Left bundle branch area pacing in heart failure: A systematic review and meta-analysis with meta-regression.

INTRODUCTION: Left bundle branch area pacing is an alternative to biventricular pacing. In this study, we aim to summarize the available evidence on the feasibility, efficacy, and safety of left bundle branch block area pacing (LBBAP). OBJECTIVES: The study summarizes the available evidence on the feasibility, efficacy, and safety of left bundle branch block area pacing (LBBAP). BACKGROUND: Cardiac resynchronization therapy (CRT) reduced mortality and hospitalizations in heart failure (HF) patients with a left ventricular ejection fraction (LVEF) ≤ 35% and concomitant LBBB. Recently LBBAP has been studied as a more physiological alternative to achieve CRT. METHOD: A search of PubMed, EMBASE, and Cochrane databases were performed to identify studies examining the role of LBBAP for CRT in heart failure. Comprehensive meta-analysis version 4 was used for meta-regression to examine variables that contribute to data heterogeneity. RESULT: Eighteen studies, 17 observational and one randomized controlled trial (RCT) were examined. A total of 3906 HF patients who underwent CRT (2036 LBBAP vs. 1870 biventricular pacing [BVP]) were included. LBBAP was performed successfully in 90.4% of patients. Compared to baseline, LBBAP was associated with a reduction in QRS duration (MD: -47.23 ms 95% confidence interval [CI]: -53.45, -41.01), an increase in LVEF (MD: 15.22%, 95% CI: 13.5, 16.94), and a reduction in NYHA class (MD: -1.23, 95% CI: -1.41, -1.05). Compared to BVP, LBBAP was associated with a significant reduction in QRS duration (MD: -20.69 ms, 95% CI: -25.49, -15.88) and improvement in LVEF (MD: 4.78%, 95% CI: 3.30, 6.10). Furthermore, LBBAP was associated with a significant reduction in HF hospitalization (odds ratio [OR]: 0.44, 95% CI: 0.34, 0.56) and all-cause mortality (OR: 0.67, 95% CI: 0.52, 0.86) compared to BVP. CONCLUSION: LBBAP was associated with improved ventricular electrical synchrony compared to BVP, as well as better echocardiographic and clinical outcomes.

Assessment of left ventricular global longitudinal strain in patients with hypertrophic cardiomyopathy and coronary artery disease.

Impaired left ventricular global longitudinal strain (GLS) and coronary artery disease (CAD) each confer adverse prognosis in hypertrophic cardiomyopathy (HCM). Despite their prevalence, data on GLS in co-existent HCM and CAD is lacking. Ninety-six patients with HCM and CAD were retrospectively identified between 2005 and 2021, and analyzed using 2D speckle-tracking echocardiography. Obstructive and non-obstructive CAD patients were compared, multivariate linear regression tested associations between clinical and echocardiographic variables with GLS, and Receiver Operating Characteristic Curve assessed the utility of GLS to predict all-cause mortality at follow-up. Mean age was 71 ± 12.2 years, 41% had obstructive HCM, 78% had obstructive CAD, and 75% had prior acute coronary syndrome. At 4.8-year follow-up, GLS decreased compared with baseline (- 12.5 ± 4.5 vs. - 14 ± 4.2%, p = 0.007), with basal segments experiencing the greatest impairment. GLS was lower in obstructive versus non-obstructive CAD patients at follow-up, although the magnitude was attenuated (baseline: - 13.2 vs. - 17.1%, p < 0.001; follow-up: - 12 vs. - 14.1%, p = 0.05). Interventricular septal thickness (ß = 0.54), apical HCM (ß = 0.48), and right ventricular systolic pressure (ß = 0.39) were associated with more impaired GLS (all p < 0.001), independent of obstructive CAD (ß = 0.09, p = 0.44). There were 9 follow-up deaths, with baseline GLS > - 13.5% being a good predictor of all-cause mortality (AUC 0.78, 95% CI 0.64-0.92, sensitivity 88%, specificity 57%, p = 0.01). Patients with HCM and CAD experience progressive GLS impairment over long-term follow-up, with GLS > - 13.5% appearing to be a threshold for predicting all-cause mortality. Apical HCM phenotype is independently associated with worse GLS.

Left ventricular strain and myocardial work in apical hypertrophic cardiomyopathy.

Background: Apical hypertrophic cardiomyopathy (ApHCM) is recognized for its associated cardiovascular morbidity. Herein we describe left ventricular (LV) function and mechanics over long-term follow-up in ApHCM. Methods: A retrospective study of 98 consecutive ApHCM patients was performed (mean age: 64±15 years, 46% female) using 2D and speckle-tracking echocardiography. LV function and mechanics were characterized by global longitudinal strain (GLS), segmental strain, and myocardial work indices. Myocardial work was calculated by integrating longitudinal strain and blood pressure as estimated by the brachial artery cuff pressure, to generate an LV pressure-strain loop with adjusted ejection and isovolumetric periods. Composite complications were defined as all-cause mortality, sudden death, myocardial infarction, and/or stroke. Results: Mean LV ejection fraction measured 67%±11% and GLS was -11.7%±3.9%. Global work index (GWI) was 1,073±349 mmHg%, constructive work was 1,379±449 mmHg%, wasted work was 233±164 mmHg%, and work efficiency was 82%±8%. In 72 patients with follow-up echocardiography, at a median of 3.9 years there was progressive impairment in GLS (-11.9% vs. -10.7%; P=0.006), GWI (1,105 vs. 989 mmHg%; P=0.02), and global constructive work (1,432 vs. 1,312 mmHg%; P=0.03), without change in wasted work or work efficiency. Atrial fibrillation (ß=0.37; P<0.001), mitral annular e' velocity (ß=-0.32; P=0.001), and glomerular filtration rate (ß=-0.2; P=0.03) were independently associated with follow-up GLS; atrial fibrillation (ß=-0.27; P=0.01) and glomerular filtration rate (ß=0.23; P=0.04) were also associated with follow-up GWI. Global wasted work >186 mmHg% was predictive of composite complications (AUC =0.7, 95% CI: 0.53-0.82, sensitivity 93%, specificity 41%). Conclusions: ApHCM is associated with preserved LV ejection fraction but abnormal LV GLS and work indices, with progressive impairment. Important clinical and echocardiographic measures are independently predictive of long-term follow-up LV GLS, GWI and adverse events.

Right ventricular hypertrophy in apical hypertrophic cardiomyopathy.

BACKGROUND: Right ventricular hypertrophy (RVH+) in hypertrophic cardiomyopathy occurs in one third of patients, however, outcomes in apical hypertrophic cardiomyopathy (ApHCM) have not been described. We hypothesized that RVH+ in ApHCM is associated with more ventricular remodeling and dysfunction, and increased adverse events when compared with those without RVH (RVH-). METHODS: Ninety-one ApHCM patients were retrospectively analyzed using 2D and speckle-tracking echocardiography (64 ± 16 years old, 43% female). RVH+ was defined as wall thickness >5 mm and was present in 23 (25%). Ventricular mechanics were characterized by global longitudinal strain (GLS), RV free wall strain, and myocardial work. RESULTS: New York Heart Association functional class > II, atrial fibrillation, and prior stroke were more prevalent in RVH+. Left ventricular (LV) size and ejection fraction were similar between groups, with greater septal (17 vs. 14 mm, p = .001) and apical (20 vs. 18 mm, p = .04) wall thickness in RVH+. When compared with RVH- patients, RVH+ had worse LV GLS (-8.6 vs. -12.8%), global work index (820 vs. 1172 mmHg%) (both p < .001), and work efficiency (76 vs. 83%, p = .001), as well as RV GLS (-14 vs. -17.5%) and free wall strain (-17.3 vs. -21.3%) (both p = .02). At 3-year follow-up RVH+ had greater incidence of heart failure hospitalization compared with RVH- (35 vs. 7%, p = .003). RVH+ was associated with RV GLS (ß = .2, p = .03), independent of clinical and echocardiographic variables. CONCLUSIONS: RVH+ patients with ApHCM have worse biventricular mechanics and myocardial work, and more heart failure hospitalization, as RVH- at mid-term follow-up.

Echocardiographic Features of Longevity: A Cross-Sectional Study of Centenarians.

BACKGROUND: Centenarians represent an under-studied population within cardiovascular medicine. This study aimed to describe the echocardiographic characteristics of a cohort of centenarians at a tertiary referral center. MATERIALS AND METHODS: The institutional Echocardiography database was retrospectively reviewed and identified 100 consecutive centenarians referred for transthoracic echocardiography between January 2009 and December 2020. Cardiac chamber quantification, diastology, and valvular heart disease were assessed according to the American Society of Echocardiography guidelines. Independent t-tests and Mann-Whitney U-tests compared data between males and females. RESULTS: The mean age was 101.5 ± 1.7 years, 78% were female, and the most common co-morbidities were hypertension (77%), coronary artery disease (46%), and congestive heart failure (42%). The mean left ventricular (LV) ejection fraction measured 56.9 ± 11.3% (females vs males, 58.4 ± 9.8 vs 51.6 ± 14.6%, p = 0.01). Males had larger LV end-diastolic (2.8 ± 0.6 vs 2.5 ± 0.5, p = 0.03) and end-systolic diameter (1.9 ± 0.6 vs 1.6 ± 0.4, p = 0.001) indices; a smaller relative wall thickness (0.54 ± 0.18 vs 0.69 ± 0.36, p = 0.06); and a lower E/e' ratio (13.3 [10.3-19.6] vs 17.3 [13.2-23], p = 0.05), when compared with females. The prevalence of severe valvular lesions was 13.5%, and similar between genders. However, in patients with aortic stenosis, the transaortic pressure gradients were significantly higher in females (mean gradient: 32.0 ± 17.7 vs 18.7 ± 9.2 mmHg, p = 0.04). CONCLUSIONS: The present study on centenarians affords a cross-sectional evaluation of cardiac structure and function in a growing population, and highlights important differences between male and female patients.

Dual Antiplatelet Therapy in Patients Aged 75 Years and Older with Coronary Artery Disease: A Meta-Analysis and Systematic Review.

Objectives: This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). Background: The safety and efficacy of DAPT in elderly patients with ACS is not well characterized. Methods: We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public. Results: Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, p < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, p=0.17). Conclusions: This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.

Systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: a narrative review.

Background and Objective: The prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) obstruction present in 60% to 70%. In this narrative review, we aim to elucidate the pathophysiology of SAM-septal contact and LVOT obstruction in HCM by presenting a detailed review on the anatomy of the MV apparatus in HCM, examining the various existing theories pertaining to the SAM phenomenon as supported by cardiac imaging, and providing a critical assessment of management strategies for SAM in HCM. Methods: A literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane Library, of all scientific articles published through December 2021. A focus was placed on descriptive studies, reports correlating echocardiographic findings with pathologic diagnosis, and outcomes studies. Key Content and Findings: The pathophysiology of SAM involves the complex interplay between HCM morphology, MV apparatus anatomic abnormalities, and labile hemodynamic derangements. Echocardiography and cardiac magnetic resonance (CMR) vector flow mapping have identified drag forces, as opposed to the "Venturi effect", as the main hydraulic forces responsible for SAM. The degree of mitral regurgitation with SAM is variable, and its severity is correlated with degree of LVOT obstruction and outcomes. First line therapy for the amelioration of SAM and LVOT obstruction is medical therapy with beta-blockers, non-dihydropyridine calcium-channel blockers, and disopyramide, in conjunction with lifestyle modifications. In refractory cases septal reduction therapy is performed, which may be combined with a 'resect-plicate-release' procedure, anterior mitral leaflet extension, surgical edge-to-edge MV repair, anterior mitral leaflet retention plasty, or secondary chordal cutting. Conclusions: Recent scientific advances in the field of HCM have allowed for a maturation of our understanding of the SAM phenomenon. Cardiac imaging plays a critical role in its diagnosis, treatment, and surveillance, and in our ability to apply the appropriate therapeutic regimens. The increasing prevalence of HCM places an emphasis on continued basic and clinical research to further improve outcomes for this challenging population.

The trial to assess chelation therapy 2 (TACT2): Rationale and design.

BACKGROUND: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design. METHODS: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na2EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are followed for 2.5 to 5 years. The primary endpoint is time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial has >;85% power to detect a 30% relative reduction in the primary endpoint. TACT2 also includes a Trace Metals and Biorepository Core Lab, to test whether benefits of treatment, if present, are due to chelation of lead and cadmium from patients. Design features of TACT2 were chosen to replicate selected features of the first TACT, which demonstrated a significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes. RESULTS: Results are expected in 2024. CONCLUSION: TACT2 may provide definitive evidence of the benefit of edetate disodiumbased chelation on cardiovascular outcomes, as well as the clinical importance of longitudinal changes in toxic metal levels of participants.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

AIMS: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). METHODS AND RESULTS: The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30-60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (Pinteraction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14-0.78, P = 0.011). CONCLUSION: Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr.

A systematic review and pooled analysis of septal myectomy and edge-to-edge mitral valve repair in obstructive hypertrophic cardiomyopathy.

Left ventricular outflow tract (LVOT) obstruction and systolic anterior motion (SAM) of the mitral valve (MV) occurs in 70% of hypertrophic cardiomyopathy (HCM) patients. In individuals undergoing septal myectomy, concomitant MV surgery is considered for SAM with residual LVOT obstruction or mitral regurgitation (MR); however, the optimal approach remains debated. A literature search was performed in Pubmed, EMBASE, Ovid, and the Cochrane library of published articles through June 2021 reporting on combined septal myectomy and edge-to-edge MV repair for obstructive HCM. Continuous variables were weighted and compared using a student's t-test, and categorical variables using a chi-square test with Yates correction. Six studies with 158 total patients were included. The mean follow-up was 2.8 ± 2.7 years. Compared with pre-operative values, there were significant reductions in the LV ejection fraction (69 ± 10 vs 59 ± 8%), peak LVOT gradient (82 ± 34 vs 16 ± 13 mmHg), prevalence of moderate or greater MR (84 vs 5 %), and presence of SAM (96% vs 0) (p < 0.001 for all). There was no change in LV internal diastolic diameter (4.2 ± 1.3 vs 4.4 ± 1.5 cm, p = 0.32). There were 2 (1%) operative mortalities. At follow-up, the survival rate was 97%, there were 3 (2%) re-operative MV replacements, 4 (3%) patients remained in New York Heart Association functional class III/IV, and 8 (6%) required permanent pacemaker implantation. In conclusion, combined septal myectomy and edge-to-edge MV repair is a safe and effective treatment strategy in carefully selected patients requiring surgical HCM management.

The Role of False Tendons in Left Ventricular Remodeling and Secondary Mitral Regurgitation After Acute Myocardial Infarction.

BACKGROUND: Left ventricular false tendons (LVFT) are common structures visualized on transthoracic echocardiography (TTE). The present study tested the hypothesis that LVFT, via a possible 'constraint' mechanism, attenuate left ventricular (LV) remodeling and secondary mitral regurgitation after acute myocardial infarction. METHODS: Seventy-one patients admitted to the Coronary Care Unit following an ST-elevation (n = 63) or non-ST-elevation (n = 8) myocardial infarction were analyzed; 29 (41%) had LVFT, and 42 (59%) did not (no-LVFT). All had a TTE and at least 1 follow-up study after revascularization. The χ² analysis, Student's t-test, and Mann Whitney U test were used for the statistical analyses. RESULTS: The mean age (64 vs. 66 years), left ventricular ejection fraction (LVEF) (41% vs. 39%), left ventricular end-diastolic diameter (LVEDd) index (23 mm/m² for both), and prevalence of ≥ moderate secondary/functional mitral regurgitation (MR) (17% vs. 14%) were similar between the LVFT and no-LVFT groups. At 1-year follow-up, there was no significant difference in chamber remodeling amongst the LVFT versus no-LVFT group when assessed by: 1) ≥ 10% decrease in the relative LVEF (24% vs. 26%; p = 0.83); 2) ≥ 10% increase in the LVEDd index (41% vs. 38%, p = 0.98); and, 3) ≥ 10% increase in the LV mass index (48% vs. 41%, p = 0.68). There was no difference in the prevalence of ≥ moderate secondary/functional MR (17% vs. 12%, p = 0.77). Outcomes remained similar when stratifying by LVFT morphology or ischemic territory. CONCLUSIONS: In patients with mild to moderate LV dysfunction and normal chamber size, LVFT do not affect the development of LV remodeling or secondary/functional MR post-myocardial infarction.

Transthoracic versus intra-operative transesophageal echocardiography in right heart assessment.

METHODS: Fifty-four patients who had combined mitral and tricuspid valve surgery were included. Right heart measurements were performed in the TTE apical 4-chamber (A4C) and RV inflow views, and TEE mid-esophageal 4-chamber (ME4C) and transgastric RV inflow views at end-diastole. Spearman correlation coefficients (r) were applied to test for associations between the imaging modalities. RESULTS: The mean age was 65 years and 39% were male. All patients had ≥ moderate tricuspid regurgitation (TR), and a secondary/functional etiology was present in 89%. The median TAd and RV basal (RVd) diameters in the TTE-A4C view measured 37 mm [interquartile range (IQR), 34-44] and 43 mm (IQR, 40-51), respectively. The TTE-A4C TAd strongly correlated with the TEE-ME4C measurement (r=0.72), with an overestimation of 1 mm (IQR, -2 to 4) by TEE (P<0.01). For RVd, the TTE-A4C measurement correlated moderately with the TEE-ME4C view (r=0.61), underestimating the RVd by -1 mm (IQR, -4 to 3.3) (P<0.01). No correlation was observed between TAPSE measured by TTE and TEE (r=0.22, P=0.13). CONCLUSIONS: Intra-operative TEE may reliably quantitate TA and RV size and geometry. The current findings are best interpreted as hypothesis-generating for future validative studies.

Tricuspid regurgitation and in-hospital outcomes after transcatheter aortic valve replacement in high-risk patients.

BACKGROUND: The prognostic impact of tricuspid regurgitation (TR) following transcatheter aortic valve replacement (TAVR) is uncertain, and the management of patients with severe aortic stenosis and significant TR undergoing TAVR is unclear. METHODS: Retrospective study investigating the role of TR severity on hospital outcomes in high risk patients with severe aortic stenosis undergoing TAVR. RESULTS: A total of 174 participants were included in the present study. The median age was 84 years and 48% were women. The median (IR) STS score was 7.3 (4.7-13.6). The pre-procedural mean (SD) aortic valve area (AVA) was 0.69 (0.2) cm2 and the average (SD) peak and mean gradients were 71 [23]/42 [15] mmHg. Pre TAVR, 28.7% of patients had significant (moderate or severe) TR. Significant TR pre-TAVR increased the risk of in-hospital cardiovascular (CV) and all-cause and mortality [adjusted relative risk (RR) (95% CI): 14.67 (1.35-159.51) and 5.09 (1.14-22.72), respectively], and those with severe TR post-TAVR had longer hospital stay [median (IR): 9.9 (2.9-17.0) days]. No improvement or worsened TR (greater than mild) post-TAVR was associated with higher CV and all-cause mortality [adjusted RR (95% CI): 21.5 (1.81-255.96) and 8.19 (1.67-40.29), respectively]. Right ventricular systolic pressure (RVSP) was independently associated with TR severity pre and post TAVR. CONCLUSIONS: Significant TR was common among patients undergoing high risk TAVR, and is associated with increased in hospital mortality and longer hospital stay. Patients with elevated RVSP and persistent moderate or severe TR after TAVR are at higher risk of in hospital death.

Relationship between compliance and pulmonary vascular resistance in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial compliance (PAC) was previously shown to be an important prognostic factor in pulmonary arterial hypertension (PAH), in addition to the conventional pulmonary vascular resistance (PVR). The product of PAC and PVR, the arterial time (RC) constant, expresses the logarithmic relationship between the hemodynamic parameters. The objective of the study was to test RC constant stability in PAH patients followed beyond 12 months after diagnosis, and to report possible RC variations in different etiologies. METHODS: Fourteen PAH patients followed between 2008 and 2019 were included. Type 1 PAH was defined as a mean pulmonary artery pressure (PAP) ≥25 mmHg at rest and PVR ≥3 Wood units (WU). All patients who fulfilled WHO group I PAH criteria and had undergone two right heart catheterizations at least 1 year apart were included. The recorded hemodynamic data for each patient were used to compute PVR and PAC. RESULTS: PAH etiologies included scleroderma (n=2), liver cirrhosis (n=1), hereditary hemorrhagic telangiectasia (HHT) (n=1), mixed connective tissue disease (MCTD) (n=3), and idiopathic (n=7). The RC constant remained stable for all 14 patients over a follow-up period of 3.9±2 years. Patients with MCTD displayed more favorable hemodynamics, evidenced by higher RC (12.54 vs. 10.01, P<0.01) and PAC values (2.59 vs. 1.62, P=0.02), when compared with non-MCTD PAH patients. For the entire cohort the mean PAP measured 51±14 mmHg at baseline, and 46±13 mmHg at follow-up, respectively. CONCLUSIONS: The relationship between PAC and PVR remains stable in follow-up periods averaging 4 years, making compliance an important disease marker past the early stages. Patients with MCTD displayed more advantageous hemodynamic profiles when compared with patients with other PAH etiologies.

Possible differential benefits of edetate disodium in post-myocardial infarction patients with diabetes treated with different hypoglycemic strategies in the Trial to Assess Chelation Therapy (TACT).

BACKGROUND: The NIH-funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stable patients age ≥50 who were ≥6 months post myocardial infarction to 40 infusions of an edetate disodium-based regimen or placebo. In 633 patients with diabetes, edetate disodium significantly reduced the primary composite endpoint of mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.79, p < 0.001). The principal secondary endpoint of a composite of cardiovascular death, myocardial infarction, or stroke was also reduced (HR 0.60, 95% CI 0.39-0.91, p = 0.017). It is unknown if the treatment effect differs by diabetes therapy. METHODS: We grouped the subset of 633 patients with diabetes according to glucose-lowering therapy at time of randomization. The log-rank test was used to compare active therapy versus placebo. All treatment comparisons were performed using 2-sided significance tests at the significance level of 0.05 and were as randomized. Relative risks were expressed as HR with associated 95% CI, calculated using the Cox proportional hazards model. RESULTS: There were 162 (25.7%) patients treated with insulin; 301 (47.5%) with oral hypoglycemics only; and 170 (26.8%) receiving no pharmacologic treatment for diabetes. Patients on insulin reached the primary endpoint more frequently than patients on no pharmacologic treatment [61 (38%) vs 49 (29%) (HR 1.56, 95% CI 1.07-2.27, p = 0.022)] or oral hypoglycemics [61 (38%) vs 87 (29%) (HR 1.46, 1.05-2.03, p = 0.024)]. The primary endpoint occurred less frequently with edetate disodium based therapy versus placebo in patients on insulin [19 (26%) vs 42 (48%) (HR 0.42, 95% CI 0.25-0.74, log-rank p = 0.002)], marginally in patients on oral hypoglycemics [38 (25%) vs 49 (34%) (HR 0.66, 95% CI 0.43-1.01, log-rank p = 0.041)], and no significant difference in patients not treated with a pharmacologic therapy [23 (25%) vs 26 (34%) (HR 0.69, 95% CI 0.39-1.20, log-rank p = 0.225)]. The interaction between randomized intravenous treatment and type of diabetes therapy was not statistically significant (p = 0.203). CONCLUSIONS: Edetate disodium treatment in stable, post-myocardial infarction patients with diabetes suggests that patients on insulin therapy at baseline may accrue the greatest benefit. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: http://clinicaltrials.gov/ct2/show/NCT00044213?term=TACT&rank=7 identifier Trial to Assess Chelation Therapy (TACT), NCT00044213.

The effect of EDTA-based chelation on patients with diabetes and peripheral artery disease in the Trial to Assess Chelation Therapy (TACT).

OBJECTIVE: Approximately 1 in 7 US adults have diabetes; and over 60% of deaths in patients with diabetes have cardiac disease as a principal or contributing cause. Both coronary and peripheral artery disease (PAD) identify high-risk cohorts among patients with diabetes. We have previously demonstrated improved cardiovascular outcomes with edetate disodium-based chelation in post-MI patients with diabetes, enrolled in the Trial to Assess Chelation Therapy (TACT). In these analyses we further studied the effect size of patients with diabetes and severe disease in 2 vascular beds; coronaries, and lower extremity arteries. We questioned whether greater atherosclerotic burden would attenuate the observed beneficial effect of edetate disodium infusions. RESEARCH DESIGN AND METHODS: The multicenter TACT used a double blind, placebo controlled, 2 × 2 factorial design with 1708 participants, randomly assigned to receive edetate disodium-based chelation, or placebo and high dose oral vitamins or placebo. There were 162 (9.5% of 1708) post-MI patients with a diagnosis of diabetes mellitus and PAD for this post hoc analysis. Patients received up to 40 double-blind intravenous infusions of edetate disodium-based chelation, or placebo. The composite primary endpoint of TACT consisted of death from any cause, myocardial infarction, stroke, coronary revascularization and hospitalization for angina. RESULTS: The median age was 66 years, 15% female, 5% non-Caucasian, and BMI was 31. Insulin was used by 32% of patients. Active infusions significantly reduced the primary endpoint compared with placebo infusions (HR, 0.52; 95% CI, 0.30-0.92; P = 0.0069), with a 30% absolute risk reduction in the primary endpoint. There was a marked reduction in total mortality from 24% to 11%, although of borderline significance (P = 0.052). CONCLUSION: Atherosclerotic disease in multiple vascular beds did not attenuate the beneficial effect of edetate disodium infusions in post MI patients with diabetes. Studies now in progress will prospectively test this post hoc finding.

Potential Role of Metal Chelation to Prevent the Cardiovascular Complications of Diabetes.

CONTEXT: For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double-blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the prespecified subgroup of patients with diabetes. DESIGN: We review the published literature focusing on the atherogenic nature of diabetes, as well as available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in patients with diabetes. RESULTS: The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in patients with diabetes. CONCLUSIONS: The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.

Thromboembolic Outcomes of Different Anticoagulation Strategies for Patients with Atrial Fibrillation in the Setting of Hypertrophic Cardiomyopathy: A Systematic Review.

OBJECTIVE: Limited data is available assessing the efficacy and safety of different anticoagulation (AC) strategies for prevention of thromboembolic events, major bleeding, and all-cause mortality in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). In this systematic review, we conducted a literature search to examine the possible association between different AC strategies and prevention of these adverse outcomes. METHODS: Scientific databases (PubMed, EMBASE, and Scopus) were searched using relevant medical subject headings and keywords to retrieve studies published through September of 2019. Studies assessing the outcomes of interest in patients with HCM and AF receiving AC, no AC as well as direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) were selected. RESULTS: This review identified 14 observational studies evaluating thromboembolic events by AC strategies in 8,479 participants with concomitant HCM and AF. The use of AC was associated with a lower pooled incidence rate of total thromboembolic events at 9.5% (112 events in 1,175 patients) compared to 22.1% with no AC (108 events in 489 patients). In addition, the use of DOACs was associated with a lower pooled incidence rate of thromboembolic events at 4.7% (169 events in 3,576 patients) compared to 8.7% with VKAs (281 events in 3,239 patients). Furthermore, the use of DOACs compared to VKAs was associated with a lower pooled incidence rate of major bleeding and all-cause mortality at 3.8% (136 events in 3,576 patients) versus 6.8% (220 events in 3,239 patients) and 4.1% (124 events in 3,008 patients) versus 16.1% (384 events in 2,380 patients), respectively. CONCLUSIONS: AC of patients with concomitant HCM and AF was associated with a lower incidence of thromboembolic events when compared to antiplatelet therapy or no treatment. Treatment with DOACs was also associated with a lower incidence of thromboembolic events, major bleeding, and all-cause mortality when compared to VKAs.

Stress Cardiomyopathy in a Patient with Hypertrophic Cardiomyopathy: Case Presentation and Review of the Literature.

Stress cardiomyopathy and hypertrophic cardiomyopathy are two distinct entities with different pathophysiologic causes. In the recent medical literature their concurrency has been described. During the acute phase of a stress cardiomyopathy making the diagnosis of a concomitant hypertrophic cardiomyopathy may be challenging, and has important implications in both the acute and longterm clinical management. Herein, we present a case of a stress cardiomyopathy occurring in a patient with hypertrophic cardiomyopathy, along with a review of the literature.

Percutaneous Closure of Two Acquired Aorto-Right Ventricular Fistulae Following Right Ventricular Outflow Tract Surgery.

The present case illustrates the successful transcatheter closure of an unusual double aortic root-to-right ventricular outflow tract fistula utilizing two Amplatzer duct occluders II.