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Circulation Jun 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.
METHODS
This was a collaborative trial-level meta-analysis from the SGLT2i Meta-analysis Cardio-Renal Trialists Consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across 3 patient populations (patients with diabetes at high risk for atherosclerotic cardiovascular disease, heart failure [HF], or chronic kidney disease). The outcomes of interest were MACE (composite of cardiovascular death, myocardial infarction , or stroke), individual components of MACE (inclusive of fatal and nonfatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i versus placebo were meta-analyzed across trials and examined across key subgroups (established atherosclerotic cardiovascular disease, previous myocardial infarction, diabetes, previous HF, albuminuria, chronic kidney disease stages, and risk groups).
RESULTS
A total of 78 607 patients across 11 trials were included: 42 568 (54.2%), 20 725 (26.4%), and 15 314 (19.5%) were included from trials of patients with diabetes at high risk for atherosclerotic cardiovascular disease, HF, or chronic kidney disease, respectively. SGLT2i reduced the rate of MACE by 9% (hazard ration [HR], 0.91 [95% CI, 0.87-0.96], <0.0001) with a consistent effect across all 3 patient populations (=0%) and across all key subgroups. This effect was primarily driven by a reduction in cardiovascular death (HR, 0.86 [95% CI, 0.81-0.92], <0.0001), with no significant effect for myocardial infarction in the overall population (HR, 0.95 [95% CI, 0.87-1.04], =0.29), and no effect on stroke (HR, 0.99 [95% CI, 0.91-1.07], =0.77). The benefit for cardiovascular death was driven primarily by reductions in HF death and sudden cardiac death (HR, 0.68 [95% CI, 0.46-1.02] and HR, 0.86 [95% CI, 0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (=0.02).
CONCLUSIONS
SGLT2i reduce the risk of MACE across a broad range of patients irrespective of atherosclerotic cardiovascular disease, diabetes, kidney function, or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of cardiovascular death, particularly HF death and sudden cardiac death, without a significant effect on myocardial infarction in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.
Topics: Sodium-Glucose Transporter 2 Inhibitors; Humans; Cardiovascular Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2; Female; Male; Treatment Outcome; Aged
PubMed: 38583093
DOI: 10.1161/CIRCULATIONAHA.124.069568 -
EuroIntervention : Journal of EuroPCR... Aug 2023Transcatheter mitral valve replacement (TMVR) using dedicated devices is an alternative therapy for high-risk patients with symptomatic mitral regurgitation (MR).
BACKGROUND
Transcatheter mitral valve replacement (TMVR) using dedicated devices is an alternative therapy for high-risk patients with symptomatic mitral regurgitation (MR).
AIMS
This study aimed to assess the 2-year outcomes and predictors of mortality in patients undergoing TMVR from the multicentre CHOICE-MI Registry.
METHODS
The CHOICE-MI Registry included consecutive patients with symptomatic MR treated with 11 different dedicated TMVR devices at 31 international centres. The investigated endpoints included mortality and heart failure hospitalisation rates, procedural complications, residual MR, and functional status. Multivariable Cox regression analysis was applied to identify independent predictors of 2-year mortality.
RESULTS
A total of 400 patients, median age 76 years (interquartile range [IQR] 71, 81), 59.5% male, EuroSCORE II 6.2% (IQR 3.8, 12.0), underwent TMVR. Technical success was achieved in 95.2% of patients. MR reduction to ≤1+ was observed in 95.2% at discharge with durable results at 1 and 2 years. New York Heart Association Functional Class had improved significantly at 1 and 2 years. All-cause mortality was 9.2% at 30 days, 27.9% at 1 year and 38.1% at 2 years after TMVR. Chronic obstructive pulmonary disease, reduced glomerular filtration rate, and low serum albumin were independent predictors of 2-year mortality. Among the 30-day complications, left ventricular outflow tract obstruction, access site and bleeding complications showed the strongest impact on 2-year mortality.
CONCLUSIONS
In this real-world registry of patients with symptomatic MR undergoing TMVR, treatment with TMVR was associated with a durable resolution of MR and significant functional improvement at 2 years. Two-year mortality was 38.1%. Optimised patient selection and improved access site management are mandatory to improve outcomes.
Topics: Humans; Male; Aged; Female; Mitral Valve; Heart Valve Prosthesis Implantation; Heart Valve Prosthesis; Cardiac Catheterization; Treatment Outcome; Risk Factors; Mitral Valve Insufficiency; Registries
PubMed: 37235388
DOI: 10.4244/EIJ-D-22-01037 -
Journal of Cardiovascular Medicine... Feb 2024In the latest ESC/EACTS Guidelines for the Management of Valvular Heart Disease, right ventricular dilatation and dysfunction, severe pulmonary hypertension and... (Review)
Review
In the latest ESC/EACTS Guidelines for the Management of Valvular Heart Disease, right ventricular dilatation and dysfunction, severe pulmonary hypertension and tricuspid annulus dilatation were reported to be the most important parameters to consider in patient selection for tricuspid valve interventions. Indeed, comprehensive right ventricular assessment is crucial in patients with severe tricuspid regurgitation who may benefit from transcatheter or surgical procedures. However, the only guideline parameter considered for intervention has been tricuspid annular dilatation in the presence of at least mild to moderate tricuspid regurgitation, with no other right ventricular markers used in the decision-making process for invasive treatment. Notably, challenges in the assessment of right ventricular function may limit establishing thresholds for defining right ventricular dysfunction. The aim of this review is to summarize current evidence on the prognostic significance of right ventricular function in patients with tricuspid regurgitation undergoing percutaneous or surgical interventions.
Topics: Humans; Tricuspid Valve; Tricuspid Valve Insufficiency; Heart Ventricles; Prognosis; Heart Valve Diseases
PubMed: 38149699
DOI: 10.2459/JCM.0000000000001574 -
JACC. Cardiovascular Imaging Jun 2024Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the... (Review)
Review
Conflicting results from 2 randomized clinical trials of transcatheter mitral valve edge-to-edge repair in secondary mitral regurgitation (SMR) have led to the recognition that SMR is a heterogeneous disease entity presenting with different functional and morphological phenotypes. This review summarizes the current knowledge on SMR caused primarily by atrial secondary mitral regurgitation (aSMR) and ventricular SMR pathology. Although aSMR is generally characterized by severe left atrial enlargement in the setting of preserved left ventricular anatomy and function, different patterns of mitral annular distortion cause different phenotypes of aSMR. In ventricular SMR, the relation of SMR severity to left ventricular dilation as well as the degree of pulmonary hypertension and right ventricular dysfunction are important phenotypic characteristics, which are key for a better understanding of prognosis and treatment response.
Topics: Mitral Valve Insufficiency; Humans; Phenotype; Mitral Valve; Echocardiography, Transesophageal; Predictive Value of Tests; Severity of Illness Index; Ventricular Function, Left; Randomized Controlled Trials as Topic; Treatment Outcome; Cardiac Catheterization; Heart Valve Prosthesis Implantation
PubMed: 38551534
DOI: 10.1016/j.jcmg.2024.01.012 -
Circulation May 2024Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often... (Review)
Review
Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.
Topics: Humans; Tricuspid Valve; American Heart Association; United States; Heart Valve Diseases; Tricuspid Valve Insufficiency; Heart Valve Prosthesis Implantation
PubMed: 38660790
DOI: 10.1161/CIR.0000000000001232 -
JACC. Cardiovascular Interventions Jan 2024Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy...
BACKGROUND
Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce.
OBJECTIVES
This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort.
METHODS
Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability.
RESULTS
In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models.
CONCLUSIONS
The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.
Topics: Humans; Child; Pulmonary Valve; Tetralogy of Fallot; Retrospective Studies; Heart Valve Prosthesis Implantation; Treatment Outcome; Pulmonary Valve Insufficiency
PubMed: 38127022
DOI: 10.1016/j.jcin.2023.10.070 -
Journal of the American Society of... Nov 2023Echocardiographic surrogates of right ventricle-to-pulmonary artery (RV-PA) coupling have been reported to be associated with outcomes in patients with secondary...
BACKGROUND
Echocardiographic surrogates of right ventricle-to-pulmonary artery (RV-PA) coupling have been reported to be associated with outcomes in patients with secondary tricuspid regurgitation (STR). However, pulmonary artery systolic pressure (PASP) is difficult to estimate using echocardiography in patients with severe STR. The aim of the present study was to evaluate the predictive power of a surrogate of RV-PA coupling obtained using right ventricular (RV) volumes measured on three-dimensional echocardiography.
METHODS
One hundred eight patients (mean age, 73 ± 13 years; 61% women) with moderate or severe STR were included.
RESULTS
At a median follow-up of 24 months (interquartile range, 2-48 months), 72 patients (40%) had reached the composite end point of death of any cause and heart failure hospitalization. RV-PA coupling was computed as the ratio between RV forward stroke volume (SV) (i.e., RV SV - regurgitant volume) and RV end-systolic volume (ESV). RV forward SV/ESV was significantly more related to the composite end point than RV ejection fraction (area under the curve, 0.85 [95% CI, 0.78-0.93] vs 0.73 [95% CI, 0.64-0.83], respectively; P = .03). A value of 0.40 was found to best correlate with outcome. On multivariate Cox regression, RV forward SV/ESV, tricuspid annular plane systolic excursion/PASP, and RV free wall longitudinal strain/PASP were all independently associated with the occurrence of the composite end point when added to a group of parameters including STR severity (severe vs moderate), atrial fibrillation, pulmonary arterial hypertension, right atrial volume, RV end-diastolic volume, and RV free wall longitudinal strain. RV forward SV/ESV < 0.40 (HR, 3.36; 95% CI, 1.49-7.56; P < .01) carried higher related risk than RV free wall longitudinal strain/PASP < -0.42%/mm Hg (HR, 3.1; 95% CI, 1.26-7.84; P = .01) and tricuspid annular plane systolic excursion/PASP < 0.36 mm/mm Hg (HR, 2.69; 95% CI, 1.29-5.58; P = .01). RV ejection fraction did not correlate independently with prognosis when added to the same group of variables.
CONCLUSIONS
RV forward SV/ESV is associated with the risk for death and heart failure hospitalization in patients with STR.
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Male; Tricuspid Valve Insufficiency; Pulmonary Artery; Heart Ventricles; Echocardiography, Three-Dimensional; Stroke Volume; Heart Failure; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 37406715
DOI: 10.1016/j.echo.2023.06.014 -
Diabetes Care Oct 2023To develop a risk assessment tool to identify patients with type 2 diabetes (T2D) at higher risk for kidney disease progression and who might benefit more from...
OBJECTIVE
To develop a risk assessment tool to identify patients with type 2 diabetes (T2D) at higher risk for kidney disease progression and who might benefit more from sodium-glucose cotransporter 2 (SGLT2) inhibition.
RESEARCH DESIGN AND METHODS
A total of 41,204 patients with T2D from four Thrombolysis In Myocardial Infarction (TIMI) clinical trials were divided into derivation (70%) and validation cohorts (30%). Candidate predictors of kidney disease progression (composite of sustained ≥40% decline in estimated glomerular filtration rate [eGFR], end-stage kidney disease, or kidney death) were selected with multivariable Cox regression. Efficacy of dapagliflozin was assessed by risk categories (low: <0.5%; intermediate: 0.5 to <2%; high: ≥2%) in Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58.
RESULTS
There were 695 events over a median follow-up of 2.4 years. The final model comprised eight independent predictors of kidney disease progression: atherosclerotic cardiovascular disease, heart failure, systolic blood pressure, T2D duration, glycated hemoglobin, eGFR, urine albumin-to-creatinine ratio, and hemoglobin. The c-indices were 0.798 (95% CI, 0.774-0.821) and 0.798 (95% CI, 0.765-0.831) in the derivation and validation cohort, respectively. The calibration plot slope (deciles of predicted vs. observed risk) was 0.98 (95% CI, 0.93-1.04) in the validation cohort. Whereas relative risk reductions with dapagliflozin did not differ across risk categories, there was greater absolute risk reduction in patients with higher baseline risk, with a 3.5% absolute risk reduction in kidney disease progression at 4 years in the highest risk group (≥1%/year). Results were similar with the 2022 Chronic Kidney Disease Prognosis Consortium risk prediction model.
CONCLUSIONS
Risk models for kidney disease progression can be applied in patients with T2D to stratify risk and identify those who experience a greater magnitude of benefit from SGLT2 inhibition.
Topics: Humans; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Disease Progression; Glomerular Filtration Rate; Kidney; Myocardial Infarction; Renal Insufficiency, Chronic; Risk Assessment; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37556796
DOI: 10.2337/dc23-0492 -
JACC. Heart Failure Oct 2023Among patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular...
BACKGROUND
Among patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU.
OBJECTIVES
This study aims to explore the pathophysiological significance of HFpEF-latentPVD.
METHODS
The authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients.
RESULTS
Out of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (P = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O tension (R = 0.33) and stroke volume (R = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO (P < 0.05), which correlated with resting PVR (R = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05).
CONCLUSIONS
The results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, and pulmonary vascular hyperreactivity, portending a poor prognosis.
Topics: Humans; Stroke Volume; Heart Failure; Tricuspid Valve Insufficiency; Cardiac Output; Vascular Diseases; Exercise Test
PubMed: 37115127
DOI: 10.1016/j.jchf.2023.03.003