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Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.
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BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.
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BACKGROUND: Microvascular resistance reserve (MRR) has been proposed as a specific metric to quantify coronary microvascular function. The long-term prognostic value of MRR measured in stable patients immediately after percutaneous coronary intervention (PCI) is unknown. This study sought to determine the prognostic value of MRR measured immediately after PCI in patients with stable coronary artery disease. METHODS: This study included 502 patients with stable coronary artery disease who underwent elective PCI and coronary physiological measurements, including pressure and flow estimation using a bolus thermodilution method after PCI. MRR was calculated as coronary flow reserve divided by fractional flow reserve times the ratio of mean aortic pressure at rest to that at maximal hyperemia induced by hyperemic agents. An abnormal MRR was defined as ≤2.5. Major adverse cardiac events (MACEs) were defined as a composite of all-cause mortality, any myocardial infarction, and target-vessel revascularization. RESULTS: During a median follow-up of 3.4 years, the cumulative MACE rate was significantly higher in the abnormal MRR group (12.5 versus 8.3 per 100 patient-years; hazard ratio 1.53 [95% CI, 1.10-2.11]; P<0.001). A higher all-cause mortality rate primarily drove this difference. On multivariable analysis, a higher MRR value was independently associated with lower MACE and lower mortality. When comparing 4 subgroups according to MRR and the index of microcirculatory resistance, patients with both abnormal MRR and index of microcirculatory resistance (≥25) had the highest MACE rate. CONCLUSIONS: An abnormal MRR measured immediately after PCI in patients with stable coronary artery disease is an independent predictor of MACE, particularly all-cause mortality.
Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Microcirculation , Percutaneous Coronary Intervention , Predictive Value of Tests , Vascular Resistance , Humans , Male , Coronary Artery Disease/physiopathology , Coronary Artery Disease/mortality , Coronary Artery Disease/therapy , Coronary Artery Disease/diagnosis , Female , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Aged , Middle Aged , Treatment Outcome , Risk Factors , Time Factors , Thermodilution , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Retrospective Studies , Coronary Circulation , Coronary AngiographyABSTRACT
BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.
Subject(s)
Acetylcholine , Angina Pectoris , Coronary Artery Disease , Coronary Circulation , Coronary Vasospasm , Coronary Vessels , Predictive Value of Tests , Vasodilator Agents , Humans , Female , Male , Middle Aged , Aged , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Vasodilator Agents/administration & dosage , Coronary Vasospasm/physiopathology , Coronary Vasospasm/diagnosis , Acetylcholine/administration & dosage , Angina Pectoris/physiopathology , Angina Pectoris/diagnosis , Angina Pectoris/etiology , Coronary Artery Disease/physiopathology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Cardiac Catheterization , Coronary Angiography , Reproducibility of Results , Vasodilation , VasoconstrictionABSTRACT
Background: Certain patients with functional mitral regurgitation survive longer with fewer heart failure hospitalizations after undergoing transcatheter edge-to-edge repair (TEER); however, clinical markers identifying who will benefit have not been established. The 'proportionality' of mitral regurgitation (MR) severity compared to left ventricular size has been hypothesized to predict clinical outcome. Methods: We sought to combine existing studies to compare outcomes between 'proportionate' MR and 'disproportionate' MR in patients undergoing TEER. PubMed and Medline were searched from January 2018 until May 2023. Data was extracted and synthesized by 2 independent authors using random effects models with risk ratios (RRs) for binary outcomes. The primary outcome was a combined endpoint of all-cause mortality or heart failure hospitalization (ACM/HFH). Other outcomes of interest included ACM and residual >2+ MR after TEER. Results: Six trials with a total of 1594 patients (mean age 71 years, 66% male) were included, which assessed MR proportionality using either a ratio of estimated regurgitant orifice area to left ventricular end-diastolic volume (EROA:LVEDV) or regurgitant fraction. Seven hundred and five (mean age 70 years, 75% male) were classified as proportionate MR, and 889 (mean age 72 years, 60% male) had disproportionate MR. There was no significant association between MR proportionality (by EROA:LVEDV) and ACM (RR 0.79, 95% confidence interval [CI] 0.44-1.42). Proportionality did not significantly associate with ACM/HFH, though there were divergent effect signals when proportionality was measured by EROA:LVEDV (RR 0.80, 95% CI 0.45-1.44) or regurgitant fraction (RR 1.48, 95% CI 0.53-4.11). Disproportionate MR showed a greater association with residual MR > 2+ post-TEER that did not meet statistical significance (RR 1.86, 95% CI 0.77-4.49). Conclusions: In patients undergoing TEER for functional mitral regurgitation, MR proportionality was not significantly associated with ACM/HFH, all-cause mortality, or residual MR.
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Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2-/- mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2-/- and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.
Subject(s)
Angiogenesis , Endothelial Cells , Animals , Mice , Endothelial Cells/metabolism , Hindlimb/blood supply , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Inflammation/metabolism , Ischemia/metabolism , Neovascularization, Pathologic/metabolism , Neovascularization, Physiologic/geneticsABSTRACT
BACKGROUND/PURPOSE: This prospective, open-label, single-arm study evaluated transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis with ACURATE Prime XL, an iteration of the ACURATE neo2 device designed with improved radial force and adaptations for compatibility with a larger annulus diameter (≥ 26.5 mm and ≤ 29 mm based on pre-procedure diagnostic imaging). METHODS: The composite primary device success endpoint was based on Valve Academic Research Consortium (VARC)-2 criteria. The primary safety endpoint was a composite of all-cause mortality and all stroke at 30 days. Aortic valve (AV) performance, including mean AV gradient, AV area, and grade of paravalvular leak (PVL), was assessed by an independent core laboratory. RESULTS: 13 male patients were enrolled at 3 Australian centers (mean age: 83.1 years; 10 of 13 were considered high/extreme operative risk). 61.5 % of patients met the primary device success endpoint. At 30 days, no patients experienced death or stroke; one patient received a permanent pacemaker. Mean AV gradient improved from baseline (42.7 ± 11.0 mmHg) to discharge (7.7 ± 2.5 mmHg) and through 30 days (7.2 ± 2.3 mmHg). Mean AV area was 0.8 ± 0.1 cm2 at baseline, 1.9 ± 0.3 cm2 at discharge, and 1.7 ± 0.3 cm2 at 30 days. Per core-laboratory adjudication, no patient had moderate or severe PVL at 30 days; 91.7 % had no/trace PVL and 8.3 % had mild PVL. CONCLUSIONS AND RELEVANCE: In this first-in-human feasibility study of the ACURATE Prime XL valve, there were no safety concerns, and no deaths or strokes within 30 days. Valve hemodynamics were favorable, and no patient had >mild PVL.
Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Stroke , Transcatheter Aortic Valve Replacement , Aged, 80 and over , Humans , Male , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Australia , Feasibility Studies , Prospective Studies , Prosthesis Design , Stroke/etiology , Treatment OutcomeABSTRACT
Approximately 50% of patients with severe aortic stenosis (AS) in clinical practice present with 'low-gradient' haemodynamics. Stroke Volume Index (SVI) is a measure of left ventricular output, with 'normal-flow' considered as > 35 ml/m2. The association between SVI and prognosis in severe low-gradient AS (LGAS) in currently not well-understood. We analysed the National Echo Database of Australia (NEDA) and identified 109,990 patients with sufficiently comprehensive echocardiographic data, linked to survival information. We identified 1,699 with severe LGAS and preserved ejection fraction (EF) (≥ 50%) and 774 with severe LGAS and reduced EF. One- and three-year survival in each subgroup were assessed (follow-up of 74 ± 43 months), according to SVI thresholds. In patients with preserved EF the mortality "threshold" was at SVI < 30 ml/m2; 1- and 3-year survival was worse for those with SVI < 30 ml/m2 relative to those with SVI > 35 ml/m2 (HR 1.80, 95% CI 1.32-2.47 and HR 1.38, 95% CI 1.12-1.70), while survival was similar between those with SVI 30-35 ml/m2 and SVI > 35 ml/m2. In patients with reduced EF the mortality "threshold" was 35 ml/m2; 1- and 3-year survival was worse for both those with SVI < 30 ml/m2 and 30-35 ml/m2 relative to those with SVI > 35 ml/m2 (HR 1.98, 95% CI 1.27-3.09 and HR 1.41, 95% CI 1.05-1.93 for SVI < 30 ml/m2 and HR 2.02, 95% CI 1.23-3.31 and HR 1.56, 95% CI 1.10-2.21 for SVI 30-35 ml/m2). The SVI prognostic threshold for medium-term mortality in severe LGAS patients is different for those with preserved LVEF (< 30 ml/m2) compared to those with reduced LVEF (< 35 ml/m2).
Subject(s)
Aortic Valve Stenosis , Ventricular Dysfunction, Left , Humans , Stroke Volume , Prognosis , Retrospective Studies , Severity of Illness Index , Predictive Value of Tests , Ventricular Function, Left , Aortic Valve/diagnostic imagingABSTRACT
BACKGROUND: Mitral valve transcatheter edge-to-edge repair (M-TEER) is an effective option for treatment of mitral regurgitation (MR). We previously reported favorable 2-year outcomes for the PASCAL transcatheter valve repair system. OBJECTIVES: We report 3-year outcomes from the multinational, prospective, single-arm CLASP study with analysis by functional MR (FMR) and degenerative MR (DMR). METHODS: Patients with core-lab determined MR ≥ 3+ were deemed candidates for M-TEER by the local heart team. Major adverse events were assessed by an independent clinical events committee to 1 year and by sites thereafter. Echocardiographic outcomes were evaluated by the core laboratory to 3 years. RESULTS: The study enrolled 124 patients, 69% FMR; 31% DMR (60% NYHA class III-IVa, 100% MR ≥ 3+). The 3-year Kaplan-Meier estimate for survival was 75% (66% FMR; 92% DMR) and freedom from heart failure hospitalization (HFH) was 73% (64% FMR; 91% DMR), with 85% reduction in annualized HFH rate (81% FMR; 96% DMR) (p < 0.001). MR ≤ 2+ was achieved and maintained in 93% of patients (93% FMR; 94% DMR) and MR ≤ 1+ in 70% of patients (71% FMR; 67% DMR) (p < 0.001). The mean left ventricular end-diastolic volume (181 mL at baseline) decreased progressively by 28 mL [p < 0.001]. NYHA class I/II was achieved in 89% of patients (p < 0.001). CONCLUSIONS: The 3-year results from the CLASP study demonstrated favorable and durable outcomes with the PASCAL transcatheter valve repair system in patients with clinically significant MR. These results add to the growing body of evidence establishing the PASCAL system as a valuable therapy for patients with significant symptomatic MR.
Subject(s)
Cardiac Surgical Procedures , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Humans , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Prospective Studies , Treatment OutcomeABSTRACT
AIMS: Atrial functional mitral regurgitation (AFMR) is characterised by left atrial and consequent mitral annular dilatation causing mitral regurgitation. AFMR is likely to become more common with population ageing, alongside increases in atrial fibrillation and heart failure with preserved ejection fraction; conditions causing atrial dilatation. Here, we aim to define the prevalence and characterise the patient and survival characteristics of AFMR in the National Echocardiographic Database of Australia (NEDA). METHODS AND RESULTS: 14 004 adults with moderate or severe FMR were identified from NEDA. AFMR or ventricular FMR (VFMR) was classified by LA size, LV size and LVEF. AFMR was found in 40% (n=5562) and VFMR in 60% (n=8442). Compared with VFMR, the AFMR subgroup were significantly older (mean age 78±11 years), with a higher proportion of females and of AF. Participants were followed up for a median of 65 months (IQR 36-116 months). After adjustment for age, sex, AF, and pulmonary hypertension, the prognosis for VFMR was significantly worse than for AFMR (HR 1.57, 95% CI 1.47 to 1.68 for all-cause and 1.73, 95% CI 1.60 to 1.88, p<0.001 for both). After further adjustment for LVEF, mortality rates were similar in VFMR and AFMR patients (HR 0.93, p=NS), though advancing age and pulmonary hypertension remained independently associated with prognosis. CONCLUSIONS: AFMR is a common cause of significant functional MR that predominantly affects elderly female patients with AF. Advancing age and pulmonary hypertension independently associated with survival in FMR. Prognosis was better in AFMR compared with VFMR; however, this difference was accounted for by LV systolic impairment and not by MR severity.
Subject(s)
Atrial Fibrillation , Hypertension, Pulmonary , Mitral Valve Insufficiency , Adult , Humans , Female , Aged , Aged, 80 and over , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/epidemiology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/complications , Prevalence , Heart AtriaABSTRACT
Background: Patients with a cardiac implantable electronic device (CIED)-induced tricuspid regurgitation (TR) have an increased mortality and morbidity. However, the impact of CIED-lead extraction and its indications are not well-defined. Case summary: A 69-year-old woman presented with recurrent hospital admissions for right heart failure refractory to medical therapy, on the background of a single-chamber permanent pacemaker (Biotronik) implanted 6 years ago for tachycardia-bradycardia syndrome. Transoesophageal echocardiography identified severe TR which was predominantly CIED-induced from a lead impingement of the posterior tricuspid valve (TV) leaflet preventing adequate leaflet coaptation. This had progressed to cause a degree of secondary functional TR. The patient underwent pacing lead extraction followed by epicardial lead placement via minithoracotomy, with significant symptomatic and echographic improvement of TR. Discussion: CIED-induced TR from a lead impingement of TV leaflets carries the highest risk of TR and its consequences. This case illustrates the significance of the relationship between CIED-leads and the TV, which impacts management strategy. We recommend a mechanistic approach and incorporating CIED-lead interaction with the TV apparatus as the underlying principle in developing future management guidelines for CIED-induced TR.
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Endothelial dysfunction, hallmarked by an imbalance between vasoconstriction and vasorelaxation, is associated with diabetes. Thioredoxin Interacting protein (TXNIP), controlled by an exquisitely glucose sensitive gene, is increasingly recognized for its role in diabetes. However, the role of TXNIP in modulating diabetes-related endothelial dysfunction remains unclear. To elucidate the role of TXNIP, we generated two novel mouse strains; endothelial-specific TXNIP knockout (EKO) and a Tet-O inducible, endothelial-specific TXNIP overexpression (EKI). Hyperglycemia was induced by streptozotocin (STZ) treatment in floxed control (fl/fl) and EKO mice. Doxycycline (DOX) was given to EKI mice to induce endothelial TXNIP overexpression. The ablation of endothelial TXNIP improved glucose tolerance in EKO mice. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in STZ-treated fl/fl mice while this STZ impaired vasorelaxation was attenuated in EKO mice. Hyperglycemia induction of NLRP3 and reductions in Akt and eNOS phosphorylation were also mitigated in EKO mice. Overexpression of endothelial TXNIP did not impair glucose tolerance in DOX-treated EKI mice, however induction of endothelial TXNIP led to impaired vasorelaxation in EKI mice. This was associated with increased NLRP3 and reduced Akt and eNOS activation. In conclusion, deletion of endothelial TXNIP is protective against and overexpression of endothelial TXNIP induces endothelial dysfunction; thus, endothelial TXNIP plays a critical role in modulating endothelial dysfunction.
Subject(s)
Endothelium , Hyperglycemia , Thioredoxins , Vasodilation , Animals , Carrier Proteins/genetics , Carrier Proteins/metabolism , Endothelium/metabolism , Endothelium/physiopathology , Glucose , Hyperglycemia/metabolism , Hyperglycemia/physiopathology , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Streptozocin , Thioredoxins/genetics , Thioredoxins/metabolism , Vasodilation/genetics , Vasodilation/physiologyABSTRACT
Background The pathophysiological mechanism behind adverse outcomes associated with ischemia-inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave-free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (ß) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (ß=-0.44; 95% CI, -0.62 to -0.25; P<0.001) and maximum lesion WSS (ß=-0.53; 95% CI, -0.70 to -0.36; P<0.001) after adjusting for percentage diameter stenosis and index of microcirculatory resistance. Similarly, instantaneous wave-free ratio also independently predicted the total area of low WSS (ß=-0.45; 95% CI, -0.62 to -0.28; P<0.001) and maximum lesion WSS (ß=-0.58; 95% CI, -0.73 to -0.43; P<0.001). The index of microcirculatory resistance did not predict either low or high WSS. Conclusions Fractional flow reserve and instantaneous wave-free ratio independently predicted the total burden of low WSS and maximum lesion WSS in coronary arteries. No relationship was found between microcirculatory dysfunction and WSS.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Constriction, Pathologic , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Stenosis/diagnosis , Coronary Vessels/diagnostic imaging , Humans , Microcirculation , Predictive Value of Tests , Severity of Illness IndexABSTRACT
Background: Continued development of transcatheter mitral repair technologies is needed to address the large and diverse population of high-risk patients with symptomatic mitral regurgitation (MR). The new PASCAL Ace implant system, with its narrower profile, complements the original PASCAL transcatheter valve repair system. The aim of this study is to report 1-year outcomes from the early, compassionate-use observational experience with the novel PASCAL Ace implant system. Methods: After heart team assessment, adults with symptomatic moderate-to-severe (3+) or severe (4+) MR despite optimal medical therapy were treated under compassionate use at 3 hospitals internationally. Data were prospectively collected, and outcomes were assessed over a 12-month follow-up period. Results: Seventeen patients (mean age 76 years, 65% male, mean Society of Thoracic Surgeons Predicted Risk of Operative Mortality score 9.6) were treated. MR etiology was degenerative in 29%, functional in 65%, and mixed in 6%; 59% were in New York Heart Association (NYHA) class III-IV. Technical success was achieved in 100%, and procedural success in 94%. At 1 year, MR grade ≤2+ was achieved in 93% (p < 0.001) with 88% survival rate and 94% free from heart failure hospitalization. The composite major adverse event rate was 6% and 100% of patients had ≤NYHA class II symptoms (p < 0.001). Conclusions: At 1 year, the PASCAL Ace implant system demonstrated feasibility in this early, compassionate use experience in a small group of symptomatic patients with anatomically complex MR. The unique features of the PASCAL Ace implant may expand the treatable MR population.
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BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort. METHODS AND RESULTS: All patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20-0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07-0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07-0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25-0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27-0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08-0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09-0.83, P = 0.02). CONCLUSIONS: In this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.
Subject(s)
Percutaneous Coronary Intervention/methods , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Cause of Death , Coronary Artery Disease/surgery , Female , Heart Diseases/surgery , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/mortality , Percutaneous Coronary Intervention/adverse effects , Proportional Hazards Models , Treatment OutcomeABSTRACT
Background The prevalence and outcomes of the different subtypes of severe low-gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high-gradient and 6412 patients (53%) had low-gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All-cause and cardiovascular-related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow-up of 88±45 months. Actual 1-year and 5-year all-cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high-gradient severe AS, 11.6% and 53.6% in patients with normal-flow, low-gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high-gradient severe AS, the 5-year age-adjusted and sex-adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85-1.03) in patients with normal-flow, low-gradient severe AS; 1.01 (95% CI, 0.92-1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48-1.84) in patients with classical LFLG severe AS. Conclusions Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low-gradient hemodynamics, which is associated with long-term mortality comparable with or worse than high-gradient severe AS. The poorest survival was associated with classical LFLG severe AS.
Subject(s)
Aortic Valve Stenosis , Aortic Valve/diagnostic imaging , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/epidemiology , Humans , Prevalence , Retrospective Studies , Severity of Illness Index , Stroke Volume , Treatment Outcome , Ventricular Function, LeftABSTRACT
OBJECTIVES: The authors propose a novel pressure-regulated method for balloon-expandable transcatheter heart valve (THV) deployment, aimed at optimizing prosthesis-annulus apposition while preventing significant tissue injury. BACKGROUND: The optimal method for balloon-expandable THV deployment remains debated. Current protocols are volume dependent, relying on under- and overfilling of the deployment apparatus. During deployment, the annular wall tension exerted by the expanding prosthesis is determined by maximal THV diameter and balloon pressure (Laplace's law). METHODS: Three hundred thirty consecutive patients with severe native aortic stenosis who underwent TAVR with SAPIEN 3 THVs were included. One hundred and six patients were considered at high risk for annular rupture. THVs were deployed until reaching a predetermined balloon pressure. Postdilatation was performed to reduce mild or greater angiographic paravalvular regurgitation (PVR). Using a biomechanical model, annular wall stress was estimated for each case and assessed against rates of postdilatation, mild or greater PVR on transthoracic echocardiography, new permanent pacemaker placement or left bundle branch block, and annular rupture. RESULTS: Patients with wall stress >3 MPa had reduced postdilatation rate (P < 0.001) and reduced final PVR (P = 0.014). Annular rupture occurred in 2 of 3 high-risk patients with wall stress >3.5 MPa (3.69 and 3.84 MPa); no rupture occurred in 95 high-risk patients with wall stress ≤3.5 MPa. We defined a single target deployment pressure per THV size to ensure deployment within target wall stress levels of 3 to 3.5 MPa: 6.25 atm for 23-mm THVs, 5.5 atm for 26-mm THVs, and 5 atm for 29-mm THVs. Patients within this target range (n = 136) had a 10.0% postdilatation rate, 12.7% mild PVR, and no moderate to severe PVR. The relationship between balloon filling volume and associated pressure and wall stress was inconsistent. CONCLUSIONS: Pressure-regulated THV deployment is a simple, reproducible, safe, and effective method, regardless of high-risk anatomical complexities.