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.

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.

Preoperative evaluation before MitraClip®: present and future perspective.

Mitral regurgitation (MR) is the second most common heart valve disease worldwide. Currently, the management of MR is based on medical therapy (including biventricular pacing), surgery (mitral valve replacement or repair) and percutaneous therapy. However, in spite of guideline recommendations, 50% of individuals assessed in the Euro Heart Survey were not referred to surgical intervention due to comorbidities or real or perceived high risks for cardiac surgery; thus, in recent years, the focus of research has shifted to the development of percutaneous approaches to treat severe MR in order to restore valve function in a minimally invasive fashion. Among these techniques, the percutaneous mitral valve repair procedure using the MitraClip(®) system (Abbott Vascular, IL, USA) is one of the most promising. Usually, patient selection for MitraClip implantation is based on careful echocardiographic assessment of valve disease; however, although definitive data are lacking, evidence is mounting for a multiparametric approach including the evaluation of the functional status of patients.

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.

Preoperative, postoperative and 1-year follow-up N-terminal pro-B-type natriuretic peptide levels in severe chronic aortic regurgitation: correlations with echocardiographic findings.

B-type natriuretic peptide is synthesized in response to increased ventricular wall stress (WS) and hypertrophy. To serially evaluate amino-terminal-pro-BNP (NT-pBNP) serum levels in patients undergoing aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR), blood samples were drawn preoperatively, 15 days postoperatively, at 6- and 12-month follow-up in 25 consecutive patients. Two-dimensional echocardiography was performed concomitantly, assessing left ventricular (LV) dimensional and functional parameters, including WS. Correlations between NT-pBNP, clinical and echocardiographic data were assessed by non-parametric statistics. Median preoperative NT-pro-BNP was 276 pg/ml (IQR=85-1056), being normal or mildly increased in 20 patients, overly increased in five. The most significant correlations of preoperative NT-pBNP were with diastolic (r=0.80, P<0.001) and systolic (r=0.75, P<0.001) meridional WS and inversely with time from symptom onset (r=-0.67, P=0.001). NT-pBNP increased 15 days postoperatively (568 pg/ml, P=0.006 vs. preoperative), then decreased at 6 months (144 pg/ml, P<0.001) to remain stable at 1 year (108 pg/ml, P=0.16). Long-term follow-up NT-pBNP showed direct correlation with diastolic WS (r=0.56, P=0.02). Higher preoperative levels of NT-pBNP predicted greater magnitude of total LV mass regression at follow-up (r=-0.65, P=0.002) independent of preoperative LV mass index, showing that NT-pBNP may have a potential prognostic usefulness in adjunct to echocardiography.