Transcatheter Treatment of Mitral Valve Regurgitation in the Setting of Concomitant Coronary or Multivalvular Heart Disease: A Focused Review.

Treatment for mixed valve disease has historically been limited, often surgery being the only option. With the recent advancement of transcatheter therapies, percutaneous approaches are quickly becoming viable therapeutic considerations in inoperable or high-risk patients, also offering the option for a staged or same-session treatment. Guidelines are primarily focused on single-valve disease. However, patients often present with multiple pathologies. This review summarizes the data and literature on transcatheter treatment of patients with mitral regurgitation who concomitantly have aortic stenosis or regurgitation, tricuspid regurgitation, or ischemic cardiomyopathy. Pathophysiology, hemodynamics, available therapies as well as order and timing of interventions are discussed.

Shortened Duration of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Contemporary Clinical Review.

Percutaneous coronary intervention with stent implantation is an integral aspect of minimally interventional cardiac procedures. The technology and techniques behind stent design and implantation have evolved rapidly over several decades. However, continued discourse remains around optimal peri- and post-interventional management with dual antiplatelet therapy to minimise both major cardiovascular or cerebrovascular events and iatrogenic bleeding risk. Standard guidelines around dual antiplatelet therapy historically recommended long-term dual antiplatelet therapy for 12 months (with consideration for >12 months in certain patients); however, emerging data and generational improvements in the safety of drug-eluting stents have ushered in a new era of short-term therapy to reduce the incidence of major bleeding events. This case review will provide an overview of the current state of guidelines around duration of dual antiplatelet therapy and examine recent updates and continued gaps in existing research.

Safety and efficacy of minimalist transcatheter aortic valve implantation using a new-generation balloon-expandable transcatheter heart valve in bicuspid and tricuspid aortic valves.

BACKGROUND: Bicuspid aortic valve may be associated with increased complications during transcatheter aortic valve implantation (TAVI). AIMS: Compare balloon-expandable transcatheter heart valve (THV) safety and efficacy in severe tricuspid (TAV) and bicuspid (BAV) aortic stenosis. METHODS: Transfemoral TAVI was performed in 743 patients (Jan 2014-June 2019) using the SAPIEN 3 THV. Aortic valve morphology was determined using computed tomography. Valve Academic Research Consortium-2 (VARC-2) derived safety and efficacy endpoints at 1 year were evaluated. RESULTS: BAV patients (n = 78), were younger (77 [72, 81] vs. 81 [78, 85] years, p < 0.001) with lower surgical risk (EuroSCORE II 2.96% vs. 4.51% p < 0.001). Bicuspid valves were more calcified (BAV 1308mm3, TAV 848mm3 p < 0.001) with more asymmetric calcification (BAV 63/78 (81%), TAV 239/665 (36%), p < 0.001). Device success (BAV 94%, TAV 90%, p = 0.45) and major vascular complications (BAV 6%, TAV 9%, p = 0.66) were comparable. At 1 year, there was a trend toward lower combined all-cause mortality and rehospitalization for congestive heart failure in BAV patients (BAV 7%, TAV 13%, p = 0.08) with significantly lower all-cause mortality in this cohort (BAV 1%, TAV 9%, p = 0.020). VARC-2 time-related valve safety (BAV 22%, TAV 20%, p = 0.60) was comparable; however, bioprosthetic valve thrombosis remained more common in BAV patients (BAV 7%, TAV 2%, p = 0.010, Hazard ratio 3.57 [95% confidence interval 1.26, 10.10]). After propensity score matching, only bioprosthetic valve thrombosis remained significantly different. CONCLUSIONS: Safety and efficacy of the SAPIEN 3 balloon-expandable THV in BAV is comparable with TAV. Higher rates of bioprosthetic valve thrombosis require further investigation.

Evaluation of a Low-Dose Radiation Protocol During Transcatheter Aortic Valve Implantation.

We aimed to evaluate the efficacy and safety of a low-dose imaging protocol to reduce intraprocedural radiation during transcatheter aortic valve implantation (TAVI). Observational analysis: 802 transfemoral TAVI patients receiving balloon-expandable devices ≥23 mm at a high-volume centre. After propensity score matching, a standard-dose group (SD, n = 333) treated between January 2014 and February 2016 was compared with a low-dose group (LD, n = 333) treated between August 2017 and March 2019 after departmental uptake of a low-dose imaging protocol (reduced field size, high table height, use of "fluoro save," 3.75 frames/second acquisition, increased filtering). Primary end point was dose-area product (DAP). Secondary safety end points were VARC-2 device success and a composite of in-hospital complications. The LD protocol was associated with lower DAP (4.64 [2.93, 8.42] vs 22.73 [12.31, 34.58] Gy⋅cm2, p <0.001) and fluoroscopy time (10.4 [8.1, 13.9] vs 11.5 [9.1, 15.3] minutes, p = 0.001). Contrast use was higher in the LD group (LD 110 [94, 130] vs SD 100 [80, 135] milliliters, p = 0.042). Device success (LD 88.3% vs SD 91.3%, p = 0.25), and the composite end point (LD 8.1% vs SD 11.4%, p = 0.19) were similar. In multivariate analysis, the low-dose protocol was associated with a 19.8 Gy⋅cm2 reduction in procedural DAP (p <0.001). In conclusion, compared with standard imaging, a low-dose protocol for TAVI significantly reduced radiation dose without compromising outcomes.

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry.

AIMS: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). METHODS AND RESULTS: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. CONCLUSION: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Predictors of Left Ventricular Outflow Tract Obstruction After Transcatheter Mitral Valve Replacement.

OBJECTIVES: The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR). BACKGROUND: LVOT obstruction is a major concern with TMVR, but limited data exist regarding its predictors and impact on outcomes. METHODS: Patients with pre-procedural multidetector row computed tomography (MDCT) undergoing TMVR for failed mitral bioprosthetic valves (valve-in-valve), annuloplasty rings (valve-in-ring), and mitral annular calcification (valve-in-MAC) were included in this study. Echocardiographic and procedural characteristics were recorded, and comprehensive assessment with MDCT was performed to identify the predictors of LVOT obstruction (defined as an increment of mean LVOT gradient ≥10 mm Hg from baseline). The new LVOT (neo-LVOT) area left after TMVR was estimated by embedding a virtual valve into the mitral annulus on MDCT, simulating the procedure. RESULTS: Among 194 patients with pre-procedural MDCT undergoing TMVR (valve-in-valve, 107 patients; valve-in-ring, 50 patients; valve-in-MAC, 37 patients), LVOT obstruction was observed in 26 patients (13.4%), with a higher rate after valve-in-MAC than valve-in-ring and valve-in-valve (54.1% vs. 8.0% vs. 1.9%; p < 0.001). Patients with LVOT obstruction had significantly higher procedural mortality compared with those without LVOT obstruction (34.6% vs. 2.4%; p < 0.001). Receiver-operating characteristic curve analysis showed that an estimated neo-LVOT area ≤1.7 cm2 predicted LVOT obstruction with sensitivity of 96.2% and specificity of 92.3%. CONCLUSIONS: LVOT obstruction after TMVR was associated with higher procedural mortality. A small estimated neo-LVOT area was significantly associated with LVOT obstruction after TMVR and may help identify patients at high risk for LVOT obstruction.

Aortic annulus sizing in stenotic bicommissural non-raphe-type bicuspid aortic valves: reconstructing a three-dimensional structure using only two hinge points.

Bicuspid aortic valve (BAV) anatomy is becoming an increasingly frequently encountered challenge in transcatheter aortic valve implantation (TAVI). Bicommissural non-raphe-type BAV (Sievers and Schmidtke Type 0) is composed morphologically of two aortic cusps with no raphe and is less common than the tricommissural or bicommissural raphe-type configurations. Precise annular sizing is a key step for successful TAVI in BAV. The challenge in bicommissural non-raphe-type BAV is that a three-dimensional structure has to be reconstructed using only two anatomical hinge points. For this reason, available software are limited when it comes to bicommissural non-raphe-type BAV. We propose that manual assessment of the aortic root in bicommissural non-raphe-type BAV using multi-planar reconstruction (MPR) software can be performed successfully by aligning the two available hinge points and measuring the smallest identifiable annular dimensions in the transverse plane (Fig. 1). We identified 12 patients with bicommissural non-raphe-type BAV undergoing TAVI between January 2013 and December 2017 in our high-volume institution. Our novel sizing strategy was employed prospectively in three patients-with good clinical outcomes-and evaluated retrospectively in the remainder (Table 1). No patient suffered a central major vascular complication or required new permanent pacemaker implantation. Device success occurred in all patients except one (post-procedural echocardiographic transvalvular gradient of 23 mmHg). In the retrospectively assessed cases, the novel annulus measure was concordant with the implanted THV size in 7 out of 9 procedures and, importantly, did not overestimate the annulus dimensions in any case. Furthermore, in two balloon-expandable THV cases the new measure may, in retrospect, have prompted consideration of a smaller implant size. To be noted, balloon sizing of the aortic annulus has additional value when selecting the valve size in BAV anatomy. Further prospective validation of this novel MDCT sizing technique is required.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Prognostic Value of SYNTAX Score II in Patients with Acute Coronary Syndromes Referred for Invasive Management: A Subanalysis from the SPUM and COMFORTABLE AMI Cohorts.

AIMS: To assess the incremental prognostic value of SYNTAX score II (SxSII) as compared to anatomical SYNTAX Score (SxS) and GRACE risk score in patients with acute coronary syndromes who underwent percutaneous coronary intervention. METHODS AND RESULTS: SxSII and SxS were determined in 734 ACS patients. Patients were enrolled in the prospective Special Program University Medicine ACS and the COMFORTABLE AMI cohorts and later on stratified according to tertiles of SxSII (SxSIILow ≤21.5 (n=245), SxSIIMid 21.5-30.6 (n=245), and SxSIIHigh ≥30.6 (n=244). The primary endpoint of adjudicated all-cause mortality and secondary endpoints of MACE (cardiac death, repeat revascularization, and myocardial infarction) and MACCE (all-cause mortality, cerebrovascular events, MI, and repeat revascularization) were determined at 1-year follow-up. SxSII provided incremental predictive information for risk stratification when compared to SxS and GRACE risk score (AUC 0.804, 95% CI 0.77-0.84, p < 0.001 versus 0.67, 95% CI 0.63-0.72, p=0.007 versus 0.69, 95% CI 0.6-0.8, p=0.002), respectively. In a multivariable Cox regression analysis, we found that unlike SxS (adjusted HR 1.013, 95% CI (0.96-1.07), p=0.654), SxSII was significantly associated with all-cause mortality (HR = 1.095, 95% CI (1.06-1.11), p < 0.001). This was also true for the prediction of both secondary outcomes MACE (n=60) and MACCE (n=70) with an adjusted HR = 1.055, 95% CI (1.03-1.08), p < 0.001, and HR = 1.065, 95% CI (1.04-1.09), p < 0.001. CONCLUSION: In patients with ACS who underwent PCI, SxSII is an independent predictor of mortality during 1-year follow-up. SxSII shows superiority in discriminating risk compared to conventional SxS and GRACE for all-cause mortality.

Long-term effectiveness and safety of transcatheter closure of patent foramen ovale compared with antithrombotic therapy alone: a meta-analysis of six randomised clinical trials and 3,560 patients with reconstructed time-to-event data.

AIMS: Although three recent trials have shown a significant stroke risk reduction after tPFOc, the individual statistical power is limited and the impact on pooled evidence needs to be explored. We aimed to pool data from available randomised clinical trials (RCT) to assess whether tPFOc is more effective and safe than antithrombotic therapy alone (ATA). METHODS AND RESULTS: Major electronic databases and tangential sources were searched. Six trials (3,560 patients) were identified. At a median follow-up of 3.6 (2.0-5.2) years (13,930 person-years), the risk of stroke was significantly lower after tPFOc compared with ATA (HR 0.28, 95% CI: 0.12-0.64, p=0.003). Significant heterogeneity was detected (I2=66.1%), although single trials did not significantly influence the results. Reconstructed time-to-event data revealed that tPFOc benefits accrue after approximately one year and persist over time without significant variations (96.4% versus 88.0%; HR 0.25, 95% CI: 0.09-0.66, p=0.005; NNT=11). Although results showed a greater benefit in patients <45 years old, male, and with substantial shunt, interaction between subgroups was not significant. Trial sequential analysis showed that accumulated evidence appeared to be sufficient. However, tPFOc did not confer protection against transient ischaemic attack (TIA; HR 0.69, 95% CI: 0.31-1.54, p=0.365) and a significant excess in the risk of atrial fibrillation was observed (OR 4.99, 95% CI: 1.99-10.10, p<0.001), though generally early and transient. Major bleeding and migraine were comparable between treatments. CONCLUSIONS: Compared with ATA, tPFOc significantly reduces the risk of stroke at long-term follow-up but no benefit is observed in terms of TIA. Atrial fibrillation is higher after tPFOc, though generally early and transient. The risks of major bleeding and migraine are comparable between the groups.

Transcatheter versus Surgical Aortic Valve Replacement after Previous Cardiac Surgery: A Systematic Review and Meta-Analysis.

AIM: Aortic valve replacement (AVR) in patients with prior cardiac surgery might be challenging. Transcatheter aortic valve replacement (TAVR) offers a promising alternative in such patients. We therefore aimed at comparing the outcomes of patients with aortic valve diseases undergoing TAVR versus those undergoing surgical AVR (SAVR) after previous cardiac surgery. METHODS AND RESULTS: MEDLINE, EMBASE, and the Cochrane Central Register were searched. Seven relevant studies were identified, published between 01/2011 and 12/2015, enrolling a total of 1148 patients with prior cardiac surgery (97.6% prior CABG): 49.2% underwent TAVR, whereas 50.8% underwent SAVR. Incidence of stroke (3.8 versus 7.9%, p=0.04) and major bleeding (8.3 versus 15.3%, p=0.04) was significantly lower in the TAVR group. Incidence of mild/severe paravalvular leakage (14.4/10.9 versus 0%, p < 0.0001) and pacemaker implantation (11.3 versus 3.9%, p=0.01) was significantly higher in the TAVR group. There were no significant differences in the incidence of acute kidney injury (9.7 versus 8.7%, p=0.99), major adverse cardiovascular events (8.7 versus 12.3%, p=0.21), 30-day mortality (5.1 versus 5.5%, p=0.7), or 1-year mortality (11.6 versus 11.8%, p=0.97) between the TAVR and SAVR group. CONCLUSIONS: TAVR as a redo procedure offers a safe alternative for patients presenting with aortic valve diseases after previous cardiac surgery especially those with prior CABG.

Interaction of systolic blood pressure and resting heart rate with clinical outcomes in takotsubo syndrome: insights from the International Takotsubo Registry.

AIMS: The present study aimed to determine the prognostic impact of resting heart rate (HR) and systolic blood pressure (SBP) in takotsubo syndrome (TTS). METHODS AND RESULTS: Patients from the International Takotsubo Registry with complete data on HR and SBP were enrolled. We analysed all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) in tertiles of HR (<77 b.p.m., 77-94 b.p.m., >94 b.p.m.) and SBP (<119 mmHg, 119-140 mmHg, >140 mmHg). In addition, linear splines with interactions between HR and SBP were analysed. The risk of all-cause mortality was higher in the second HR tertile (1.89, 1.15-3.10; P = 0.012) and the third HR tertile (3.01, 1.90-4.79; P < 0.001) than in the first tertile. Similar effects were observed for MACCE. Low SBP was related to an increased risk of all-cause mortality (P < 0.001) and MACCE (P = 0.002). In a multivariable analysis of all-cause mortality, at HR >70 b.p.m., every 1 b.p.m. increase in HR was associated with a 1.7% increase (P < 0.001), and every 1 mmHg increase in SBP up to 130 mmHg was associated with a 2% risk reduction (P < 0.001). The risk of all-cause mortality thus was particularly elevated when low SBP occurred together with high HR. CONCLUSIONS: High HR and low SBP are associated with an increased risk of all-cause mortality in TTS. HR reduction might be worthy of being investigated as a therapeutic strategy for this condition and high HR and low SBP can be used to evaluate risk in this acute presentation of TTS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01947621.