Functional relevance of coronary artery disease by cardiac magnetic resonance and cardiac computed tomography : myocardial perfusion and fractional flow reserve

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality and it is responsible for an increasing resource burden. The identification of patients at high risk for adverse events is crucial to select those who will receive the greatest benefit from revascularization. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but the diagnostic yield of elective invasive coronary angiography remains unfortunately low. Stress myocardial perfusion imaging by cardiac magnetic resonance (stress-CMR) has emerged as an accurate technique for diagnosis and prognostic stratification of the patients with known or suspected CAD thanks to high spatial and temporal resolution, absence of ionizing radiation, and the multiparametric value including the assessment of cardiac anatomy, function, and viability. On the other side, cardiac computed tomography (CCT) has emerged as unique technique providing coronary arteries anatomy and more recently, due to the introduction of stress-CCT and noninvasive fractional flow reserve (FFR-CT), functional relevance of CAD in a single shot scan. The current review evaluates the technical aspects and clinical experience of stress-CMR and CCT in the evaluation of functional relevance of CAD discussing the strength and weakness of each approach

Targeted next-generation sequencing detects novel gene-phenotype associations and expands the mutational spectrum in cardiomyopathies

Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity and mortality. These diseases are genetically diverse and associated with rare mutations in a large number of genes, many of which overlap among the phenotypes. To better investigate the genetic overlap between these three phenotypes and to identify new genotype-phenotype correlations, we designed a custom gene panel consisting of 115 genes known to be associated with cardiomyopathic phenotypes and channelopathies. A cohort of 38 unrelated patients, 16 affected by DCM, 14 by HCM and 8 by ARVC, was recruited for the study on the basis of more severe phenotypes and family history of cardiomyopathy and/or sudden death. We detected a total of 142 rare variants in 40 genes, and all patients were found to be carriers of at least one rare variant. Twenty-eight of the 142 rare variants were also predicted as potentially pathogenic variants and found in 26 patients. In 23 out of 38 patients, we found at least one novel potential gene-phenotype association. In particular, we detected three variants in OBSCN gene in ARVC patients, four variants in ANK2 gene and two variants in DLG1, TRPM4, and AKAP9 genes in DCM patients, two variants in PSEN2 gene and four variants in AKAP9 gene in HCM patients. Overall, our results confirmed that cardiomyopathic patients could carry multiple rare gene variants; in addition, our investigation of the genetic overlap among cardiomyopathies revealed new gene-phenotype associations. Furthermore, as our study confirms, data obtained using targeted next-generation sequencing could provide a remarkable contribution to the molecular diagnosis of cardiomyopathies, early identification of patients at risk for arrhythmia development, and better clinical management of cardiomyopathic patients

CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy international registry: Design and rationale of the DERIVATE study.

Implantable cardioverter defibrillator (ICD) represents the most valuable sudden cardiac death (SCD) prophylactic strategy in patients with heart failure and severely reduced left ventricular ejection fraction (LVEF). To date, it is still unknown how to integrate the information given by cardiac magnetic resonance (CMR) into clinical and transthoracic echocardiography (TTE) work-up of non-ischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) patients for accurate risk stratification. DERIVATE is a prospective, international, multicenter, observational registry of NICM and ICM patients with chronic heart failure and reduced LVEF who will undergo clinical evaluation, TTE and CMR. The registry will enrol cohorts from 34 sites. Complete risk factor, clinical presentation, TTE and CMR data will be collected and each patient will be followed-up for outcomes. Primary end point of the study is all-cause mortality. Secondary end points are: cardiovascular death, SCD, aborted SCD, sustained ventricular tachycardia (VT), and major adverse cardiac events (MACE) defined as a composite endpoint of SCD, aborted SCD, and sustained VT. Specifically, we will determine CMR findings that predict outcomes, with incremental value over LVEF and NYHA classification. Secondary aims consist in providing a comprehensive clinical and imaging score and testing the contribution of machine learning to determine prognostic CMR parameters. The final objective of the study consists in the identification of prognostic CMR parameters in a large prospective cohort for a better selection of patients with heart failure being worthy of primary prevention ICD therapy. (clinicaltrials.gov registration: RTT# NCT03352648)

Distribution of active mitochondria in canine oocytes is related to reproductive cycle stage but can be damaged during IVM culture

Aim We investigated the effect of the reproductive cycle stage on the distribution of active mitochondria in canine oocytes examined 1) at collection and 2) after in vitro maturation (IVM). Methods Cumulus-oocyte complexes (ooplasmic size >120 µm in diameter) were recovered from 20 bitches divided into five groups based on their reproductive status: anestrous (A, n=4), follicular phase (F, n=4), ovulation (O, n=2), early luteal phase (until 15 days after ovulation, EL, n=7) and mid/late luteal phase (MLL, n=3). IVM culture was performed in TCM199 with 10% estrous canine serum (72h, 5% CO2). Oocyte mitochondrial (mt) distribution pattern was revealed after 30’ incubation in 280 nM MitoTracker Orange CMTM Ros and confocal laser scanning microscopy. Data were analyzed by Chi-square Test. Results In oocytes examined at collection, three mt patters were found: I) small granules diffused throughout the cytoplasm; II) diffused tubular networks; III) pericortical tubular networks. Significantly higher rates of oocytes showing heterogeneous mt patterns (II and III) were obtained from bitches in F (21/28, 75%) and in O (23/24, 96%) compared with bitches in A (4/13, 31%; F vs A: P<0.05; O vs A: P<0.001), in EL (27/44, 61%; F vs EL: NS; O vs EL: P<0.01), or in MLL (0/9, 0%; F vs MLL: P<0.05; O vs MLL: P<0.001). In cultured oocytes, the maturation rates (MII+PB) did not differ statistically among reproductive stages (1%, 1/72 vs 6%, 12/189 vs 2% 1/58 vs 4% 2/47 vs 9%, 5/53, for oocytes from bitches in A, F, O, EL and MLL, respectively). The only oocyte from an A bitch had reticular mt pattern. The 12 oocytes from bitches in F showed tubular networks (3/12, 25%) or granular mt distribution (9/12, 75%). The only oocyte from an O bitch and all oocytes from bitches in EL (n=2 oocytes) and from bitches in MLL (n=5 oocytes) showed granular mt distribution. Conclusions Our data demonstrate that the distribution of active mt in canine immature oocytes is related to cycle stage. However, the used IVM culture system did not yield high MII rates as well as mt distribution patterns expressive of full cytoplasmic maturation. This compromised oocyte energy status may be one of the factors responsible for overall reported low MII rates in this species

Distribution of active mitochondria in canine oocytes is related to reproductive cycle stage but can be damaged during IVM culture

Aim We investigated the effect of the reproductive cycle stage on the distribution of active mitochondria in canine oocytes examined 1) at collection and 2) after in vitro maturation (IVM). Methods Cumulus-oocyte complexes (ooplasmic size >120 µm in diameter) were recovered from 20 bitches divided into five groups based on their reproductive status: anestrous (A, n=4), follicular phase (F, n=4), ovulation (O, n=2), early luteal phase (until 15 days after ovulation, EL, n=7) and mid/late luteal phase (MLL, n=3). IVM culture was performed in TCM199 with 10% estrous canine serum (72h, 5% CO2). Oocyte mitochondrial (mt) distribution pattern was revealed after 30’ incubation in 280 nM MitoTracker Orange CMTM Ros and confocal laser scanning microscopy. Data were analyzed by Chi-square Test. Results In oocytes examined at collection, three mt patters were found: I) small granules diffused throughout the cytoplasm; II) diffused tubular networks; III) pericortical tubular networks. Significantly higher rates of oocytes showing heterogeneous mt patterns (II and III) were obtained from bitches in F (21/28, 75%) and in O (23/24, 96%) compared with bitches in A (4/13, 31%; F vs A: P<0.05; O vs A: P<0.001), in EL (27/44, 61%; F vs EL: NS; O vs EL: P<0.01), or in MLL (0/9, 0%; F vs MLL: P<0.05; O vs MLL: P<0.001). In cultured oocytes, the maturation rates (MII+PB) did not differ statistically among reproductive stages (1%, 1/72 vs 6%, 12/189 vs 2% 1/58 vs 4% 2/47 vs 9%, 5/53, for oocytes from bitches in A, F, O, EL and MLL, respectively). The only oocyte from an A bitch had reticular mt pattern. The 12 oocytes from bitches in F showed tubular networks (3/12, 25%) or granular mt distribution (9/12, 75%). The only oocyte from an O bitch and all oocytes from bitches in EL (n=2 oocytes) and from bitches in MLL (n=5 oocytes) showed granular mt distribution. Conclusions Our data demonstrate that the distribution of active mt in canine immature oocytes is related to cycle stage. However, the used IVM culture system did not yield high MII rates as well as mt distribution patterns expressive of full cytoplasmic maturation. This compromised oocyte energy status may be one of the factors responsible for overall reported low MII rates in this species

Clinical recommendations on Cardiac-CT in 2015 : A position paper of the Working Group on Cardiac-CT and Nuclear Cardiology of the Italian Society of Cardiology

We worked out a position paper on cardiac-computed tomography (CCT) endorsed by the Working Group on CCT and Nuclear Cardiology of the Italian Society of Cardiology. The CCT clinical indications were discussed and formulated according to the following two modalities: a brief paragraph dedicated to each indication, with the description of clinical usefulness of different indications; and each indication was rated by the technical panel for appropriateness, using a score assessing whether the use of CCT for each indication is appropriate, uncertain, or inappropriate. All conventional CCT clinical indications, regarding coronary and noncoronary evaluation, were discussed and rated. Moreover, we wrote specific sections regarding the newest CCT applications, such as stress perfusion computed tomography, noninvasive evaluation of fractional flow reserve, and CCT use in athletes. The present study has the following two main objectives: because the diagnostic performance of coronary computed tomography angiography (CCTA) is strictly dependent on adequate technology and local expertise, we strove to provide clinical recommendations on CCTA that may help Italian physicians involved with this diagnostic tool; and to give an update on new indications of CCTA, such as its use for safely discharging patients with suspected acute coronary syndromes from the emergency department, and latest clinical results that have been made possible by the remarkable technology developments of the scanners