Coronary microvascular dysfunction in patients with Takotsubo syndrome.

BACKGROUND: The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. OBJECTIVES: We sought to evaluate CMD in patients with TTS. METHODS: Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. RESULTS: Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). CONCLUSION: CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

Conduction disorders following transcatheter aortic valve replacement using acurate Neo2 transcatheter heart valve: A propensity matched analysis.

BACKGROUND: The ACURATE neo2 transcatheter aortic valve was developed to improve paravalvular leak (PVL) rates while maintaining low rates of conduction disturbances and permanent pacemaker implantation (PPMI) seen with its predecessor. We aimed to compare conduction disturbances rates of transcatheter aortic valve replacement (TAVR) using ACURATE Neo2 with other commonly used valves. METHODS: A retrospective analysis of the Israeli TAVR registry between the years 2014-2023 was performed to compare conduction disturbances and PVL rates, and procedural outcomes, among patients treated with ACURATE neo2, Edwards Sapien 3 (S3), and Evolut PRO valves. Propensity score matching was performed to compare groups with similar characteristics. RESULTS: Following exclusion of patients with non-femoral access, unknown valve type, older-generation valves, and less commonly used valves or (n = 4387), our analysis included 3208 patients undergoing TAVR using ACURATE neo2, Edwards S3, and Evolut PRO valves. Propensity matched groups comprised 169 patients each. Rates of any conduction disturbances [left bundle branch block (LBBB), atrioventricular block, or PPMI] were lower in the ACURATE neo2 group compared to both other valves [15.8 %, S3-37.5 % (p < 0.001), Evolut PRO-27.5 % (p = 0.02)] as were LBBB rates [9.0 %, S3-31.3 % (p < 0.001); Evolut PRO-20.1 % (p = 0.01). Atrioventricular block and PPMI rates were lower without statistical significance, as were rates of above-moderate PVL. CONCLUSIONS: In this analysis, TAVR using ACURATE neo2 was associated with a lower composite rate of conduction disturbances in comparison to the Evolut PRO and Edwards S3 valves, mainly due to lower left bundle branch block rates, with non-significantly lower rates of PPMI and PVL.

Traditional Cardiovascular Risk Factors and Coronary Microvascular Dysfunction in Women and Men: A Single-Center Study.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex-associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. METHODS: In this single-center, prospective registry, we enrolled patients with nonobstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. RESULTS: Overall, 245 patients with nonobstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range: 59, 75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p = 0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (ß = -0.29; p < 0.01 and ß = -0.15; p = 0.05, respectively) and lower resistive reserve ratio (ß = -0.28; p < 0.01 and ß = -0.17; p = 0.04, respectively). CONCLUSION: For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

First-Phase Ejection Fraction and Long-Term Survival in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Early recognition of deteriorating left ventricular function plays a key prognostic role in patients with aortic stenosis (AS). First-phase ejection fraction (EF1), the ejection fraction (EF) up to time of maximal contraction, has been suggested for detection of early left ventricular dysfunction in patients with AS with preserved EF. This work aims to evaluate the predictive value of EF1 for assessment of long-term survival in patients with symptomatic severe AS and preserved EF who undergo transcatheter aortic valve implantation (TAVI). We included 102 consecutive patients (median age 84 years [interquartile range 80 to 86 years]) who underwent TAVI between 2009 and 2011. Patients were retrospectively stratified into tertiles by EF1. Device success and procedural complications were defined according to the Valve Academic Research Consortium-3 criteria. Mortality data were retrieved from a computerized interface of the Israeli Ministry of Health. Baseline characteristics, co-morbidities, clinical presentation, and echocardiographic findings were similar among groups. The groups did not differ significantly regarding device success and in-hospital complications. During a potential follow-up period of >10 years, 88 patients died. Kaplan-Meier analysis (log-rank p = 0.017) followed by multivariable Cox regression analysis showed that EF1 predicted long-term mortality independently, either as continuous variable (hazard ratio 1.04, 95% confidence interval 1.01 to 1.07, p = 0.012) or for each decrease in tertile group (hazard ratio 1.40, 95% confidence interval 1.05 to 1.86, p = 0.023). In conclusion, low EF1 is associated with a significant decrease in adjusted hazard for long-term survival in patients with preserved EF who undergo TAVI. Low EF1 might delineate a population at great risk who would benefit from prompt intervention.

Vascular Complications in Transcatheter Aortic Valve Replacement With Plug-Based vs Suture-Based Closure Devices.

BACKGROUND: There are conflicting data regarding the efficacy and safety of suture vs plug-based vascular closure devices (VCDs) for large-bore catheter management in patients undergoing transcatheter aortic valve replacement (TAVR). We compared the rates of vascular complications (VCs) associated with 2 commonly used VCDs in a large cohort of patients undergoing TAVR. METHODS: We conducted a single-centre, all-comer, prospective registry study, enrolling patients undergoing TAVR for symptomatic severe aortic stenosis (AS) between the years 2009 and 2022. Clinical outcomes were compared between patients undergoing closure of the femoral access point using the MANTA VCD (M-VCD) (Teleflex, Wayne, PA) vs the ProGlide VCD (P-VCD) (Abbott Vascular, Abbott Park, IL). The main outcome measures were researcher adjudicated events of VARC-2 defined major and minor VCs. RESULTS: Overall, 2368 patients were enrolled in the registry; 1315 (51.0% male, 81.0 ± 7.0 years) patients were included in the current analysis. P-VCD was used in 813 patients, whereas M-VCD was used in 502 patients. In-hospital VCs were more frequent in the M-VCD vs the P-VCD group (17.3% vs 9.8%; P < 0.001). This outcome was mainly driven by elevated rates of minor VCs in the M-VCD group, whereas no significant difference was observed for major VCs (15.1% vs 8.4%; P < 0.001 and 2.2% vs 1.5%; P = 0.33, respectively). CONCLUSIONS: In patients undergoing TAVR for severe AS, M-VCD was associated with higher rates of VCs. This outcome was mainly driven by minor VCs. The rate of major VCs was low in both groups.

Does the use of polymer-free drug eluting stents improve clinical outcomes of patients undergoing percutaneous coronary interventions?

BACKGROUND: Implantation of drug eluting stents (DES) is the mainstay treatment for patients requiring percutaneous coronary intervention (PCI). The polymer coating of DES has been associated with inflammatory response, increased arterial injury and long-term in-stent restenosis and thrombosis. Polymer-free stents (PFS) were designed to overcome limitations of polymer-coated stents (PCS). Our aim was to compare clinical outcomes of patients undergoing PCI with PFS versus contemporary PCS. METHODS: This is a prospective, open-label registry study enrolling consecutive all-comers patients admitted to a single center and undergoing PCI using contemporary DES. Clinical outcomes were compared between patients treated with PFS and PCS. The primary endpoint was target lesion revascularization (TLR) at 12 months. Subgroup analyses were conducted for diabetic and nondiabetic patients. RESULTS: Overall, 1664 patients were included: 928 (55.8%) of which were treated with PFS and 736 (44.2%) with PCS for 2046 and 1462 lesions, respectively. At 12 months, TLR rates were not significantly different between the groups (1.7% vs. 2.3% for PFS and PCS, respectively, P = 0.48). The use of PFS did not improve clinical outcomes among diabetic patients in comparison with PCS. Target vessel revascularization and major adverse cardiac events rates were also similar between groups, regardless of diabetes status. CONCLUSION: Newer generation DES offer excellent results in diabetic and nondiabetic patients without significant differences in outcomes between PCS and PFS.

Impact of Valve Size on Paravalvular Leak and Valve Hemodynamics in Patients With Borderline Size Aortic Valve Annulus.

Background: Transcatheter heart valve (THV) selection for transcatheter aortic valve implantation (TAVI) is crucial to achieve procedural success. Borderline aortic annulus size (BAAS), which allows a choice between two consecutive valve sizes, is a common challenge during device selection. In the present study, we evaluated TAVI outcomes in patients with BAAS according to THV size selection. Methods: We performed a retrospective study including patients with severe aortic stenosis (AS) and BAAS, measured by multi-detector computed tomography (MDCT), undergoing TAVI with self-expandable (SE) or balloon-expandable (BE) THV from the Israeli multi-center TAVI registry. The aim was to evaluate outcomes of TAVI, mainly paravalvular leak (PVL) and valve hemodynamics, in patients with BAAS (based on MDCT) according to THV sizing selection in between 2 valve sizes. In addition, to investigate the benefit of shifting between different THV types (BE and SE) to avoid valve size selection in BAAS. Results: Out of 2,352 patients with MDCT measurements, 598 patients with BAAS as defined for at least one THV type were included in the study. In BAAS patients treated with SE-THV, larger THV selection was associated with lower rate of PVL, compared to smaller THV (45.3 vs. 64.5%; pv = 0.0038). Regarding BE-THV, larger valve selection was associated with lower post-procedural transvalvular gradients compared to smaller THV (mean gradient: 9.9 ± 3.7 vs. 12.5 ± 7.2 mmHg; p = 0.019). Of note, rates of mortality, left bundle branch block, permanent pacemaker implantation, stroke, annular rupture, and/or coronary occlusion did not differ between groups. Conclusion: BAAS is common among patients undergoing TAVI. Selection of a larger THV in these patients is associated with lower rates of PVL and optimized THV hemodynamics with no effect on procedural complications. Additionally, shift from borderline THV to non-borderline THV modified both THV hemodynamics and post-dilatation rates.

Outcomes of Patients Undergoing PCI of Ostial Coronary Lesions: A Single-Center Study.

INTRODUCTION: Ostial coronary lesions are a subset of proximal coronary lesions, which are relatively more difficult to treat and were associated with worse clinical outcomes in the early percutaneous coronary intervention (PCI) era. Data regarding the outcomes of ostial lesions' PCI in the contemporary era are lacking. METHODS: We conducted a single-center, all-comer, prospective registry study, enrolling patients undergoing PCI with the use of contemporary drug-eluting stents (DES) between July 2016 and February 2018. Included in the present analysis were only patients treated for proximal lesions. Clinical outcomes were compared between patients undergoing PCI of ostial versus proximal nonostial lesions. The primary endpoint was target vessel revascularization (TVR). Secondary endpoints included target lesion revascularization (TLR) and major cardiovascular adverse events (MACE) at 12 months. RESULTS: A total of 334 (84.7% male, 67.3 ± 10.7 years) patients were included, of which 91 patients were treated for ostial lesions and 243 were treated for proximal nonostial lesions. Baseline and procedural characteristics were similar between the two groups. At 12 months, TVR and TLR were numerically higher among patients undergoing PCI of ostial versus nonostial lesions without reaching statistical significance (5.5% vs. 3.3%; p = 0.35 and 4.4% vs. 2.5%; p = 0.47, respectively). The rate of MACE was similar between the two groups. CONCLUSION: In patients undergoing PCI with the use of contemporary DES, clinical outcomes were similar among patients treated for ostial compared to proximal nonostial lesions. Larger studies are required to further evaluate the performance of contemporary DES in this subset of lesions.

Arrhythmic storm from ischemic ventricular fibrillation treated with intravenous quinidine.

We present a case who developed an acute right ventricular infarction. The leads demonstrating ST-segment elevation were different than those expected based on previous publications. We explain why this happened with the aid of 3-dimentional imaging. Our case then developed an arrhythmic storm caused by ischemic ventricular fibrillation (VF). Emergency revascularization failed and the VF-storm failed to respond to sedation, lidocaine and amiodarone but responded to intravenous quinidine.

Double S-Curve Versus Cusp-Overlap Technique: Defining the Optimal Fluoroscopic Projection for TAVR With a Self-Expanding Device.

OBJECTIVES: The purpose of this study was to assess the concordance between transcatheter aortic valve implantation angles generated by the "double S-curve" and "cusp-overlap" techniques. BACKGROUND: The "double S-curve" and "cusp-overlap" methods aim to define optimal fluoroscopic projections for transcatheter aortic valve replacement (TAVR) with a self-expandable device. METHODS: The study included 100 consecutive patients undergoing TAVR with self-expanding device planned by multidetector computed tomography. TAVR was performed using the double S-curve model, as a view in which both the aortic valve annulus and delivery catheter planes are displayed perpendicularly on fluoroscopy. Optimal projection according to the cusp-overlap technique was retrospectively generated by overlapping the right and left cups on the multidetector computed tomography annular plane. The angular difference between methods was assessed in spherical 3 dimensions and on the left and right anterior oblique (RAO) and cranial and caudal (CAU) axes. RESULTS: The double S-curve and cusp-overlap methods provided views located in the same quadrant, mostly the RAO and CAU, in 92% of patients with a median 3-dimensional angular difference of 10.0° (interquartile range: 5.5° to 17.9°). The 3-dimensional deviation between the average angulation obtained by each method was not statistically significant (1.49°; p = 0.349). No significant differences in average coordinates were noted between the double S-curve and cusp-overlap methods (RAO: 14.7 ± 15.2 vs. 12.9 ± 12.5; p = 0.36; and CAU: 27.0 ± 9.4 vs. 26.9 ± 10.4; p = 0.90). TAVR using the double S-curve was associated with 98% device success, low complication rate, and absence of moderate-to-severe paravalvular leak. CONCLUSIONS: The double S-curve and cusp-overlap methods provide comparable TAVR projections, mostly RAO and CAU. TAVR using the double S-curve model is associated with a high rate of device success and low rate of procedural complications.

The impact of normal range estimated glomerular filtration rate on mortality in selected patients undergoing coronary angiography - a long-term follow-up.

BACKGROUND: Estimated glomerular filtration rate (eGFR) predicts mortality and adverse cardiovascular events in people with chronic kidney disease. The significance of eGFR within the normal range and its long-term effect on clinical adverse events is unknown. We examined the effect of normal range or mildly reduced eGFR on long-term mortality in a large prospective registry. METHODS: The study included consecutive patients undergoing clinically-driven coronary angiography who had an eGFR ≥60 ml/min/1.73 m2. Baseline clinical characteristics were assessed, and patients were followed-up for the occurrence of all-cause mortality. Cox regression analysis was used to evaluate the impact of eGFR. RESULTS: A total of 4186 patients were recruited. Median follow-up time was 2883 days (7.9 years). Mean age was 62.0 ± 11.3 years with 77.4% males. Clinical presentation included acute coronary syndrome and stable angina. In a multivariable model adjusted for possible confounding factors, decreasing eGFR within the normal and mildly reduced range was inversely associated with long-term all-cause mortality with a hazard ratio (HR) of 1.32 for every decrease of 10 ml/min/1.732 in eGFR. Compared to eGFR > 100 ml/min/1.732, there was a graded association between lower eGFR values and increased long term mortality with a HR of 1.16 (0.59-2.31) for eGFR 90-100 ml/min/1.732, HR 1.54 (0.81-2.91) for eGFR 80-90 ml/min/1.732, HR 2.62 (1.41-4.85) for eGFR 70-80 ml/min/1.732 and HR 2.93 (1.58-5.41) for eGFR 60-70 ml/min/1.732. CONCLUSION: eGFR within the normal and mildly reduced range is an independent predictor of long-term all-cause mortality in selected patients undergoing clinically driven coronary angiography.

Optimal Fluoroscopic Projections of Coronary Ostia and Bifurcations Defined by Computed Tomographic Coronary Angiography.

OBJECTIVES: The aim of this study was to define the optimal fluoroscopic viewing angles of both coronary ostia and important coronary bifurcations by using 3-dimensional multislice computed tomographic data. BACKGROUND: Optimal fluoroscopic projections are crucial for coronary imaging and interventions. Historically, coronary fluoroscopic viewing angles were derived empirically from experienced operators. METHODS: In this analysis, 100 consecutive patients who underwent computed tomographic coronary angiography (CTCA) for suspected coronary artery disease were studied. A CTCA-based method is described to define optimal viewing angles of both coronary ostia and important coronary bifurcations to guide percutaneous coronary interventions. RESULTS: The average optimal viewing angle for ostial left main stenting was left anterior oblique (LAO) 37°, cranial (CRA) 22° (95% confidence interval [CI]: LAO 33° to 40°, CRA 19° to 25°) and for ostial right coronary stenting was LAO 79°, CRA 41° (95% CI: LAO 74° to 84°, CRA 37° to 45°). Estimated mean optimal viewing angles for bifurcation stenting were as follows: left main: LAO 0°, caudal (CAU) 49° (95% CI: right anterior oblique [RAO] 8° to LAO 8°, CAU 43° to 54°); left anterior descending with first diagonal branch: LAO 11°, CRA 71° (95% CI: RAO 6° to LAO 27°, CRA 66° to 77°); left circumflex bifurcation with first marginal branch: LAO 24°, CAU 33° (95% CI: LAO 15° to 33°, CAU 25° to 41°); and posterior descending artery and posterolateral branch: LAO 44°, CRA 34° (95% CI: LAO 35° to 52°, CRA 27° to 41°). CONCLUSIONS: CTCA can suggest optimal fluoroscopic viewing angles of coronary artery ostia and bifurcations. As the frequency of use of diagnostic CTCA increases in the future, it has the potential to provide additional information for planning and guiding percutaneous coronary intervention procedures.

Correction: Cardiac remodeling secondary to chronic volume overload is attenuated by a novel MMP9/2 blocking antibody.

[This corrects the article DOI: 10.1371/journal.pone.0231202.].

Predictors of Outcomes Following Transcatheter Edge-to-Edge Mitral Valve Repair.

Transcatheter edge-to-edge mitral valve repair is a viable alternative to surgery in patients with severe mitral regurgitation and high surgical risk. Yet the specific group of patients who would optimally benefit from this therapy remains to be determined. Selection of patients for transcatheter strategy is currently based on surgical prognostic scores and technical feasibility. Meanwhile, various clinical, anatomic, and procedural factors have been recently recognized as predictors of adverse outcomes following transcatheter edge-to-edge mitral valve repair, including device failure, recurrent mitral regurgitation, and mortality. Integration of these prognostic factors in the decision-making process of the heart team might improve patient management and outcomes. Herein, the authors review the different factors related to symptomatic status, comorbidity, serum biomarkers, echocardiographic findings, and procedural technique that have been identified as independent predictors of adverse outcome following transcatheter edge-to-edge mitral valve repair and discuss their potential application in everyday clinical practice.

Cardiac remodeling secondary to chronic volume overload is attenuated by a novel MMP9/2 blocking antibody.

OBJECTIVE: Monoclonal antibody derivatives are promising drugs for the treatment of various diseases due to their high matrix metalloproteinases (MMP) active site specificity. We studied the effects of a novel antibody, SDS3, which specifically recognizes the mature active site of MMP9/2 during ventricular remodeling progression in a mouse model of chronic volume overload (VO). METHODS: VO was induced by creating an aortocaval fistula (ACF) in 10- to 12-week-old C57BL male mice. The VO-induced mice were treated with either vehicle control (PBS) or with SDS3 twice weekly by intraperitoneal (ip) injection. The relative changes in cardiac parameters between baseline (day 1) and end-point (day 30), were evaluated by echocardiography. The effects of SDS3 treatment on cardiac fibrosis, cardiomyocyte volume, and cardiac inflammation were tested by cardiac staining with Masson's trichrome, wheat Germ Agglutinin (WGA), and CD45, respectively. Serum levels of TNFα and IL-6 with and without SDS3 treatment were tested by ELISA. RESULTS: SDS3 significantly reduced cardiac dilatation, left ventricular (LV) mass, and cardiomyocyte hypertrophy compared to the vehicle treated animals. The antibody also reduced the heart-to-body weight ratio of the ACF animals to values comparable to those of the controls. Interestingly, the SDS3 group underwent significant reduction of cardiac inflammation and pro-inflammatory cytokine production, indicating a regulatory role for MMP9/2 in tissue remodeling, possibly by tumor necrosis factor alpha (TNFα) activation. In addition, significant changes in the expression of proteins related to mitochondrial function were observed in ACF animals, these changes were reversed following treatment with SDS3. CONCLUSION: The data suggest that MMP9/2 blockage with SDS3 attenuates myocardial remodeling associated with chronic VO by three potential pathways: downregulating the extracellular matrix proteolytic cleavage, reducing the cardiac inflammatory responses, and preserving the cardiac mitochondrial structure and function.