Three-year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study.

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.

Sex differences in time to primary percutaneous coronary intervention and outcomes in patients presenting with ST-segment elevation myocardial infarction.

OBJECTIVES: We assessed sex differences in treatment and outcomes in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). BACKGROUND: Historically, delays to timely reperfusion and poorer outcomes have been described in women who suffer STEMI. However, whether these sex discrepancies still exist with contemporary STEMI treatment remains to be evaluated. METHODS: Consecutive STEMI patients treated with primary PCI patients over a 10-year period (January 1, 2010 to December 31, 2019) from a tertiary referral center were assessed. Comparisons were performed between patient's sex. Primary outcomes were 30-day and 1-year mortality. Secondary outcomes were STEMI performance measures. RESULTS: Most patients (n = 950; 76%) were male. Females were on average older (66.8 vs. 61.4 years males; p < 0.001). Prehospital treatment delays did not differ between sexes (54 min [IQR: 44-65] females vs. 52 min [IQR: 43-62] males; p = 0.061). STEMI performance measures (door-to-balloon, first medical contact-to-balloon [FMCTB]) differed significantly with longer median durations in females and fewer females achieving FMCTB < 90 min (28% females vs. 39% males; p < 0.001). Women also experienced greater rates of initial radial arterial access failure (11.3% vs. 3.1%; p < 0.001). However, there were no significant sex differences in crude or adjusted mortality between sexes at 30-days (3.6% male vs. 5.1% female; p = 0.241, adjusted OR: 1.1, 95% CI: 0.5-2.2, p = 0.82) or at 1-year (4.8% male vs. 6.8% female; p = 0.190, adjusted OR: 1.0, (95% CI: 0.5-1.8; p = 0.96). CONCLUSION: Small discrepancies between sexes in measures of timely reperfusion for STEMI still exist. No significant sex differences were observed in either 30-day or 1-year mortality.

1-Year Outcomes for Transcatheter Repair in Patients With Mitral Regurgitation From the CLASP Study.

OBJECTIVES: The authors report the CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) expanded experience, 1-year outcomes, and analysis by functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR). BACKGROUND: The 30-day results from the CLASP study of the PASCAL transcatheter valve repair system for clinically significant mitral regurgitation (MR) have been previously reported. METHODS: Eligible patients had symptomatic MR ≥3+, were receiving optimal medical therapy, and were deemed candidates for transcatheter mitral repair by the local heart team. Primary endpoints included procedural success, clinical success, and major adverse event rate at 30 days. Follow-up was continued to 1 year. RESULTS: One hundred nine patients were treated (67% FMR, 33% DMR); the mean age was 75.5 years, and 57% were in New York Heart Association functional class III or IV. At 30 days, there was 1 cardiovascular death (0.9%), MR ≤1+ was achieved in 80% of patients (77% FMR, 86% DMR) and MR ≤2+ in 96% (96% FMR, 97% DMR), 88% of patients were in New York Heart Association functional class I or II, 6-min walk distance had improved by 28 m, and Kansas City Cardiomyopathy Questionnaire score had improved by 16 points (p < 0.001 for all). At 1 year, Kaplan-Meier survival was 92% (89% FMR 96% DMR) with 88% freedom from heart failure hospitalization (80% FMR, 100% DMR), MR was ≤1+ in 82% of patients (79% FMR, 86% DMR) and ≤2+ in 100% of patients, 88% of patients were in New York Heart Association functional class I or II, and Kansas City Cardiomyopathy Questionnaire score had improved by 14 points (p < 0.001 for all). CONCLUSIONS: The PASCAL transcatheter valve repair system demonstrated a low complication rate and high survival, with robust sustained MR reduction accompanied by significant improvements in functional status and quality of life at 1 year. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study [CLASP]; NCT03170349).

The effects of normovolemic anemia and blood transfusion on cerebral microcirculation after severe head injury.

BACKGROUND: Cerebral regional microcirculation is altered following severe head injury. In addition to tissue disruption, partial pressure of tissue oxygenation is impaired due to an increase in the oxygen tissue gradient. The heterogenic distribution of cerebral microcirculation is multifactorial, and acute anemia challenges further the delivery of oxygen to tissues. Currently, a restrictive transfusion threshold is globally applied; however, it is unclear how anemia modifies regional cerebral microcirculation; hence, it is unclear if by aiming to a global endpoint, specific anatomical regions undergo ischemia. This study aims to quantify the temporal changes in cerebral microcirculation after severe head injury, under the effect of anemia and transfusion. It also aims to assess its effects specifically at the ischemic penumbra compared to contralateral regions and its interactions with axonal integrity in real time. Twelve ovine models were subjected to a severe contusion and acceleration-deceleration injury. Normovolemic anemia to a restrictive threshold was maintained after injury, followed by autologous transfusion. Direct quantification of cerebral microcirculation used cytometric count of color-coded microspheres. Axonal injury was assessed using amyloid precursor protein staining. RESULTS: A mixed-effect regression model from pre-transfusion to post-transfusion times with a random intercept for each sheep was used. Cerebral microcirculation amongst subjects with normal intracranial pressure was maintained from baseline and increased further after transfusion. Subjects with high intracranial pressure had a consistent reduction of their microcirculation to ischemic thresholds (20-30 ml/100 g/min) without an improvement after transfusion. Cerebral PtiO2 was reduced when exposed to anemia but increased in a 9.6-fold with transfusion 95% CI 5.6 to 13.6 (p value < 0.001). CONCLUSIONS: After severe head injury, the exposure to normovolemic anemia to a restrictive transfusion threshold, leads to a consistent reduction on cerebral microcirculation below ischemic thresholds, independent of cerebral perfusion pressure. Amongst subjects with raised intracranial pressure, microcirculation does not improve after transfusion. Cerebral oxymetry is impaired during anemia with a statistically significant increase after transfusion. Current transfusion practices in neurocritical care are based on a rigid hemoglobin threshold, a view that excludes cerebral metabolic demands and specific needs. An RCT exploring these concepts is warranted.

Percutaneous Transvenous Mitral Valve-in-Valve Implantation Using Commercially Available Transcatheter Valve. First Australian Experience.

In patients with a degenerative mitral bioprosthesis and prohibitive surgical risk there is emerging evidence for the feasibility of valve-in-valve procedures via a percutaneous transvenous transseptal approach. This paper describes the first time this procedure has been performed in Australia.

Successful hybrid coronary artery revascularisation in a patient with severe cerebrovascular disease: a new treatment option to minimise the risk of stroke.

Here we present a case involving a patient with severe distal left main coronary artery stenosis with extensive coexisting extracranial cerebrovascular disease where hybrid coronary artery revascularisation was successfully performed. This illustrates the potential for hybrid revascularisation in those patients with an inherit risk of stroke.

Cerebral microcirculation during mild head injury after a contusion and acceleration experimental model in sheep.

BACKGROUND: Cerebral microcirculation after head injury is heterogeneous and temporally variable. Regions at risk of infarction such as peri-contusional areas are vulnerable to anaemia. However, direct quantification of the cerebral microcirculation is clinically not feasible. This study describes a novel experimental head injury model correlating cerebral microcirculation with histopathology analysis. OBJECTIVE: To test the hypothesis that cerebral microcirculation at the ischaemic penumbrae is reduced over time when compared with non-injured regions. METHODS: Merino sheep were instrumented using a transeptal catheter to inject coded microspheres into the left cardiac atrium, ensuring systemic distribution. After a blunt impact over the left parietal region, cytometric analyses quantified cerebral microcirculation and amyloid precursor protein staining identified axonal injury in pre-defined anatomical regions. A mixed effect regression model assessed the hourly blood flow results during 4 hours after injury. RESULTS: Cerebral microcirculation showed temporal reductions with minimal amyloid staining except for the ipsilateral thalamus and medulla. CONCLUSION: The spatial heterogeneity and temporal reduction of cerebral microcirculation in ovine models occur early, even after mild head injury, independent of the intracranial pressure and the level of haemoglobin. Alternate approaches to ensure recovery of regions with reversible injury require a targeted assessment of cerebral microcirculation.

Transcatheter valve-in-valve replacement of degenerated bioprosthetic aortic valves: a single Australian Centre experience.

BACKGROUND: Patients with degenerated surgical bioprosthetic valves may be at high risk for further surgery because of age, comorbidities and the difficulties of repeat procedures. Percutaneous valve-in-valve implantation offers what may be a simpler and safer procedure. METHODS: From May 2009 to March 2014 at the Prince Charles Hospital 1625 patients underwent surgical aortic valve replacement while 262 underwent transcatheter aortic valve implantation. Twelve patients had valve-in-valve implants for degenerated bioprosthetic aortic valves. RESULTS: These implants were deployed successfully without major valvular or paravalvular regurgitation. There were no periprocedural deaths, myocardial infarcts, neurological events or major vascular complications. Two patients died after 1624 and 1319days. Median survival for the remainder is 581days; they are stable with New York Heart Association class I/II functional status although 4 have a degree of patient-prosthesis mismatch, one has moderate aortic regurgitation and one required surgery for a late aortic dissection. CONCLUSION: Transcatheter valve-in-valve implantation is safe and effective treatment for patients with failed bioprosthetic aortic valves for whom reoperation is considered to be hazardous.

The long-term outcomes of transcoronary ablation of septal hypertrophy compared to surgical myectomy in patients with symptomatic hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The aim of this study was to compare the long-term outcomes of transcoronary ablation of septal hypertrophy (TASH) with open surgical myomectomy (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). METHODS: We reviewed patients who underwent either procedure at our institution. The demographics, clinical outcomes, echocardiographic parameters, and complications were compared. RESULTS: Seventy patients with HOCM were treated with either TASH (n = 47, 26 male) or SM (n = 23, 10 male). Compared to those treated with SM, patients undergoing TASH were older (57+/- 14.7 years versus 47 +/- 20.6 years, P = 0.021) and more symptomatic. A higher proportion of patients had syncope as a presenting feature in the TASH group compared to the SM group (57.5% vs. 17.4%, P = 0.002) respectively. They were also more likely to be in New York Heart Association (NYHA) class III/IV compared to the patients who underwent SM (85.1% vs. 39.1%; P < 0.001). Patients were followed for a mean period of 43 months (TASH) and 46 months (SM). Repeat procedures were more common in the TASH group (17% vs. 0%, P = 0.04) but mitral valve replacement was more common in the SM group (0% vs. 8.7%, P = 0.105). Symptom improvement, the rate of complications and all cause mortality rates were similar in both groups. CONCLUSIONS: TASH compares favorably with surgical myectomy with regard to symptom resolution, rate of complications and mortality in a tertiary referral centre and should be seen as an attractive alternative to surgical myectomy in the appropriate patient population.

Intracardiac echocardiography guided transeptal catheter injection of microspheres for assessment of cerebral microcirculation in experimental models.

The use of microspheres for the determination of regional microvascular blood flow (RMBF) has previously used different approaches. This study presents for the first time the intracardiac injection of microspheres using transeptal puncture under intracardiac echocardiography guidance. Five Merino sheep were instrumented and cardiovascularly supported according to local guidelines. Two catheter sheaths into the internal jugular vein facilitated the introduction of an intracardiac probe and transeptal catheter, respectively. Five million colour coded microspheres were injected into the left atrium via this catheter. After euthanasia the brain was used as proof of principle and the endpoint for determination of microcirculation at different time points. Homogeneous allocation of microspheres to different regions of the brain was found over time. Alternate slices from both hemispheres showed the following flow ranges: for slice 02; 0.57-1.02 mL/min/g, slice 04; 0.45-1.42 mL/min/g, slice 06; 0.35-1.87 mL/min/g, slice 08; 0.46-1.77 mL/min/g, slice 10; 0.34-1.28 mL/min/g. A mixed effect regression model demonstrated that the confidence interval did include zero suggesting that the apparent variability intra- and intersubject was not statistically significant, supporting the stability and reproducibility of the injection technique. This study demonstrates the feasibility of the transeptal injection of microspheres, showing a homogeneous distribution of blood flow through the brain unchanged over time and has established a new interventional model for the measurement of RMBF in ovine models.

Quantification of coronary stenosis by dual source computed tomography in patients: a comparative study with intravascular ultrasound and invasive angiography.

OBJECTIVE: To determine the accuracy of dual-source CT (DSCT) to quantify coronary stenosis compared to intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). METHODS: 21 patients (23 vessels) were examined with DSCT, IVUS and invasive coronary angiography. Coronary minimal luminal diameter (MLD) and area (MLA) were measured in cross-sectional multi-planar reformatted images perpendicular to the vessel long-axis. The vessel cross-sectional area stenosis (MLA/CSA ratio) was calculated. DSCT results were compared with IVUS and QCA. RESULTS: A good correlation between DSCT and IVUS was noted for diameter and area stenosis (r=0.69 and r=0.73), with an overestimation of MLD stenosis by DSCT (+9.1%) and an underestimation of MLA stenosis (-5.8%). For MLD and MLA, high correlation coefficients (r=0.78 and r=0.90, respectively) were found between DSCT and IVUS; and the bias was almost zero (-0.41 mm and +0.1mm(2), respectively). The correlation between DSCT and QCA was moderate (r=0.60) for MLD stenosis with minor overestimation by DSCT (+4.0%) and moderate (r=0.59) for MLD (bias, +0.01 mm). The cross-sectional area stenosis showed a moderate correlation (r=0.59) between DSCT and IVUS (+0.00). CONCLUSIONS: DSCT allows accurate quantification of coronary stenosis as compared to IVUS. An excellent correlation was found for the MLA between DSCT and IVUS.

Comparison of atrial and brain natriuretic peptide for the assessment of mitral stenosis.

BACKGROUND: Accurate evaluation of the functional consequences of mitral stenosis (MS) can be difficult. The aim of this study was to evaluate the relationship between both atrial (ANP) and brain natriuretic peptides (BNP) and symptoms, exercise capacity and echocardiographic measures of MS severity. METHODS: Thirty patients with moderate to severe MS and 14 normal controls underwent clinical assessment, exercise stress echocardiography, measurement of ANP and BNP and two years follow up for clinical events. RESULTS: BNP was higher in MS patients than controls (BNP 58 [IQR 34, 93] vs. 16 [14, 25], p < 0.0001). There was considerable overlap in exercise capacity and echocardiographic severity between asymptomatic and symptomatic patients. An increase in BNP was associated with a larger left atrial area index (r = 0.67, p < 0.0001), reduced mitral valve area (r = -0.38, p = 0.05) and higher resting pulmonary artery pressure (r = 0.47, p = 0.008). Increased BNP predicted lower treadmill exercise capacity (AUC = 0.82 [95% confidence interval 0.67, 0.97], p = 0.004), guideline criteria for intervention (AUC = 0.87 [0.74, 0.99], p = 0.006) and adverse events during follow up (AUC = 0.81 [0.64, 0.99], p = 0.03). Associations for ANP in general were similar but slightly weaker, and ANP did not provide additional predictive information to BNP. CONCLUSION: BNP may improve risk stratification of patients with MS, particularly when symptoms are equivocal.

Prognostic differences between different types of bundle branch block during the early phase of acute myocardial infarction: insights from the Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial.

AIMS: Bundle branch block (BBB) early during acute myocardial infarction (AMI) is often considered high risk for mortality. Little is known about how different BBB types influence prognosis. METHODS AND RESULTS: The HERO-2 trial recruited 17 073 patients with ischaemic symptoms lasting >30 min and either ST elevation with or without right bundle branch block (RBBB) or presumed-new left bundle branch block (LBBB). Electrocardiograms were performed before and 60 min after the start of fibrinolytic therapy. Using patients with normal intraventricular conduction as a reference, odds ratios (ORs) for 30-day mortality were calculated for different BBB types (LBBB, RBBB with anterior AMI, and RBBB with inferior AMI) present at randomization and/or 60 min, with adjustment for recruitment region, pre-infarction characteristics, time to randomization, hemodynamics, and Killip class. At randomization, the 873 patients (5.11%) with BBB had worse baseline characteristics than patients without BBB. In patients presenting with LBBB (n=300), the ORs for 30-day mortality were 1.90 (95% CI 1.39-2.59) before and 0.68 (0.48-0.99) after adjustment for other prognosticators. In patients presenting with RBBB (n=415) and anterior AMI, the ORs were 3.52 (2.82-4.38) before and 2.48 (1.93-3.19) after adjustment. In patients presenting with RBBB and inferior AMI (n=158), the ORs were 1.74 (1.06-2.86) before and 1.22 (0.71-2.08) after adjustment. Within 60 min, 143 patients (0.92%) developed new BBB. The adjusted ORs for 30-day mortality were 2.97 (1.16-7.57) in the 25 patients with new LBBB, 3.84 (2.38-6.22) in the 100 with new RBBB and anterior AMI, and 2.23 (0.54-9.21) in the 18 with new RBBB and inferior AMI. CONCLUSION: RBBB accompanying anterior AMI at presentation and new BBB (including LBBB) early after fibrinolytic therapy are independent predictors of high 30-day mortality. These electrocardiographic features should be considered in risk stratification to identify high-risk patients.