Clinical Risk Prediction in Patients With Left Ventricular Myocardial Noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. OBJECTIVES: This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. METHODS: This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. RESULTS: A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. CONCLUSIONS: LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management.

CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy in Non-Ischaemic dilated CardioMyopathy: an international Registry.

AIMS: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. METHODS AND RESULTS: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. CONCLUSION: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Evolution of acute myocarditis in a pediatric population: An MRI based study.

BACKGROUND: Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis. METHODS: CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214-923) days. RESULTS: LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70-746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08-10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16-18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery. CONCLUSIONS: In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.

Accuracy of right atrial pressure estimation using a multi-parameter approach derived from inferior vena cava semi-automated edge-tracking echocardiography: a pilot study in patients with cardiovascular disorders.

The echocardiographic estimation of right atrial pressure (RAP) is based on the size and inspiratory collapse of the inferior vena cava (IVC). However, this method has proven to have limits of reliability. The aim of this study is to assess feasibility and accuracy of a new semi-automated approach to estimate RAP. Standard acquired echocardiographic images were processed with a semi-automated technique. Indexes related to the collapsibility of the vessel during inspiration (Caval Index, CI) and new indexes of pulsatility, obtained considering only the stimulation due to either respiration (Respiratory Caval Index, RCI) or heartbeats (Cardiac Caval Index, CCI) were derived. Binary Tree Models (BTM) were then developed to estimate either 3 or 5 RAP classes (BTM3 and BTM5) using indexes estimated by the semi-automated technique. These BTMs were compared with two standard estimation (SE) echocardiographic methods, indicated as A and B, distinguishing among 3 and 5 RAP classes, respectively. Direct RAP measurements obtained during a right heart catheterization (RHC) were used as reference. 62 consecutive 'all-comers' patients that had a RHC were enrolled; 13 patients were excluded for technical reasons. Therefore 49 patients were included in this study (mean age 62.2 ± 15.2 years, 75.5% pulmonary hypertension, 34.7% severe left ventricular dysfunction and 51% right ventricular dysfunction). The SE methods showed poor accuracy for RAP estimation (method A: misclassification error, ME = 51%, R2 = 0.22; method B: ME = 69%, R2 = 0.26). Instead, the new semi-automated methods BTM3 and BTM5 have higher accuracy (ME = 14%, R2 = 0.47 and ME = 22%, R2 = 0.61, respectively). In conclusion, a multi-parametric approach using IVC indexes extracted by the semi-automated approach is a promising tool for a more accurate estimation of RAP.

Cardiac Magnetic Resonance Evaluation of Pulmonary Transit Time and Blood Volume in Adult Congenital Heart disease.

BACKGROUND: Management of adults with repaired congenital heart disease (CHD) is still challenging. Heart failure secondary to residual anatomical sequels or arrhythmic events is not rare in this population. MRI has emerged as an accurate tool to quantify pulmonary transit time (PTT) of intravenous contrast agents and pulmonary blood volume (PBV). PURPOSE: To determine the relationship between PTT, and conventional indexes of ventricular dysfunction and heart failure in a cohort of adults with CHD and to assess its association with adverse outcomes. STUDY TYPE: Retrospective. SUBJECTS: 89 adult CHD patients (56 males, age 34 ± 11 years) and 14 age- and sex-matched healthy subjects. FIELD STRENGTH/SEQUENCE: First-pass perfusion and standard sequences for ventricular volumes and function and flow analysis at 1.5T. ASSESSMENT: PTT was calculated as the time required for a bolus of contrast agent to pass from the right ventricle to the left atrium, expressed both in seconds (PTTS) and number of heartbeats (PTTB). The pulmonary blood volume index (PBVI) was measured by the product of PTTB and the pulmonary artery stroke volumes. STATISTICAL TESTS: Student's independent t-test analysis of variance (ANOVA) and Mann-Whitney nonparametric; Pearson's or Spearman's correlation; Kaplan-Meier method. RESULTS: PTTS and PTTB were significantly higher in patients than in controls (7.6 ± 3 vs. 5.6 ± 1.2 sec, P = 0.01 and 8 ± 3 vs. 6 ± 1 bpm, P = 0.01, respectively). PTTS showed negative correlation with left ventricle ejection fraction (LVEF) and cardiac index (CI) (r = -0.3, P = 0.004, and r = -0.4, P < 0.001, respectively) as well as with left ventricle and atrial volumes. By Kaplan-Meier survival analysis, PTTB >8 bpm was associated with significant increased risk of adverse outcome at mid-term follow-up. Moreover, patients with both increased PTTB and PBV have higher amino-terminal portion of the prohormone brain natriuretic peptide (NT-proBNP) and lower LVEF. DATA CONCLUSION: PTT is prolonged in adult CHD in comparison with healthy subjects, likely reflecting reduced CI and ventricular dysfunction. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:779-786.

Late gadolinium enhancement as a predictor of functional recovery, need for defibrillator implantation and prognosis in non-ischemic dilated cardiomyopathy.

BACKGROUND: Aim of the study was to investigate whether late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) predict reverse remodeling (RR) in non-ischemic dilated cardiomyopathy (NIDCM). METHODS: Seventy-one NIDCM patients (age 57±14years, 43 males, median left ventricular ejection fraction [LVEF] 35%, [interquartile range 27-41%]) with two CMR scans within 5years were included. RR was defined as ≥10% reduction in left ventricular (LV) end-diastolic volume and ≥10% LVEF increase. The end-point was a composite of all-cause death, cardiovascular hospitalization or appropriate defibrillator discharge. LGE was assessed both visually and as percentage of LV mass (LGE%). RESULTS: LGE was present in 42 patients (59%). During the interval between the 2 CMR scans (median 28 [15-44]months), 22 patients (31%) displayed RR. LGE absence predicted RR irrespectively of baseline LV volumes and LVEF. Over a median 42[15-73]-month follow-up, the endpoint occurred in 36 patients (51%). LGE absence was associated with better prognosis (P=0.043), with best quantitative LGE cut-point <7% at ROC analysis (P=0.017), but RR was the strongest prognostic predictor. Among 35 patients with baseline LVEF <35%, 25 (69%) crossed the 35% LVEF threshold. Both LGE absence and quantitative LGE <7% were associated with crossing of the 35% LVEF threshold for defibrillator implantation; patients with either LGE or quantitative LGE≥7% had a worse prognosis. CONCLUSIONS: In NIDCM, the absence of LGE at baseline CMR is associated with RR. When baseline LVEF is <35%, LGE absence is associated with more frequent crossing of the 35% LVEF threshold for defibrillator implantation.

Left and right ventricular morphology, function and late gadolinium enhancement extent and localization change with different clinical presentation of acute myocarditis Data from the ITAlian multicenter study on MYocarditis (ITAMY).

AIMS: Poor data exist about cardiac magnetic resonance (CMR) findings in a large sample of acute myocarditis with different clinical presentations (heart failure, arrhythmias, and infarct-like presentation). METHODS: Five hundred and forty-three in-patients with a clinical suspected of acute myocarditis confirmed by CMR were enrolled. The clinical indications to perform CMR were chest pain and/or dyspnea and/or palpitations, or effort intolerance/malaise in the last month; elevated troponin and/or new ventricular dysfunction, and/or new ECG abnormalities; and suspected inflammatory cause. CMR examination has permitted to identify epicardial and mid-layer distribution of late gadolinium enhancement (LGE) and to quantify left ventricular (LV) and right ventricular (RV) volumes, and ejection fraction. RESULTS: According to the main clinical pattern of presentation, three groups were categorized: heart failure (heart failure group; 35 patients, 6.4%), arrhythmias (arrhythmias group; 24 patients, 4.4%), and infarct-like (infarct-like group, 484 patients, 89.2%).Heart failure group and arrhythmias group had significantly higher LV volumes and number of LGE segments and lower LV and RV ejection fraction than the infarct-like group.Epicardial LGE in the LV inferolateral wall was the most frequent LGE location in each group. Mid-layer LV septal LGE showed a greater prevalence in the heart failure (52%) and arrhythmias (47%) groups than in the infarct-like group (27%, P < 0.0001). CONCLUSION: In patients with CMR-detected acute myocarditis, heart failure, and arrhythmias have both a higher prevalence of LV and RV dysfunction, segments with LGE, and septal LGE with respect to the infarct-like group.

Clinical recommendations of cardiac magnetic resonance, Part II: inflammatory and congenital heart disease, cardiomyopathies and cardiac tumors: a position paper of the working group 'Applicazioni della Risonanza Magnetica' of the Italian Society of Cardiology.

The current document was developed by the working group on the 'application of cardiac magnetic resonance' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical cardiac magnetic resonance applications and to inform cardiologists how to implement their clinical and diagnostic pathway with the introduction of this technique in the clinical practice. Appropriateness criteria were defined using a score system: score 1-3 = inappropriate (test is not generally acceptable and is not a reasonable approach for the indication), score 4-6 = uncertain (test may be generally acceptable and may be a reasonable approach for the indication but more research and/or patient information is needed to classify the indication definitively) and score 7-9 = appropriate (test is generally acceptable and is a reasonable approach for the indication).

Long-Term Prognostic Value of Cardiac Magnetic Resonance in Left Ventricle Noncompaction: A Prospective Multicenter Study.

BACKGROUND: Cardiac magnetic resonance (CMR) is useful for the diagnosis of left ventricular noncompaction (LVNC). However, there are limited data regarding its prognostic value. OBJECTIVES: The goal of this study was to evaluate the prognostic relevance of CMR findings in patients with LVNC. METHODS: A total of 113 patients with an echocardiographic diagnosis of LVNC underwent CMR at 5 referral centers. CMR diagnostic criterion of LVNC (noncompacted/compacted ratio >2.3 in end-diastole) was confirmed in all patients. We performed left ventricular (LV) and right ventricular quantitative analysis and late gadolinium enhancement (LGE) assessments and analyzed the following LVNC diagnostic criteria: left ventricular noncompacted myocardial mass (LV-ncMM) >20% and >25%, total LV-ncMM index >15 g/m2, noncompacted/compacted ratio ≥3:1 ≥1 of segments 1 to 3 and 7 to 16 or ≥2:1 in at least 1 of segments 4 to 6 of the American Heart Association model. Outcome was a composite of thromboembolic events, heart failure hospitalizations, ventricular arrhythmias, and cardiac death. RESULTS: At a mean follow-up of 48 ± 24 months, cardiac events (CEs) occurred in 36 patients (16 heart failure hospitalizations, 10 ventricular arrhythmias, 5 cardiac deaths, and 5 thromboembolic events). LV dilation, impaired LV ejection fraction, and LV-ncMM >20% was significantly more frequent in patients with CEs. LV fibrosis was detected by using LGE in 11 cases. CMR predictors of CEs were LV dilation and LGE. LGE was associated with improved prediction of CEs, compared with clinical data and CMR functional parameters in all 3 models. No CEs occurred in patients without dilated cardiomyopathy and/or LGE. CONCLUSIONS: In patients with LVNC evaluated by using CMR, the degree of LV trabeculation seems to have no prognostic impact over and above LV dilation, LV systolic dysfunction, and presence of LGE.

Left atrial function in cardiac amyloidosis.

AIMS: Left atrium can be involved by amyloid deposition in familial amyloid polyneuropathy (FAP). The aim of our study is to assess left atrium function in atrial amyloidosis. METHODS: Twenty-eight FAP patients (53 ±â€Š12 years) and a control group of 22 asymptomatic individuals (49 ±â€Š11 years) underwent strain echocardiography and cardiac magnetic resonance (CMR). CMR by late gadolinium enhancement (LGE) was used to assess the left atrium amyloid deposition, whereas strain echocardiography was used to quantify the left atrium deformation. The following atrial longitudinal strain (ALS) parameters were assessed: peak at the end of ventricular systole (peak-ALS), peak at early diastole (early-ALS), negative peak in late diastole, precontraction (prec)-ALS (difference between peak-ALS and early-ALS), and late ALS (sum of negative peak and prec-ALS). RESULTS: CMR showed atrial LGE in 14 FAP patients (LGE-atrial group), whereas 14 FAP patients showed no LGE (no-LGE-atrial group). Peak-ALS was significantly lower in the LGE-atrial group (22.8 ±â€Š13%) compared with the no-LGE-atrial group (59.6 ±â€Š33.1%; P = 0.001) and controls (47.4 ±â€Š16.4%; P = 0.001). Early-ALS was lower in the LGE-atrial group (10.2 ±â€Š6.2%) compared with the controls (26.3 ±â€Š11.9%; P = 0.02) and the no-LGE-atrial group (30.2 ±â€Š22.4%; P = 0.01). Prec-ALS was lower (P = 0.001) in the LGE-atrial group (12.6 ±â€Š7.8%) compared with the no-LGE-atrial group (26.2 ±â€Š15%). Conversely, late-ALS was higher (P = 0.04) in the no-LGE-atrial group (22.8 ±â€Š12.3%) compared with the controls (13.9 ±â€Š9%); no significant differences were found in the negative peak among groups. CONCLUSIONS: Patients with atrial amyloidosis have an adverse left atrium remodeling associated with left atrium dysfunction. Left atrium assessment may provide useful information in the clinical and prognostic stratification of amyloidotic patients.

Right ventricular dysfunction: an independent and incremental predictor of cardiac deaths late after acute myocardial infarction.

Prognostic implication of right ventricular dysfunction and infarction scar in the chronic phase of the myocardial infarction has been little analyzed. In 299 consecutive patients (age 63 ± 11 years) with >3 months old myocardial infarction, we quantified right and left ventricular volumes and ejection fractions by cine cardiac magnetic resonance, and right and left ventricular scar tissue by late gadolinium enhancement. During follow-up (median, 2.4 years) cardiac events (cardiac-related deaths or appropriate intra-cardiac defibrillator shocks) occurred in 21 patients. Right ventricular systolic dysfunction (ejection fraction lower the reference mean values-2 SD) was present in 67 patients (22 %), right ventricular late gadolinium enhancement was observed in 15 patients (5 %). After adjustment for left ventricular end-diastolic volume, wall motion score index, and global extent of late gadolinium enhancement, right ventricular dysfunction was an independent and incremental predictor of cardiac events (p = 0.0053), while right ventricular scar tissue extent was not. Right ventricular dysfunction is an independent and incremental predictor of cardiac events also in the chronic phase of the myocardial infarction. In these patients, right ventricular dysfunction does not necessarily mean right ventricular infarction scar, but likely reflects the effects of hemodynamic and biohumoral factors.

Magnetic resonance assessment of prevalence and correlates of right ventricular abnormalities in isolated left ventricular noncompaction.

The aim of the present study was to evaluate the prevalence and correlates of right ventricular (RV) noncompaction (RVNC), RV systolic dysfunction, and RV myocardial fibrosis in patients with isolated left ventricular (LV) noncompaction (LVNC). For this purpose, cine and contrast-enhanced cardiac magnetic resonance imaging (MRI) was used. A total of 56 consecutive patients with isolated LVNC were included in the study. The diagnosis of isolated LVNC was based on the presence of standard cardiac MRI and clinical criteria. For each patient, cine and contrast-enhanced cardiac MR images were analyzed to evaluate the prevalence and correlates of RVNC, RV dysfunction, and late gadolinium enhancement (a surrogate of myocardial fibrosis) involving the RV. Mean age of the patient population was 45 ± 19 years; 35 patients (63%) were men. RVNC was observed in 5 patients (9%). Impaired RV systolic function was observed in 9 patients (16%). Late gadolinium enhancement was not observed in any RV segment. No association was found between wall motion abnormalities and noncompaction at RV segmental level (φ coefficient 0.041, p = 0.26). At multivariate analysis, LV ejection fraction was the only variable independently related to RV ejection fraction (ß = 0.62, p <0.001). In conclusion, RV systolic dysfunction is present in a non-negligible proportion of patients with isolated LVNC; LV systolic function is the only variable independently related to RV systolic function.

Apoptotic transcriptional profile remains activated in late remodeled left ventricle after myocardial infarction in swine infarcted hearts with preserved ejection fraction.

Apoptosis is involved in both acute and chronic loss of cardiomyocytes after myocardial infarction (MI). To date, the pathophysiological significance of an apoptotic transcriptional profile activated in the post-ischemic remodeled myocardium, in the absence of hemodynamic factors secondary to left ventricular (LV) dysfunction, still remains to be determined. The mRNA expression of pro- and anti-apoptotic factors was determined in a swine model of non-reperfused MI with preserved LV ejection fraction. The extent of cell death was evaluated by histological analysis. Male adult farm pigs with MI (n=5), induced by permanent surgical ligation of the left anterior descending coronary artery and sham-operated adult farm pigs as control (n=7) were studied. Tissue samples were collected from the border (BZ) and remote zone (RZ) of the infarcted area to identify possible regional effects. After 4 weeks post-MI, the infarct size was 13±1% of the LV wall mass in absence of contractile dysfunction. In BZ, there was increased mRNA expression of Casp-3 (BZ vs Controls: 0.51±0.15 vs 1.39±0.04, p<0.001), a significant decrease in Bcl-2 (by 63%), associated with an increase in apoptotic cells, as revealed by TUNEL staining and cleaved-Casp-3 presence. In contrast, in the RZ there was a significant reduction of pro-apoptotic factors compared to BZ (by 80% for Casp-3), in presence of scattered apoptotic cells, increased gene expression of Hsp72 (1.82±0.21 vs 1.34±0.08, p=0.037) and iNOS (1.51±0.14 vs 1.19±0.05, p<0.05) compared to control. In conclusion, the LV distribution of apoptotic transcriptional profile revealed that apoptotic cell death is highly detectable in BZ, possibly explaining the local abnormalities of myocardial cell survival in a porcine model of MI with normal overall function.

A prospective randomized trial of thrombectomy versus no thrombectomy in patients with ST-segment elevation myocardial infarction and thrombus-rich lesions: MUSTELA (MUltidevice Thrombectomy in Acute ST-Segment ELevation Acute Myocardial Infarction) trial.

OBJECTIVES: The aim of this study was to evaluate whether thrombectomy during primary percutaneous coronary intervention (pPCI) in patients with high thrombus burden improves myocardial reperfusion and reduces infarct size. BACKGROUND: Thrombectomy aims at reducing distal thrombotic embolization during pPCI, improving myocardial reperfusion and clinical outcome. METHODS: We randomized 208 patients with high thrombus burden in a 1:1 ratio to either pPCI with thrombectomy (Group T) or standard pPCI (Group S). Thrombectomy was performed with either rheolytic or manual aspiration catheters. Three-month magnetic resonance imaging was performed to assess infarct size and transmurality and microvascular obstruction (MVO). The primary endpoints were ST-segment elevation resolution (STR) >70% at 60 min and 3-month infarct size. RESULTS: The baseline profile was similar between groups, except for a higher rate of initial Thrombolysis In Myocardial Infarction flow grade 3 in Group S (p = 0.002). Group T showed a significantly higher rate of STR (57.4% vs. 37.3%; p = 0.004) and of final myocardial blush 3 (68.3% vs. 52.9%; p = 0.03). Group T and Group S did not differ with regard to infarct size (20.4 ± 10.5% vs. 19.3 ± 10.6%; p = 0.54) and transmurality (11.9 ± 12.0% vs. 11.6 ± 12.7%; p = 0.92), but Group T showed significantly less MVO (11.4% vs. 26.7%; p = 0.02) and a higher prevalence of inhomogeneous scar (p < 0.0001). One-year freedom from major adverse cardiac events was similar between groups. CONCLUSIONS: Thrombectomy as an adjunct to pPCI in patients with high thrombus load yielded better post-procedural STR and reduced MVO at 3 months but was not associated with a reduction in infarct size and transmurality. Thromboaspiration in Patients With High Thrombotic Burden Undergoing Primary Percutaneous (Coronary Intervention; NCT01472718).

Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model.

BACKGROUND: The role of systemic and myocardial adiponectin (ADN) in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK) activity in a swine model of non-ischemic dilated cardiomyopathy. METHODS AND RESULTS: Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV) free wall (180 beats/min, 3 weeks), both from pacing (PS) and opposite sites (OS), and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p < 0.05), yet ADN receptor 1 was significantly up-regulated (p < 0.05). No modifications of AMPK were observed in either region of the failing heart. Similarly, myocardial mRNA levels of PPARγ, PPARα, TNFα, iNOS were unchanged compared to controls. CONCLUSIONS: Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

Pacing-induced regional differences in adenosine receptors mRNA expression in a swine model of dilated cardiomyopathy.

The adenosinergic system is essential in the mediation of intrinsic protection and myocardial resistance to insult; it may be considered a cardioprotective molecule and adenosine receptors (ARs) represent potential therapeutic targets in the setting of heart failure (HF). The aim of the study was to test whether differences exist between mRNA expression of ARs in the anterior left ventricle (LV) wall (pacing site: PS) compared to the infero septal wall (opposite region: OS) in an experimental model of dilated cardiomyopathy. Cardiac tissue was collected from LV PS and OS of adult male minipigs with pacing-induced HF (n = 10) and from a control group (C, n = 4). ARs and TNF-α mRNA expression was measured by Real Time-PCR and the results were normalized with the three most stably expressed genes (GAPDH, HPRT1, TBP). Immunohistochemistry analysis was also performed. After 3 weeks of pacing higher levels of expression for each analyzed AR were observed in PS except for A(1)R (A(1)R: C = 0.6±0.2, PS = 0.1±0.04, OS = 0.04±0.01, p<0.0001 C vs. PS and OS respectively; A(2A)R: C = 1.04±0.59, PS = 2.62±0.79, OS = 2.99±0.79; A(2B)R: C = 1.2±0.1, PS = 5.59±2.3, OS = 1.59±0.46; A(3)R: C = 0.76±0.18, PS = 8.40±3.38, OS = 4.40±0.83). Significant contractile impairment and myocardial hypoperfusion were observed at PS after three weeks of pacing as compared to OS. TNF-α mRNA expression resulted similar in PS (6.3±2.4) and in OS (5.9±2.7) although higher than in control group (3.4±1.5). ARs expression was mainly detected in cardiomyocytes. This study provided new information on ARs local changes in the setting of LV dysfunction and on the role of these receptors in relation to pacing-induced abnormalities of myocardial perfusion and contraction. These results suggest a possible therapeutic role of adenosine in patients with HF and dyssynchronous LV contraction.

Endocardial and epicardial deformations in cardiac amyloidosis and hypertrophic cardiomyopathy.

BACKGROUND: The aim of the present study was to analyze epicardial (EPI) and endocardial (ENDO) strain (S) in patients with transthyretin-related cardiac amyloidosis (TTR-CA) and hypertrophic cardiomyopathy (HCM) using echocardiography (TTE) with 2-dimensional feature tracking imaging (FTI). METHODS AND RESULTS: Thirty-three subjects (11 with HCM, 11 with TTR-CA, and 11 healthy subjects as controls) with a New York Heart Association functional class ≤ II underwent conventional TTE and FTI. TTE was used for the evaluation of left ventricle (LV) wall thickness, mass, systolic and diastolic function. FTI was used for the evaluation of EPI and ENDO longitudinal, and circumferential, and radial S. LV wall thickness and mass were higher in both TTR-CA and HCM in comparison with controls (P < 0.001), but ejection fraction (EF) was similar among patients with TTR-CA, HCM and controls (63 ± 6%, 64 ± 6%, 61 ± 5%, respectively). ENDO and EPI longitudinal and circumferential S and radial S were significantly lower in HCM and TTR-CA when compared with controls (P < 0.01). No differences in EPI and ENDO longitudinal S, ENDO circumferential S and radial S were found between TTR-CA and HCM groups, while EPI circumferential S was significantly lower in the TTRCA group (6 ± 3.3%) than in the HCM group (8.1 ± 4.3%; P < 0.0001). CONCLUSIONS: Longitudinal, circumferential and radial LV deformations are impaired in patients with TTR-CA and HCM with a preserved EF. Impairment of EPI circumferential strain is greater in TTR-CA than in HCM.

Ferritin as a reporter gene for in vivo tracking of stem cells by 1.5-T cardiac MRI in a rat model of myocardial infarction.

The methods currently utilized to track stem cells by cardiac MRI are affected by important limitations, and new solutions are needed. We tested human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Swine cardiac stem/progenitor cells were transduced with a lentiviral vector to overexpress hFTH and cultured to obtain cardiospheres (Cs). Myocardial infarction was induced in rats, and, after 45 min, the animals were subjected to intramyocardial injection of ∼200 hFTH-Cs or nontransduced Cs or saline solution in the border zone. By employing clinical standard 1.5-Tesla MRI scanner and a multiecho T2* gradient echo sequence, we localized iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 wk after infarction, and its size did not change significantly after 4 wk (6.33 ± 3.05 vs. 4.41 ± 4.38 mm(2)). Cs transduction did not affect their cardioreparative potential, as indicated by the significantly better preserved left ventricular global and regional function and the 36% reduction in infarct size in both groups that received Cs compared with control infarcts. Prussian blue staining confirmed the presence of differentiated, iron-accumulating cells containing mitochondria of porcine origin. Cs-derived cells displayed CD31, α-smooth muscle, and α-sarcomeric actin antigens, indicating that the differentiation into endothelial, smooth muscle and cardiac muscle lineage was not affected by ferritin overexpression. In conclusion, hFTH can be used as a MRI reporter gene to track dividing/differentiating stem cells in the beating heart, while simultaneously monitoring cardiac morpho-functional changes.