Focus on arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease generally caused by desmosomal mutations and characterized by progressive replacement of cardiomyocites with fibro-adipose tissue. In the classic form of the disease right ventricle is predominantly affected. However, biventricular and left-dominant variants have been recently recognized, leading to the new nosological definition of arrhythmogenic cardiomyopathy. The condition affects mostly young adults and athletes and is clinically characterized by ventricular arrhythmias, heart failure and sudden cardiac death. The diagnosis is based on clinical-instrumental criteria, including family history, morpho-functional and electrocardiographic abnormalities, ventricular arrhythmias and genetic defects (Task Force Criteria, 2010). The main goal in the management of patients is the prevention of sudden cardiac death, where implantable cardioverter-defibrillator is the only effective therapeutic strategy. Many arrhythmic risk factors have been described. Recently, an on-line calculator has been proposed, but it needs further validation.

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.

Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Acute Hemodynamic Response to Cardiac Resynchronization in Dilated Cardiomyopathy: Effect on Late Mitral Regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is associated with reduced survival in dilated cardiomyopathy (DCM). Cardiac resynchronization therapy (CRT) can improve FMR. We sought to identify the predictors of FMR improvement after CRT in DCM. METHODS: From January 2003 to December 2013, 430 DCM patients consecutively enrolled were retrospectively analyzed. Inclusion criteria were successful CRT implantation in the presence of conventional indications (i.e., left bundle branch block, left ventricular ejection fraction ≤35%, New York Heart Association functional class ≥II) and moderate-to-severe FMR at the time of procedure. Early echocardiographic evaluation after CRT implantation (median 2.5 days) has been performed in each patient. Improvement in FMR (absent/mild) at midterm (7 months; interquartile range 4-10) was considered as the primary study end point. RESULTS: A total of 44 patients (10% of the overall cohort) were included. A significant reduction in FMR severity was observed in 21 patients (48%) at midterm after CRT (median time 7 months). No preimplantation variables predicted FMR evolution, but FMR improvement at midterm was strongly predicted by an acute favorable hemodynamic response (persistence/development of normal right ventricular function and 10-mm Hg decrease or normalization [≤35 mm Hg] of systolic pulmonary artery pressure) at postimplantation echocardiography (odds ratio: 13.7; 95% confidence interval: 1.27-42.8; P = 0.016). FMR improvement at midterm was stable during follow-up and was associated with superior long-term transplant-free survival (P = 0.022). CONCLUSIONS: Stable FMR improvement frequently occurs after CRT implantation in DCM and is associated with improved transplant-free survival. Echocardiographic evaluation of acute hemodynamic response to CRT is helpful to early identification of the favorable FMR evolution.

Titin and desmosomal genes in the natural history of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Genotype-phenotype correlations are poorly characterised in arrhythmogenic right ventricular cardiomyopathy (ARVC). We investigated whether carriers of rare variants in desmosomal genes (DC) and titin gene (TTN) display different phenotypes and clinical outcomes compared with non-carriers (NT-ND). METHODS AND RESULTS: Thirty-nine ARVC families (173 subjects, 67 affected) with extensive follow-up (mean 9 years), prospectively enrolled in the International Familial Cardiomyopathy Registry since 1991, were screened for rare variants in TTN and desmosomal genes (DSP, PKP2, DSG2, DSC2). Multiple clinical and outcome variables were compared between three genetic groups (TTN, DC, NT-ND) to define genotype-phenotype associations. Of the 39 ARVC families, 13% (5/39) carried TTN rare variants (11 affected subjects), 13% (5/39) DC (8 affected), while 74% (29/39) were NT-ND (48 affected). When compared with NT-ND, DC had a higher prevalence of inverted T waves in V2-3 (75% vs 31%, p=0.004), while TTN had more supraventricular arrhythmias (46% vs 13%, p=0.013) and conduction disease (64% vs 6% p<0.001). When compared with the NT-ND group, the DC group experienced a worse prognosis (67% vs 11%, p=0.03) and exhibited a lower survival free from death or heart transplant (59% vs 95% at 30 years, and 31% vs 89% at 50 years, HR 9.66, p=0.006), while the TTN group showed an intermediate survival curve (HR 4.26, p=0.037). CONCLUSIONS: TTN carriers display distinct phenotypic characteristics including a greater risk for supraventricular arrhythmias and conduction disease. Conversely, DC are characterised by negative T waves in anterior leads, severe prognosis, high mortality and morbidity.

Long-term evolution and prognostic stratification of biopsy-proven active myocarditis.

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 model: area 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.

Asymmetric ring annuloplasty for ischemic mitral regurgitation: early and mid-term outcomes.

BACKGROUND AND AIM OF THE STUDY: The Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring was specifically designed to treat ischemic mitral regurgitation (IMR) associated with asymmetric mitral annular dilation and leaflet tethering. The study aim was to review, retrospectively, the results of mitral annuloplasty with this asymmetric ring in a representative number of patients. METHODS: Between January 2005 and July 2012, the IMR ETlogix ring was implanted in 190 consecutive patients (mean age 69.5 +/- 7.6 years) with grade > or =2+ IMR (graded from 0 to 3+). Preoperatively, 37 patients (19.5%) were in NYHA class IV, and 73 (38.4%) suffered from unstable angina. The operative risk according to the European System for Cardiac Operative Risk Evaluation II was 15.6 +/- 14.5%. Using two- dimensional echocardiography, postoperative changes in mitral annular diameter (MAD) and tenting height (TH) of the mitral valve in four-chamber, two-chamber and long-axis views, were assessed at mid-systole. RESULTS: Thirty-eight patients (20.0%) received one or more concomitant major cardiac surgical procedure(s) other than, or in addition to, coronary artery bypass grafting or tricuspid valve annuloplasty. Nineteen (10.0%) hospital deaths occurred, and one patient underwent immediate reoperation for residual MR. During the follow up (mean 4.8 +/- 2.1 years) there were 26 cardiac deaths, 14 non-cardiac deaths, and three mitral valve replacements. The seven-year actuarial survival, freedom from grade > or =2+ MR and reoperation were 62.0%, 93.1% and 97.6%, respectively. Renal impairment (p = 0.012) and extracardiac arteriopathy (p = 0.047) were predictors of death; bilateral internal thoracic artery grafting was a protective factor (p = 0.033). Heart failure symptoms were improved (p <0.01). Left ventricular reverse remodeling was achieved in 50.6% of patients. The MAD and TH were each decreased in all three echocardiographic views (p < 0.001), the reductions being greater in the long-axis view. CONCLUSION: By restoring the mitral apparatus geometry and competence, asymmetric annuloplasty with the IMR ETlogix ring provides good mid-term outcomes and helps left ventricular reverse remodeling in IMR.

Aortic root replacement with a stented bioprosthetic valved conduit: mid-term results.

BACKGROUND AND AIM OF THE STUDY: For patients who require aortic root replacement but are unwilling or unable to receive anticoagulants, a composite conduit was assembled intraoperatively that contained a stented biological valve sutured inside a vascular tube graft, rather than at its extremity. This simple modification of the Bentall concept may provide several advantages. The results obtained with this conduit over an 11-year period were analyzed. METHODS: Between May 2001 and April 2012, 101 consecutive patients (mean age 68.3 +/- 9.2 years) underwent aortic root replacement with the bioprosthetic valved conduit. Aortic pathologies included degenerative disease in 61 patients (60.4%), atherosclerosis in 20 (19.8%), annuloaortic ectasia in 12 (11.9%), porcelain aorta in four (4.0%), and acute dissection in four (4.0%). The whole ascending aorta was replaced in 79 patients (78.2%); a hemiarch reconstruction and a total arch replacement were added in 18 (17.8%) and four (4.0%) patients, respectively. Hypothermic circulatory arrest was performed in 60 cases (59.4%). Forty patients (39.6%) underwent additional cardiac procedures. All perioperative data were collected prospectively. RESULTS: There were five (5.0%) hospital deaths. During a mean follow up of 3.8 +/- 2.4 years there were two non-valve-related cardiac deaths and five noncardiac deaths. The seven-year actuarial survival was 79.2% (95% CI 67.0-91.4%). Bioprosthetic structural dysfunction occurred in only one patient; reoperation was easily performed by replacing the valve within the vascular graft. In the remaining 88 patients (87.1%), echocardiographic assessment showed a low transaortic mean pressure gradient (7.2 +/- 4.7 mmHg) and left ventricular wall mass reduction (p = 0.0002). CONCLUSION: This valved conduit is a safe and durable option for replacing the aortic root, thus facilitating the technique of implantation and simplifying reoperation in the case of valve failure.

Long term survival in patients with cardiac amyloidosis. Prevalence and characterisation during follow-up.

BACKGROUND AND AIMS: Cardiac amyloidosis (CA) is usually characterised by a poor outcome in the short-term; clinical and instrumental features are heterogeneous and could characterise subgroups with different prognoses. The aim of our study was to describe a subgroup of patients with CA showing an impressive favourable long-term survival. METHODS: Out of 50 patients (males 65%, 63 ± 11 years) with an echocardiographic and bioptic diagnosis of CA observed from 1991 to 2009, we selected a subgroup of patients surviving more than 50 months from diagnosis (group 1). We described their features at enrolment and during follow-up, comparing them with patients surviving less than 12 months (group 2). RESULTS: We found seven patients (14%) belonging to group 1 and 26 (52%) to group 2. Four out of seven long term survivors suffered from AL amyloidosis, in one case the underlying aetiology was a chronic inflammatory disease, while in two cases remained unknown. At enrolment, group 1 patients showed higher systolic blood pressure with respect to group 2 (140 ± 25 vs. 112 ± 18 mmHg, respectively, p=0.011), and a less thick interventricular septum (IVS) (IVS thickness > 15 mm in 29% vs. 69% of patients, p = 0.049). No patient of group 1 presented left ventricular restrictive filling pattern (0 vs. 31% in group 1 and 2 respectively, p = 0.035), atrial fibrillation (0 vs. 35%, p = 0.024), or progression towards a more severe disease during follow-up. CONCLUSIONS: A not negligible proportion of patients with CA can have a long-term survival. They showed a less severe disease at diagnosis, with substantial stability over time. Further studies on larger populations are necessary to understand the mechanisms underlying this more favourable natural history of the disease.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with type 2 diabetes mellitus without myocardial ischemia.

BACKGROUND/OBJECTIVE: Left ventricular (LV) circumferential or longitudinal shortening may be impaired in patients with type 2 diabetes mellitus (DM). In the present study, patients with type 2 DM without myocardial ischemia and combined impairment of circumferential and longitudinal (C+L) shortening were studied to assess the prevalence and factors associated with this condition. METHODS: Data from 386 patients with type 2 DM enrolled in the SHORTening of midWall and longitudinAl left Ventricular fibers in diabEtes study were analyzed. One hundred twenty healthy subjects were used to define C+L dysfunction. Stress-corrected midwall shortening and mitral annular peak systolic velocity were considered as indexes of C+L shortening and classified as low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). RESULTS: Combined C+L dysfunction was detected in 66 patients (17%). The variables associated with this condition were lower glomerular filtration rate (OR 0.98 [95% CI 0.96 to 0.99], greater LV mass (OR 1.05 [95% CI 1.02 to 1.08]), high pulmonary artery wedge pressure (OR 1.23 [95% CI 1.04 to 1.44]) and mitral annular calcifications (OR 3.35 [95% CI 1.71 to 6.55]). Considering the entire population, the relationship between stress-corrected midwall shortening and peak systolic velocity was poor (r=0.20), and the model was linear. The relationship was considerably closer and nonlinear in patients with combined C+L dysfunction (r=0.61; P<0.001), having the best fit by cubic function. CONCLUSIONS: Combined C+L dysfunction was present in one-sixth of patients with type 2 DM without myocardial ischemia. This condition was associated with reduced renal function, worse hemodynamic status and structural LV abnormalities, and may be considered a preclinical risk factor for heart failure.

Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes.

BACKGROUND: 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. METHODS AND RESULTS: 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%). CONCLUSIONS: 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.

Mitral annuloplasty with IMR ETlogix ring for ischemic mitral regurgitation and left ventricular dysfunction.

BACKGROUND AND AIM OF THE STUDY: Chronic ischemic mitral regurgitation (IMR) is associated with asymmetric mitral leaflet tethering and annular dilation. The Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring is designed specifically to treat these asymmetric pathological changes. In the present study, the results of mitral annuloplasty with this ring in a selected subset of patients with significant IMR and left ventricular (LV) dysfunction were analyzed. METHODS: Between May 2005 and September 2009, the IMR ETlogix ring was implanted in 140 consecutive patients with grade > OR = 2+ IMR (graded from 0 to 3+). Of these patients, 41 (29%) suffered from preoperative LV dysfunction (defined as LV ejection fraction < OR = 0.35). Ten of these 41 patients underwent combined aortic valve replacement or LV restoration, and thus were excluded from this retrospective study; consequently, 31 patients (mean age 67.1 +/- 7.7 years) were enrolled into the study. Preoperatively, 18 patients (58%) were in NYHA class III or IV, and 16 (52%) were in CCS class 3 or 4. The expected operative risk according to the logistic EuroSCORE was 22.4 +/- 16.5%. Using two-dimensional echocardiography, postoperative changes in the mitral annular diameter (MAD), tethering area (TA), and tenting height (TH) of the mitral valve in four-chamber, two-chamber, and long-axis views, were assessed at mid-systole. RESULTS: All patients underwent complete myocardial revascularization. One (3%) in-hospital (non-cardiac) death occurred. During a mean follow up of 3.4 +/- 1.5 years (range: 0.2 to 5.9 years), one early mitral replacement was required (due to endocarditis), and there were two cardiac deaths and three non-cardiac deaths. The four-year actuarial survival and freedom from heart failure hospital readmission were 82% and 75%, respectively. Heart failure symptoms were improved (p = 0.001), and IMR was well controlled within grade 1+ (p < 0.0001) for the 24 remaining patients. The MAD, TA and TH were each decreased in all three echocardiographic views (p < OR = 0.0006). The MAD reduction was greater in the long-axis view than in the four-chamber (56% versus 49%, p = 0.002) and two-chamber (56% versus 43%, p = 0.0003) views. CONCLUSION: In selected patients with chronic ischemic LV dysfunction, mitral annuloplasty with the IMR ETlogix ring, combined with complete myocardial revascularization, restored the mitral apparatus geometry and competence.

Prognostic predictors in arrhythmogenic right ventricular cardiomyopathy: results from a 10-year registry.

AIMS: We sought to examine the clinical presentation and natural history and to identify long-term prognostic predictors in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) as information concerning the natural history and risk stratification of ARVC is still incomplete. METHODS AND RESULTS: A cohort of 96 ARVC patients (68% males, 35 ± 15 years) was enrolled and underwent structured diagnostic protocol and follow-up. Primary study endpoints were death and heart transplantation (HTx). Clinical and echo-Doppler data were assessed as prognostic indicators. Sixty-five per cent of patients had right ventricular (RV) systolic dysfunction (RV fractional area change < 33%) and 24% had left ventricular (LV) systolic dysfunction (LV ejection fraction <50%). During a mean follow-up of 128 ± 92 months, 20 patients (21%) experienced cardiac death or underwent HTx. At multivariate analysis (Model 1), RV dysfunction [hazard ratio (HR): 4.12; 95% confidence interval (CI): 1.01-18.0; P = 0.05], significant tricuspid regurgitation (HR: 7.6; 95% CI: 2.6-22.0; P < 0.001), and amiodarone treatment (HR: 3.4; 95% CI: 1.3-8.8; P = 0.01) resulted as predictors of death/HTx. When inserting in the model, the 'ordinal dysfunction' (Model 2), which considers the presence of both RV and LV dysfunctions, this variable emerged as an independent prognostic predictor (HR: 6.3; 95% CI: 2.17-17.45; P < 0.001). At the receiver operating characteristic analysis, Model 2 was significantly more accurate in predicting long-term outcome compared with Model 1 (area under the curve 0.84 vs. 0.78, respectively; P = 0.04). CONCLUSION: In our tertiary referral centre ARVC population, the presence of LV dysfunction at diagnosis has an incremental power in predicting adverse outcome compared with RV dysfunction alone.

Echocardiographic evaluation of systolic and mean pulmonary artery pressure in the follow-up of patients with pulmonary hypertension.

AIMS: To identify a correction of the modified Bernoulli formula used to estimate systolic and mean pulmonary artery pressure [sPAP and mPAP; respectively: sPAP = 4 × TRv (tricuspid regurgitation velocity)(2)+ RAP (right atrial pressure); and mPAP = 0.61sPAP + 2], applicable in the follow-up of pulmonary hypertension (PH) patients. METHODS AND RESULTS: From January 1979 to December 2009, 60 patients with precapillary (class I and IV) and 'out of proportion' PH were consecutively enrolled in the PH Registry of Trieste. All patients underwent both echocardiographic and right heart catheter evaluation. We used a simple-linear-regression method in order to compare sPAP and mPAP Doppler-estimated values with the respective right-heart catheterization invasive variables. The comparison of the estimated with the traditional modified Bernoulli formula echo-Doppler data and the effective invasive values confirmed a significant association between them (for sPAP P< 0.001; for mPAP P= 0.006). Simple-linear-regression-derived formulas were sPAP = 1.07 × (4TRv(2)+ RAP) + 7.4 (1) and mPAP = 1.1 × (0.61sPAP + 2) + 2.5 (2). These regression-corrected formulas were validated in an external population of PH patients. CONCLUSION: Our data suggest that formulas (1) and (2) could be more reliable with respect to the traditional modified Bernoulli equation, when estimating echocardiographically sPAP and mPAP in patients with PH confirmed by right-heart catheterization.

A case of primary cardiac sarcoma with an acute presentation: The role of multimodality imaging.

The case highlights the value of contrast echocardiography in raising clinical suspicion of malignancy, allowing a diagnostic work-up and the treatment of the primitive heart tumors.

High prevalence of subtle systolic and diastolic dysfunction in genotype-positive phenotype-negative relatives of dilated cardiomyopathy patients.

BACKGROUND: The early diagnosis of genetically determined dilated cardiomyopathy (DCM) could improve the prognosis in mutation carriers. Left ventricular global longitudinal strain (LV GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of subtle systolic and diastolic dysfunction. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives. METHODS AND RESULTS: In this retrospective study, we analyzed echocardiograms of forty-one GPFN relatives of DCM patients. They were compared with age and sex matched healthy individuals (control group). Reduced LV GLS and PALS were defined as >18% and <23.1%, respectively. GPFN relatives (37 ± 14 years, 48.8% male) and controls were similar according to standard echocardiographic measurements. Conversely, LV GLS was -18.8 ± 2.7% in the GPFN group vs. -24.0 ± 1.8% in the control group (p < 0.001). Twenty subjects (48.8%) in the GPFN group and no subjects in the control group had a reduced LV GLS. PALS was 29.2 ± 6.7% in the GPFN group vs. 40.8 ± 8.5% in the control group (p < 0.001). Seven subjects (18.4%) in the GPFN group and one (2%) in the control group had a reduced PALS. A cohort of 17 genotype-negative phenotype-negative relatives showed higher values of LV GLS compared to GPFN. CONCLUSIONS: Despite standard echocardiographic parameters are within the normal range, LV GLS and PALS are lower in GPFN relatives of DCM patients when compared to healthy individuals, suggesting a consistent proportion of subtle systolic and diastolic dysfunction in this population.

Prevalence and Evolution of Right Ventricular Dysfunction Among Different Genetic Backgrounds in Dilated Cardiomyopathy.

BACKGROUND: Titin (TTN)-related dilated cardiomyopathy (DCM) has a higher likelihood of left ventricular reverse remodelling compared with other genetic etiologies. No data regarding the evolution of right ventricular dysfunction (RVD) according to genetic background are available. METHODS: Consecutive 104 DCM patients with confirmed pathogenic genetic variants (51 TTN-related DCM; 53 other genetic DCM) and a control group of 139 patients with negative genetic testing and available follow-up data at 12-24 months were analysed. RVD was defined as a right ventricular fractional area change (RVFAC) < 35%. The main study end point was the comparison of the evolution of RVD and the change of RVFAC throughout the follow-up according to etiology. A composite of all-cause mortality and heart transplantation was included as outcome measure. RESULTS: At enrollment, RVD was present in 29.1% of genetically positive DCM without differences between genetic cohorts. At 14 months follow-up, 5.9% of TTN-related DCM patients vs 35.8% of other genetic DCM patients had residual RVD after treatment (P < 0.001). Accordingly, RVFAC significantly improved in the TTN-related DCM cohort and remained stably impaired in other genetic DCM patients. However, the evolution of RVD was similar between TTN-related DCM and patients without a genetic mutation. After adjusting for RVD at follow-up, no differences in the outcome measure were seen in the study cohorts. CONCLUSIONS: The evolution of RVD in DCM is heterogeneous in different genetic backgrounds. TTN-related DCM is associated with a higher chance of RVD recovery compared with other genetic etiologies.

Towards standardization of echocardiography for the evaluation of left ventricular function in adult rodents: a position paper of the ESC Working Group on Myocardial Function.

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.

Right ventricle in pulmonary arterial hypertension: haemodynamics, structural changes, imaging, and proposal of a study protocol aimed to assess remodelling and treatment effects.

Although right ventricular (RV) failure is the main cause of death in patients with pulmonary arterial hypertension (PAH), there is insufficient data about the effects of PAH treatment on RV geometry and function mainly because the RV assessment has been hampered by its complex crescentic shape, large infundibulum, and its trabecular nature. Echocardiography is a widely available imaging technique particularly suitable for follow-up studies, because of its non-invasive nature, low cost, and lack of ionizing radiation or radioactive agent. Real-time three-dimensional echocardiography (RT3DE) has been shown to be accurate in assessing RV and left ventricular (LV) volumes, stroke volumes, and ejection fractions in comparison with cardiac magnetic resonance imaging. In this review, we describe RV structural and functional changes which occur in patients with PAH and strengths and weaknesses of current non-invasive imaging techniques to assess them. Finally, we describe an ongoing multicentre, prospective observational study involving seven centres expert in treating patients with PAH from four different countries. Investigators will use conventional and advanced echo parameters from RT3DE and speckle-tracking echocardiography to assess the extent of LV and RV remodelling before symptom onset and during pharmacological treatment in patients with PAH. Seventy patients who will survive for at least 1 year will be recruited. All the participating institutions will perform comprehensive standard 2D and Doppler as well as RT3DE examinations with a pre-defined imaging protocol. Measurements will be performed at the core echocardiography laboratory by experienced observers who will be unaware of each patient's treatment assignment and whether the examination was a baseline or a follow-up study. Enrolment duration is expected to be 1 year.

Atrial thrombi or cardiac tumours? The image-challenge of intracardiac masses: a case report.

BACKGROUND: Cardiac masses (CM) encompass a broad set of lesions that can be either neoplastic or non-neoplastic. A stepwise diagnostic strategy through multimodality imaging evaluation is the cornerstone for the appropriate approach. CASE SUMMARY: We report the case of an 83-year-old man presenting at the emergency department for acute heart failure showing bilateral atrial masses without unequivocal aetiological aspects at several imaging techniques, emphasizing the critical aspects in the differential diagnosis. DISCUSSION: In the complex field of CM, a proper differential diagnosis is very important in order to start the appropriate treatment; however, sometimes it could be challenging despite a multimodality imaging approach, therefore still requiring histologic examination.