Immediate and Evolutionary Recovery of Left Ventricular Diastolic Function after Transcatheter Aortic Valve Replacement: Comparison with Surgery

PURPOSE: We aimed to compare the effect of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (sAVR) on recovery of left ventricular (LV) diastolic function and afterload through serial echocardiographic examinations in patients with symptomatic high-risk severe aortic stenosis during early follow-up. MATERIALS AND METHODS: We included 38 patients undergoing TAVR (mean age, 80±6 years; male:female=18:20) and 27 patients undergoing sAVR (mean age, 78±3 years; male:female=12:15). We compared changes in the LV diastolic function and afterload before, immediately after, and 3 months after the procedure using serial transthoracic echocardiography. RESULTS: Immediately after the procedure, 16 (42%) and 3 (11%) patients in the TAVR and sAVR groups, respectively, showed rapid improvement in diastolic filling patterns. E wave to e' ratio (E/e') and right ventricular systolic pressure (RVSP) decreased significantly in the TAVR group (E/e': TAVR, from 24.6±12.9 to 20±9.5, p=0.048 vs. sAVR, from 21.5±9.4 to 20.64±6.4, p=0.361; RVSP: TAVR, 38.4±17.2 vs. 34±12.4, p=0.032 vs. sAVR, 32.2±11.7 vs. 30±6.8, p=0.27). After 3 months, diastolic grade distribution, E/e', and RVSP were similar. Valvuloarterial impedance significantly decreased immediately after the procedure in both groups (TAVR, from 5.1±1.4 to 3.1±1.0 vs. sAVR, from 4.5±1.5 to 3.1±0.8 mm Hg · mL⁻¹ · m⁻², p=0.001), but after 3 months, decreases were greater in the sAVR group (from 3.1±0.8 to 2.2±1.5 mm Hg · mL⁻¹ · m⁻², p=0.093). CONCLUSION: LV diastolic function improved more rapidly and earlier in patients treatment with TAVR than in patients treated with sAVR. These results might explicate the remarkable clinical improvement in improvements in advanced diastolic dysfunction immediately after the TAVR procedure than sAVR.ope

Morphological and functional characteristics of mitral annular calcification and their relationship to stroke

BACKGROUND: Mitral annular calcification (MAC) is associated with risk of stroke. This study aimed to define the morphological and functional characteristics of MAC that are related to stroke. METHODS: A total of 460 subjects with MAC from transthoracic echocardiography in a single center from 2012 to 2016 was retrospectively reviewed. Subjects were classified into two groups according to history of stroke [Group 1 (n = 366): without stroke; Group 2 (n = 94): with stroke]. Morphological and functional features of MAC on echocardiogram were scored from 0 to 3 according to MAC mobility, presence of echodense mass with central echolucencies in the periannular region suggesting caseous necrosis, and functional stenosis. RESULTS: Significantly more patients in group 2 were men and had history of diabetes mellitus, dyslipidemia, atrial fibrillation, or infective endocarditis. Although MAC thickness and extent did not differ between the two groups, group 2 showed a considerably higher MAC score than group 1 (0.50 ± 0.77 vs. 0.23 ±0.52 p<0.001) as a result of the higher prevalence of each component in group 2 [mobility (22 vs. 11%, p = 0.003), echodense mass with central areas of echolucencies suggesting caseous necrosis (23 vs. 7%, p<0.001), and functional mitral stenosis (12 vs. 7%, p = 0.042)]. On logistic regression analysis, MAC score was independently associated with stroke and showed significant incremental value to demographic factors and comorbidities in association with stroke in a consecutive manner. CONCLUSIONS: In conclusion, morphological and functional characteristics of MAC had incremental value in association with stroke over traditional risk factors. MAC score consisting of MAC mobility, typical echodense mass with central echolucencies suggesting caseous necrosis, and functional mitral stenosis was independently associated with stroke. MAC with high-risk features may act as a source of stroke or more potent composite surrogate markers for stroke-related risk factors.ope

Noninvasive Aortic Ultrafast Pulse Wave Velocity Associated With Framingham Risk Model: in vivo Feasibility Study

Background: Aortic pulse wave velocity (PWV) enables the direct assessment of aortic stiffness, which is an independent risk factor of cardiovascular (CV) events. The aim of this study is to evaluate the association between aortic PWV and CV risk model classified into three groups based on the Framingham risk score (FRS), i.e., low-risk (20%). Methods: To noninvasively estimate local PWV in an abdominal aorta, a high-spatiotemporal resolution PWV measurement method (>1 kHz) based on wide field-of-view ultrafast curved array imaging (ufcPWV) is proposed. In the ufcPWV measurement, a new aortic wall motion tracking algorithm based on adaptive reference frame update is performed to compensate errors from temporally accumulated out-of-plane motion. In addition, an aortic pressure waveform is simultaneously measured by applanation tonometry, and a theoretical PWV based on the Bramwell-Hill model (bhPWV) is derived. A total of 69 subjects (aged 23-86 years) according to the CV risk model were enrolled and examined with abdominal ultrasound scan. Results: The ufcPWV was significantly correlated with bhPWV (r = 0.847, p < 0.01), and it showed a statistically significant difference between low- and intermediate-risk groups (5.3 ± 1.1 vs. 8.3 ± 3.1 m/s, p < 0.01), and low- and high-risk groups (5.3 ± 1.1 vs. 10.8 ± 2.5 m/s, p < 0.01) while there is no significant difference between intermediate- and high-risk groups (8.3 ± 3.1 vs. 10.8 ± 2.5 m/s, p = 0.121). Moreover, it showed a significant difference between two evaluation groups [low- (<10%) vs. higher-risk group (≥10%)] (5.3 ± 1.1 vs. 9.4 ± 3.1 m/s, p < 0.01) when the intermediate- and high-risk groups were merged into a higher-risk group. Conclusion: This feasibility study based on CV risk model demonstrated that the aortic ufcPWV measurement has the potential to be a new approach to overcome the limitations of conventional systemic measurement methods in the assessment of aortic stiffness.ope

A randomized, double-blind, multicenter, phase III study on the efficacy and safety of a combination treatment involving fimasartan, amlodipine, rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy

Background: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. Methods: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. Results: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions. Conclusions: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. Trial registration: NCT03156842, Registered 17 May 2017.ope

Early percutaneous mitral commissurotomy or conventional management for asymptomatic mitral stenosis: a randomised clinical trial

Objective: The decision to perform percutaneous mitral commissurotomy (PMC) on asymptomatic patients requires careful weighing of the potential benefits against the risks of PMC, and we conducted a multicentre, randomised trial to compare long-term outcomes of early PMC and conventional treatment in asymptomatic, severe mitral stenosis (MS). Methods: We randomly assigned asymptomatic patients with severe MS (defined as mitral valve area between 1.0 and 1.5 cm2) to early PMC (84 patients) or to conventional treatment (83 patients). The primary endpoint was a composite of major cardiovascular events, including PMC-related complications, cardiovascular mortality, cerebral infarction and systemic thromboembolic events. The secondary endpoints were death from any cause and mitral valve (MV) replacement during follow-up. Results: In the early PMC group, there were no PMC-related complications. During the median follow-up of 6.4 years, the composite primary endpoint occurred in seven patients in the early PMC group (8.3%) and in nine patients in the conventional treatment group (10.8%) (HR 0.77; 95% CI 0.29 to 2.07; p=0.61). Death from any cause occurred in four patients in the early PMC group (4.8%) and three patients in the conventional treatment group (3.6%) (HR 1.30; 95% CI 0.29 to 5.77). Ten patients (11.9%) in the early PMC group and 17 patients (20.5%) in the conventional treatment group underwent MV replacement (HR 0.59; 95% CI 0.27 to 1.29). Conclusions: Compared with conventional treatment, early PMC did not significantly reduce the incidence of cardiovascular events among asymptomatic patients with severe MS during the median follow-up of 6 years. Trial registration number: NCT01406353.ope

Fabry disease and COVID-19: international expert recommendations for management based on real-world experience

The rapid spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has raised questions about Fabry disease (FD) as an independent risk factor for severe COVID-19 symptoms. Available real-world data on 22 patients from an international group of healthcare providers reveals that most patients with FD experience mild-to-moderate COVID-19 symptoms with an additional complication of Fabry pain crises and transient worsening of kidney function in some cases; however, two patients over the age of 55 years with renal or cardiac disease experienced critical COVID-19 complications. These outcomes support the theory that pre-existent tissue injury and inflammation may predispose patients with more advanced FD to a more severe course of COVID-19, while less advanced FD patients do not appear to be more susceptible than the general population. Given these observed risk factors, it is best to reinforce all recommended safety precautions for individuals with advanced FD. Diagnosis of FD should not preclude providing full therapeutic and organ support as needed for patients with FD and severe or critical COVID-19, although a FD-specific safety profile review should always be conducted prior to initiating COVID-19-specific therapies. Continued specific FD therapy with enzyme replacement therapy, chaperone therapy, dialysis, renin-angiotensin blockers or participation to clinical trials during the pandemic is recommended as FD progression will only increase susceptibility to infection. In order to compile outcome data and inform best practices, an international registry for patients affected by Fabry and infected by COVID-19 should be established.ope

Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late-onset phenotype

Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey.This study included 94 patients from 46 independent pedigrees: 38 adult males, 46 symptomatic females, and 10 pediatric males. Each diagnosis was based on an enzyme assay and GLA gene mutation analysis.The mean age at presentation was 24 years (range, 5-65 years); however, the diagnoses were delayed by 21 ± 19 years after the onset of symptoms. Those patients with late-onset Fabry disease were diagnosed by family screening or milder symptoms at a later age. Forty different mutations were identified: 20 missense (50%), 10 nonsense (25%), 8 frameshift (20%), and 2 splice site (5%) mutations. Five of them were novel. IVS4+919G>A (c.936+919 G>A) was not detected among the 6505 alleles via newborn screening using dried blood spots. Enzyme replacement therapy (ERT) was performed in all the males and pediatric patients, whereas 75% of the symptomatic females underwent ERT for 4.2 ± 3.6 years.This study described the demographic data, wide clinical spectrum of phenotypes, and GLA mutation spectrum of Fabry disease in Korea. Most of the patients had classical Fabry disease, with a 4 times higher incidence than that of late-onset Fabry disease, indicating an underdiagnosis of mild, late-onset Fabry disease.ope

Transcatheter Mitral Valve Repair: Growing Evidence Regarding It's Efficacy and Optimal Indication

ope

The impact of cardiopulmonary exercise-derived scoring on prediction of cardio-cerebral outcome in hypertrophic cardiomyopathy

Background: Sudden cardiac death (SCD) and stroke-related events accompanied by atrial fibrillation (AF) can affect morbidity and mortality in hypertrophic cardiomyopathy (HCM). This study sought to evaluate a scoring system predicting cardio-cerebral events in HCM patients using cardiopulmonary exercise testing (CPET). Methods: We investigated the role of a previous prediction model based on CPET, the HYPertrophic Exercise-derived Risk score for Heart Failure-related events (HyperHF), which is derived from peak circulatory power ventilatory efficiency and left atrial diameter (LAD), for predicting a composite of SCD-related (SCD, serious ventricular arrhythmia, death from cardiac cause, heart failure admission) and stroke-related (new-onset AF, acute stroke) events. The Novel HyperHF risk model using left atrial volume index (LAVI) instead of LAD was proposed and compared with the previous HCM Risk-SCD model. Results: A total of 295 consecutive HCM patients (age 59.9±13.2, 71.2% male) who underwent CPET was included in the present study. During a median follow-up of 742 days (interquartile range 384-1047 days), 29 patients (9.8%) experienced an event (SCD-related event: 14 patients (4.7%); stroke-related event: 17 patients (5.8%)). The previous model for SCD risk score showed fair prediction ability (AUC of HCM Risk-SCD 0.670, p = 0.002; AUC of HyperHF 0.691, p = 0.001). However, the prediction power of Novel HyperHF showed the highest value among the models (AUC of Novel HyperHF 0.717, p<0.001). Conclusions: Both conventional HCM Risk-SCD score and CPET-derived HyperHF score were useful for prediction of overall risk of SCD-related and stroke-related events in HCM. Novel HyperHF score using LAVI could be utilized for a better prediction power.ope

Timing and Indications for Aortic Valve Surgery in Korean Bicuspid Aortic Valve Patients

ope