Cardiovascular Involvement in Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is a systemic disorder resulting from the extracellular deposition of amyloid fibrils of misfolded transthyretin protein in the heart. ATTR-CA is a life-threatening disease, which can be caused by progressive deposition of wild type transthyretin (wtATTR) or by aggregation of an inherited mutated variant of transthyretin (mATTR). mATTR Is a rare condition transmitted in an autosomal dominant manner with incomplete penetrance, causing heterogenous phenotypes which can range from predominant neuropathic involvement, predominant cardiomyopathy, or mixed. Diagnosis of ATTR-CA is complex and requires integration of different imaging tools (echocardiography, bone scintigraphy, magnetic resonance) with genetics, clinical signs, laboratory tests, and histology. In recent years, new therapeutic agents have shown good efficacy and impact on survival and quality of life in this subset of patients, nevertheless patients affected by ATTR-CA may still carry an unfavorable prognosis, thus highlighting the need for new therapies. This review aims to assess cardiovascular involvement, diagnosis, and management of patients affected by ATTR-CA.

Percutaneous Left Atrial Appendage Occlusion: An Emerging Option in Patients with Atrial Fibrillation at High Risk of Bleeding.

Atrial fibrillation (AF) is a common cardiac arrhythmia with an estimated prevalence of 1% in the general population. It is associated with an increased risk of ischemic stroke, silent cerebral ischemia, and cognitive impairment. Due to the blood flow stasis and morphology, thrombus formation occurs mainly in the left atrial appendage (LAA), particularly in the setting of nonvalvular AF (NVAF). Previous studies have shown that >90% of emboli related to NVAF originate from the LAA, thus prevention of systemic cardioembolism is indicated. According to the current guidelines, anticoagulant therapy with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), represents the standard of care in AF patients, in order to prevent ischemic stroke and peripheral embolization. Although these drugs are widely used and DOACs have shown, compared to VKAs, non-inferiority for stroke prevention with significantly fewer bleeding complications, some issues remain a matter of debate, including contraindications, side effects, and adherence. An increasing number of patients, indeed, because of high bleeding risk or after experiencing life-threatening bleedings, must take anticoagulants with extreme caution if not contraindicated. While surgical closure or exclusion of LAA has been historically used in patients with AF with contradictory results, in the recent years, a novel procedure has emerged to prevent the cardioembolic stroke in these patients: The percutaneous left atrial appendage occlusion (LAAO). Different devices have been developed in recent years, though not all of them are approved in Europe and some are still under clinical investigation. Currently available devices have shown a significant decrease in bleeding risk while maintaining efficacy in preventing thromboembolism. The procedure can be performed percutaneously through the femoral vein access, under general anesthesia. A transseptal puncture is required to access left atrium and is guided by transesophageal echocardiography (TEE). Evidence from the current literature indicates that percutaneous LAAO represents a safe alternative for those patients with contraindications for long-term oral anticoagulation. This review summarizes scientific evidences regarding LAAO for stroke prevention including clinical indications and an adequate patient selection.

Management of Bradyarrhythmias in Heart Failure: A Tailored Approach.

Patients with heart failure (HF) may develop a range of bradyarrhythmias including sinus node dysfunction, various degrees of atrioventricular block, and ventricular conduction delay. Device implantation has been recommended in these patients, but the specific etiology should be sought as it may influence the choice of the type of device required (pacemaker vs. implantable cardiac defibrillator). Also, pacing mode must be carefully set in patients with heart failure (HF) and left ventricular systolic dysfunction.In this chapter, we summarize the knowledge required for a tailored approach to bradyarrhythmias in patients with heart failure.

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients.

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up.

Left atrial volume index in healthy subjects: clinical and echocardiographic correlates.

Left atrial (LA) size is related to cardiovascular morbidity and mortality. The relative role of multiple determinants of LA morphology in healthy subjects remains incompletely defined. The aim of this study is to define normal ranges for LA diameters and volume index (LAVi), and to investigate clinical and echocardiographic correlates. A total of 1480 healthy individuals (mean age 36.1 ± 15.5 years, range 20-80; 61% males) underwent a comprehensive transthoracic echocardiography exam including assessment of LAVi calculated using the biplane area-length method at the apical four-chamber and two-chamber views at ventricular end systole (maximum LA size) and indexed for body surface area (BSA). Mean LAVi in the overall population was 29.5 ± 10.8 mL/m(2) (range: 26.1-41.8 mL/m(2) ). Distinct higher values were found in subjects ≥50 years as compared with those <50 years of age (33.4 ± 12.5 vs. 29.1 ± 13.5; P < 0.001). On univariate analysis, LA volume was significantly associated with age (r = 0.48, P < 0.0001), male gender (r = 0.28, P < 0.05), BSA (r = 0.51, P < 0.0001), mitral E/E' (r = 0.47, P < 0.0001), LV end-diastolic volume (r = 0.52, P < 0.0001), and LV mass index (r = 0.31, P < 0.05). Multivariable analysis identified age, BSA, LV end-diastolic volume, and mitral E/E' ratio as the only independent determinants of LA volume (model R(2) = 0.54, P < 0.0001). Gender was an independent predictor of most absolute LA volume, but following normalization to BSA, some associations became nonsignificant. In healthy individuals LAVi vary significantly by age, BSA, diastolic function, and LV dimensions, with lesser effects of gender.

Right ventricular ejection fraction and left ventricular dyssynchrony by 3D echo correlate with functional impairment in patients with dilated cardiomyopathy.

BACKGROUND: The aim of the study was to detect if right ventricular (RV) ejection fraction assessed by real-time 3-dimensional echocardiography (RT3DE) could predict patients with dilated cardiomyopathy (DCM) with greater functional impairment in response to cardiopulmonary exercise. METHODS AND RESULTS: Seventy chronic heart failure patients with DCM (55.5 ± 9.1 years; 48 males; 30 ischemic; New York Heart Association Class III: 48) underwent both left ventricular (LV) and RV analysis by RT3DE. Postprocessing software provided data of RT3DE systolic dyssynchrony index of 16 LV segments (systolic dyssynchrony index [SDI]) and of both LV and RV ejection fraction. Cardiac magnetic resonance was performed in a subgroup of 40 DCM patients to confirm RT3DE measurements. All the patients underwent also bicycle cardiopulmonary exercise test with evaluation of oxygen consumption (VO2) peak% (percentage of the predicted value), VE/VCO2 slope, and circulatory power (CP). Mean LV ejection fraction was 29.8 ± 4.6%. RT3DE LV SDI index was 8.4.4 ± 4.2, and RV ejection fraction was 51.3 ± 4.6%. By cardiopulmonary test, mean VO2 peak was 15.2 ± 4.4 mL·kg·min, and mean CP was 2.1 ± 0.8. By univariable analyses, significant correlations were detectable between SDI index and VO2 peak% (r = -0.56; P < .0001) and peak CP (r = -0.48; P < .0005). Also RV ejection fraction directly correlated with VO2 peak% (r = 0.58; P < .0001) and inversely with VE/VCO2 slope (r = -0.44; P < .001). By multivariable analysis, SDI index (ß coefficient = -0.46; P < .001) and 3D RV ejection fraction (ß coefficient = 0.42; P < .001) emerged as the only independent determinants of VO2 peak% during cardiopulmonary test. CONCLUSIONS: Increased LV electromechanical dyssynchrony and impaired RV function in DCM patients are independently associated with worse ability to perform aerobic exercise.

Left atrial volume index in highly trained athletes.

BACKGROUND: Increase of left atrial (LA) diameter in trained athletes has been regarded as another component of the "athlete's heart". AIMS: To evaluate the possible impact of competitive training on LA volume and to define reference values of LA volume index in athletes. METHODS AND RESULTS: Six hundred fifteen consecutive elite athletes (370 endurance- [ATE] vs 245 strength-trained athletes [ATS]; 385 men; 28.4 +/- 10.2 years, range 18-40 years) underwent a comprehensive transthoracic echocardiography exam. LA maximal volume was measured at the point of mitral valve opening using the biplane area-length method, and corrected for body surface area. LA mild dilatation was defined as a LA volume index between 29 and 33 mL/m(2), while a moderate dilatation was identified by a LA volume index > or =34 mL/m(2). Left ventricular (LV) mass index and ejection fraction did not significantly differ between the 2 groups. Conversely, ATS showed increased body surface area, sum of wall thickness (septum + LV posterior wall), LV circumferential end-systolic stress (ESSc) and relative wall thickness, whereas LA volume index, LV stroke volume and LV end-diastolic volume were greater in ATE. The range of LA volume index was 26 to 36 mL/m(2) (mean 28.2 +/- 9.2) in men and 22 to 33 mL/m(2) (mean 26.5 +/- 7.2) in women (P < .01). LA volume index was mildly enlarged in 150 athletes (24.3%) and moderately enlarged only in 20, all males (3.2%). Mild mitral regurgitation was observed in 64 athletes (10.3%). LA volume index was significantly greater in ATE (P < .01). By multivariate analysis, the overall population type (P < .01) and duration (P < .01) of training and LV end-diastolic volume (P < .001) were the only independent predictors of LA volume index. CONCLUSIONS: In a large population of highly trained athletes, a mild enlargement of LA volume index was relatively common and may be regarded as a physiologic adaptation to exercise conditioning.

Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking two-dimensional strain analysis.

AIMS: To analyse right ventricular (RV) myocardial deformation in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HCM) or athlete's competitive endurance training. METHODS AND RESULTS: Standard Doppler echo, exercise stress echo, and 2D speckle-tracking strain echocardiography (2DSE) of RV longitudinal deformation in RV septal and lateral walls were performed in 50 top-level endurance athletes and in 35 patients with HCM, all men, having evidence of LV hypertrophy. Right ventricular global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. The two groups were comparable for age and blood pressure, whereas athletes showed lower heart rate and increased body surface area than HCM. Interventricular septal thickness was higher in HCM, whereas both LV and RV end-diastolic diameters (LVEDD and RVEDD) and LV stroke volume were increased in athletes. Right ventricular tricuspid annulus systolic excursion was comparable between the two groups. Conversely, RV GLS and regional peaks of RV myocardial strain were significantly impaired in patients with HCM (all P < 0.001). Multiple linear regression models detected an independent association between RV GLS and LVEDD (beta-coefficient = -0.68, P < 0.0001) in athletes, as well as an independent correlation of the same RV GLS with septal thickness (beta = 0.63, P < 0.0001) in HCM. An RV GLS cut-off value of -0.16% differentiated athletes and HCM with an 86% sensitivity and a 92% specificity. Furthermore, in the overall population, RV GLS (beta = 0.51, P < 0.0001) was a powerful independent predictor of maximal workload during exercise stress echo. CONCLUSION: Right ventricular myocardial systolic deformation is positively influenced by preload increase in athletes and negatively associated with increased septal thickness in HCM. Therefore, 2DSE may represent a useful tool in the differential diagnosis between athlete's heart and HCM, underlining the different involvement of RV myocardial function in either physiological or pathological LV hypertrophy.

[Prevention and management of paravalvular leak post-transcatheter aortic valve implantation]. / Prevenzione e gestione dei leak paravalvolari post-impianto transcatetere di valvola aortica.

During transcatheter aortic valve implantation (TAVI) the native valve is not removed but crushed. Thus, a slight prosthesis insufficiency is not uncommon and has been reported up to 25% of patients for both available types of percutaneous valves. However, the definition of "clinically significant" valve regurgitation is not fully established yet. In most cases, aortic insufficiency is mild and clinical acceptable; however, severe insufficiency can occur. Paravalvular insufficiency is usually prevalent, and it may be the consequence of prosthesis-patient mismatch due to an undersizing of the implanted device or an incomplete expansion of the prosthesis stent frame, or also to incorrect site of prosthesis implantation. Thus, accurate assessment of the aortic valve annulus before TAVI is mandatory in order to select the optimal valve size. The presence of large calcium burden or bicuspid valve as well as the correct implantation of the device are other key determinants of final valve insufficiency. When severe regurgitation is present, an integration of hemodynamic, angiographic, transthoracic and transesophageal echocardiography data is necessary to tailor the best clinical decision on a per-patient basis.

Effect of Sacubitril-Valsartan in reducing depression in patients with advanced heart failure.

BACKGROUND: Depression is highly prevalent in Heart Failure (HF). Treatment with sacubitril/valsartan improved quality of life and survival in HF patients. Aim of the study was to investigate prospectively the effect of sacubitril/valsartan on depression in advanced HF patients in waiting list for heart transplant (HT). METHODS: 37 consecutive patients with advanced HF in waiting list for HT were treated with sacubitril/valsartan. We analyzed data derived from the assessment performed the year before the beginning of sacubitril/valsartan, at study entry, and at one year of follow-up. Depression was assessed with Beck Depression Inventory II (BDI) scale. Cognitive function were assessed with Mini-Mental State Examination (MMSE). Functioning was evaluated measuring meters at 6 Minute Walking Test (6MWT) and maximum rate of oxygen consumption (VO2 max). RESULTS: At baseline, 64.9% of HF patients were in NYHA III and 35.1% NYHA IIIB, BDI was 15.2 ± 5.2 with 59.5% of patients with a score > 13. MMSE was 27.8 ± 2.6. After one year of follow-up NYHA class improved significantly, with 56.8% in NYHA II, 40.5% in NYHA III and 2.7% NYHA in IIIB (p < 0.001). VO2 max and 6MWT increased. Notably, BDI was 9.5 ± 3.9 with 21.6% of patients with a score > 13. MMSE remain stable (28.2 ± 2.1) (p = 0.104). No statistical differences are observed between data collected in the evaluation 1-year before and soon before treatment with sacubitril/valsartan. Multivariate regression analysis demonstrate a relationship between reduction in BDI-II score and improvement in six-minute walking test independently by the effect of sex, age, selective serotonin reuptake inhibitors, VO2 max, NT-proBNP, PAPs, NYHA class differences evaluated at follow-up versus baseline. CONCLUSIONS: Our study showed a reduction in depressive symptomatology in heart transplant waiting list patients treated with sacubitril/valsartan. The improvement in depressive symptomatology was paralleled by 6MWT increase in the follow-up.

Prevalence and clinical significance of red flags in patients with hypertrophic cardiomyopathy.

INTRODUCTION: We sought to determine prevalence and predictive accuracy of clinical markers (red flags, RF), known to be associated with specific systemic disease in a consecutive cohort of patients with hypertrophic cardiomyopathy (HCM). METHODS: We studied 129 consecutive patients (23.7 ±â€¯20.9 years, range 0-74 years; male/female 68%/32%). Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography; imaging; and laboratory. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and predictive accuracy of RF were analyzed in the genotyped population. RESULTS: In the overall cohort of 129 patients, 169 RF were identified in 62 patients (48%). Prevalence of RF was higher in infants (78%) and in adults >55 years old (58%). Following targeted genetic and clinical evaluation, 94 patients (74%) had a definite diagnosis (sarcomeric HCM or specific causes of HCM). We observed 14 RF in 13 patients (21%) with sarcomeric gene disease, 129 RF in 34 patients (97%) with other specific causes of HCM, and 26 RF in 15 patients (45%) with idiopathic HCM (p < 0.0001). Non-sarcomeric causes of HCM were the most prevalent in ages <1yo and > 55yo. Se, Sp, PPV, NPV and PA of RF were 97%, 70%, 55%, 98% and 77%, respectively. Single and clinical combination of RF (clusters) had an high specificity, NPV and predictive accuracy for the specific etiologies (syndromes/metabolic/infiltrative disorders associated with HCM). CONCLUSIONS: An extensive diagnostic work up, focused on analysis of specific diagnostic RF in patients with unexplained LVH facilitates a clinical diagnosis in 74% of patients with HCM.

Sacubitril/valsartan in patients listed for heart transplantation: effect on physical frailty.

AIMS: The aim of this study was to investigate prospectively the effect of sacubitril/valsartan in advanced heart failure (HF) patients in waiting list for heart transplantation (HT) and the effect on physical frailty (PF). METHODS AND RESULTS: We treated 37 consecutive patients with advanced HF with sacubitril/valsartan. Patients were followed up until HT, device implant, or last follow-up visit after 2 years of follow-up. At baseline, mean New York Heart Association (NYHA) class was 3.1 ± 0.4, with 64.9% in NYHA III and 35.1% NYHA IIIB. Left ventricular ejection fraction was 23.5 ± 5.8%, VO2 max was 10.3 ± 2.3 mL/kg/min, cardiac index was 2.3 ± 0.5 L/min/m2 , and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) was 4943.0 ± 5326.8 pg/mL. After a mean follow-up of 17.1 ± 4.4 months, no deaths were observed, but NYHA class improved significantly with 56.8% in NYHA II, 40.5% in NYHA III, and 2.7% in NYHA IIIB (P < 0.001). VO2 max and 6 min walk test (6MWT) increased, whereas pulmonary systolic blood pressure, E/E', VE/VCO2 slope, and NT-pro-BNP decreased. At right heart catheterization performed after 1 year of follow-up, cardiac index and pulmonary vascular resistance remained stable, while a decrease in systolic pulmonary artery pressure and pulmonary capillary wedge pressure is observed. Furosemide dosage decrease from 102.7 ± 69.4 to 78.7 ± 66.3 mg (P = 0.040). PF decreased from 3.35 ± 1.0 at baseline to 1.57 ± 1.3 at the end of follow-up (P < 0.001), with a reduction in all PF domains. CONCLUSIONS: Our study showed a rapid improvement in PF in HT waiting list patients treated with sacubitril/valsartan. The improvement in all PF domains was paralleled by VO2 and 6MWT increase and together with an NT-pro-BNP reduction constant over the follow-up.

Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients.

BACKGROUND: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. OBJECTIVES: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. METHODS: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p < 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. CONCLUSIONS: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM.

Effects of global longitudinal strain and total scar burden on response to cardiac resynchronization therapy in patients with ischaemic dilated cardiomyopathy.

AIMS: To evaluate whether quantification of the extent of scarred left ventricular (LV) tissue by speckle-tracking strain echo (2DSE) can predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Forty-five patients (58.3 +/- 8.3 years; 24 males) with ischaemic DCM scheduled for CRT, and 25 controls were studied. A week before implantation all the patients underwent standard Doppler echo, 2DSE, and contrast-enhanced magnetic resonance (MR). Clinical and echocardiographic evaluation was repeated 6 months after CRT. The patients were considered as responders to CRT if LV end-systolic volume decreased by 15%. In DCM patients, LV ejection fraction was 29.2 +/- 5.1%. By evaluating the 765 segments with MR, subendocardial infarct was identified in 17.0% and transmural infarct in 18.3%. With 2DSE, the average global longitudinal strain (GLS) was -23.1 +/- 3.6% in controls and -15.1 +/- 5.1% in DCM (P = 0.001). GLS showed a close correlation with total scar burden using MR (r = 0.64, P < 0.001). At follow-up, patients were subdivided into responders (n = 30; 66.7%) and non-responders (n = 15; 33.3%) to CRT. GLS was significantly different in non-responders than in responders (GLS: -10.4 +/- 5.1 in non-responders vs. -18.4 +/- 14% in responders, P < 0.001). In a multivariable analysis, GLS (P < 0.0001) and radial intraventricular dyssynchrony (P < 0.001) were powerful independent determinants of response to CRT. CONCLUSION: GLS is strongly associated with total scar burden assessed by MR, and is an excellent independent predictor of response to CRT.

Right ventricular myocardial function in patients with either idiopathic or ischemic dilated cardiomyopathy without clinical sign of right heart failure: effects of cardiac resynchronization therapy.

OBJECTIVE: In dilated cardiomyopathy (DCM), right ventricular (RV) dysfunction has been reported and attributed both to altered loading conditions and to RV involvement in the myopathic process. The aim of the study was to detect RV myocardial function in DCM using two-dimensional (2D) strain echocardiography and to assess the effects of cardiac resynchronization therapy (CRT) on RV myocardial strain during a 6-month follow-up. METHODS AND RESULTS: A total of 110 patients (mean age: 55.4 +/- 11.2 years) with either idiopathic (n = 60) or ischemic (n = 50) DCM, without overt clinical signs of RV failure, underwent standard echo and 2D strain analysis of RV longitudinal strain in RV septal and lateral walls. The two groups were comparable for clinical variables (New York Heart Association class III in 81.8%). Left ventricular volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler mitral and tricuspid inflow measurements. RV diameters were mildly increased in patients with idiopathic DCM, while RV tricuspid annulus systolic excursion and Tei-index were comparable between the two groups. RV global longitudinal strain and regional peak myocardial strain were significantly impaired in patients with idiopathic DCM compared with those having ischemic DCM (all P < 0.001). Using left ventricular end-systolic volume as marker for response to CRT, 70 patients (63.3%) were long-term responders. Ischemic DCM patient responders to CRT showed a significant improvement in RV peak systolic strain. Conversely, in patients with idiopathic DCM and in ischemic patients nonresponders to CRT, no improvement in RV function was evidenced. By multivariable analysis, in the overall population, ischemic etiology of DCM (P < 0.0001), positive response to CRT (P < 0.001), and longitudinal intraventricular dyssynchrony (P <0.01) emerged as the only independent determinants of RV global longitudinal strain after CRT. CONCLUSIONS: Two-dimensional strain represents a promising noninvasive technique to assess RV myocardial function in patients with DCM. RV myocardial deformation at baseline and after CRT are more impaired in idiopathic compared with ischemic DCM patients. Future longitudinal studies are warranted to understand the natural history of RV myocardial function, the extent of reversibility of RV dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.

Clinical outcome in patients with intermediate stenosis of left anterior descending coronary artery after deferral of revascularization on the basis of noninvasive coronary flow reserve measurement.

BACKGROUND: Several reports suggest that noninvasive measurements of coronary flow reserve (CFR) by use of echocardiography may support decision making in intermediate stenosis of the left anterior descending coronary artery (LAD). The aim of the present study was therefore to analyze the clinical outcome in patients with intermediate stenosis of LAD after deferral of coronary revascularization on the basis of noninvasive CFR measurement. METHODS: the study population included 280 patients with intermediate LAD stenosis (50-70% by angiography) (62.2 +/- 9.6 years). All the patients underwent transthoracic CFR assessment of LAD (after dipyridamole infusion) within 2 weeks from coronary angiography. If CFR of LAD was < or = 2, PTCA was recommended; if CFR was > 2, medical treatment was chosen. Primary end points were cardiac death, myocardial infarction, coronary revascularization procedure, and unstable angina. RESULTS: mean follow-up was 43 +/- 11 months (range 12-52 months). In 150 patients (53.6%) (CFR < or = 2), coronary artery revascularization was performed (PTCA group); the remaining 130 patients (46.4%) (CFR > 2) were medically treated (medical group). Survival from cardiac death was 94% in the PTCA group and 92.4% in the medical group (P = 0.56). As for all cardiac events, the Kaplan-Meier percentage survival from cardiac events was 88.3% in the PTCA group and 86.4% in the medical group (P = 0.36). CONCLUSIONS: even if CFR as a "stand-alone" diagnostic criterion suffers from several structural limitations, a combined strategy including also other clinical and instrumental measurements before undergoing interventional procedures could improve the cost-benefit practice, in particular, for the management of patients with intermediate LAD stenosis.

Diagnostic Clues for the Diagnosis of Nonsarcomeric Hypertrophic Cardiomyopathy (Phenocopies): Amyloidosis, Fabry Disease, and Mitochondrial Disease.

Hypertrophic cardiomyopathy (HCM) is the most common known inherited heart disorder, with a prevalence of 1:500 of the adult population. Etiology of HCM can be heterogeneous, with sarcomeric gene disease as the leading cause in up to 60% of the patients, and with a number of possible different diseases (phenocopies) in about 10%-15% of the patients. Early diagnosis of storage and infiltrative disorders, particularly those with specific treatments (i.e., Fabry disease and/or amyloidosis), means early management and treatment, with a significant impact on patients prognosis. Here, we report on four different cases of HCM, highlighting difficulties to make differential diagnosis of different forms of cardiomyopathies, and their potential impact on the management.

Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis.

BACKGROUND: Anabolic androgenic steroids (AAS) are sometimes used by power athletes to improve performance by increasing muscle mass and strength. Recent bioptical data have shown that in athletes under the pharmacological effects of AAS, a focal increase in myocardial collagen content might occur as a repair mechanism against myocardial damage. OBJECTIVE: To investigate the potential underlying left ventricular myocardial dysfunction after chronic misuse of AAS in athletes by use of Doppler myocardial imaging (DMI) and strain rate imaging (SRI). METHODS: Standard Doppler echocardiography, DMI, SRI and ECG treadmill test were undertaken by 45 bodybuilders, including 20 athletes misusing AAS for at least 5 years (users), by 25 anabolic-free bodybuilders (non-users) and by 25 age-matched healthy sedentary controls, all men. The mean (SD) number of weeks of AAS use per year was 31.3 (6.4) in users, compared with 8.9 (3.8) years in non-users, and the mean weekly dosage of AAS was 525.4 (90.7) mg. RESULTS: The groups were matched for age. Systolic blood pressure was higher in athletes (145 (9) vs 130 (5) mm Hg) than in controls. Left ventricular mass index did not significantly differ between the two groups of athletes. In particular, both users and non-users showed increased wall thickness and relative wall thickness compared with controls, whereas left ventricular ejection fraction, left ventricular end-diastolic diameter and transmitral Doppler indexes were comparable for the three groups. Colour DMI analysis showed significantly lower myocardial early: myocardial atrial diastolic wave ratios in users at the level of the basal interventricular septum (IVS) and left ventricular lateral wall (p<0.01), in comparison with both non-users and controls. In addition, in users, peak systolic left ventricular strain rate and strain were both reduced in the middle IVS (both p<0.001) and in the left ventricular lateral free wall (both p<0.01). By stepwise forward multivariate analyses, the sum of the left ventricular wall thickness (beta coefficient = -0.32, p<0.01), the number of weeks of AAS use per year (beta = -0.42, p<0.001) and the weekly dosage of AAS (beta = -0.48, p<0.001) were the only independent determinants of middle IVS strain rate. In addition, impaired left ventricular strain in users was associated with a reduced performance during physical effort (p<0.001). CONCLUSIONS: Several years after chronic misuse of AAS, power athletes show a subclinical impairment of both systolic and diastolic myocardial function, strongly associated with mean dosage and duration of AAS use. The combined use of DMI and SRI may therefore be useful for the early identification of patients with more diffused cardiac involvement, and eventually for investigation of the reversibility of such myocardial effects after discontinuation of the drug.