexed left ventricular end-systolic volume (LVESVI) (82 ± 49 ml/m2 vs. 67 ± 34 ml/m2; p = 0.049), as compared to patients without early SCD/MVAs. Beta-blockers were less tolerated (59% vs. 83% in patients with no early SCD/MVAs; p = 0.008), mostly due to hemodynamic intolerance. At multivariate analysis, LVESVI (odds ratio [OR]: 1.012; 95% confidence interval [CI]: 1.000 to 1.024; p = 0.043) and QRS complex duration (OR: 1.017; 95% CI: 1.003 to 1.030; p = 0.015) were independently associated with the primary endpoint, whereas beta-blockers demonstrated a protective effect (OR: 0.169, CI: 0.048 to 0.593; p = 0.006). CONCLUSIONS: Patients with DCM present a significant risk of major arrhythmic events in the first phase of the disease. Baseline LVESVI, QRS duration, and intolerance to beta-blocker therapy might be useful tools in the arrhythmic early risk assessment.

Factor-V HR2 haplotype and thromboembolic disease.

OBJECTIVES: The objective of this study is to evaluate the prevalence of HR2 polymorphism among patients with pulmonary embolism (PE) and healthy subjects. BACKGROUND: Polymorphism in the factor V gene named HR2 has been described as a possible risk factor for venous thromboembolism (VTE) development. Contradictive results on this association have been reported. METHODS: Eighty-five patients admitted for PE and 72 healthy subjects were included in the study. Thrombophilia screening using genetic tests for factor V Leiden (G1691A/Leiden and HR2 haplotype) and other genetic mutations were investigated. RESULTS: Of 85 patients with PE, 20 (23.53%) carried the HR2 haplotype. Further, a majority of the patients with HR2 haplotype had recurrent venous thrombosis or PE (15 out of 20 patients). The HR2 haplotype was detected in 6 (8.3%) out of 72 healthy subjects. Patients had significantly higher HR2 haplotype frequency than healthy controls (P = 0.001). HR2 carriers had a three-fold increase in risk of developing PE (OR = 3.38, 95% CI = 1.27-8.96, P = 0.011). After adjustment for other tested defects for thrombophilia, HR2 haplotype was associated with increased risk of thromboembolic events (OR = 3.05, 95% CI = 1.11-8.35, P = 0.03). However, after adjustment for sex and age, HR2 polymorphism was no longer associated with the risk of thromboembolic event (OR = 1.22, 95% CI = 0.34-4.38, P = 0.76). CONCLUSIONS: Our study does not support the notion that factor V HR2 haplotype might be a risk factor for thrombosis despite its high prevalence among patients with PE.