Role of advanced CMR features in identifying a positive genotype of hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. Cardiac magnetic resonance (CMR) imaging has emerged as a powerful tool for the non-invasive assessment of HCM. CMR can accurately quantify the extent and distribution of hypertrophy, assess the presence and severity of myocardial fibrosis, and detect associated abnormalities. We will study basic and advanced features of CMR in 2 groups of HCM patients with negative and positive genotype, respectively. MATERIALS AND METHODS: The study population consisted in consecutive HCM patients referred to Centro Cardiologico Monzino who performed both CMR and genetic testing. Clinical CMR images were acquired at 1.5 T Discovery MR450 scanner (GE Healthcare, Milwaukee, Wisconsin)) using standardized protocols T1 mapping, T2 mapping and late gadolinium enhancement (LGE). Population was divided in 2 groups: group 1 with HCM patients with a negative genotype and group 2 with a positive genotype. RESULTS: The analytic population consisted of 110 patients: 75 in group 1 and 35 patients in group 2. At CMR evaluation, patients with a positive genotype had higher LV mass (136 vs. 116 g, p = 0.02), LV thickness (17.5 vs. 16.9 mm), right ventricle ejection fraction (63 % vs. 58 %, p = 0.002). Regarding the LGE patients with positive genotype have a higher absolute (33.8 vs 16.7 g, p = 0.0003) and relative LGE mass (31.6 % vs 14.6 %, p = 0.0007). On a segmental analysis all the septum (segments 2, 8, 9, and 14) had a significantly increased native T1 compared to others segments. ECV in the mid antero and infero-septum (segments 8 and 9) have lower values in positive genotype HCM. Interestingly the mean T2 was lower in positive genotype HCM as compared to negative genotype HCM (50,1 ms vs 52,4). CONCLUSIONS: Our paper identifies the mid septum (segments 8 and 9) as a key to diagnose a positive genotype HCM.

Prognostic value of cardiopulmonary exercise testing in a European cohort with cardiovascular risk factors absent of a cardiovascular disease diagnosis.

INTRODUCTION: Cardiorespiratory fitness (CRF) is now considered a vital sign. Cardiopulmonary exercise testing (CPET) is the gold-standard assessment of CRF; peak oxygen consumption (VO2) and the minute ventilation/carbon dioxide production (VE/VCO2) slope are considered primary CPET measures of CRF. More work is needed to determine the role of this exercise assessment in the primary care setting. METHODS: 695 subjects (mean age: 62 ± 13 years, body mass index: 28.9 ± 5.3 kg/m2, 375 female and 320 male) underwent CPET using a cycle ergometer. 95% of the cohort had one or more major cardiovascular risk factor (i.e., obesity, smoking, dyslipidemia, hypertension, diabetes); no subject was diagnosed with cardiovascular disease (CVD) at the time of CPET. Subjects were tracked for the composite endpoint of cardiovascular mortality or hospital admission. RESULTS: Mean peak VO2, VE/VCO2 slope and peak respiratory exchange ratio were 17.8 ± 5.8 mlO2•kg-1•min-1, 26.7 ± 4.1, and 1.18 ± 0.13, respectively. There were 42 composite events during the 64 ± 18 month tracking period. Both peak VO2 (Chi-square 16.3, p < 0.001) and the VE/VCO2 slope (Chi-square 14.9, p < 0.001) were significant univariate predictors of the composite endpoint. The VE/VCO2 slope added significant predictive value to peak VO2 and was retained in the multivariate regression (residual Chi-square 7.0, p = 0.008). DISCUSSION: These results support the prognostic value of CPET prior to a CVD diagnosis. The prognostic value of the VE/VCO2 slope, not commonly the focus of CPET trials in patients with one or more major cardiovascular risk factors but without a confirmed CVD diagnosis, is a particularly novel finding in the current study.

Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study.

Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR < 30 mL/min). In HF patients, ischaemic aetiology was more prevalent in the LEVO group than in the OMT group (60 vs. 40%, p < 0.001). The New York Heart Association (NYHA) functional class was worse in the LEVO group, as well as in NT-proBNP (5636.7 ± 6164.6 ng/dL and 1243.7 ± 1487.2 ng/dL, in the LEVO and OMT groups, respectively, p = 0.005). The FMD was significantly higher in the healthy control group compared to that of the OMT group (15.7 ± 6.4 vs. 9.1 ± 6.0%, p = 0.007) while it showed an intermediate value in LEVO patients (12.4 ± 7.1%) (ANOVA p = 0.010). In conclusion, levosimendan therapy seems to ameliorate endothelial dysfunction related to heart failure. Longitudinal studies in patients on periodic therapy are needed in order to confirm the long-term effects of levosimendan on ED.

Prognostic significance of right ventricle to pulmonary artery coupling in patients with mitral regurgitation treated with the MitraClip system.

OBJECTIVES: To evaluate the prognostic impact of baseline tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio, as an expression of the right ventricle-pulmonary artery (RV-PA) coupling, in patients with mitral regurgitation (MR) treated with the MitraClip. BACKGROUND: Impaired RV to PA coupling is considered a marker of RV dysfunction. METHODS: From February 2016 to February 2020, a total of 165 patients were evaluated and stratified in two groups according to a prespecified value of TAPSE/PASP ratio ≤ 0.36. RESULTS: The median patients' age was 79 (men: 62.4%). Sixty-three patients (38.1%) presented TAPSE/PASP ≤ 0.36 and were then compared with patients with TAPSE/PASP > 0.36. Functional MR etiology was more frequent in TAPSE/PASP ≤ 0.36 (71.4%; p = 0.046). Acute technical success was achieved in 92.7% of the population, without any significant difference between the two groups of study and with sustained results at 30-day (device success: 85.5%; procedural success: 84.8%). On multivariate Cox regression analysis, after correction for body mass index, chronic kidney disease and left ventricle ejection fraction ≥30% but <50%, TAPSE/PASP ≤ 0.36 remained a sustained predictor of mortality and hospitalization for heart failure at one year after MitraClip (hazard ratio: 3.87; 95% confidence interval: 1.83-8.22; p ≤ 0.001). Kaplan-Meier all-cause mortality and heart failure hospitalization rates at one year were consequently higher in patients with TAPSE/PASP ≤ 0.36 (39.4% vs. 14.8%; log-rank p ≤ 0.001). CONCLUSION: Baseline TAPSE/PASP ratio seems independently associated with all-cause mortality and heart failure hospitalization after MitraClip both in functional and degenerative MR.

Impact of Nodular Calcifications in the Aortic Annulus and Left Ventricular Outflow Tract on TAVI Outcome with New-Generation Devices.

Background: The impact of nodular calcifications in left ventricular outlow tract (LVOT) and aortic annulus on the procedural outcome of transcatheter aortic valve implantation (TAVI) with new-generation devices is yet to be elucidated. Similarly, computational simulations may provide a novel insight into the biomechanical features of TAVI devices and their interaction with nodular calcifications. Methods: This retrospective single-center study included 232 patients submitted to TAVI with Evolut-R (53.4%), Portico (33.6%) and Lotus (13.0%) devices with available preoperative computed tomography (CT) angiography and evidence of nodular calcifications in aortic annulus and/or LVOT. Calcification severity was defined ≥ moderate in presence of at least two nodules or one nodule ≤ 5 mm. Three virtual simulation models of aortic root presenting a nodular calcification of increasing size were implemented. Stress distribution, stent-root contact area and paravalvular orifice area were computed. Results: At least moderate calcifications were found in 123 (53.0%) patients, with no sex differences. Among the ≥ moderate calcification group, lower device success rate was evident (87.8% vs. 95.4%; p = 0.039). Higher rates of ≥ moderate paravalvular leak (PVL) (11.4% vs. 3.7%; p = 0.028) and vascular complications (9.8% vs. 2.8%; p = 0.030) were also observed. Among the Evolut-R group, higher rates of at ≥ moderate PVL (12.1%) were observed compared to Portico (3.8%; p = 0.045) and Lotus (0.0%; p = 0.044) groups. Calcification of both annulus and LVOT (odds ratio [OR] 0.105; p = 0.023) were independent predictors of device success. On computational simulations, Portico exhibited homogeneous stress distribution by increasing calfications and overall a larger paravalvular orifice areas compared to Evolut-R and Lotus. Evolut-R showed higher values of average stress than Portico, although with a more dishomogeneous distribution leading to greater paravalvular orifice areas by severe calcifications. Lotus showed overall small paravalvular orifice areas, with no significant increase across the three models. Conclusions: At least moderate nodular calcifications in the annulus/LVOT region significantly affected TAVI outcome, as they were independent predictors of device success. Lotus and Portico seemed to perform better than Evolut-R as for device success and ≥ moderate PVL. Computational simulations revealed unique biomechanical features of the investigated devices in terms of stent compliance and radial force.