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Purpose: In Ireland, over 3000 patients are diagnosed with breast cancer annually, and 1 in 9 Irish women will be diagnosed with breast cancer in their lifetime. There is evidence that female breast cancer survivors are more likely to die of cardiovascular disease than their age-matched counterparts. Specific services for cancer patients suffering from cancer therapy related cardiovascular toxicity have led to a higher incidence of safe anti-cancer treatment completion. Such services are not widely available in our jurisdiction, and the purpose of this trial is to remedy this situation. Methods: This protocol describes a prospective, single arm, pilot feasibility study implementing a dedicated Cardio-Oncology assessment and surveillance pathway for patients receiving multimodal breast cancer treatment. It incorporates novel biomarker and radiomic surveillance and monitoring approaches for cancer-therapy related cardiac dysfunction into routine care for breast cancer patients undergoing adjuvant systemic chemotherapy. Results: Declaration of results will via peer reviewed academic journals, and communicated directly to key knowledge users both nationally and internationally. This engagement will be critical to enable to healthcare services and policy sector make informed decisions or valuable changes to clinical practice, expenditure and/or systems development to support specialized Cardio-Oncology clinical pathways. All data is to be made available upon request. Conclusion: Dedicated cardio-oncology services have been recommended in recent literature to improve patient outcomes. Our protocol describes a feasibility study into the provision of such services for breast cancer. [ABSTRACT FROM AUTHOR]

Background: The detection of small renal masses has significantly increased due to the widespread use of cross-sectional imaging in recent years. Among these masses, clear cell renal cell carcinoma (ccRCC) is the most common subtype and progresses quickly, resulting in the advancement of the disease and the development of metastases. In this prospective study, our goal is to assess the effectiveness of multiparametric MRI clear cell Likelihood Score in small solid renal masses and its utility in predicting tumor grade. Results: In total, 103 patients (mean age 52.5 ± 13.16 years) with small solid renal masses of stage T1a (≤ 4 cm) were identified. Mean tumor size was 3.4 ± 0.6 cm. According to our study results, the clear cell Likelihood Score (ccLS) had sensitivity of 75.6%, specificity of 93.5%, PPV of 88.6%, NPV of 85.3% and accuracy of 86.4% in diagnosing ccRCC using a ccLS threshold of 4 and 5. As regard the assessment of ccLS threshold of 1 or 2 in excluding ccRCC pathological subtype, our study found that out of 29 patients with ccLS 1 or 2, there was only 1 ccRCC case with false result (3% false positive). It was also noted that there is significant relation between Arterial-to-delayed-enhancement-ratio (ADER) value and the grade of the ccRCC. The median interquartile range (IQR) of ADER parameter was statistically significant higher in grade II compared to grade I (Median was 1.6 and 0.9 respectively) and much higher in grade III compared to grades I and II (Median was 2.9) with P value < 0.001. Conclusion: This ccLS showed promising efficacy in prediction and exclusion of ccRCC subtype. Moreover, it aids in predicting the ccRCC grade. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro–B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients. [ABSTRACT FROM AUTHOR]

Background: Estimation of regurgitant fraction by videodensitometry (VD-AR) of aortic root angiograms is a new tool for objective grading of paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI). Stratification with boundaries at 6% and 17% has been proposed to reflect "none/trace", "mild" and "moderate or higher" PVR. Objective: We sought to investigate the association of strata of VD-AR with 3-year mortality and to compare VD-AR with visual grading of angiograms. Methods: We interrogated our database for patients undergoing transfemoral TAVI from 2008 to 2018. Vital status of the patients was obtained from population registers. To test differences in survival and estimate adjusted hazard ratios (HRs) we fitted Cox models. Results: Our retrospective study included 699 patients with evaluable angiograms at completion of the TAVI procedure. Cumulative 3-year mortality was 35.0% in 261 (37.3%) patients with VD-AR < 6%, 33.9% in 325 (46.5%) patients with VD-AR between 6 and 17% (HR [95% confidence interval] 1.06 [0.80–1.42]; P = 0.684) and 47.2% in 113 (16.2%) patients with VD-AR > 17% (HR 1.57 [1.11–2.22]; P = 0.011). Visually, PVR was graded as "none/trace" in 470 (67.2%) patients, as "mild" in 219 (31.3%) and as "moderate" in 10 (1.4%). Both mild PVR and moderate PVR on visual grading were significantly associated with mortality (HRs 1.31 [1.12–1.54]; P = 0.001 and 1.92 [1.13–3.24]; P = 0.015; respectively). Conclusions: VD-AR > 17%, but not VD-AR 6–17%, was independently associated with mortality. Compared with subjective visual evaluation, VD-AR resulted in a smaller proportion of patients with PVR classified as prognostically relevant. [ABSTRACT FROM AUTHOR]

We sought to synthesize the available evidence regarding safety and efficacy of intermittent levosimendan (LEVO) infusions in ambulatory patients with end-stage heart failure (HF). Safety and efficacy of ambulatory intermittent LEVO infusion in patients with end-stage HF are yet not established. We systematically searched MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane databases, from inception to January 30, 2021 for studies reporting outcome of adult ambulatory patients with end-stage HF treated with intermittent LEVO infusion. Fifteen studies (8 randomized and 7 observational) comprised 984 patients (LEVO [N = 727] and controls [N = 257]) met the inclusion criteria. LEVO was associated with improved New York Heart Association (NYHA) functional class (weighted mean difference [WMD] −1.04, 95%CI: −1.70 to −0.38, p < 0.001, 5 studies, I2 = 93%), improved left ventricular (LV) ejection fraction (WMD 4.0%, 95%CI: 2.8% to 5.3%, p < 0.001, 6 studies, I2 = 9%), and reduced BNP levels (WMD −549 pg/mL, 95%CI −866 to −233, p < 0001, 3 studies, I2 = 66%). All-cause death was not different (RR 0.65, 95%CI: 0.38 to 1.093, p = 0.10, 6 studies, I2 = 0), but cardiovascular death was lower on LEVO (RR 0.34, 95%CI: 0.13 to 0.87, p = 0.02, 3 studies, I2 = 0) compared to controls. Furthermore, health-related quality of life (HRQoL) was improved alongside with reduced LV size following LEVO infusions. Major adverse events were not different between LEVO and placebo. In conclusion, intermittent LEVO infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels, and LV function. However, the current evidence is limited by heterogeneous and relatively small studies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to analyze early mortality after continuous-flow left ventricular assist device (LVAD) implantation which remains high. Methods: We analyzed consecutive (n = 2689) patients from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) undergoing continuous-flow LVAD implantation. The primary outcome was early (< 90 days) mortality. Secondary outcomes were differential causes of early post-operative death following LVAD implantation. Results: Univariable and multivariable analysis as well as regression analysis were used to examine determinants and differential causes of early (< 90 days) mortality after LVAD implantation. During the first 90 days, 2160 (80%) patients were alive with ongoing LVAD support, 40(2%) patients underwent heart transplantation, and 487(18%) deceased. The main causes of early death were MOF (36%), sepsis (28%), cardiopulmonary failure (CPF; 10%), CVA (9%), and right-sided heart failure (RHF, 8%). Furthermore, MOF and sepsis are 70% of causes of death in the first week. Independent clinical predictors of early death were age, female sex, INTERMACS profile 1 to 3, and ECMO. Laboratory predictors included elevated serum creatinine, total bilirubin, lactate, and low hemoglobin. Furthermore, hemodynamic predictors included elevated RA-to-PCWP ratio, pulmonary vascular resistance, and low systemic vascular resistance. Longer total implantation time was also independent predictor of early mortality. A simple model of 12 variables predicts early mortality following LVAD implantation with a good discriminative power with area under the curve of 0.75. Conclusions: In the EUROMACS registry, approximately one out of five patients die within 90 days after LVAD implantation. Early mortality is primarily dominated by multiorgan failure followed by sepsis. A simple model identifies important parameters which are associated with early mortality following LVAD implantation. [ABSTRACT FROM AUTHOR]

Paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) is challenging to quantitate. Transthoracic echocardiography (TTE) is the main tool used for the assessment of PVL but is modestly reproducible. We sought to develop a reproducible echocardiographic approach to assess PVL in the post-TAVI setting. Four observers independently analyzed eleven parameters of PVL severity in 50 pre-discharge TTE studies performed after TAVI. The parameters included color-Doppler parameters [jet circumferential extent (CE) and planimetered vena contracta area in the short-axis view and jet breadth and qualitative features in the long-axis views], continuous-wave Doppler parameters [jet velocity time integral (VTI) and pressure half time (PHT)], quantitative Doppler parameters (regurgitation volume and fraction and effective regurgitant orifice area), aortic diastolic flow reversal and valve stent eccentricity. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) for numerical parameters and kappa coefficient (κ) for categorical parameters were calculated for inter- and intra-observer comparisons. Inter-observer ICC was highest and CV lowest for CE (0.88 and 0.36), jet origin breadth (0.82 and 0.39), jet qualitative features in long-axis views (0.87 and 0.26), jet VTI (0.87 and 0.04) and PHT (0.73 and 0.10). Similar results were found in intra-observer comparisons. A 2-step granular approach combining the most reproducible parameters was used to grade PVL by the four observers. Inter-observer agreement was achieved in 86 % of cases (κ = 0.79). Combining color Doppler and continuous wave Doppler parameters in a granular algorithm yields excellent reproducibility of PVL assessment by TTE. [ABSTRACT FROM AUTHOR]

Significant paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) is related to patient mortality. Predicting the development of PVL has focused on computed tomography (CT) derived variables but literature targeting CoreValve devices is limited, controversial, and did not make use of standardized echocardiographic methods. The study included 164 consecutive patients with severe aortic stenosis that underwent TAVI with a Medtronic CoreValve system©, with available pre-TAVI CT and pre-discharge transthoracic echocardiography. The predictive value for significant PVL of the CT-derived Agatston score, aortic annulus size and eccentricity, and "cover index" was assessed, according to both echocardiographic Valve Academic Research Consortium (VARC) criteria and angiographic Sellers criteria. Univariate predictors for more than mild PVL were the maximal diameter of the aortic annulus size (for both angiographic and echocardiographic assessment of PVL), cover index (for echocardiographic assessment of PVL only), and Agatston score (for both angiographic and echocardiographic assessment of PVL). The aortic annulus eccentricity index was not predicting PVL. At multivariate analysis, Agatston score was the only independent predictor for both angiographic and echocardiographic assessment of PVL. Agatston score is the only independent predictor of PVL regardless of the used imaging technique for the definition of PVL. [ABSTRACT FROM AUTHOR]

Econazole nitrate (EC) is an active, imidazole antifungal agent. However, low aqueous solubility and dissolution rate of EC has discouraged its usage for the treatment of ophthalmic fungal infection. In this study, inclusion complexes of EC with cyclodextrins were prepared to enhance its solubility, dissolution, and ocular bioavailability. To achieve this goal, EC was complexed with β-CyD/HP-β-CyD using kneading, co-precipitation, and freeze-drying techniques. Phase-solubility studies were performed to investigate the complexes in the liquid form. Additionally, the complexes in the solid form were characterized with Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and transmission electron microscopy (TEM). Furthermore, different eye drops containing EC-CyD complexes were prepared using different polymers and then characterized regarding their drug contents, pH, viscosity, mucoadhesive strength, and in vitro release characteristics. The results showed that stable EC-CyD complexes were formed in 1:1 molar ratio as designated by B-type diagram. Econazole nitrate water solubility was significantly increased in about three- and fourfold for β-CyD and HP-β-CyD, respectively. The results showed that the prepared complexes were spherical in shape having an average particle diameter from 110 to 288.33 nm with entrapment efficiency ranging from 64.24 to 95.27%. DSC investigations showed the formation of real inclusion complexes obtained with co-precipitation technique. From the in vitro studies, all eye drops containing co-precipitate complexes exhibited higher release rate than that of other complexes and followed the diffusion-controlled mechanism. In vivo study proved that eye drops containing EC-CyD complexes showed higher ocular bioavailability than EC alone which indicated by higher AUC, C, and relative bioavailability values. [ABSTRACT FROM AUTHOR]

Loteprednol etabonate (LE) is a soft corticosteroid that maintains therapeutic activity with much reduced adverse effects. Yet, its ocular bioavailability is hindered by its poor aqueous solubility. Early attempts of LE complexation with cyclodextrins (CDs) did not involve the study of the effects of various complexation methods on the characteristics of the complexes formed. Formulation of complexes into different delivery systems as well in vitro and in vivo assessments has not been accomplished in the earlier studies. In this study, complexation of LE with each of hydroxypropyl-β-cyclodextrin (HP-β-CD) and β-cyclodextrin (β-CD) by kneading, freeze drying, and co-precipitation was attempted. These complexes were incorporated into gels, drops, and ocuserts using hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and sodium alginate (ALG). These formulae were examined with respect to drug content, pH, viscosity, in vitro release, and stability for 6 months. Kinetic analysis of release data was done. Selected formulations were assessed for their efficacy in the treatment of ocular allergic conjunctivitis and their ocular bioavailability in rabbits' eyes. All formulations exhibited accepted drug content, pH, and viscosity. The drug release was increased by complexation particularly with HP-β-CD in the order of ocuserts ≥ drops > gels, being the highest for HPMC preparations that also exhibited the greatest stability and anti-inflammatory activity especially in case of LE-HP-β-CD complexes. Ocuserts of co-precipitated LE-HP-β-CD using HPMC (5% w/ w) and Carbopol 934P (0.1% w/ w) provided a significantly enhanced stability ( p < 0.05), ocular anti-inflammatory efficacy ( p < 0.05), and ocular bioavailability ( p < 0.0001), to be represented as a potential ocular delivery system of LE. [ABSTRACT FROM AUTHOR]

Purpose: Preparation and evaluation of topical ophthalmic formulations containing nimodipine-CD complexes prepared using HP-β-CD, SBE-β-CD and M-β-CD for the management of glaucoma. Methods: Nimodipine-CD complexes were prepared using a freeze-drying method. Two different molar ratios (NMD:CD) were used for each cyclodextrin. The inclusion complexes were characterized using DSC, FTIR, yield (%), drug content and in vitro release characteristics. NMD-CD complexes incorporated into chitosan eye drops and a temperature-triggered in situ gelling system were evaluated for their pH, viscosity and in vitro release characteristics. We determined the intraocular pressure (IOP) lowering effect of NMD-hydroxypropylmethylcellulose (HPMC) eye drops through a single dose response design using C57BL/6J mice. The minimum effective concentration (MEC) of nimodipine was further applied to mice that vary in the parental allele of Cacna1s, the drug target of nimodipine. Cytotoxicity was also evaluated. Results: Our ophthalmic formulations possessed pH and viscosity values that are compatible with the eye. In vitro release of nimodipine was significantly increased from chitosan eye drops containing NMD-CD complexes compared to uncomplexed drug. Administration of nimodipine can lower IOP significantly after a single drop of drug HPMC suspension. The IOP-lowering response of the MEC (0.6%) was significantly influenced by the parental allele of Cacna1s. Conclusions: Nimodipine can be used as a promising topical drug for management of glaucoma through ocular delivery. [ABSTRACT FROM AUTHOR]

To assess the feasibility and accuracy in measuring left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) with Siemens single-beat real-time 3D transthoracic echocardiography. The LV volumes and EF were measured in 3D datasets acquired by six imaging modes (time-1-harmonic (T1H), time-1-fundamental, time-2-harmonic, time-2-fundamental, space-1-harmonic (S1H), and space-1-fundamental) in 41 patients using the automated contouring algorithm and compared with manually corrected 3DE QLAB measurements. The main determinates of the temporal and spatial resolutions of 3D datasets acquired were the fundamental and harmonic modes. Consequently, the S1H mode had the lowest volume rate and highest spatial resolution. Compared with the 3DE QLAB analysis, the S1H mode resulted in the best LV volumes and EF estimates in all patients (0 ± 10 % for EF, −7 ± 44 ml for EDV, −7 ± 39 ml for ESV) and in the 10 patients with correct LV contour tracking according to a visual assessment from the multiplanar reconstruction views in all six modes (0 ± 9 % for EF, −3 ± 23 ml for EDV, −2 ± 14 ml for ESV). The T1H mode was the best alternative. Overall 28 patients (68 %) could be analysed automatically and satisfyingly with the S1H and T1H modes: 0 ± 8 % (EF), 0 ± 27 ml (EDV) and −1 ± 16 ml (ESV). The accuracy of the Siemens automated RT-3D algorithm in measuring LV volumes and EF is significantly influenced by the different imaging modes. The S1H mode may be the preferred 3D acquisition mode, supplemented by the T1H mode in enlarged LVs that do not fit in the S1H acquisition sector. [ABSTRACT FROM AUTHOR]

Purpose: Preparation of topical ophthalmic formulations containing brimonidine-loaded nanoparticles prepared from various biodegradable polymers-PCL, PLA and PLGA-for sustained release of brimonidine as a once daily regimen for management of glaucoma. Methods: Nanoparticles were prepared using spontaneous emulsification solvent diffusion method then characterized regarding their particle size, zeta potential, morphology and drug contents. Brimonidine-loaded nanoparticles were incorporated into eye drops, temperature-triggered in situ gelling system and preformed gel and characterized regarding their pH, viscosity, uniformity of drug contents, in vitro release study, in vitro cytotoxicity and in vivo intraocular pressure (IOP) lowering effects. Results: The results of optimized brimonidine-loaded PCL-, PLGA- and PLA-NPs respectively, are: particle sizes of 117.33 ± 4.58 nm, 125.67 ± 5.15 nm and 131.67 ± 3.79 nm; zeta potentials of −18.5 ± 2.87 mV, −21.82 ± 2.7 mV and −28.11 ± 2.21 mV; and encapsulation efficiencies of 77.97 ± 1.38%, 68.65 ± 3.35% and 73.52 ± 2.92%. TEM analyses revealed that all NPs have spherical shapes with dense core and distinct coat. In vitro release data showed a sustained release without any burst effect with Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are non-toxic. Also all formulations possessed a sustained IOP lowering effect compared to Alphagan® P eye drops. Conclusions: Our formulations showed prolonged management of glaucoma that should meet with better patient compliance as a once-daily formulation. [ABSTRACT FROM AUTHOR]

Nonsurgical management of patients with symptomatic mitral valve stenosis has been established as the therapeutic modality of choice for two decades. Catheter-based balloon dilation of the stenotic valvular area has been shown, at least, as effective as surgical interventions. Unfavorable results of catheter-based interventions are largely due to unfavorable morphology of the valve apparatus, particularly leaflets calcification and subvalvular apparatus involvement. A mitral valve score has been proposed in Boston, MA, about two decades ago, based on morphologic assessment of mitral valve apparatus by two-dimensional (2D) echocardiography to predict successful balloon dilation of the mitral valve. Several other scores have been developed in the following years in order to more successfully predict balloon dilatation outcome. However, all those scores were based on 2D echocardiography, which is limited by ability to distinguish calcification and subvalvular involvement. The introduction of new matrix-based ultrasound probe has allowed 3D echocardiography (3DE) to provide more detailed morphologic analysis of mitral valve apparatus including calcification and subvalvular involvement. Recently, a new 3DE scoring system has been proposed by our group, which represents an important leap into refinement of the use of echocardiography guiding mitral valve interventions. [ABSTRACT FROM AUTHOR]

Reduction in coronary flow velocity reserve (CFR) is a recognized feature in hypertrophic cardiomyopathy (HCM). We sought to assess the long-term prognostic value of CFR by pulsed-wave Doppler transesophageal echocardiography (TEE) in HCM patients. The study comprised 20 patients with typical features of HCM. The patients were enrolled in 1999. All patients underwent a standard transthoracic echo-Doppler study to evaluate left ventricular function and a stress vasodilator TEE study to evaluate CFR. The success rate of follow-up was 18 out of 20 (90%). During a mean follow-up of 90 ± 24 months, four patients suffered cardiovascular death (2 sudden cardiac deaths and 2 strokes). The other seven patients underwent invasive procedures (coronary angiography, implantable cardioverter defibrillator implantation, percutaneous transluminal septal myocardial ablation) or showed cerebrovascular events. Using receiver operator characteristic analysis, CFR < 2.35 was a significant predictor for cardiovascular event-free survival (sensitivity 91%, specificity 71%, area under the curve 74%, P = 0.05). Multivariable regression analysis showed that only CFR (hazard ratio (HR) 4.21, P < 0.05) was an independent predictor of cardiovascular event-free survival. Despite the relatively small number of patients involved in the study, results could suggest that CFR should be considered as an independent predictor for future cardiovascular events in HCM patients. However, further studies with larger HCM patient populations are warranted. [ABSTRACT FROM AUTHOR]

In recent studies it has been demonstrated that a reduced coronary flow reserve (CFR) is independently associated with a less benign long-term outcome. Aortic stiffness is one of the most important cardiovascular risk factors predicting cardiovascular morbidity and mortality. Vasodilator stress transesophageal echocardiography (TEE) is a suitable method to evaluate simultaneously CFR and elastic properties of the descending thoracic aorta. The aim of the present study was to assess the relative prognostic value of simultaneously measured CFR and aortic elastic properties by pulsed-wave Doppler TEE in patients with suspected or known coronary artery disease (CAD). The study comprised 157 in-hospital patients with chest pain. In all patients, stress TEE was used for the simultaneous evaluation of CFR and aortic distensibility indices [elastic modulus E( p) and Young’s circumferential static elastic modulus E( s)]. During a mean follow-up of 48 ± 8 months, 13 patients suffered cardiovascular death. By univariate analysis older age, diabetes mellitus, increased left ventricular (LV) end-diastolic diameter, increased LV mass index, lower LV ejection fraction, and lower CFR were significant predictors of cardiovascular survival. Multivariate regression analysis showed that only CFR (hazard ratio [HR] 10.31, P = 0.04), age (HR 1.20, P = 0.001), and increased left ventricular (LV) end-diastolic diameter (HR 1.14, P = 0.02) were independent predictors of cardiovascular survival. Only in the small number of patients without CAD and abnormal CFR aortic distensibility seemed to provide complementary prognostic information over CFR. In the majority of patients aortic distensibility did not offer complementary prognostic information to CFR during vasodilator stress TEE testing. [ABSTRACT FROM AUTHOR]

Background: Noncompaction cardiomyopathy (NCCM) is a rare disorder with persistance of the embryonic pattern of myoarchitecture. NCCM is characterized by loosened, spongy myocardium associated with a high incidence of systolic and diastolic left ventricular (LV) dysfunction and heart failure (HF). It is known that LV dysfunction contributes to elevated left atrial (LA) and pulmonary vascular pressures, however atrial function has not been examined in NCCM. The objective of the present study was to assess LA systolic function characterized by LA ejection force (LAEF) in NCCM patients using real-time three-dimensional echocardiography (RT3DE) and to compare to control subjects. Methods: The study comprised 17 patients with an established diagnosis of NCCM and their results were compared to 17 healthy age-matched controls with no evidence of cardiovascular disease. Forty-one percent of NCCM patients were in NYHA functional class II / III HF. Previously proposed echocardiographic diagnostic criteria for NCCM were used. All patients underwent conventional two-dimensional echocardiography and RT3DE. LAEF was measured based on MA annulus diameter (LAEF 3D-MAD) and area (LAEF 3D-MAA) using RT3DE. Results: The presence and severity of mitral regurgitation were more frequent in NCCM patients than in control subjects. LV diameters and mitral annulus were significantly increased in NCCM patients. Compared with control subjects, both LAEF 3D-MAD (3.8 +/- 2.2 vs 2.3 +/- 1.0 kdyne, P < 0.05) and LAEF 3D-MAA (12.7 +/- 7.6 vs 4.9 +/- 2.1 kdyne, P < 0.01) were significantly increased in NCCM patients. Conclusions: LAEF as a characteristic of LA systolic function is increased in NCCM patients compared to normal individuals. These results can suggest compensating left atrial work against the dysfunctional LV in NCCM patients. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type I (MPS IS) is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme α- L-iduronidase, which is involved in the degradation of sulfated glycosaminoglycans (GAGs). The deficiency results in the intra-and pericellular accumulation of the GAGs heparan sulfate and dermatan sulfate. Eight adult patients with typical features of MPS IS aged 31.5 ± 6.8 years (five men) were included and compared to age-and gender-matched controls. With transthoracic echocardiography, cyclic ascending aortic diameter changes were measured and ascending aortic elastic properties were calculated to characterize aortic elasticity. In MPS IS patients, aortic stiffness index was significantly increased (23.1 ± 10.4 vs 3.9 ± 1.5, P < 0.001), while aortic distensibility was significantly decreased (1.6 ± 0.8 vs 1.6 ± 1.9 Ca2/dynes 10−6, P < 0.001) compared to age-and sex-matched controls. The results of the present study demonstrate that in addition to the known cardiac complications, MPS IS patients have an impairment of ascending aortic elasticity. Further follow-up studies are needed to examine arterial elasticity using other methods in this patient population, and to detect possible effects of enzyme replacement therapy. [ABSTRACT FROM AUTHOR]

Methods: The study included 25 hypertrophic cardiomyopathy (HCM) patients (15 non-obstructive and 10 obstructive) and 25 controls for assessment of left atrial (LA) volume, mass and function by two-dimensional echocardiography. Measurement included mean LA diameter (LAD), LA mass = {(mean LAD + anterior LA wall + posterior LA wall)3 - mean LAD3} x 0.8 + 0.6, LA volume = [(8/3 pi L . A1 . A2), where L is LA length, A1 and A2 are LA area in 4-chambers and 2-chambers, respectively] including maximum (V max), minimum (V min), and pre-atrial contraction (V pre-A), total atrial stroke volume (TA-SV), TA emptying fraction (TA-EF), active atrial SV (AA-SV), AA-EF, passive atrial SV (PA-SV), PA-EF, atrial expansion index (AEI), and LA kinetic energy (LA-KE) = (1/2) x AA-SV x P x V2. Results: LAD, LA mass, V max, V min, and V pre-A were significantly higher in HCM than controls. TA-SV and TA-EF were comparable in both HCM subgroups and controls. AA-SV and LA-KE were significantly higher in both HCM subgroups than controls. LA-KE was significantly higher in obstructive HCM than non-obstructive (P < 0.001). PA-EF and AEI were significantly lower in obstructive HCM than controls (P < 0.05). Conclusion: HCM is associated with increased LA size and augmented LA pump function especially obstructive type. LA conduit and reservoir functions are impaired in obstructive HCM. [ABSTRACT FROM AUTHOR]

Background: Noncompaction cardiomyopathy (NCCM) is a recently recognized disorder frequently associated with systolic and diastolic heart failures. This study was designed to examine aortic stiffness in NCCM patients and to compare these results to age- and gender-matched controls. Methods: A total of 20 patients with typical echocardiographic features of NCCM (age 38 +/- 16 years, eight males) were investigated. Their results were compared to 20 age- and gender-matched controls. All subjects underwent a complete two-dimensional transthoracic echocardiographic examination. Systolic (SD) and diastolic (DD) ascending aortic diameters were recorded in M-mode at a level of 3 cm above the aortic valve from a parasternal long-axis view. Aortic stiffness index (beta) was calculated as a characteristic of aortic elasticity, as ln(SBP/DBP)/[(SD - DD)/DD], where SBP and DBP are the systolic and diastolic blood pressures, respectively, and ln is the natural logarithm. Results: The number of noncompacted segments in the NCCM patients was 4.6 +/- 2.0. NCCM patients had significantly increased left ventricular dimensions and reduced left ventricular ejection fraction. Compared to controls, aortic stiffness index (beta) was significantly increased in NCCM patients (8.3 +/- 5.2 vs. 3.5 +/- 1.1, p < 0.001). Conclusion: Increased aortic stiffness can be observed in patients with NCCM with moderate to severe heart failure. These alterations may be due to neurohormonal changes in heart failure. [ABSTRACT FROM AUTHOR]