scholarly journals Survival analysis in hypertrophic cardiomyopathy caused by the three most common pathogenic TPM1 variants

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Lamounier Junior ◽  
D Alonso Garcia ◽  
G Fernandez Ferro ◽  
I J Cardenas Reyes ◽  
M Noel Brogger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Survival Data ◽  
Cardiovascular Death ◽  
Rank Test ◽  
Private Company ◽  
Male And Female ◽  
Missense Variants ◽  
Male Carriers ◽  
Female Carriers

Abstract Purpose To evaluate survival free of cardiovascular events in carriers of the three most frequent TPM1 pathogenic hypertrophic cardiomyopathy (HCM) variants. Methods Clinical and genetic data on families carrying TPM1 variants in the literature and identified in our center were systematically revised and collected in a database. Classification of variant's pathogenicity was in accordance with ACMG criteria. We evaluated available follow-up data and constructed Kaplan-Meier survival curves to cardiovascular death (sudden death, appropriate cardiodefibrillator shock, heart failure death, and stroke-related death) or heart transplant. Long-rank test was used to compare event-free survival time. Results 562 carriers (343 HCM-probands and 219 relatives; 51.3% male carriers) were identified carrying 73 missense variants considered disease causing. TPM1 p.Asp175Asn (87 probands, 109 relatives, 6 unaffected), p.Arg21Leu (52 probands, 25 relatives, 16 unaffected), and p.Met281Val (37 probands, 8 relatives, 9 unaffected) were the most prevalent HCM-variants. Among these three variants, survival data was reported for 508 individuals. Eight-nine carriers had suffered events: 74 sudden deaths (55% males), nine heart failure deaths (44% males), two transplants (50% males), and five stroke-related death (25% males). Incidence of cardiovascular death or transplant was similar between TPM1 p.Arg21Leu and p.Met281Val (p=0.75) and different than p.Asp175Asn (p=0.03 and p=0.06, respectively) and all TPM1 variants (p=0.004 and p=0.04). Analysis by sex showed TPM1 p.Arg21Leu female carriers had better prognosis than p.Asp175Asn male carriers (p=0.048) and all TPM1 male and female carriers (p=0.02 and p=0.04) (curves not showed in the graph). Conclusion TPM1 p.Arg21Leu and p.Met281Val could have a better prognosis than p.Asn175Asn and all other TPM1 missense variants in HCM. No marked difference was observed between male and female carriers. More than 80% of the events were arrhythmic deaths. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): HEALTH IN CODE SL

Survival analysis in arrhythmogenic/dilated cardiomyopathy caused by pathogenic DSP truncating variants

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lamounier Junior ◽  
D Alonso Garcia ◽  
G Fernandez Ferro ◽  
I.J Cardenas Reyes ◽  
J Salazar-Mendiguchia Y Garcia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Dilated Cardiomyopathy ◽  
Survival Data ◽  
Cardiovascular Death ◽  
Rank Test ◽  
Funding Source ◽  
Survival Curves ◽  
Private Company ◽  
Splicing Site

Abstract Background Desmoplakin (DSP) truncating variants have been associated with arrhythmogenic cardiomyopathy (ACM), which can exclusively affect the left ventricle up to 30% of the cases. Nonetheless, data on prognosis in carriers is still limited. Purpose To evaluate survival free of cardiovascular events in carriers of pathogenic DSP truncating variants. Methods Clinical and genetic data on families carrying DSP truncating variants (nonsense, frameshift, and splicing-site) in the literature were systematically revised and collected in a dedicated database. Classification of variant pathogenicity was in accordance with ACMG criteria. We evaluated available follow-up data and constructed Kaplan-Meier survival curves free from cardiovascular death (sudden death, appropriate cardiodefibrillator shock, heart failure death, and stroke-related death) or heart transplant based. Long-rank test was used to compare event-free survival time between genders. Results 707 carriers (336 index cases and 371 relatives; 51.1% were female carriers) were identified carrying 198 variants (90 nonsense, 89 frameshift, 19 splicing-site). 292 had ACM, 136 dilated cardiomyopathy (DCM), eight cases of unexplained sudden death, 120 were unaffected carriers, and no clinical data was reported in 151 carriers. In addition, 73 affected relatives without genetic testing were reported (28 had ACM, 28 DCM, and 17 unexplained sudden deaths). Survival data was reported for 449 individuals (221 males; 228 females). Eight-one had suffered events: 57 sudden cardiac death (32 males), 10 heart failure deaths (7 males), 7 transplants (5 males), 6 cardiodefibrillator shock (4 females), and one stroke-related death (1 female). Incidence of cardiovascular death or transplant was higher in males than females (p=0.012), with annual incidence between ages 30–70 of 0.84%/year in males and 0.72%/year in females. Mortality at the age of 50 years was 31% for males and 16% for females. Conclusion DSP truncating variants are associated with a relevant risk of cardiovascular death, which is higher in males, especially after age 30. More than 70% of the events were sudden deaths. DSP truncating variants survival curves Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Health in Code SA

scholarly journals Effects of canagliflozin on cardiovascular death and hospitalization for heart failure by baseline estimated glomerular filtration rate: integrated analyses from the CANVAS Program and CREDENCE

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.W Mahaffey ◽  
G Bakris ◽  
J Blais ◽  
C.P Cannon ◽  
D Cherney ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Funding Source ◽  
Private Company ◽  
Interaction Terms ◽  
Hazard Ratios ◽  
Death Event ◽  
Cv Disease

Abstract Background People with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular (CV) disease, including hospitalization for heart failure (HHF), a complication that is more common as renal function declines. The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin (CANA) reduced the risk of HHF in patients with T2DM and high CV risk or nephropathy in the CANVAS Program and CREDENCE trials, respectively. Methods This post hoc analysis included integrated, pooled data from the CANVAS Program and the CREDENCE trial. The effects of CANA compared with placebo on CV death or HHF, HHF, and CV death were assessed in subgroups defined by baseline eGFR (<45, 45–60, and >60 mL/min/1.73 m2). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity. Interaction P values were calculated by including treatment group and baseline eGFR in the model. Results A total of 14,543 participants from the CANVAS Program (N=10,142) and CREDENCE (N=4,401) were included, with mean age, 65 y; 65% male; 75% white; mean eGFR 70.3 mL/min/1.73 m2. 1919 (13.2%) participants had baseline eGFR <45 mL/min/1.73 m2 (mean, 36.7 mL/min/1.73 m2), 2972 (20.4%) participants had eGFR 45–60 mL/min/1.73 m2 (mean, 53.1 mL/min/1.73 m2), and 9649 (66.3%) participants had eGFR >60 mL/min/1.73 m2 (mean, 82.3 mL/min/1.73 m2). Rates of CV death or HHF, HHF, and CV death increased as eGFR declined (Figure). CANA significantly reduced the risk of CV death or HHF and HHF compared with PBO, with consistent effects observed across subgroups. Conclusions CV death or HHF, HHF, and CV death event rates increased with lower baseline eGFR. CANA significantly reduced the risk of CV death or HHF, jointly and individually, in participants with T2DM and high CV risk or CKD in the CANVAS Program and the CREDENCE trial, with consistent benefits observed regardless of baseline eGFR. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Janssen Scientific Affairs, LLC

Clinical characteristics and prognostic impact of pulmonary hypertension in heart failure with preserved ejection fraction: the PURSUIT HFpEF study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Sera ◽  
T Ohtani ◽  
K Nakamoto ◽  
T Yamada ◽  
Y Yasumura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Right Atrial ◽  
Rank Test ◽  
Heart Catheterization ◽  
Funding Source ◽  
Prognostic Impact ◽  
Preserved Ejection Fraction ◽  
Private Company

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pulmonary hypertension (PH), which can result from pre-capillary PH as well as post-capillary PH. However, the prevalence and clinical significance of pre-capillary component of PH in HFpEF remain unknown. Purpose We aimed to investigate prevalence, clinical features, and prognostic impact of pre-capillary and/or post capillary PH associated with HFpEF. Methods From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 204 patients (men: 46%, age: 79±9 years) who were hospitalized with HF and underwent right heart catheterization were divided into 4 groups according to the PH guidelines: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). Patients who had been diagnosed with idiopathic pulmonary arterial hypertension were excluded from the analysis. Results The prevalence of PH was 31% (Ipc-PH: 22%, pre-capillary PH: 3%, Cpc-PH: 6%). The prevalence of subcategories of PH was significantly different depending on mean right atrial pressure (RAP) (figure). Echocardiography at discharge showed no significant differences in RV diameter or TAPSE, but smaller LV diameter and higher E/e' in pre-capillary PH and Cpc-PH, which resulted in a higher operant diastolic elastance (Ed). Composite endpoint of all-cause mortality and HF hospitalization at 1 year occurred 13% in non-PH, 25% in Ipc-PH, 49% in pre-capillary PH, and 63% in Cpc-PH, respectively (p=0.001 by log-rank test). Conclusions Distinct prevalence of PH was observed in the groups with different RAP levels. Pre-capillary component of PH was associated with impaired LV diastolic function and worse outcomes in HFpEF. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd

scholarly journals Significant Improvement of Survival By T2* Cardiovascular Magnetic Resonance in Thalassemia Major

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4567-4567
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giovanni Carlo Del Vecchio ◽  
Maria Antonietta Romeo ◽  
Maria Rita Gamberini ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Survival Data ◽  
Cox Model ◽  
Thalassemia Major ◽  
Rank Test ◽  
Cardiac Siderosis ◽  
Kaplan Meier ◽  
Significant Difference

Abstract Background: In 2004 seven Italian centers reported survival data for patients with thalassemia major (TM) and showed that heart disease due to iron overload was the most common cause of death (Borgna et al Haematologica 2004). In the same years the accurate and noninvasive assessment of cardiac siderosis was made possible in Italy by the introduction of the T2* cardiovascular magnetic resonance (CMR). Purpose: We aimed to evaluate if the deployment of T2* CMR had an impact on the mortality rate. Methods: Four centers contributed to the present study, updating the data of the enrolled patients until August 31, 2010. For the patients who died, the date of the death represented the end of the study. 577 patients (264 females and 313 males) were included. Results: One-hundred and fifty-nine (27.6%) patients died, 124 of whom (77.9%) died before the year 2000. The Table shows the comparison between dead patients and survivors. Dead patients were significantly younger and they were more frequently males. Dead patients started chelation therapy significantly later. HIV, arrhythmias and heart failure were significantly more frequent in dead patients. According to the Cox model, the following variables were identified as significant univariate prognosticators for the death: male sex (HR=1.87, 95%CI=1.34-2.60, P<0.0001), HIV (HR=2.55, 95%CI=1.25-5.20, P=0.010) and heart failure (HR=8.86, 95%CI=6.37-12.31, P<0.0001). MRI was not performed in 406 patients (70.4%) and no patient had been scanned before his/her death. Among the survivors, MRI was not performed in the 59% of the cases (P<0.0001). The absence of an MRI scan was a significant univariate prognosticator for death (HR=43.25, 95%CI=11.32-165.33, P<0.0001). The study was restricted to the patients dead after 2004 (19/159=12%) or followed until August 2010 (N=357). In this subgroup of 376 patients, MRI was not performed in the 52.4% of the survivors and in all dead patients (P<0.0001). The absence of a MRI exam was reconfirmed as a strong predictive factor for death (HR=49.37, 95%CI=1.08-2263.24, P=0.046). The Kaplan-Meier curve is showed in Figure 1. The log-rank test revealed a significant difference in the curves (P<0.0001). Conclusions: Our data suggests that the use of T2* CMR, that enables individually tailored chelation regimes reducing the likelihood of developing decompensated cardiac failure, allowed the reduction of cardiac mortality in chronically transfused TM patients. Table 1. Table 1. Figure 1. Figure 1. Disclosures Pepe: Novartis: Speakers Bureau; Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau.

scholarly journals Marfan syndrome: genetic variant determinants of cardiovascular outcomes

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M N Brogger ◽  
G Fernandez Ferro ◽  
I Cardenas Reyes ◽  
J P Ochoa ◽  
S Garcia Hernandez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Aortic Dissection ◽  
Marfan Syndrome ◽  
Genetic Variants ◽  
Genetic Variant ◽  
Cysteine Residue ◽  
Private Company ◽  
Missense Variants ◽  
Fbn1 Gene ◽  
Worse Prognosis

Abstract Background Marfan syndrome is a systemic connective tissue disorder caused by genetic variants in the fibrillin-1 (FBN1) gene. Cardiovascular complications are the leading cause of mortality. Purpose To compare cardiovascular outcome by gender and by type of the genetic variant in the FBN1 gene. Materials and methods We analyzed clinical data on 1956 carriers and affected relatives with 1430 pathogenic or likely pathogenic genetic variants in the FBN1 gene (including cases identified in our laboratory and cases described in the literature) in whom age at last follow-up was available. We excluded patients with pathogenic or likely pathogenic genetic variants located in the so-called “neonatal region” (exon 24–32); they are recognized to have an early onset/severe phenotype. Kaplan-Meier survival curves were generated to examine gender and type of genetic variant in relation to survival free of surgical intervention or cardiovascular (CV) death (composite of deaths related to aortic dissection, heart failure/transplant, sudden, stroke or CV surgery). Genetic variants were classified as truncating (nonsense, frameshift and splicing), “missense non-neonatal” and only those missense eliminating a Cysteine residue in the non-neonatal region (“Cys non-neonatal”). Results Data were examined on 896 patients with truncating variants (53% male; 47% female) and 1060 with missense variants, located outside the “neonatal region” (54% male; 46% female). Of these, 475 were missense variants substituting a cysteine residue (52% male; 48% female). Those with truncating variants had worse prognosis versus those with missense and Cys variants (p=0.000108 and p=0.000115), with earlier onset of cardiovascular events. Overall, patients with missense variants had similar prognosis to those with missense variants eliminating a Cysteine residue. By age 65, however, almost 50% of patients with any type of variant had suffered a CV event, and with each variant type males had worse prognosis (see Figure 1). This was most evident in males aged 30 to 50 with missense variants that substituted a Cysteine residue, while female carriers of these variants had a prognosis similar to other missense variants (see Figure 2). During the first decade carriers of missense and truncating variants mainly died of heart failure. From age 10 to 50, aortic dissection was the most common event, while later other events became more frequent, e.g. vascular intervention and sudden death. Conclusion In our cohort, male carriers of pathogenic or likely pathogenic variants had worse prognosis versus females. Carriers of truncating variants had the worst CV outcomes. However, it is noteworthy that by age 65, regardless of gender or mutation type, close to 50% of patients had experienced a major CV event/death. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Health in Code Figure 2. Type by gender

scholarly journals Narrowing of the neonatal region in the FBN1 gene

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M N Brogger ◽  
G Fernandez Ferro ◽  
I Cardenas Reyes ◽  
J P Ochoa ◽  
S Garcia Hernandez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Variants ◽  
Severe Form ◽  
Private Company ◽  
Missense Variants ◽  
Funding Sources ◽  
Fbn1 Gene ◽  
Pathogenic Variants ◽  
Kaplan Meier ◽  
Worse Prognosis

Abstract Background Neonatal Marfan syndrome (MFS) is considered the most severe form of MFS and is characterized by early childhood death due to congestive heart failure. It has been suggested that genetic variants associated with this clinical presentation, cluster in a specific region between exons 24 and 32. It has been reported that patients carrying genetic variants in these exons have worse prognosis. Purpose Our purpose was to analyze cardiovascular outcome by location of the genetic variants in the “neonatal region” of the FBN1 gene. Materials and methods We analyzed clinical data on 1353 carriers and affected relatives with 683 missense pathogenic or likely pathogenic genetic variants of FBN1 gene (including cases identified in our laboratory and cases described in the literature) in whom age at last follow-up was available. Kaplan-Meier survival curves were generated to examine location of the genetic variant in the FBN1 gene in relation to survival free of surgical intervention or cardiovascular (CV) death (composite of deaths related to aortic dissection, heart failure/transplant, sudden, stroke or CV surgery). Missense genetic variants were classified as located in the “neonatal region” (residues 952–1363, corresponding to exons 24–32) and in the “non-neonatal region” (residues 45–951 and 1364–2731). In the “neonatal region”, we have also analyzed a sub-region of “over-representation” of heart failure deaths in the first year of life, which we called “critical neonatal region” (amino acids 1028–1088, corresponding to exon 25 and few residues from exon 26) in comparison to the “non-critical neonatal region”. Results Data were examined on 1060 patients with missense variants located in the “non neonatal region” and on 293 patients with missense variants located in the “neonatal region”. Of these, 96 patients were carriers of missense variants in the “critical neonatal region”, the rest of patients carried variants in the neonatal region, outside this particular domain (“non-critical neonatal region”). Patients carrying missense variants in the neonatal region had worse prognosis than those carrying variants outside this region. This poorer outcome was due to events occurring in patients carrying variants in the “critical neonatal region” (see Figure). These patients had the worse prognosis (p=0.000108, vs. the other groups). Furthermore, events in the non-critical neonatal region were similar to other missense variants located outside the neonatal region. There were no differences in the “neonatal region” when analyzing by gender. Conclusion In our cohort, the worse prognosis seen in patients carrying missense pathogenic or likely pathogenic variants in the “neonatal region” compared to the “non-neonatal region”, was due to events in patients carrying missense variants in a small subregion which we called the “critical-neonatal region” (exons 25 and 26). These patients had the worse prognosis, irrespective of gender. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Health in Code Figure 1. Neonatal region FBN1

Abstract 17387: Time Difference Between Mitral and Tricuspid Opening Has a Prognostic Value in Patients With Heart Failure

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Masataka Sugahara ◽  
Masanori Asakura ◽  
Akiko Goda ◽  
Kumiko Masai ◽  
Tohru Masuyama
Keyword(s):  
Heart Failure ◽  
Pulmonary Artery ◽  
Prognostic Value ◽  
Cardiovascular Death ◽  
Time Difference ◽  
Rank Test ◽  
Hemodynamic Assessment ◽  
Patients With Heart Failure ◽  
Valve Opening ◽  
Cox Analysis

Introduction: It is certain that comprehensive noninvasive assessment of LV and RV hemodynamics is valuable in the management of patients with heart failure (HF); however, the value of the noninvasive bi-ventricular hemodynamic assessment has been hampered by methodological limitations. Dual Doppler echocardiography was used to overcome the limitations by measuring a time difference between the mitral and tricuspid valve opening (MO-TO time) in a real-time fashion. Hypothesis: We hypothesized that MO-TO time was of additive prognostic value in patients with HF. Methods: We prospectively enrolled 60 patients with sinus rhythm who were admitted because of worsening of HF and underwent an invasive hemodynamic study after stabilization of the acute phase of HF. MO-TO time was measured in addition to routine echo parameters, invasive hemodynamic parameters and plasma BNP level in all patients. Patients were divided into either of two groups based on the MO-TO time: MOP (MO precedes to TO), and TOP (TO precedes to MO) groups. We followed up the predefined adverse outcome, cardiovascular death, and hospitalization due to worsening HF in all patients for a year. Results: The pulmonary artery wedge pressure (PAWP) and mean pulmonary artery pressure (mPAP) were higher in the MOP group than in the TOP group (21 ± 8.5 vs. 11 ± 4.5 mmHg, p < 0.001; 32 ± 8.8 vs. 21 ± 5.5, p < 0.001), respectively. PAWP and mPAP correlated with the MO-TO time (r = -0.74, p < 0.001; r = -0.70, p < 0.001). MOP had a high probability of adverse cardiovascular outcome (Log-rank test; p = 0.002). In univariate Cox analysis, mitral E/A ratio, BNP, and MO-TO time were significant predictors (p = 0.044, p = 0.019, and p = 0.012), respectively. An addition of MOP improved the predictive power of univariate predictors (mitral E/A ratio, BNP) in the bivariate Cox analysis. Conclusions: The MO-TO time may be a useful marker to detect the elevation of PAWP and mPAP. MOP reflects pulmonary hypertension due to left heart disease and has a prognostic value in predicting adverse cardiovascular events in patients with HF.

Abstract 12390: Right Heart Failure Predicts Higher Mortality in Patients With Hypertrophic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Stephen A McCullough ◽  
Yuichi J Shimada ◽  
Aaron L Baggish ◽  
Patricia A Lowry ◽  
Caitlin O’Callaghan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Right Heart Failure ◽  
Cox Proportional Hazards Model ◽  
Right Atrial ◽  
Rank Test ◽  
Mortality Data ◽  
Heart Catheterization ◽  
Right Heart ◽  
Clinical Correlates

Introduction: The clinical correlates of right heart failure (RHF) and its association with mortality in hypertrophic cardiomyopathy (HCM) have not been reported previously. Methods: We performed a retrospective cohort study of patients in our HCM program who underwent right heart catheterization between 1997 and 2012. RHF was assessed by right atrial pressure (RAP). Clinical correlates assessed were mean pulmonary artery pressure (PAP), mean pulmonary capillary wedge pressure (PCWP), atrial fibrillation (AF), ventricular tachycardia/fibrillation (VT/VF), and mortality. Data were analyzed with linear regression for PAP and PCWP, logistic regression for AF and VT/VF, and the Cox-proportional hazards model and the log-rank test for mortality. Results: 147 patients (age 68 ± 14 years, 54% women) were included in the study, with median follow-up for mortality 7.0 years. Median RAP was 6 mmHg [interquartile range, 4-9 mmHg]. Higher RAP was associated with higher PAP (+7.4 ± 0.8 mmHg per 5 mmHg increase, p < 0.001) and PCWP (+5.0 ± 0.5 mmHg per 5 mmHg increase, p < 0.001). Higher RAP was associated with prior AF (odds ratio [OR] = 1.6 [1.05 - 2.5] per 5 mmHg increase, p = 0.03) and prior VT/VF (OR = 1.6 [1.04 - 2.4] per 5 mmHg increase, p = 0.03). Higher RAP was found to predict overall mortality (hazard ratio [HR] = 2.5 [1.2 - 5.0] per 5 mmHg increase, p = 0.01). When data were dichotomized, RAP > 10 mmHg was associated with increased mortality (p = 0.002, Figure). Conclusions: (1) As in other causes of heart failure, RHF in HCM is associated with higher PAP and PCWP. (2) RHF in HCM is associated with a higher prevalence of AF and VT/VF. (3) RHF in HCM is associated with increased mortality.

scholarly journals The effects of dapagliflozin on kidney and cardiovascular outcomes in patients with chronic kidney disease with and without heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J L Heerspink ◽  
D C Wheeler ◽  
P Vart ◽  
N Jongs ◽  
F F Hou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Premature Mortality ◽  
Cardiovascular Death ◽  
Private Company ◽  
Double Blind ◽  
Funding Sources

Abstract Background Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and the severity of kidney impairment increases risk of HF, highlighting the deleterious interplay between the conditions. The DAPA-CKD trial showed that dapagliflozin reduced the risk of kidney failure and HF hospitalization in patients with CKD. Purpose This prespecified analysis of DAPA-CKD aimed to determine the effects of dapagliflozin on kidney, cardiovascular and mortality outcomes according to presence or absence of HF. Methods DAPA-CKD (NCT03036150) was a randomized, double blind, controlled trial, which enrolled 4,304 participants with CKD. Participants were randomized to dapagliflozin 10 mg/day or placebo, as adjunct to standard care, and were followed for a median 2.4 years. The primary endpoint was a composite of sustained decline in eGFR ≥50%, end-stage kidney disease, or renal or cardiovascular death. Key secondary endpoints included a composite of cardiovascular death or HF hospitalization and all-cause mortality. Results Overall, 468 (11%) participants had a HF diagnosis at baseline. Participants with HF were older (65.3 vs 61.4 years) and more frequently diagnosed with type 2 diabetes (77% vs 66%) compared with those without HF; mean eGFR was similar (43.2 vs 43.1 mL/min/1.73m2) in the two groups. The primary outcome occurred more frequently in those with versus without HF (8.8 vs 5.7 events per 100 patient-years, respectively). The effect of dapagliflozin on the primary outcome was consistent among those with (hazard ratio [HR] 0.58; 95% CI 0.37, 0.91) or without HF (HR 0.62; 95% CI 0.51, 0.75; p-interaction 0.59). The composite of cardiovascular death or HF hospitalization (HR 0.68; 95% CI 0.44, 1.05 vs 0.70; 95% CI 0.51, 0.97; p-interaction 0.90), and the relative risk reduction for mortality (HR 0.56; 95% CI 0.34, 0.93; vs 0.73; 95% CI 0.54, 0.97; p-interaction 0.39) were also consistent in those with or without HF. Conclusion Patients with co-existing CKD and HF are at high risk of kidney and cardiovascular events and premature mortality. Dapagliflozin consistently reduced the proportional risk of these events, regardless of the presence or absence of HF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca

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