Objectives The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). Background Tailored ...medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. Methods We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of ≥10 U or a left ventricular ejection fraction of ≥50% and a decrease in indexed left ventricular end-diastolic diameter of ≥10% or indexed left ventricular end-diastolic diameter of ≥33 mm/m2 at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 ± 53 months; there were 55 deaths (23%) and 32 HTx (13%). Results LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. Conclusions LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease.
Abstract 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.
Abstract
Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of ...echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions.
Graphical Abstract
BACKGROUND—Active myocarditis is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of ...patients with biopsy-proven active myocarditis, looking for accessible and valid early predictors of long-term prognosis.
METHODS AND RESULTS—From 1981 to 2009, 82 patients with biopsy-proven active myocarditis were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or presence of LVEF≥50%, was assessed. At baseline, left ventricular dysfunction (LVEF<50%) and left atrium enlargement were independently associated with long-term heart transplantation–free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of New York Heart Association III to IV classes, left atrium enlargement, and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term reevaluation showed a significant incremental prognostic value in comparison with the baseline evaluation (baseline model versus 6 months modelarea under the curve 0.79 versus 0.90, P=0.03).
CONCLUSIONS—Baseline left ventricular function is a marker for prognosis regardless of the clinical pattern of disease onset, and its reassessment at 6 months appears useful for assessing longer-term outcome.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease characterized by fibrofatty replacement of the myocardium and a predisposition to cardiac arrhythmias ...and sudden death. We evaluated the cardiomyopathy gene titin (TTN) as a candidate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the titin protein to the transitional junction at intercalated disks.
All 312 titin exons known to be expressed in human cardiac titin and the complete 3' untranslated region were sequenced in 38 ARVC families. Eight unique TTN variants were detected in 7 families, including a prominent Thr2896Ile mutation that showed complete segregation with the ARVC phenotype in 1 large family. The Thr2896IIe mutation maps within a highly conserved immunoglobulin-like fold (Ig10 domain) located in the spring region of titin. Native gel electrophoresis, nuclear magnetic resonance, intrinsic fluorescence, and proteolysis assays of wild-type and mutant Ig10 domains revealed that the Thr2896IIe exchange reduces the structural stability and increases the propensity for degradation of the Ig10 domain. The phenotype of TTN variant carriers was characterized by a history of sudden death (5 of 7 families), progressive myocardial dysfunction causing death or heart transplantation (8 of 14 cases), frequent conduction disease (11 of 14), and incomplete penetrance (86%).
Our data provide evidence that titin mutations can cause ARVC, a finding that further expands the origin of the disease beyond desmosomal proteins. Structural impairment of the titin spring is a likely cause of ARVC and constitutes a novel mechanism underlying myocardial remodeling and sudden cardiac death.
This open access book presents a comprehensive overview of dilated cardiomyopathy, providing readers with practical guidelines for its clinical management. The first part of the book analyzes in ...detail the disease’s pathophysiology, its diagnostic work up as well as the prognostic stratification, and illustrates the role of genetics and gene-environment interaction. The second part presents current and future treatment options, highlighting the importance of long-term and individualized treatments and follow-up. Furthermore, it discusses open issues, such as the apparent healing phenomenon, the early prognosis of arrhythmic events or the use of genetic testing in clinical practice. Offering a multidisciplinary approach for optimizing the clinical management of DCM, this book is an invaluable aid not only for the clinical cardiologists, but for all physicians involved in the care of this challenging disease.
The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy ...(IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate—free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval CI 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.
Patients with symptomatic heart failure (HF), reduced left ventricular ejection fraction (LVEF), and high-grade functional mitral regurgitation (MR) may benefit from percutaneous edge-to-edge mitral ...valve repair (PMVR). However, patient selection still remains a central issue. We sought to investigate the potential role of the global longitudinal strain- (GLS-) based left ventricular contractile reserve (LVCR) at dobutamine stress echocardiography (DSE) in this setting.
Thirty-three stable HF patients (MR grade ≥ 3+; median LVEF, 29%; median GLS, -8.3%) who were candidates for PMVR were prospectively enrolled. All patients underwent DSE to assess LVCR (LVEF increase ≥ 5%; GLS increase ≥ 2%; stroke volume SV increase ≥ 20% of the measured SV value).
After DSE, a positive LVCR
was detected in 21 patients (64%), positive LVCR
in 12 patients (36%), and positive LVCR
in 14 patients (42%). LVCR
was associated with better symptom relief, MR improvement, and LV reverse remodeling in a short-term follow-up. A significant improvement of GLS during DSE (hazard ratio HR, 0.549; 95% CI, 0.395-0.765; P < .001), along with history of HF hospitalization (HR, 1.48; 95% CI, 1.119-1.967; P = .006) and beta-blocker therapy (HR, 0.146; 95% CI, 0.046-0.462; P = .001), were independently associated with risk of death/heart transplantation/HF-related hospitalizations.
LVCR, assessed by speckle-tracking DSE, is associated with better results after PMVR in the setting of advanced HF. Improvement of longitudinal function emerged, beyond the ejection fraction, as an independent predictor of outcomes and could improve the selection of best candidates for the percutaneous correction of functional MR.
Structured Abstract Background The role of percutaneous mitral valve repair (PMVR) in patients with end-stage heart failure (HF) and functional mitral regurgitation (FMR) is unclear. Methods ...Seventy-five consecutive patients with FMR grade ≥ 3 + and severe HF symptoms despite optimal medical therapy and resynchronization therapy underwent PMVR with the MitraClip system (Abbott, Abbott Park, IL, USA) at 3 centers. Clinical evaluation, echocardiography and pro-BNP measurement were performed at baseline and 6-month. Results Mean age was 67 ± 11 years, logistic EuroSCORE = 23 ± 18%, left ventricle ejection fraction (LVEF) 30 ± 9%. In 6 patients (8%) PMVR was performed as a bridge to heart transplant; many patients were dependent from iv diuretics and/or inotropes. Rate of serious adverse in-hospital events was 1.3% (1 patient who died after conversion to cardiac surgery). Sixty-three patients (84%) were discharged with MR ≤ 2 +. At 6-month, 4 patients died (5%), 80% had MR ≤ 2 + and 75% were in New York Heart Association class ≤ II. Median pro-BNP decreased from 4395 pg/mL to 2594 pg/mL (p = 0.003). There were no significant changes in LV end-diastolic volume (222 ± 75 ml vs. 217 ± 79, p = 0.19), end-systolic volume (LVESV, 159 ± 66 ml vs. 157 ± 69, p = 0.54) and LVEF (30 ± 9% vs. 30 ± 12%, p = 0.86). Significant reverse remodeling (reduction of LVESV ≥ 10%) was observed in 25%, without apparent association with baseline characteristics. The number of hospitalizations for HF in comparison with the 6 months before PMVR were reduced from 1.1 ± 0.8 to 0.3 ± 0.6 (p < 0.001). Conclusions In extreme risk HF patients with FMR, PMVR improved symptoms and reduced re-hospitalization and pro-BNP levels at 6 months, despite the lack of LV reverse remodeling.
Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We ...lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities.
In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy).
We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios.
The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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