Ventricular Embolization of Mitral Valve in Valve Rescued With a Second Valve.

Valve embolization is a catastrophic complication of mitral valve-in-valve and valve-in-ring procedures and occurs due to inadequate ventricular positioning, undersizing, or insufficient anchoring. Emergent cardiac surgery to retrieve the embolized valve is usually required for overt embolization. In the situation described herein, a decision was made to attempt to deploy a second valve at a proper depth to anchor the embolized valve and prevent further migration. This case highlights the technique of deploying a second valve to anchor the embolized valve if valve migration has occurred with minimal movement.

Characteristics and outcomes of patients screened for transcatheter mitral valve implantation: 1-year results from the CHOICE-MI registry.

AIMS: Transcatheter mitral valve implantation (TMVI) represents a novel treatment option for patients with mitral regurgitation (MR) unsuitable for established therapies. The CHOICE-MI registry aimed to investigate outcomes of patients undergoing screening for TMVI. METHODS AND RESULTS: From May 2014 to March 2021, patients with MR considered suboptimal candidates for transcatheter edge-to-edge repair (TEER) and at high risk for mitral valve surgery underwent TMVI screening at 26 centres. Characteristics and outcomes were investigated for patients undergoing TMVI and for TMVI-ineligible patients referred to bailout-TEER, high-risk surgery or medical therapy (MT). The primary composite endpoint was all-cause mortality or heart failure hospitalization after 1 year. Among 746 patients included (78.5 years, interquartile range [IQR] 72.0-83.0, EuroSCORE II 4.7% [IQR 2.7-9.7]), 229 patients (30.7%) underwent TMVI with 10 different dedicated devices. At 1 year, residual MR ≤1+ was present in 95.2% and the primary endpoint occurred in 39.2% of patients treated with TMVI. In TMVI-ineligible patients (n = 517, 69.3%), rates of residual MR ≤1+ were 37.2%, 100.0% and 2.4% after bailout-TEER, high-risk surgery and MT, respectively. The primary endpoint at 1 year occurred in 28.8% of patients referred to bailout-TEER, in 42.9% of patients undergoing high-risk surgery and in 47.9% of patients remaining on MT. CONCLUSION: This registry included the largest number of patients treated with TMVI to date. TMVI with 10 dedicated devices resulted in predictable MR elimination and sustained functional improvement at 1 year. In TMVI-ineligible patients, bailout-TEER and high-risk surgery represented reasonable alternatives, while MT was associated with poor clinical and functional outcomes.

National Trends and Outcomes of Surgical Aortic Valve Replacement With Concomitant Mitral Valve Surgery.

BACKGROUND: Incidence of multivalvular heart disease is increasing, with aortic stenosis and mitral regurgitation being the most common. Data are limited on outcomes of patients undergoing multivalvular surgery. The purpose of this study was to evaluate contemporary trends and in-hospital outcomes for combined surgical aortic valve replacement (SAVR) and mitral valve repair (MVr) or replacement (MVR). METHODS: We identified patient hospitalizations aged ≥18 years who underwent SAVR + MVr or MVR between 2004 and 2018 using the National Inpatient Sample. Data were weighted to estimate national estimates of the entire US hospitalized population. Exclusion criteria included endocarditis, history of heart transplant or left ventricular assist device, and any other concomitant valve surgery. RESULTS: Between January 1, 2004, and December 31, 2018, there were 68,882 weighted admissions for SAVR with concomitant mitral valve surgery. Overall, in-hospital mortality was 8.34% with significantly higher inpatient mortality in SAVR + MVR group compared with SAVR + MVr group (9.91% vs 5.57%, p < 0.001). During the study period, adjusted in-hospital mortality decreased in both SAVR + MVr group (p-trend 0.004) and SAVR + MVR group (p-trend <0.001). Age ≥70 years was associated with higher in-hospital mortality compared to those < 70 years (9.95% vs 6.70%, p < 0.001). CONCLUSION: Combined aortic and mitral valve surgery is associated with a high risk of in-hospital mortality, especially in patients ≥ 70 years of age. Further research is needed to assess the role of transcatheter approaches in the treatment of multivalvular heart disease.

Surgical Explantation After TAVR Failure: Mid-Term Outcomes From the EXPLANT-TAVR International Registry.

OBJECTIVES: The aim of this study was to evaluate clinical characteristics, mechanisms of failure, and outcomes of transcatheter aortic valve replacement (TAVR) explantation. BACKGROUND: Surgical explantation following TAVR may be required for structural valve degeneration, paravalvular leak, infection, or other reasons. However, in-depth data on indications and outcomes are lacking. METHODS: Data from a multicenter, international registry (EXPLANT-TAVR) of patients who underwent TAVR explantation were reviewed retrospectively. Explantations performed during the same admission as initial TAVR were excluded. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 6.7 months (interquartile range [IQR]: 1.0-18.8 months) after TAVR explantation and was 97.7% complete at 30 days and 86.1% complete at 1 year. RESULTS: From November 2009 to September 2020, 269 patients across 42 centers with a mean age of 72.7 ± 10.4 years underwent TAVR explantation. About one quarter (25.9%) were deemed low surgical risk at index TAVR, and median Society of Thoracic Surgeons risk at TAVR explantation was 5.6% (IQR: 3.2%-9.6%). The median time to explantation was 11.5 months (IQR: 4.0-32.4 months). Balloon-expandable and self-expanding or mechanically expandable valves accounted for 50.9% and 49.1%, respectively. Indications for explantation included endocarditis (43.1%), structural valve degeneration (20.1%), paravalvular leak (18.2%), and prosthesis-patient mismatch (10.8%). Redo TAVR was not feasible because of unfavorable anatomy in 26.8% of patients. Urgent or emergency cases were performed in 53.1% of patients, aortic root replacement in 13.4%, and 54.6% had concomitant cardiac procedures. Overall survival at last follow-up was 76.1%. In-hospital, 30-day, and 1-year mortality rates were 11.9%, 13.1%, and 28.5%, respectively, and stroke rates were 5.9%, 8.6%, and 18.7%, respectively. CONCLUSIONS: The EXPLANT-TAVR registry reveals that surgical risks associated with TAVR explantation are not negligible and should be taken into consideration in the lifetime management of aortic stenosis.

Optimal positioning of self-expanding valves before deployment decreases paravalvular regurgitation following transcatheter aortic valve replacement.

OBJECTIVES: To evaluate the association between measurements performed during Medtronic CoreValve (MCV) deployment and paravalvular leak (PVL). BACKGROUND: The MCV can be recaptured and repositioned, allowing the TAVR operator to implant at a more favorable position. The association between angiographic measurements of MCV position while the valve is recapturable and PVL post deployment has not been investigated. METHODS: 493 patients undergoing TAVR with MCV (January 2011-July 2017) were included. PVL was defined as intraprocedural aortic regurgitation that was judged clinically to require balloon postdilation. Depth of the valve at the left coronary cusp (LCC) and noncoronary cusp (NCC) were measured when the valve was 80% deployed. An optimal cutoff value for the ratio LCC/NCC for PVL was identified in 40 patients. Using this cutoff value, the association between LCC/NCC and PVL was then validated in 453 patients. RESULTS: The median LCC/NCC was 1.51 (interquartile range 1.06-1.89).The optimal cutoff value for LCC/NCC was 1.48 (93% sensitivity, 77% specificity, AUC0.85). In the validation group 112 (24.7%) patients had PVL. For LCC/NCC ≥ 1.48, the incidence of PVL was lower compared to LCC/NCC < 1.48 (9.58% vs. 41.78%, P < 0.0001). LCC/NCC of 1.48 had a sensitivity of 79.5% and specificity of 63.6% for PVL (AUC0.72). In a multivariate model, LCC/NCC < 1.48 independently predicted PVL (OR = 6.67, 95% CI 3.96-11.23, P < 0.0001). CONCLUSION: Positioning the MCV such that the LCC/NCC is ≥1.48 may result in less PVL.

Cardiovascular disease and cognitive decline in postmenopausal women: results from the Women's Health Initiative Memory Study.

BACKGROUND: Data on cardiovascular diseases (CVD) and cognitive decline are conflicting. Our objective was to investigate if CVD is associated with an increased risk for cognitive decline and to examine whether hypertension, diabetes, or adiposity modify the effect of CVD on cognitive functioning. METHODS AND RESULTS: Prospective follow-up of 6455 cognitively intact, postmenopausal women aged 65 to 79 years old enrolled in the Women's Health Initiative Memory Study (WHIMS). CVD was determined by self-report. For cognitive decline, we assessed the incidence of mild cognitive impairment (MCI) or probable dementia (PD) via modified mini-mental state examination (3 MS) score, neurocognitive, and neuropsychiatric examinations. The median follow-up was 8.4 years. Women with CVD tended to be at increased risk for cognitive decline compared with those free of CVD (hazard ratio [HR], 1.29; 95% CI: 1.00, 1.67). Women with myocardial infarction or other vascular disease were at highest risk (HR, 2.10; 95% CI: 1.40, 3.15 or HR, 1.97; 95% CI: 1.34, 2.87). Angina pectoris was moderately associated with cognitive decline (HR 1.45; 95% CI: 1.05, 2.01) whereas no significant relationships were found for atrial fibrillation or heart failure. Hypertension and diabetes increased the risk for cognitive decline in women without CVD. Diabetes tended to elevate the risk for MCI/PD in women with CVD. No significant trend was seen for adiposity. CONCLUSIONS: CVD is associated with cognitive decline in elderly postmenopausal women. Hypertension and diabetes, but not adiposity, are associated with a higher risk for cognitive decline. More research is warranted on the potential of CVD prevention for preserving cognitive functioning.

Meta-analysis: diagnostic performance of low-radiation-dose coronary computed tomography angiography.

BACKGROUND: A new radiation dose-saving technique for noninvasive coronary artery imaging with computed tomography (CT) is available. PURPOSE: To summarize current evidence about the ability of low-dose coronary CT angiography to rule out coronary artery disease (CAD) in symptomatic adults. DATA SOURCES: Online databases, including MEDLINE, EMBASE, and the Cochrane Library, from inception through 31 October 2010; abstract databases; gray literature; reference lists of identified articles; and experts. No language restrictions were applied. STUDY SELECTION: All investigators screened and selected studies that compared prospective electrocardiography-gated coronary CT angiography with catheter coronary angiography (the reference standard) in symptomatic patients with suspected CAD. DATA EXTRACTION: Two investigators independently extracted patient and study protocol characteristics and rated methodological quality; differences were resolved by consensus or by a third reader. Multivariate random-effects models were used to obtain pooled estimates. DATA SYNTHESIS: 16 studies, comprising 960 patients, were found (7 studies of single-source, 64-slice CT; 4 of dual-source, 64-slice CT; 2 of single-source, 320-slice CT; 1 dual-source, 128-slice CT; 1 of single-source, 128-slice CT; and 1 of single-source, 256-slice CT). On average, 2.4% of the coronary arterial segments were of nondiagnostic image quality, and 1 or more segments were nondiagnostic in 9.5% of the patients. The patient-level sensitivity and specificity of CT angiography were 1.00 (95% CI, 0.98 to 1.00) and 0.89 (CI, 0.85 to 0.92), respectively. The pooled vessel- and segment-level estimates showed lower sensitivity and higher specificity than the patient-level estimates. Statistically significant heterogeneity was found between studies for vessel- and segment-level estimates, which seemed to be associated with body mass index and prevalence of CAD but not with CT scanner characteristics. LIMITATIONS: The small number of studies, half of which were from a single tertiary center, limits generalizability. The potential harms of the imaging tests were not well-evaluated. CONCLUSION: Early evidence suggests that low-dose coronary CT angiography matches the sensitivity of catheter-based angiography, has low radiation exposure, and is a potentially valid alternative to catheter angiography for triaging symptomatic patients with a clinical suspicion of CAD. PRIMARY FUNDING SOURCE: None.

Paracrine factors secreted by endothelial progenitor cells prevent oxidative stress-induced apoptosis of mature endothelial cells.

Endothelial progenitor cells (EPC) play a fundamental role in tissue regeneration and vascular repair. Current research suggests that EPC are more resistant to oxidative stress as compared to differentiated endothelial cells. Here we hypothesized that EPC not only possess the ability to protect themselves against oxidative stress but also confer this protection upon differentiated endothelial cells by release of paracrine factors. To test this hypothesis, HUVEC incubated with conditioned medium obtained from early EPC cultures (EPC-CM) were exposed to H2O2 to assess the accumulation of intracellular ROS, extent of apoptosis and endothelial cell functionality. Under oxidative stress conditions HUVEC treated with EPC-CM exhibited substantially lower levels of intracellular oxidative stress (0.2+/-0.02 vs. 0.4+/-0.03 relative fluorescence units, p<0.05) compared to control medium. Moreover, the incubation with EPC-CM elevated the expression level of antioxidant enzymes in HUVEC (catalase: 2.6+/-0.4; copper/zinc superoxide dismutase (Cu/ZnSOD): 1.6+/-0.1; manganese superoxide dismutase (MnSOD): 1.4+/-0.1-fold increase compared to control, all p<0.05). Furthermore, EPC-CM had the distinct potential to reverse the functional impairment of HUVEC as measured by their capability to form tubular structures in vitro. Finally, incubation of HUVEC with EPC-CM resulted in a significant reduction of apoptosis (0.34+/-0.01 vs. 1.52+/-0.12 relative fluorescence units, p<0.01) accompanied by an increased expression ratio of the anti/pro-apoptotic factors Bcl-2/Bax to 2.9+/-0.7-fold (compared to control, p<0.05). Most importantly, neutralization of selected cytokines such as VEGF, HGF, IL-8 and MMP-9 did not significantly reverse the cyto-protective effect of EPC-CM (p>0.05), suggesting that soluble factors secreted by EPC, possibly via broad synergistic actions, exert strong cyto-protective properties on differentiated endothelium through modulation of intracellular antioxidant defensive mechanisms and pro-survival signals.

Call for a reference model of chronic hind limb ischemia to investigate therapeutic angiogenesis.

A large number of studies utilize animal models to investigate therapeutic angiogenesis. However, the lack of a standardized experimental model leaves the comparison of different studies problematic. To establish a reference model of prolonged moderate tissue ischemia, we created unilateral hind limb ischemia in athymic rnu-rats by surgical excision of the femoral vessels. Blood flow of the limb was monitored for 60 days by laser Doppler imaging. Following a short postoperative period of substantially depressed perfusion, the animals showed a status of moderate hind limb ischemia from day 14 onwards. Thereafter, the perfusion remained at a constant level (55.5% of normal value) until the end of the observation period. Histopathological assessment of the ischemic musculature on postoperative days 28 and 60 showed essentially no inflammatory cell infiltrate or fibrosis. However, the mitochondrial activity and capillary-to-fiber ratio of the muscular tissue was reduced to 52.7% of normal, presenting with a significant weakness of the ischemic limb evidenced by a progressive decline in performance. Intramuscular injection of culture-expanded human endothelial progenitor cells (EPC) resulted in a significant increase in blood flow (82.0+/-3.5% of normal), capillary density (1.60+/-0.08/muscle fiber) and smooth muscle covered arterioles (8.0+/-0.6/high power field) in the ischemic hind limb as compared to controls (55.0+/-3.1%; 0.99+/-0.03; 5.0+/-0.2). In conclusion, chronic, moderate hind limb ischemia with consistently reduced perfusion levels persisting over a prolonged period can be established reliably in rnu athymic nude rats and is responsive to pro-angiogenic treatments such as EPC transplantation. This study provides a detailed protocol of a highly reproducible reference model to test novel therapeutic options for limb ischemia.

Cell-based therapy facilitates venous thrombus resolution.

Endothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 +/- 26.7/HPF vs. 78 +/- 12.3/HPF, p<0.01; area covered by capillaries: 8.9 +/- 1.7 microm(2) vs. 2.5 +/- 1.3 microm(2), p<0.01) and was accompanied by a substantial increase in intra-thrombus blood flow (perfusion ratio: 0.7 +/- 0.07 vs. 0.3 +/- 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 +/- 4.7/HPF vs. 11.6 +/- 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.