Prognostic Power of Quantitative Assessment of Functional Mitral Regurgitation and Myocardial Scar Quantification by Cardiac Magnetic Resonance.

BACKGROUND: The severity classification of functional mitral regurgitation (FMR) remains controversial despite adverse prognosis and rapidly evolving interventions. Furthermore, it is unclear if quantitative assessment with cardiac magnetic resonance can provide incremental risk stratification for patients with ischemic cardiomyopathy (ICM) or non-ICM (NICM) in terms of FMR and late gadolinium enhancement (LGE). We evaluated the impact of quantitative cardiac magnetic resonance parameters on event-free survival separately for ICM and NICM, to assess prognostic FMR thresholds and interactions with LGE quantification. METHODS: Patients (n=1414) undergoing cardiac magnetic resonance for cardiomyopathy (ejection fraction<50%) assessment from April 1, 2001 to December 31, 2017 were evaluated. The primary end point was all-cause death, heart transplant, or left ventricular assist device implantation during follow-up. Multivariable Cox analyses were conducted to determine the impact of FMR, LGE, and their interactions with event-free survival. RESULTS: There were 510 primary end points, 395/782 (50.5%) in ICM and 114/632 (18.0%) in NICM. Mitral regurgitation-fraction per 5% increase was independently associated with the primary end point, hazards ratios (95% CIs) of 1.04 (1.01-1.07; P=0.034) in ICM and 1.09 (1.02-1.16; P=0.011) in NICM. Optimal mitral regurgitation-fraction threshold for moderate and severe FMR were ≥20% and ≥35%, respectively, in both ICM and NICM, based on the prediction of the primary outcome. Similarly, optimal LGE thresholds were ≥5% in ICM and ≥2% in NICM. Mitral regurgitation-fraction×LGE emerged as a significant interaction for the primary end point in ICM (P=0.006), but not in NICM (P=0.971). CONCLUSIONS: Mitral regurgitation-fraction and LGE are key quantitative cardiac magnetic resonance biomarkers with differential associations with adverse outcomes in ICM and NICM. Optimal prognostic thresholds may provide important clinical risk prognostication and may further facilitate the ability to derive selection criteria to guide therapeutic decision-making.

Severe mitral regurgitation in nonagenarians: Impact of symptomatic status, frailty and etiology on management and outcomes.

BACKGROUND: Data regarding mitral regurgitation (MR) in extremely elderly patients are limited. The aim of the present study was to assess symptomatic status, frailty, etiology and outcomes for nonagenarians with severe MR. METHODS: Single-center cohort study of patients ≥90 years of age with at least 3+ MR on echocardiography between September 2010 and August 2018. Out of a total of 11,998 patients with at least 3+ MR, 267 patients were included in the present study. RESULTS: The average age was 93.5 ± 2.6 years, and 57% were female. At baseline, 88% were symptomatic, with mean Charlson co-morbidity index of 6 ± 2 points, and mean frailty score of 2.9 ± 1.4 points. Primary MR was present in 50%, secondary in 47%, and prosthetic valve dysfunction in 3%. Among patients with primary MR, the most common etiology was mitral annular calcification (58%). In comparison, the most common etiology of secondary MR was atrial functional MR (52%). Of all, 95% were treated conservatively, and 5% underwent interventional management. Among 253 patients who had follow-up data with a median follow-up of 14 months (25th-75th interquartile range: 3-31 months), 191 patients (75%) died. Mortality trended higher in the conservative group versus the interventional group (60% vs. 22%, log-rank P = 0.063). CONCLUSIONS: Most nonagenarians with significant MR were symptomatic at presentation, had elevated Charlson co-morbidity index and frailty scores. Etiologies of MR were almost equally distributed between primary and secondary causes. The vast majority of nonagenarians with significant MR were conservatively managed.

Mitral Annular Calcification Related Infective Endocarditis: A Contemporary Systematic Review.

Mitral annular calcification (MAC) is a chronic degenerative process often found incidentally on imaging. MAC is associated with elevated risk of atherosclerosis and stroke. The association between MAC and the risk of infective endocarditis (IE) is less well known. Therefore, we conducted this systematic review in order to understand the diagnosis, clinical outcomes, and management of IE associated with MAC. We conducted a systematic review of published data regarding MAC related IE in various databases until November 20, 2019. Case series and cohort studies were included. A total of 8 studies with a cohort of 113 patients were included. Mean age was 69 years with equal gender distribution (50% female). Hypertension (55.8%) was the most common comorbidity seen in this patient population. IE was diagnosed by either antemortem trans esophageal echocardiographic examination (76%) or post-mortem autopsy (24%). Staphylococcus aureus (47%) was the most common pathogen identified. MAC was adjudicated to be moderate-to-severe in 100% of identified cases, with 77.9% of cases presenting with distinct vegetation's. Twenty-six percent of patients (n = 29) underwent surgery. MAC may be associated with development of IE. Echocardiography is the most common non-invasive technique for diagnosis. Due to the difficulties associated with antemortem diagnosis, diagnosis is occasionally made on post-mortem examination. Neurologic complications are frequently encountered, and reported mortality is high in MAC associated IE.

Impact of the Pandemic on Gender Differences in Scientific Publication Authorship Among Turkish Adult Cardiologists.

OBJECTIVE: Despite efforts spent on promotion of gender equity in the academia, the gender gap is feared to have widened after the coronavirus disease 2019 pandemic. Herein, we aimed to compare the distribution of female authorship by Turkish adult cardiologists in journals indexed at PubMed before and after the pandemic. METHODS: In this cross-sectional study, an advanced search on PubMed (https://pubmed.ncbi.nlm.nih.gov/) was carried out based on the following criteria: "entrez date" and keywords "Turkey" and "cardiology" to identify papers that entered the online database in April-September 2019 and April-September 2020. After the study sample was determined, type of the article and details of the author list were recorded. RESULTS: Of 1318 articles screened, 708 met the inclusion criteria. Overall, 85 (12.0%) of first authors and 67 (10.0%) of senior authors were female. Females were less likely to first author original articles, editorials, case reports/series and papers with international participation (9.5%, P = .012; 33.3%, P = .045; 18.3%, P = .033; 4.8%, P = .032, respectively). A higher proportion of females were in first and corresponding author positions in original articles (73.2%, P = .032; 76.5%, P = .019, respectively), but not in other article types (all P > .05), after emergence of the pandemic. CONCLUSION: These suggest that significant gender differences exist with regard to authorships of scientific publications that were submitted by Turkish adult cardiologists. Future studies may aim to evaluate the trends across a wider time span and based on a more extensive scientific output follow-up.

Upgrades from Previous Cardiac Implantable Electronic Devices Compared to De Novo Cardiac Resynchronization Therapy Implantations: Results from CRT Survey-II in the Turkish Population.

OBJECTIVE: Cardiac resynchronization therapy is the guideline-directed treatment option in selected heart failure with reduced left ventricular ejection fraction patients. Data regarding the contemporary clinical practice of cardiac resynchronization therapy in Turkey have been published recently. This sub-study aims to compare clinical and periprocedural characteristics between cardiac resynchronization therapy upgrade and de novo implantations. METHODS: Turkish arm of the Cardiac Resynchronization Therapy Survey-II was conducted between October 1, 2015, and December 31, 2016, at 16 centers. All consecutive patients who underwent an upgrade to cardiac resynchronization therapy system (n=60) or de novo cardiac resynchronization therapy implantation (n=335) were eligible. RESULTS: Distribution of age, gender, and heart failure etiology were similar in the 2 groups. Atrial fibrillation, valvular heart disease, and chronic kidney disease were more common in cardiac resynchronization therapy upgrade patients. Narrow intrinsic QRS duration and left ventricular ejection fraction being 75% in both groups, and only beta-blockers were prescribed at rates of >90% in both groups. CONCLUSION: Cardiac resynchronization therapy upgrades are performed with high procedural success rates and without excess periprocedural complication risk. Feared complications of cardiac resynchronization therapy upgrades due to the pre-existing device should not delay the procedure if indicated.

Sex-based differences in left ventricular remodeling in patients with chronic aortic regurgitation: a multi-modality study.

BACKGROUND: Significant aortic regurgitation (AR) leads to left ventricular (LV) remodeling; however, little data exist regarding sex-based differences in LV remodeling in this setting. We sought to compare LV remodeling and AR severity, assessed by echocardiography and cardiovascular magnetic resonance (CMR), to discern sex-based differences. METHODS: Patients with ≥ moderate chronic AR by echocardiography who underwent CMR within 90 days between December 2005 and October 2015 were included. Nonlinear regression models were built to assess the effect of AR regurgitant fraction (RF) on LV remodeling. A generalized linear model and Bland Altman analyses were constructed to evaluate differences between CMR and echocardiography. Referral for surgical intervention based on symptoms and LV remodeling was evaluated. RESULTS: Of the 243 patients (48.3 ± 16.6 years, 58 (24%) female), 119 (49%) underwent surgical intervention with a primary indication of severe AR, 97 (82%) men, 22 (18%) women. Significant sex differences in LV remodeling emerged on CMR. Women demonstrated significantly smaller LV end-diastolic volume index (LVEDVI) (96.8 ml/m2 vs 125.6 ml/m2, p < 0.001), LV end-systolic volume index (LVESVI) (41.1 vs 54.5 ml/m2, p < 0.001), blunted LV dilation in the setting of increasing AR severity (LVEDVI p value < 0.001, LVESVI p value 0.011), and LV length indexed (8.32 vs 9.69 cm, p < 0.001). On Bland Altman analysis, a significant interaction with sex and LV diameters was evident, demonstrating a significant increase in the difference between CMR and echocardiography measurements as the LV enlarged in women: LVEDVI (p = 0.006), LVESVI (p < 0.001), such that echocardiographic measurements increasingly underestimated LV diameters in women as the LV enlarged. LV length was higher for males with a linear effect from RF (p < 0.001), with LV length increasing at a higher rate with increasing RF for males compared to females (two-way interaction with sex p = 0.005). Sphericity volume index was higher for men after adjusting for a relative wall thickness (p = 0.033). CONCLUSIONS: CMR assessment of chronic AR revealed significant sex differences in LV remodeling and significant echocardiographic underestimation of LV dilation, particularly in women. Defining optimal sex-based CMR thresholds for surgical referral should be further developed. TRIAL REGISTRATION: NA.

Mitral annular calcification and valvular dysfunction: multimodality imaging evaluation, grading, and management.

Mitral annular calcification (MAC) refers to calcium deposition in the fibrous skeleton of the mitral valve. It has many cardiovascular associations, including mitral valve dysfunction, elevated cardiovascular risk, arrhythmias, and endocarditis. Echocardiography conventionally is the first-line imaging modality for anatomic assessment, and evaluation of mitral valve function. Cardiac computed tomography (CT) has demonstrated importance as an imaging modality for the evaluation and planning of related procedures. It also holds promise in quantitative grading of MAC. Currently, there is no universally accepted definition or classification system of MAC severity. We review the multimodality imaging evaluation of MAC and associated valvular dysfunction and propose a novel classification system based on qualitative and quantitative measurements derived from echocardiography and cardiac CT.

Outcomes of contemporary imaging-guided management of sinus of Valsalva aneurysms.

BACKGROUND: Sinus of Valsalva aneurysms (SVAs) are rare. We assessed the role of multimodality imaging in guiding the contemporary management. METHODS: A single-center retrospective cohort study over a 20-year period was performed. RESULTS: Between January 1997 and June 2017, 103 patients were diagnosed with SVAs (median age: 58 years). Eighty patients presented with non-ruptured SVAs, and 23 with ruptured SVAs. Seventy-six patients underwent surgery, and 27 were conservatively managed. The median durations of follow-up were: 48 months (surgical group) vs. 37.5 months (conservative group). There was no mortality directly attributable to SVA surgery. There were no late complications in the conservative group. Transthoracic echocardiography (TTE) was the first-line imaging investigation (100.0% in surgical group vs. 92.6% in conservative group, P=0.019). Additional imaging studies included: (I) transesophageal echocardiography (TEE): 93.4% in surgical group vs. 22.2% in conservative group, P<0.001; (II) multi-detector cardiac computed tomography (MDCT): 61.8% in surgical group vs. 37.0% in conservative group, P=0.041; (III) cardiac magnetic resonance (CMR): 22.4% in surgical group vs. 14.8% in conservative group, P=0.579. At diagnosis, SVA diameters were: TTE: 4.80 cm (range, 3.30 cm); TEE: 5.40 cm (range, 4.00 cm); MDCT: 5.20 cm (range, 3.90 cm); CMR: 4.80 cm (range, 3.70 cm). CONCLUSIONS: In a 20-year cohort, proper selection for surgery and conservative management resulted in excellent outcomes for SVAs. TTE was the first-line imaging investigation for assessment of SVAs, although many patients underwent an additional imaging investigation. The contemporary outcomes of imaging-guided SVA management were excellent.

Multimodality imaging for the prevention of cardiovascular events: Coronary artery calcium and beyond.

Atherosclerotic cardiovascular disease (ASCVD) has been the leading cause of death worldwide for more than a decade. Prevention is of utmost importance to reduce related mortality. The innovations in cardiovascular imaging technology, in addition to our improved understanding of coronary atherosclerosis pathogenesis, have resulted in cardiovascular imaging becoming one of the most influential tools for diagnosis and risk stratification in ASCVD. Although numerous publications have emerged on this topic, data that guide routine cardiology clinical practice currently focus on the utility of a limited number of such modalities, namely arterial ultrasonography and computed tomography. Herein, current evidence with respect to the role of multimodality cardiovascular imaging on ASCVD prevention will be reviewed.

Predictors of Cardiac Implantable Electronic Device Artifact on Cardiac MRI: The Utility of a Device Related Score.

PURPOSE: Cardiac magnetic resonance imaging (CMR) image quality can be degraded by artifact in patients with cardiac implantable electronic devices (CIED). We aimed to establish a clinical risk score, so patient selection for diagnostic CMR could be optimised. METHODS: In this retrospective cohort study, CMRs performed for clinical use in subjects with CIED from January 2016 to May 2019 were reviewed. Subject anthropometry, CIED generator/lead specifications and pre-scan chest X-ray (CXR) measurements were collected. Generator-related artifact size was measured on axial steady state free precession images. Interpretability of late gadolinium enhancement (LGE) imaging was performed based on a three-grade visual score attributed to each of 17 myocardial segments. RESULTS: Fifty-seven (57) patients (59±16 years, 74% male) fitted the inclusion criteria. Artifact precluded left ventricle (LV) evaluation (≥5 segments) in 17 (30%). Artifact was more common with implantable cardioverter-defibrillators, related to generator volume, mass, height, width, thickness, and area, along with right ventricular (RV) lead length and diameter (all p<0.05). Artifact was associated with distance from generator to LV apex, generator to RV lead tip and shortest distance from generator to heart on CXR (all p<0.05). On multivariable regression modelling, RV lead diameter (OR 5.861, 95% CI 1.866-18.407, p=0.002) and distance from generator to LV apex (OR 0.693, 95% CI 0.511-0.940, p=0.019) were independent predictors of artifact. Multivariable predictors were used to develop Device Related CMR Artifact Prediction Score (DR-CAPS), where all patients with DR-CAPS=0 had fully interpretable LGE imaging. CONCLUSION: Simple, readily available measures, such as lead characteristics and pre-scan CXR measures, can stratify patients via an artifact prediction score to optimise selection for diagnostic CMR.

Medical Therapies for Marfan Syndrome and Other Thoracic Aortic Dilatation in Adults: A Contemporary Review.

Thoracic aortic dilatation often has an asymptomatic course but may present with lethal complications such as aortic rupture or dissection, particularly when the thoracic aorta is aneurysmally enlarged; therefore, appropriate diagnosis, surveillance, and management are vital. Recommendations regarding imaging and surgical management are outlined in contemporary clinical practice guidelines. Dedicated guidelines regarding medical therapies for the management of thoracic aortic dilatation are lacking. Most of the medical treatment strategies, especially recommendations regarding pharmacological medical therapies related to ß-blockade and angiotensin receptor blockers, are derived from data on patients with Marfan syndrome. The main aims of medical therapies for the management of thoracic aortic dilatation are (1) to control the progression of the disease, and (2) to prevent complications related to the disease (such as aortic dissection and mortality). This paper reviews the contemporary evidence and highlights the gaps in evidence to be investigated in further studies.

Should We Target Global Risk or Risk Factors?

PURPOSE OF REVIEW: Recent evidence has shaped the new guidelines for the management of dyslipidemia. The importance of accurate risk estimation, subclinical disease detection, and contemporary dyslipidemia management approaches are discussed in this review. RECENT FINDINGS: Risk prediction helps determine the intensity of management strategies and identify high-risk patients. To overcome the pitfalls of the current risk prediction systems, incorporating genetic scores, biomarkers, and imaging is being explored. Key initiating event in atherogenesis is low-density lipoprotein cholesterol (LDL-C) retention in the arterial wall. Recent dyslipidemia guidelines agree that LDL-C is the primary target, but management approaches vary. Guidelines are shaped by new studies that show the benefits of high-intensity lipid lowering, especially for patients at very high-risk. Global risk assessment should be performed in all individuals for cardiovascular disease prevention. Main target should be the causal risk factors, particularly LDL-C which is one of the most important modifiable causal factors. Lower LDL-C goals will help prevent further events in very high-risk patients.

Cholesterol efflux promoting function of high-density lipoproteins in calcific aortic valve stenosis.

Background and aims: Cholesterol efflux capacity is a functional property of high-density lipoproteins (HDL) reflecting the efficiency of the atheroprotective reverse cholesterol transport process in humans. Its relationship with calcific aortic valve stenosis (CAVS) has not been fully assessed yet. Methods: We evaluated HDL-CEC in a patient population with varying degrees of aortic valvular calcific disease, assessed using echocardiography and cardiac computed tomography. Measurement of biomarkers that reflect osteogenic and tissue remodeling, along with dietary and gut microbiota-derived metabolites were performed. Results: Patients with moderate-severe CAVS had significantly lower HDL-CEC compared to both control and aortic sclerosis subjects (mean: 6.09%, 7.32% and 7.26%, respectively). HDL-CEC displayed negative correlations with peak aortic jet velocity and aortic valve calcium score, indexes of CAVS severity (ρ = -0.298, p = 0.002 and ρ = -0.358, p = 0.005, respectively). In multivariable regression model, HDL-CEC had independent association with aortic valve calcium score (B: -0.053, SE: 0.014, p < 0.001), GFR (B: -0.034, SE: 0.012, p = 0.007), as well as with levels of total cholesterol (B: 0.018, SE: 0.005, p = 0.002). Conclusion: These results indicate an impairment of HDL-CEC in moderate-severe CAVS and may contribute to identify potential novel targets for CAVS management.

A Contemporary 20-Year Cleveland Clinic Experience of Nonbacterial Thrombotic Endocarditis: Etiology, Echocardiographic Imaging, Management, and Outcomes.

BACKGROUND: Nonbacterial thrombotic endocarditis, or marantic endocarditis, is rare. Contemporary data on the etiology, echocardiographic evaluation, and management of nonbacterial thrombotic endocarditis are limited. METHODS: A single-center retrospective cohort study was performed. Electronic medical records and echocardiographic records were searched for patients ages ≥18 years with a confirmed diagnosis of nonbacterial thrombotic endocarditis between January 1999 and November 2019. Demographic, echocardiographic, and management data were collected. RESULTS: Of 600,577 transthoracic echocardiograms (TTEs) and 89,264 transesophageal echocardiograms (TEEs), 42 patients had nonbacterial thrombotic endocarditis (mean age: 54 ± 14.5 years; 66.7% were female). The median duration of follow-up was 8.2 (interquartile range 3.3-24.4) months. Seventeen patients (40.5%) had malignancy, 33.3% had systemic lupus erythematosus, and 35.7% had antiphospholipid antibody syndrome. Stroke was the most common presentation (59.5%). TTE enabled the diagnosis in 19 cases (45.2%), compared with TEE, which identified the condition in 33 of 34 (97.1%) cases in which it was utilized. Three-dimensional echocardiography was performed in 17 TEEs. The most common valves involved were mitral (61.9%), and aortic (23.8%) valves. Thirty-two patients were managed with anticoagulation. Ten patients underwent surgery. Sixteen (38.1%) patients died, most of whom had a diagnosis of advanced malignancy. CONCLUSION: In a contemporary 20-year cohort, TTE and TEE played important roles in diagnosis, with superior diagnostic performance of TEE for nonbacterial thrombotic endocarditis. Mortality was high, and advanced malignancy portended a worse prognosis. Management in most cases was therapeutic anticoagulation. In select cases, surgery provided favorable outcomes.

Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis.

BACKGROUND: Histopathological changes in calcific aortic stenosis (CAS) resemble changes in coronary atherosclerosis. Concerning recent evidence on dietary and gut microbiota-related metabolites representing players in atherosclerosis, we aimed to investigate the link between dietary and gut microbiota-derived metabolites and CAS. METHODS: We consecutively recruited eligible subjects with moderate-severe CAS (n = 60), aortic sclerosis (ASc) (n = 49) and age and gender-matched control subjects (n = 48) in May 2016-December 2016. Plasma dietary and gut microbiota-related metabolite levels, namely choline, betaine, and trimethylamine N-oxide (TMAO), were measured using ultra-performance liquid chromatography-tandem mass spectroscopy method. Histopathological examinations were performed in patients that underwent aortic valve surgery. RESULTS: Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (all p > 0.05). CAS patients had higher plasma choline levels compared to both control (p < 0.001) and ASc (p = 0.006). Plasma betaine and TMAO levels were similar (both p > 0.05). Compared to the lowest quartile choline levels (<11.15 µM), patients with the highest quartile choline levels (≥14.98 µM) had higher aortic valvular (p < 0.001) and mitral annular (p = 0.013) calcification scores. Plasma choline levels were independently associated with aortic peak flow velocity (B ± SE:0.165 ± 0.060, p = 0.009). Choline levels were elevated in subjects who had aortic valves with denser lymphocyte infiltration (p < 0.001), neovascularization (p = 0.011), osseous metaplasia (p = 0.004), more severe tissue remodelling (p = 0.002) and calcification (p = 0.002). CONCLUSION: We found a significant association between choline levels and CAS presence and severity depicted on imaging modalities and histopathological examinations. Our study may open new horizons for prevention of CAS.

Current clinical practice of cardiac resynchronization therapy in Turkey: Reflections from Cardiac Resynchronization Therapy Survey-II.

OBJECTIVE: Cardiac resynchronization therapy (CRT) has been shown to reduce mortality in selected patients with heart failure with reduced ejection fraction (HFrEF). CRT Survey-II was a snapshot survey to assess current clinical practice with regard to CRT. Herein, we aimed to compare Turkish data with other countries of European Society of Cardiology (ESC). METHODS: The survey was conducted between October 2015 and December 2016 in 42 ESC member countries. All consecutive patients who underwent a de novo CRT implantation or a CRT upgrade were eligible. RESULTS: A total of 288 centers included 11,088 patients. From Turkey, 16 centers recruited 424 patients representing 12.9% of all implantations. Compared to the entire cohort, Turkish patients were younger with a lower proportion of men and a higher proportion with ischemic etiology. Electrocardiography (ECG) showed sinus rhythm in 81.5%, a QRS duration of <130 ms in 10.1%, and ≥150 ms in 63.8% of patients. Left bundle branch block (LBBB) was more common. Median left ventricular ejection fraction (LVEF) was 25%, lower than in the overall ESC cohort, but NYHA class was more often II. Most common indication for CRT implantation was HF with a wide QRS (70.8%). Almost 98.3% of devices implanted were CRT-D, in contrast to the overall cohort. Fluoroscopy time was longer, but duration of overall procedure was shorter. LV lead implantation was unsuccessful in 2.6% patients. Periprocedural complication rate was 6.3%. The most common complication was bleeding. Remote monitoring was less utilized. CONCLUSION: These are the first observational data reflecting the current CRT practice in Turkey and comparing it with other countries of Europe. Findings of this study may help detect gaps and provide insights for improvement.