ABSTRACT
Low-Density Lipoprotein (LDL) cholesterol is one of the main target for cardiovascular (CV) prevention and therapy. In the last years, Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9-i) has emerged as a key therapeutic target to lower LDL and were introduced for prevention of CV events. Recently (June 2022) the Italian Medicines Agency (AIFA) modified the eligibility criteria for the use of PCSK9-i. We designed an observational study to estimate the prevalence of eligible subjects and evaluate the effectiveness of PCSK9-i applying a Target Trial Emulation (TTE) approach based on Electronic Health Records (EHR). Subjects meeting the eligibility criteria were identified from July 2017 (when PCSK9-i became available) to December 2020. Outcomes were all-cause death and the first hospitalization. Among eligible subjects, we identified those treated at date of the first prescription. Inverse Probability of Treatment Weights (IPTW) were estimated including demographic and clinical covariates, history of treatment with statins and the month/year eligibility date. Competing risk models on weighted cohorts were used to derive the Average Treatment Effect (ATE) and the Conditional Average Treatment Effect (CATE) in subgroups of interest. Out of 1976 eligible subjects, 161 (8%) received treatment with PCSK9-i. Treated individuals were slightly younger, predominantly male, had more severe CV conditions, and were more often treated with statin compared to the untreated subjects. The latter exhibited a higher prevalence of non-CV comorbidities. A significant absolute and relative risk reduction of death and a lower relative risk for the first hospitalization was observed. The risk reduction for death was confirmed in CATE analysis. PCSk9-i were prescribed to a minority of eligible subjects. Within the TTE framework, the analysis confirmed the association between PCSK9-i and lower risk of events, aligning with findings from randomized clinical trials (RCTs). In our study, PCSK9-i provided protection specifically against all-cause death, expanding upon the evidence from RCTs that had primarily focused on composite CV outcomes.
Subject(s)
Electronic Health Records , PCSK9 Inhibitors , Humans , Male , Female , Aged , Middle Aged , Cholesterol, LDL/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/mortality , Treatment Outcome , Proprotein Convertase 9/metabolismABSTRACT
BACKGROUND: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. METHODS: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. RESULTS: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -15,871-7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to 1,850 (95% CI 17-7,813) and 2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (3,848, 95% CI 574-10,640 vs. 3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. CONCLUSIONS: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.
Subject(s)
Antihypertensive Agents , Cost-Benefit Analysis , Hypertension , Humans , Antihypertensive Agents/economics , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/therapeutic use , Male , Female , Middle Aged , Aged , Italy , Hypertension/drug therapy , Adult , Drug Combinations , Angiotensin-Converting Enzyme Inhibitors/economics , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Calcium Channel Blockers/economics , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/administration & dosage , Markov Chains , Drug Therapy, Combination , Aged, 80 and over , Computer Simulation , Diuretics/administration & dosage , Diuretics/economics , Diuretics/therapeutic useABSTRACT
PURPOSE: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of evidence from randomized trials, real-world observational data become beneficial to study the effect of the treatment timing. In this study, a framework to estimate the expected outcome after an intervention in a time-to-event scenario is developed, with the aim of optimizing the timing in a personalized manner. METHODS: Retrospective real-world data are leveraged to emulate a target trial for treatment timing using multistate modeling and microsimulation. This case study focuses on myelodysplastic syndromes, serving as a prototype for rare cancers characterized by a heterogeneous clinical course and complex genomic background. A cohort of 7,118 patients treated according to conventional available treatments/evidence across Europe and United States is analyzed. The primary clinical objective is to determine the ideal timing for HSCT, the only curative option for these patients. RESULTS: This analysis enabled us to identify the most appropriate time frames for HSCT on the basis of each patient's unique profile, defined by a combination relevant patients' characteristics. CONCLUSION: The developed methodology offers a structured framework to address a relevant clinical issue in the field of hematology. It makes several valuable contributions: (1) novel insights into how to develop decision models to identify the most favorable HSCT timing, (2) evidence to inform clinical decisions in a real-world context, and (3) the incorporation of complex information into decision making. This framework can be applied to provide medical insights for clinical issues that cannot be adequately addressed through randomized clinical trials.
Subject(s)
Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Precision Medicine , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/methods , Hematologic Neoplasms/therapy , Transplantation, Homologous/methods , Male , Middle Aged , Female , Precision Medicine/methods , Adult , Aged , Retrospective Studies , Myelodysplastic Syndromes/therapy , Young AdultABSTRACT
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation being a crucial question. Here, we aimed to develop and validate a decision support system to define the optimal timing of HSCT for patients with MDS on the basis of clinical and genomic information as provided by the Molecular International Prognostic Scoring System (IPSS-M). PATIENTS AND METHODS: We studied a retrospective population of 7,118 patients, stratified into training and validation cohorts. A decision strategy was built to estimate the average survival over an 8-year time horizon (restricted mean survival time [RMST]) for each combination of clinical and genomic covariates and to determine the optimal transplantation policy by comparing different strategies. RESULTS: Under an IPSS-M based policy, patients with either low and moderate-low risk benefited from a delayed transplantation policy, whereas in those belonging to moderately high-, high- and very high-risk categories, immediate transplantation was associated with a prolonged life expectancy (RMST). Modeling decision analysis on IPSS-M versus conventional Revised IPSS (IPSS-R) changed the transplantation policy in a significant proportion of patients (15% of patient candidate to be immediately transplanted under an IPSS-R-based policy would benefit from a delayed strategy by IPSS-M, whereas 19% of candidates to delayed transplantation by IPSS-R would benefit from immediate HSCT by IPSS-M), resulting in a significant gain-in-life expectancy under an IPSS-M-based policy (P = .001). CONCLUSION: These results provide evidence for the clinical relevance of including genomic features into the transplantation decision making process, allowing personalizing the hazards and effectiveness of HSCT in patients with MDS.
Subject(s)
Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Transplantation, Homologous , Humans , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/genetics , Hematopoietic Stem Cell Transplantation/methods , Middle Aged , Male , Retrospective Studies , Female , Aged , Adult , Time Factors , Decision Support Systems, Clinical , Genomics , Decision Support Techniques , Risk Assessment , Young AdultABSTRACT
BACKGROUND: Patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored. OBJECTIVES: In the present study, the authors sought to define differences in LV remodeling and outcome prediction after CRT when stratifying patients according to the presence or absence of DCM-causing genetic background. METHODS: From our center, 74 patients with DCM subjected to CRT and available genetic testing were retrospectively enrolled. Carriers of causative monogenic variants in validated DCM-causing genes, and/or with documented family history of DCM, were classified as affected by genetically determined disease (GEN+DCM) (n = 25). Alternatively, by idiopathic dilated cardiomyopathy (idDCM) (n = 49). The primary outcome was long-term LV remodeling and prevalence of super response to CRT (evaluated at 24-48 months after CRT); the secondary outcome was heart failure-related death/heart transplant/LV assist device. RESULTS: GEN+DCM and idDCM patients were homogeneous at baseline with the exception of QRS duration, longer in idDCM. The median follow-up was 55 months. Long-term LV reverse remodeling and the prevalence of super response were significantly higher in the idDCM group (27% in idDCM vs 5% in GEN+DCM; P = 0.025). The heart failure-related death/heart transplant/LV assist device outcome occurred more frequently in patients with GEN+DCM (53% vs 24% in idDCM; P = 0.028). CONCLUSIONS: Genotyping contributes to the risk stratification of patients with DCM undergoing CRT implantation in terms of LV remodeling and outcomes.
Subject(s)
Cardiac Resynchronization Therapy , Cardiomyopathy, Dilated , Ventricular Remodeling , Humans , Female , Male , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/therapy , Cardiomyopathy, Dilated/physiopathology , Middle Aged , Retrospective Studies , Ventricular Remodeling/genetics , Ventricular Remodeling/physiology , Aged , Treatment Outcome , Heart Failure/genetics , Heart Failure/therapy , Heart Failure/physiopathology , Adult , Ventricular Dysfunction, Left/genetics , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy , Bundle-Branch Block/genetics , Bundle-Branch Block/therapy , Bundle-Branch Block/physiopathologyABSTRACT
INTRODUCTION: We investigated the association of cognitive reserve (CR) with transitions across cognitive states and death. METHODS: This population-based cohort study included 2631 participants (age ≥60 years) who were dementia-free at baseline and regularly examined up to 15 years. Data were analyzed using the Markov multistate models. RESULTS: Each 1-point increase in the composite CR score (range: -4.25 to 3.46) was significantly associated with lower risks of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio = 0.78; 95% confidence interval = 0.72-0.85) and death (0.85; 0.79-0.93), and from CIND to death (0.82; 0.73-0.91), but not from CIND to normal cognition or dementia. A greater composite CR score was associated with a lower risk of transition from CIND to death in people aged 60-72 but not in those aged ≥ 78 years. DISCUSSION: CR contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. HIGHLIGHTS: We use Markov multistate model to examine the association between cognitive reserve and transitions across cognitive states and death. A great cognitive reserve contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. A great cognitive reserve is associated with a lower risk of transition from cognitive impairment, no dementia to death in people at the early stage of old age, but not in those at the late stage of old age.
Subject(s)
Cognitive Dysfunction , Cognitive Reserve , Humans , Cognitive Reserve/physiology , Female , Male , Aged , Follow-Up Studies , Middle Aged , Dementia/mortality , Dementia/psychology , Cohort Studies , Markov Chains , Aged, 80 and over , Disease Progression , Cognition/physiology , Neuropsychological Tests/statistics & numerical dataABSTRACT
OBJECTIVES: This study aims to show the application of flexible statistical methods in real-world cost-effectiveness analyses applied in the cardiovascular field, focusing specifically on the use of proprotein convertase subtilisin-kexin type 9 inhibitors for hyperlipidemia. METHODS: The proposed method allowed us to use an electronic health database to emulate a target trial for cost-effectiveness analysis using multistate modeling and microsimulation. We formally established the study design and provided precise definitions of the causal measures of interest while also outlining the assumptions necessary for accurately estimating these measures using the available data. Additionally, we thoroughly considered goodness-of-fit assessments and sensitivity analyses of the decision model, which are crucial to capture the complexity of individuals' healthcare pathway and to enhance the validity of this type of health economic models. RESULTS: In the disease model, the Markov assumption was found to be inadequate, and a "time-reset" timescale was implemented together with the use of a time-dependent variable to incorporate past hospitalization history. Furthermore, the microsimulation decision model demonstrated a satisfying goodness of fit, as evidenced by the consistent results obtained in the short-term horizon compared with a nonmodel-based approach. Notably, proprotein convertase subtilisin-kexin type 9 inhibitors revealed their favorable cost-effectiveness only in the long-term follow-up, with a minimum willingness to pay of 39 000 Euro/life years gained. CONCLUSIONS: The approach demonstrated its significant utility in several ways. Unlike nonmodel-based or alternative model-based methods, it enabled to (1) investigate long-term cost-effectiveness comprehensively, (2) use an appropriate disease model that aligns with the specific problem under study, and (3) conduct subgroup-specific cost-effectiveness analyses to gain more targeted insights.
Subject(s)
Cost-Benefit Analysis , Models, Economic , PCSK9 Inhibitors , Humans , Quality-Adjusted Life Years , Hyperlipidemias/drug therapy , Hyperlipidemias/economics , Computer Simulation , Markov Chains , Male , Female , Middle Aged , Aged , Proprotein Convertase 9ABSTRACT
AIMS: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients. METHODS AND RESULTS: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non-sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high-risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow-up of 6 years (interquartile range 1.6-12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. CONCLUSION: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life-threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.
Subject(s)
Cardiomyopathy, Dilated , Death, Sudden, Cardiac , Phenotype , Humans , Female , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/complications , Male , Middle Aged , Prognosis , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Adult , Risk Assessment/methods , Syncope/genetics , Syncope/etiology , Syncope/physiopathology , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/diagnosis , Stroke Volume/physiology , Tachycardia, Ventricular/genetics , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnosis , Genetic Testing/methodsABSTRACT
BACKGROUND: The changing demographic of heart failure (HF) increases the exposure to non-cardiovascular (non-CV) events. We investigated the distribution of non-CV mortality/morbidity and the characteristics associated with higher risk of non-CV events in patients with advanced HF. METHODS: Patients from the HELP-HF registry were stratified according to the number of 2018 HFA-ESC criteria for advanced HF. Endpoints were non-CV mortality and non-CV hospitalization. Competing risk analyses were performed assessing the association between HFA-ESC criteria and study outcomes and the additional predictors of non-CV endpoints. RESULTS: One thousand one hundred and forty-nine patients were included (median age 77 years-IQR 69-83). At 6, 12, 18 and 22 months, cumulative incidence of CV vs non-CV mortality was 13% vs 5%, 17% vs 8%, 20% vs 12%, 23% vs 12%, and of CV vs non-CV hospitalization was 26% vs 11%, 38% vs 17%, 45% vs 20%, 50% vs 21%. HFA-ESC criteria were associated with increasing adjusted risk of CV death, whereas no association was observed for CV hospitalization, non-CV death and non-CV hospitalization. Predictors of non-CV death were age, chronic obstructive pulmonary disease, dementia, preserved ejection fraction, >1 HF hospitalization and hemoglobin. CONCLUSIONS: Patients with advanced HF are exposed to high, even though not predominant, burden of non-CV outcomes. HFA-ESC criteria aid to stratify the risk of CV death, but are not associated with lower competing risk of non-CV outcomes. Alternative factors can be useful to define the patients with advanced HF at risk of non-CV events in order to better select patients for treatments specifically reducing CV risk.
Subject(s)
Heart Failure , Humans , Aged , Stroke Volume , Risk Factors , Heart Failure/therapy , Morbidity , Risk Assessment , Hospitalization , PrognosisABSTRACT
BACKGROUND: There are limited data on implantable-cardioverter-defibrillator (ICD) implantation after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Therefore, we evaluated when and how frequently an ICD is implanted after pPCI, the rate of appropriate ICD interventions, and predictors of ICD implantation. METHODS: We analyzed STEMI patients treated with pPCI at the University Hospital of Trieste, Italy, between January 2010 and December 2019. We cross-matched patients' data with those present in the Trieste ICD registry. RESULTS: Among 1805 consecutive patients treated with pPCI, 3.6% underwent ICD implantation during a median follow-up of 6.7 [interquartile range (IQR) 4.3-9.2] years. At 12 months, the mean number of ICD implantations was 2.3/100 patients [95% confidence interval (95% CI) 1.7-3.1] and remained stable over time (at 24âmonths: 2.5/100 patients, 95% CI 2.0-3.5 and at 36âmonths: 2.6/100 patients, 95% CI 2.3-3.8); 83.1% of ICDs were implanted for primary prevention, and more than half (55%) were implanted in patients with ejection fraction more than 35% at the moment of STEMI discharge. The rate of appropriate ICD interventions was 16.9% at a median follow-up of 5.7âyears (IQR 3.3-8.3âyears) after ICD implantation. At 12 months, the mean number of appropriate ICD interventions was 5/100 patients and 7/100 patients after 24 months. In patients with ejection fraction more than 35% at STEMI discharge (median ejection fraction 43%; IQR 40-48), independent predictors of ICD implantation were male sex, anterior STEMI and troponin peak more than 100â000âng/dl. CONCLUSION: The rate of ICD implantations after pPCI is low; however, the rate of appropriate ICD interventions is high. A relevant subgroup of patients received ICD implantations at follow-up despite a nonsevere ejection fraction at discharge after STEMI. Among these patients, those with high troponin release deserve strict follow-up and full optimal medical treatment.
Subject(s)
Defibrillators, Implantable , Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Male , Female , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Myocardial Infarction/therapy , Registries , Troponin , Treatment OutcomeABSTRACT
AIMS: In Italy, 12-month survival in the general population between 90 and 94 years old is 26%. In very old patients, the benefit of pacemaker implantation in terms of quality and duration of life is unclear. The aim of our study was to analyse clinical characteristics, outcome and factors associated with survival in patients at least 90 years old at the time of the first pacemaker implant. METHODS: Clinical parameters, device characteristics, survival and predictors of outcome in patients at least 90 years old treated with a pacemaker in our centre in 2019-2020 were evaluated. RESULTS: Among the 554 patients undergoing pacemaker implantation in our centre during the study interval, 69 (12%) were at least 90 years old; a complete/advanced atrioventricular block was present in 65%. A cardiological comorbidity (excluding atrial fibrillation) was present in 22 patients (32%). Oncological, pulmonary and neurological comorbidities were present in 12 (17%), 19 (28%) and 32 (46%), respectively. Renal impairment was present in 25 patients (36%). After pacemaker implantation, a pneumothorax developed in two patients and lead dislodgment in one. During follow-up (median 17 months, interquartile range: 13-24), 32 patients died (46%), with a 12-month mortality probability of 24.6%. At multivariate analysis, the presence of oncological (hazard ratio (HR) 5.31; Pâ<â0.001) and neurological (HR 6.44; Pâ<â0.001) comorbidities was associated with mortality. Truncating the outcome at 6 months, renal impairment (HR 8.01; Pâ=â0.003), anticoagulant therapy (HR 8.14; Pâ=â0.003), oncological comorbidities (HR 14.1; Pâ<â0.001) and left ventricular function (5% increase of left ventricular ejection fraction: HR 0.66; Pâ<â0.001) were significantly associated with outcome. CONCLUSION: At our centre, patients at least 90 years old underwent pacemaker implantation mainly for advanced atrioventricular block. One-year survival was excellent, even better than expected in the general population.
Subject(s)
Atrial Fibrillation , Atrioventricular Block , Cardiology , Pacemaker, Artificial , Humans , Aged, 80 and over , Atrioventricular Block/therapy , Italy/epidemiology , Pacemaker, Artificial/adverse effectsABSTRACT
BACKGROUND: Hemorrhagic and infectious events represent severe complications after percutaneous nephrolithotomy (PCNLs). Existing nephrolithometric nomograms have been introduced but their reliability in predicting complications is debated. We present a newly designed nomogram with intention to predict hemorrhagic/infectious events after PCNLs. METHODS: We conducted a multicentric prospective study on adult patients undergoing standard (24 Fr) or mini (18 Fr) PCNL. Dataset was derived from previous RCT, where patients have been assigned to mini-PCNL or standard-PCNL to treat renal stones up to 40 mm. Aim of the study was to identify preoperative risk factors for early postoperative infectious/hemorrhagic complications including fever, septic shock, transfusion or angioembolization. RESULTS: A total of 1980 patients were finally included. 992 patients (50.1%) received mini-PCNL and 848 standard PCNL (49.9%). The overall SFR was 86.1% with a mean maximum stone diameter of 29 mm (SD 25.0-35.0). 178 patients (8.9%) had fever,14 (0.7%) urosepsis, 24 patients (1.2%) required transfusion and 18 (0.9%) angioembolization. The overall complication was (11.7%). After multivariable analysis, the included elements in the nomogram were age (P=0.041), BMI (P=0.018), maximum stone diameter (P<0.001), preoperative hemoglobin (P=0.005), type 1/2 diabetes (P=0.05), eGFR<30 (P=0.0032), hypertension (>135/85 mmHg, P=0.001), previous PCNL or pyelo/nephrolithotomy (P=0.0018), severe hydronephrosis (P=0.002). After internal validation, the AUC of the model was 0.73. CONCLUSIONS: This is the first nomogram predicting infections and bleedings after PCNLs, it shows a good accuracy and can support clinicians in their patients' peri-operative workout and management.
Subject(s)
Communicable Diseases , Kidney Calculi , Nephrolithotomy, Percutaneous , Adult , Humans , Nephrolithotomy, Percutaneous/adverse effects , Nomograms , Treatment Outcome , Prospective Studies , Reproducibility of Results , Kidney Calculi/surgery , Communicable Diseases/etiology , Hemorrhage/diagnosis , Hemorrhage/etiologyABSTRACT
BACKGROUND: For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). METHODS: Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device. RESULTS: Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04-1.22], p = 0.003). Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19-4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27-6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28-0.65], p < 0.001). CONCLUSIONS: In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Among 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment).
Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Humans , Prognosis , Diuretics , Sodium Potassium Chloride Symporter Inhibitors/adverse effects , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/drug therapy , Furosemide/adverse effects , Heart Failure/diagnosis , Heart Failure/drug therapy , Heart Failure/chemically induced , Stroke VolumeABSTRACT
BACKGROUND: Left atrial (LA) dilation is associated with a worse prognosis in several cardiovascular settings, but therapies can promote LA reverse remodeling. The aim of this study was to characterize and define the prognostic implications of LA volume index (LAVI) reduction in patients with dilated cardiomyopathy (DCM). METHODS: Consecutive patients with DCM from two tertiary care centers, with available echocardiograms at baseline and at 1-year follow-up, were retrospectively analyzed. LA dilation was defined as LAVI > 34 mL/m2, and change in LAVI (ΔLAVI) was defined as the 1-year relative LAVI reduction. The outcome was a composite of death, heart transplantation (HTx), or heart failure hospitalization (HFH). RESULTS: Five hundred sixty patients were included (mean age, 54 ± 13 years; mean left ventricular ejection fraction, 31 ± 10%; mean LAVI, 45 ± 18 mL/m2). Baseline LAVI had a non-linear association with the risk for death, HTx, or HFH, independent of age, left ventricular ejection fraction, mitral regurgitation, and medical therapy (P < .01). At 1-year follow-up, LAVI decreased in 374 patients (67%; median ΔLAVI, -24%; interquartile range, -37% to -11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline left ventricular ejection fraction. After multivariable adjustment, ΔLAVI showed a linear association with the risk for death, HTx, or HFH (hazard ratio, 0.96 per 5% decrease; 95% CI, 0.93-0.99; P = .042). At 1-year follow-up, patients with reductions in LAVI of >10% and LAVI normalization (i.e., follow-up LAVI ≤ 34 mL/m2; 31% of the overall cohort) were at lower risk for death, HTx, or HFH (hazard ratio, 0.37; 95% CI, 0.35-0.97; P = .028). CONCLUSIONS: In a large cohort of patients with DCM, 1-year reduction in LAVI was observed in a number of patients. The association between reduction in LAVI and death, HTx, or HFH suggests that LA structural reverse remodeling might be considered an additional parameter useful in the individualized risk stratification of patients with DCM.
Subject(s)
Atrial Fibrillation , Atrial Remodeling , Cardiomyopathy, Dilated , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Stroke Volume , Cardiomyopathy, Dilated/diagnostic imaging , Heart Atria/diagnostic imaging , Ventricular Function, Left , PrognosisABSTRACT
In many clinical applications to evaluate the effect of a treatment, randomized control trials are difficult to carry out. On the other hand, clinical observational registries are often available and they contain longitudinal data regarding clinical parameters, drug therapies, and outcomes. In the past, much research has addressed causal methods to estimate treatment effects from observational studies. In the context of time-varying treatments, marginal structural models are often used. However, most analyses have focused on binary outcomes or time-to-the-first event analyses. The novelty of our approach is to combine the marginal structural methodology with the case where correlated recurrent events and survival are the outcomes of interest. Our work focuses on solving the nontrivial problem of defining the measures of effect, specifying the model for the time-dependent weights and the model to estimate the outcome, implementing them, and finally estimating the final treatment effects in this life-history setting. Our approach provides a strategy that allows obtaining treatment effect estimates both on the recurrent events and the survival with a clear causal and clinical interpretation. At the same time, the strategy we propose is based on flexible modeling choices such as the use of joint models to capture the correlation within events from the same subject and the specification of time-dependent treatment effects. The clinical problem which motivated our work is the evaluation of the treatment effect of beta-blockers in arrhythmogenic right ventricular cardiomyopathy (ARVC/D), and the dataset comes from the Trieste Heart Muscle Disease Registry.
Subject(s)
Cardiomyopathies , RegistriesABSTRACT
AIMS: The recent definition of heart failure with improved ejection fraction outlined the importance of the longitudinal assessment of left ventricular ejection fraction (LVEF). However, long-term progression and outcomes of this subgroup are poorly explored. We sought to assess the LVEF trajectories and their correlations with outcome in non-ischaemic dilated cardiomyopathy (NICM) with improved ejection fraction (impEF). METHODS AND RESULTS: Consecutive NICM patients with baseline LVEF ≤40% enrolled in the Trieste Heart Muscle Disease Registry with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, and second evaluation showing both a ≥10% point increase from baseline LVEF and LVEF >40%. Transient impEF was defined by the documentation of recurrent LVEF ≤40% during follow-up. The primary endpoint was a composite of all-cause death, heart transplantation and left ventricular assist device (D/HT/LVAD). Among 800 patients, 460 (57%) had impEF (median time to improvement 13 months). Transient impEF was observed in 189 patients (41% of the overall impEF group) and was associated with higher risk of D/HT/LVAD compared with persistent impEF at multivariable analysis (hazard ratio 2.54; 95% confidence interval 1.60-4.04). The association of declining LVEF with the risk of D/HT/LVAD was non-linear, with a steep increase up to 8% points reduction, then remaining stable. CONCLUSIONS: In NICM, a 57% rate of impEF was observed. However, recurrent decline in LVEF was observed in ≈40% of impEF patients and it was associated with an increased risk of D/HT/LVAD.
Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Heart-Assist Devices , Humans , Prognosis , Stroke Volume/physiology , Ventricular Function, Left/physiologyABSTRACT
Pace mapping and visual comparison of the local pacing response with the intrinsic QRS morphology form the mainstay of His bundle pacing (HBP). We evaluated the performance of a surface lead morphology match algorithm for automated classification of the pacing response in patients with narrow intrinsic QRS undergoing electroanatomic mapping (EAM)-guided HBP. HBP was attempted in 43 patients. In 28 cases with narrow QRS, the EnSite AutoMap Module was used for automated assessment of the QRS morphology resulting from pace mapping in the His cloud area with either a diagnostic catheter or the His lead. An intrinsic morphology match score (IMS) was calculated for 1.546 QRS complexes and assessed regarding its accuracy and performance in classifying the individual pacing response as either selective HBP (S-HBP), nonselective HBP (NS-HBP) or right ventricular stimulation. Automated morphology comparison of 354 intrinsic beats with the individual reference determined a test accuracy of 99% (95% CI 98.96-99.04) and a precision of 97.99-99.5%. For His-lead stimulation, an IMS ≥ 89% identified S-HBP with a sensitivity, specificity and positive predictive value of 1.00 (0.99, 1.00) and a negative predictive value of 0.99 (0.98, 1.00). An IMS between 78 and < 89% indicated NS-HBP with a sensitivity and specificity of 1.00 (0.99, 1.00) and 0.99 (0.98, 1.00), respectively. IMS represents a new automated measure for standardized individual morphology classification in patients with normal QRS undergoing EAM-guided HBP.Clinical trial registration: NCT04416958.
Subject(s)
Bundle of His , Cardiac Pacing, Artificial , Cardiac Pacing, Artificial/methods , Electrocardiography , Heart Ventricles , Humans , Predictive Value of Tests , Sensitivity and Specificity , Treatment OutcomeABSTRACT
BACKGROUND: The appropriate timing to administer antithrombotic therapies in ST-elevation myocardial infarction (STEMI) remains uncertain. This study aims to evaluate the role of antithrombotic therapy administration at first medical contact (FMC) compared with the administration in the Cathlab. METHODS: We conducted a "before-after" observational study enrolling STEMI undergoing primary percutaneous coronary intervention (PCI). Outcomes were evaluated during two successive periods, before (control group: aspirin only at FMC) and after (pretreated intervention group: heparin, aspirin plus ticagrelor at FMC) the introduction of a new regional pretreatment protocol. RESULTS: A total of 537 consecutive patients (300 in control vs. 237 in intervention group) were enrolled. The pretreated compared with no pretreated population showed better basal reperfusion, expressed as basal Thrombolysis in Myocardial Infarction (TIMI)-flow (p for trend p < 0.001). Pretreated population showed lower frequency of TIMI 0 (56.5% vs. 73.7%, odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.32-0.67, p < 0.001) and higher frequency of TIMI 2-3 (33.3% vs. 19.3% OR: 2.0, 95% CI: 1.38-2.00, p < 0.001) and TIMI 3 (14.3% vs. 9.7%, OR: 1.56, 95% CI: (0.92-2.65), p = 0.094). Pretreated compared with no pretreated population showed reduced infarct size expressed as Troponin Peak (20,286 (8726-75,027) versus 48,676 (17,229-113,900), p = 0.001), and higher left ventricular ejection fraction at discharge (53% (44-59) vs. 50% (44-56), p = 0.027). In-hospital BARC ≥ 2 bleeding were similar (2.1% vs. 2.0%, p = 0.929, in pretreated versus no pretreated population, respectively). CONCLUSION: This study provides support for an early pretreatment strategy in STEMI patients and confirmed the importance of an efficient organization of STEMI networks which allow initiation of antithrombotic treatment at FMC.