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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 -
Journal of Applied Physiology... Jul 2023Adaptation of the right ventricle (RV) to a progressively increasing afterload is one of the hallmarks of pulmonary arterial hypertension (PAH). Pressure-volume loop...
Adaptation of the right ventricle (RV) to a progressively increasing afterload is one of the hallmarks of pulmonary arterial hypertension (PAH). Pressure-volume loop analysis provides measures of load-independent RV contractility, i.e., end-systolic elastance, and pulmonary vascular properties, i.e., effective arterial elastance (E). However, PAH-induced RV overload potentially results in tricuspid regurgitation (TR). TR makes RV eject to both PA and right atrium; thereby, a ratio of RV end-systolic pressure (P) to RV stroke volume (SV) could not correctly define E. To overcome this limitation, we introduced a two-parallel compliance model, i.e., E = 1/(1/E + 1/E), while effective pulmonary arterial elastance (E = P/PASV) represents pulmonary vascular properties and effective tricuspid regurgitant elastance (E) represents TR. We conducted animal experiments to validate this framework. First, we performed SV analysis with a pressure-volume catheter in the RV and a flow probe at the aorta in rats with and without pressure-overloaded RV to determine the effect of inferior vena cava (IVC) occlusion on TR. A discordance between the two techniques was found in rats with pressure-overloaded RV, not in sham. This discordance diminished after IVC occlusion, suggesting that TR in pressure-overloaded RV was diminished by IVC occlusion. Next, we performed pressure-volume loop analysis in rats with pressure-overloaded RVs, calibrating RV volume by cardiac magnetic resonance. We found that IVC occlusion increased E, suggesting that a reduction of TR increased E. Using the proposed framework, E was indistinguishable to E post-IVC occlusion. We conclude that the proposed framework helps better understanding of the pathophysiology of PAH and associated right heart failure. This study reveals the impact of tricuspid regurgitation on pressure-volume loop analysis in right ventricle pressure overload. By introducing a novel concept of parallel compliances in the pressure-volume loop analysis, a better description is provided for the right ventricular forward afterload in the presence of tricuspid regurgitation.
Topics: Tricuspid Valve Insufficiency; Heart Ventricles; Pulmonary Artery; Animals; Rats; Pulmonary Arterial Hypertension; Stroke Volume; Male; Rats, Sprague-Dawley; Vena Cava, Inferior; Balloon Occlusion
PubMed: 37227183
DOI: 10.1152/japplphysiol.00081.2023 -
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 -
The Canadian Journal of Cardiology Jul 2023Self-expanding pulmonary valve grafts have been designed for percutaneous pulmonary valve implantation (PPVI) in patients with native repaired right ventricular (RV)...
BACKGROUND
Self-expanding pulmonary valve grafts have been designed for percutaneous pulmonary valve implantation (PPVI) in patients with native repaired right ventricular (RV) outflow tracts (RVOTs). However, their efficacy, in terms of RV function and graft remodelling remain unclear.
METHODS
Patients with native RVOTs who received Venus P-valve (N = 15) or Pulsta valve (N = 38) implants between 2017 and 2022 were enrolled. We collected data on patient characteristics and cardiac catheterization parameters as well as imaging and laboratory data before, immediately after, and 6 to 12 months after PPVI and identified risk factors for RV dysfunction.
RESULTS
Valve implantation was successful in 98.1% of patients. The median duration of follow-up was 27.5 months. In the first 6 months after PPVI, all patients exhibited resolution of paradoxical septal motion and a significant reduction (P < 0.05) in RV volume, N-terminal pro-B-type natriuretic peptide levels, and valve eccentricity indices (-3.9%). Normalization of the RV ejection fraction (≥ 50%) was detected in only 9 patients (17.3%) and was independently associated with the RV end-diastolic volume index before PPVI (P = 0.03). Nine patients had residual or recurrent pulmonary regurgitation or paravalvular leak (graded as ≥ mild), which was associated with a larger eccentricity index (> 8%) and subsided by 12 months postimplantation.
CONCLUSIONS
We identified the risk factors likely to be associated with RV dysfunction and pulmonary regurgitation following PPVI in patients with native repaired RVOTs. RV volume-based patient selection is recommended for PPVI of a self-expanding pulmonary valve, along with monitoring of graft geometry.
Topics: Humans; Pulmonary Valve; Pulmonary Valve Insufficiency; Heart Valve Prosthesis Implantation; Cardiac Surgical Procedures; Heart Ventricles; Cardiac Catheterization; Treatment Outcome; Heart Valve Prosthesis
PubMed: 36933796
DOI: 10.1016/j.cjca.2023.03.013 -
Journal of Cardiovascular Magnetic... Jul 2023When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome...
BACKGROUND
When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation.
METHODS
83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group).
RESULTS
72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; - 29 ± 21 ml/m vs - 37 ± 22 ml/m respectively, p = 0.584) and left atrial volumes (- 23 ± 30 ml/m and - 39 ± 26 ml/m respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p < 0.001) baseline multivariate predictor of lower residual MR.
CONCLUSION
In primary MR, MVR with chordal preservation may offer comparable cardiac reverse remodeling and functional benefits at 6-months when compared to MVr. Larger, multicenter CMR studies are required, which if the findings are confirmed could impact future surgical practice.
Topics: Humans; Mitral Valve Insufficiency; Mitral Valve; Stroke Volume; Predictive Value of Tests; Ventricular Function, Right; Fibrosis
PubMed: 37496072
DOI: 10.1186/s12968-023-00946-9 -
Heart (British Cardiac Society) Aug 2023Aortic regurgitation (AR) can lead to pulmonary hypertension (PHT). There is a paucity of data on the prognostic importance of PHT in these patients. We therefore aimed...
OBJECTIVE
Aortic regurgitation (AR) can lead to pulmonary hypertension (PHT). There is a paucity of data on the prognostic importance of PHT in these patients. We therefore aimed to describe the prevalence and prognostic importance of PHT in such patients.
METHODS
In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction (LVEF) >50% and with moderate or greater AR were included (n=8392). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 3.1 years, IQR 1.5-5.7 years).
RESULTS
Subjects were aged 74±14 years and 58.4% (4901) were female. Overall, 1417 (16.9%) had no PHT, and 3253 (38.8%), 2249 (26.9%), 893 (10.6%) and 580 (6.9%) patients had borderline, mild, moderate and severe PHT, respectively. Mean eRVSP was slightly higher in females than males (41±13 vs 39±12 mm Hg, p<0.0001) and increased with age in both sexes. After adjustment for age and sex, the risk of long-term mortality increased as eRVSP increased (adjusted HR (aHR) 1.20, 95% CI 1.06 to 1.36 in borderline PHT, to aHR 3.32, 95% CI 2.85 to 3.86 in severe PHT, p<0.0001). There was a mortality threshold seen from mild PHT onwards (eRVSP 41.36-44.15 mm Hg; aHR 1.41, 95%CI 1.17 to 1.68).
CONCLUSIONS
In this large cohort study, we characterise the relationship between AR and PHT in adults. In patients with ≥moderate AR, PHT is associated with a progressive risk of mortality, even at mildly elevated levels.
Topics: Male; Adult; Humans; Female; Hypertension, Pulmonary; Aortic Valve Insufficiency; Cohort Studies; Retrospective Studies; Stroke Volume; Prevalence; Ventricular Function, Left
PubMed: 37012044
DOI: 10.1136/heartjnl-2022-322187 -
Early Outcomes From a Multicenter Transcatheter Self-Expanding Pulmonary Valve Replacement Registry.Journal of the American College of... Apr 2024Transcatheter pulmonary valve replacement (TPVR) with the self-expanding Harmony valve (Medtronic) is an emerging treatment for patients with native or surgically...
BACKGROUND
Transcatheter pulmonary valve replacement (TPVR) with the self-expanding Harmony valve (Medtronic) is an emerging treatment for patients with native or surgically repaired right ventricular outflow tract (RVOT) pulmonary regurgitation (PR). Limited data are available since U.S. Food and Drug Administration approval in 2021.
OBJECTIVES
In this study, the authors sought to evaluate the safety and short-term effectiveness of self-expanding TPVR in a real-world experience.
METHODS
This was a multicenter registry study of consecutive patients with native RVOT PR who underwent TPVR through April 30, 2022, at 11 U.S.
CENTERS
The primary outcome was a composite of hemodynamic dysfunction (PR greater than mild and RVOT mean gradient >30 mm Hg) and RVOT reintervention.
RESULTS
A total of 243 patients underwent TPVR at a median age of 31 years (Q1-Q3: 19-45 years). Cardiac diagnoses were tetralogy of Fallot (71%), valvular pulmonary stenosis (21%), and other (8%). Acute technical success was achieved in all but 1 case. Procedural serious adverse events occurred in 4% of cases, with no device embolization or death. Hospital length of stay was 1 day in 86% of patients. Ventricular arrhythmia prompting treatment occurred in 19% of cases. At a median follow-up of 13 months (Q1-Q3: 8-19 months), 98% of patients had acceptable hemodynamic function. Estimated freedom from the composite clinical outcome was 99% at 1 year and 96% at 2 years. Freedom from TPVR-related endocarditis was 98% at 1 year. Five patients died from COVID-19 (n = 1), unknown causes (n = 2), and bloodstream infection (n = 2).
CONCLUSIONS
In this large multicenter real-world experience, short-term clinical and hemodynamic outcomes of self-expanding TPVR therapy were excellent. Ongoing follow-up of this cohort will provide important insights into long-term outcomes.
Topics: Humans; Adult; Pulmonary Valve; Heart Valve Prosthesis Implantation; Heart Valve Prosthesis; Cardiac Catheterization; Treatment Outcome; Pulmonary Valve Insufficiency; Registries; Prosthesis Design; Retrospective Studies
PubMed: 38569760
DOI: 10.1016/j.jacc.2024.02.010 -
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 -
Pediatric Cardiology Aug 2023The implantation of percutaneous balloon expandable valves in native or patched right ventricular outflow tracts (nRVOT) is a challenging technique due to the diversity...
The implantation of percutaneous balloon expandable valves in native or patched right ventricular outflow tracts (nRVOT) is a challenging technique due to the diversity of anatomies and shapes, the large sizes, and the distensibility of the nRVOT, for which specific techniques have been developed. We present a single center experience with balloon expandable percutaneous pulmonary valves in nRVOT, describing the techniques used, complications observed, and a short-mid term follow-up.. This is a single center descriptive study of patients who underwent a percutaneous pulmonary valve implantation in a nRVOT with a balloon expandable pulmonary valve in our center between September 2012 and June 2022.. We implanted successfully 45 valves in 46 patients (20 Sapien and 25 Melody). Tetralogy of Fallot or pulmonary atresia with VSD were the main congenital heart disease (n = 32). All were pre-stented, 18 in a one step procedure. We used a Dryseal sheath in 13/21 Sapien. In 6 patients we used the anchoring technique, 5 with a very large nRVOT and one pyramidal nRVOT. In the 3.5 year follow-up 7 patients developed endocarditis and 3 required a valve redilation, no fractures were observed. PPVI of native RVOT with balloon expandable valves is feasible in a number of selected anatomies, including large or pyramidal nRVOT, using specific techniques, (presenting, LPA anchoring).
Topics: Humans; Pulmonary Valve; Heart Valve Prosthesis Implantation; Pulmonary Valve Insufficiency; Heart Valve Prosthesis; Treatment Outcome; Heart Defects, Congenital; Cardiac Catheterization; Prosthesis Design; Retrospective Studies
PubMed: 37147525
DOI: 10.1007/s00246-023-03173-2