Autore/Fonte: Federica Ponzi, Bernardino Bruno, Daniela Antenucci, Federica Tancredi, Luciano Lippa
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Novembre 2023
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Autore/Fonte: Federica Ponzi, Bernardino Bruno, Daniela Antenucci, Federica Tancredi, Luciano Lippa
Circulation, Volume 150, Issue Suppl_1, Page A4144595-A4144595, November 12, 2024. Background:Impella 5.5 provides robust support as temporary mechanical circulatory support (t-MCS) device in advanced heart failure patients in cardiogenic shock. Understanding short- and long-term outcomes is crucial.Hypothesis:Impella 5.5 supports advanced heart failure patients in cardiogenic shock and successfully bridges them to cardiac replacement without affecting long-term survival.Methods:From February 2020 to April 2024, all patients who received an Impella 5.5 and underwent evaluation for advanced therapies at Houston Methodist Hospital were identified. Implantation of Heartmate 3 (HM3) Left Ventricular Assist Device (LVAD), orthotopic heart transplantation (OHT), mortality, and device removal after Impella implantation were assessed. For HM3 LVAD patients, outcomes were categorized as death, transplantation, or survival. Survival after OHT was analyzed using Kaplan-Meier analysis and compared to patients who received OHT without Impella 5.5. Cumulative incidence rates was calculated using Competing risk regression.Results:140 patients were identified, median age 59.4 years (50.4-66.5), majority Caucasian (54%) and Black (36%). 89 (63.6%) were either bridged to advanced therapies or recovered. 52 (37.1%) underwent OHT, 21 (15%) received an HM3 LVAD, and 51 (36.4%) died post-implantation. 3 (2.1%) died post-transplant. Post-LVAD, 6 (4.3%) died, 3 (2.1%) underwent OHT, and 12 (8.6%) were alive with LVAD. 10 (7.1%) survived after Impella 5.5 removal, 2 (1.4%) went to hospice, and 1 (0.7%) was transferred to another hospital. 3 (2.1%) are currently hospitalized. Fig1a shows outcomes. Fig1b indicates death within 90 days of Impella implantation. 3-year survival of patients bridged with Impella to OHT (N=55) was 94%, comparable (p=0.27) to patients receiving OHT without Impella (N=215)(Fig 1c).Conclusion:Mortality for cardiogenic shock patients remains high. Using Impella 5.5 with a cardiac replacement strategy can salvage some patients. Long-term outcomes for patients bridged to heart transplant with Impella 5.5 are similar to those without the device. Further studies on predictors of early adverse outcomes post-implant can help mitigate risks for advanced heart failure patients in cardiogenic shock.
Circulation, Volume 150, Issue Suppl_1, Page A4145454-A4145454, November 12, 2024. Background:Despite widespread use of the Impella 5.5 to support patients with cardiogenic shock (CS), the identification of patient profiles that benefit the most from this intervention remains a challenge. Understanding the clinical and hemodynamic characteristics associated with successful outcomes is crucial for optimizing patient selection and management.Methods:Using data from a comprehensive registry of 508 patients, we evaluated clinical stabilization among those receiving Impella 5.5 for CS. Clinical stabilization was defined as weaning from the Impella 5.5 without escalation to additional mechanical circulatory support and discharge from the hospital alive, or bridging to durable heart replacement therapy (HT or LVAD) without further escalation of support.Results:Of the 508 patients analyzed, 30.7%(N=156) achieved clinical stabilization. The mean age of the cohort was 58.4±12.6 years, with 83.7% being male. Heart failure-related cardiogenic shock (HF-CS) was present in 69.5% of the patients. No significant demographic differences were observed between the stabilization and deterioration groups (p >0.05). Patients who stabilized were more likely to have HF-CS (p
Circulation, Volume 150, Issue Suppl_1, Page A4148110-A4148110, November 12, 2024. Background:Critical Limb Ischaemia (CLI) is a concerning medical emergency condition with notable mortality among older adults. This study highlights the trends and demographic disparities in mortality rates due to CLI in patients aged 55 and older in the United States from 1999 to 2020.Aim:This study aimed to evaluate patterns and geographical variations in mortality associated with CLI among adults in the United States.Methods:Death certificates from CDC WONDER database from1999 to 2020 were analyzed to investigate mortality related to CLI among adults. Age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, stratified by year, sex, race/ethnicity, and geographical regions.Results:CLI caused a concerning 620,205 deaths among US adults aged 55+ between 1999 and 2020, primarily in hospitals (42%). The overall AAMR for CLI-related deaths showed decline from 51.6 in 1999 to 40.1 in 2020, with an AAPC of -1.51 (95% CI: -1.75 to -1.25, p < 0.000001). The AAMR experienced a steeper decrease from 1999 to 2011 (APC: -3.31, p < 0.000001), followed by a slight increase from 2011 to 2020 (APC: 0.94, p = 0.031174). Men had higher AAMRs than women, though both sexes experienced reductions (men: 48.3; women: 32.6). The AAMR for men decreased from 64.9 in 1999 to 42.8 in 2011, increasing to 50.1 by 2020. For women, the AAMR decreased from 42.9 in 1999 to 28.3 in 2014, followed by a slight increase to 32.3 by 2020. Racial/ethnic disparities were apparent, with Black individuals having the highest AAMRs (58.7), followed by Whites (39.0), American Indians/Alaska Natives (38.0), Hispanics (28.5), and Asians/Pacific Islanders (13.8). All racial groups experienced decreases in AAMRs. Geographically, AAMRs varied from 20.4 in Utah to 53.2 in Ohio. The highest mortality noted in the Midwestern region (AAMR: 43). Nonmetropolitan areas unveiled higher AAMRs than metropolitan areas (nonmetropolitan: 43.5; metropolitan: 38.2). Both regions showed a decrease in AAMRs from 1999 to 2020 (metropolitan AAPC: -1.36, p < 0.000001; nonmetropolitan AAPC: -0.81, p = 0.001399).Conclusion:Our analysis highlights significant demographic and geographic differences in older adult mortality due to CLI in the U.S. Continued decreases over time but recent upturn in mortality rates emphasizes need for focused interventions to close these gaps and to improve population health outcomes for affected populations.
Circulation, Volume 150, Issue Suppl_1, Page A4146155-A4146155, November 12, 2024. Importance:Despite the increasing use of intra-aortic balloon pumps (IABP) and Impella bridge to heart transplant (HTx), there is a paucity of comparative data on their use as bridges to heart transplantation.Objective:To compare the efficacy of IABP vs Impella (5.5 and 5.0) devices as a bridge to HTx in a cohort transplanted under the current UNOS heart allocation system.Design, Setting, and Participants:A retrospective longitudinal study of the United Network for Organ Sharing (UNOS) registry included adult patients listed for HTx between Oct 2018 and April 2022 as status 2, who were supported by IABP or Impella (5.5 and 5.0) and had a complete set of demographics, hemodynamics, medical comorbidities, inotrope requirements, and biochemical variables. The primary endpoint was a successful bridging to HTx as status 2. IABP and Impella groups were propensity-matched at a 3:1 ratio for demographics, UNOS region, baseline hemodynamics, and liver and kidney function.Results:Of 32,806 HTx during the study period, 991 patients met the inclusion criteria (Impella n=88, IABP n=903). Post-matching, there were no differences between the IABP and Impella groups in any baseline characteristic. The primary outcome occurred in 89.5% of the pre-matched population (IABP 90.1% vs Impella 83%, P = 0.055). In the matched cohort, the primary outcome occurred in 85.2% (IABP 86%, Impella 83%, P = 0.603); there was no difference in the listing by exception, multiorgan transplantation, waitlist time, waitlist mortality, or delisting. Post-transplant graft survival, infection, and renal failure were not different. Impella was associated with a lower rehospitalization rate (OR 0.54, 95% CI 0.33–0.9, P = 0.02), coronary allograft vasculopathy (OR 0.23, 95% CI 0.05–1, P = 0.05), and rejection requiring hospitalization (OR 0.13, 95% CI 0.02–1, P = 0.05).Conclusions:IABP and Impella (5.5 and 5.0) devices are equally effective as bridge-to-transplant platforms with a high transplantation rate as status 2. Additionally, Impella was associated with lower post-HTx events.
Circulation, Volume 150, Issue Suppl_1, Page A4142470-A4142470, November 12, 2024. Introduction:Surgically implanted Impella 5.5 percutaneous left ventricular assist device utilization is increasing. Most centers manage Impella 5.5 patients exclusively in the ICU; however, there are concerns regarding prolonged ICU bed utilization in clinically stable patients. This study evaluates our experience managing Impella 5.5 patients in a stepdown unit (SDU).Methods:In January 2023, select patients with Impella 5.5 at our institution were admitted to a SDU after ≥24 hours in the ICU post implant. Eligible patients had no significant bleeding, device issues, or ongoing hypoperfusion. Demographics, hemodynamics, outcomes, and adverse events (Fig) were collected retrospectively and adjudicated by multidisciplinary clinician review.Results:Between Jan 1, 2023 and Mar 31, 2024, a total of 64 patients with Impella 5.5 were managed at our institution. Of these, 42 (66%) were managed in SDU for a median (IQR) of 11 (7, 21) days (range 1-82), totaling 733 of 1055 (69%) Impella-days. SDU patients with Impella 5.5 had a median age of 60 (50, 63) years, were mostly male (55%), non-ischemic (79%), and presented with Stage C (52%) or D (43%) shock. Impella strategy in SDU patients was bridge to transplant in 60% (n=25), to decision in 31% (n=13), to durable LVAD in 8% (n=3), and for VT ablation support in 1% (n=1). Five (12%) patients required transfer back to the ICU for escalation of care.Impella 5.5 patients on SDU experienced a total of 28 adverse events (0.027 events per Impella-day), with >1 adverse event in 16/42 (38%) patients (Fig). Twenty-eight (67%) SDU patients underwent heart transplant and 10 (24%) underwent LVAD implant during the hospitalization. One patient died during their hospital course, in whom care was withdrawn due to lack of a destination option.Conclusions:For select patients with Impella 5.5 who met institutional criteria, transfer to a SDU was feasible and safe. This strategy may increase ICU throughput and optimize resource allocation.
Circulation, Volume 150, Issue Suppl_1, Page A4141218-A4141218, November 12, 2024. Background:The Impella 5.5 (Abiomed; I5.5) is a temporary mechanical circulatory support (tMCS) device currently approved for periods of ≤14 days. Although many centers have reported successful I5.5 utilization beyond this duration, the indications and clinical outcomes associated with this practice are unknown.Methods:We retrospectively analyzed patients at our institution receiving I5.5 from April 2021-September 2023. Inclusion criteria were patients which received I5.5 at our institution that reached first event– specified as death/hospice, durable VAD/heart transplant, or recovery – prior to discharge or transfer. The primary outcome was differences in first event between patients receiving I5.5 support for ≤14-days vs >14-days. Secondary outcomes were complication rates, defined by occurrence of bleeding, stroke, significant hemolysis, or device migration/malfunction. Propensity-matching was utilized to help account for potential confounders. Statistical analysis involved Wilcoxon rank-sum testing and Chi-square/Fisher’s exact tests with Benjamini-Hochberg correction.Results:Among the 162 patients which met inclusion criteria, 76 (47%) required ≤14-days of support and 86 (53%) required >14-days. Baseline demographics and baseline INTERMACS profile and SCAI class were similar. In the ≤14-days group vs >14-day group, 54% vs 72% progressed to durable VAD/transplant (p = 0.02), 28% vs 21% died/pursued hospice (p = 0.48), and 18% vs 7% recovered (p = 0.04). Sub-group analysis on a propensity-matched cohort with similar INTERMACS profile and SCAI classification did not alter the above results, with similar probability of death/hospice (p = 0.52) and increased probability of durable VAD/transplant (54% ≤14-days, 71% >14-days; p = 0.04). Time-adjusted complication rates between cohorts were similar (IRR = 1.1 ≤14 vs >14-days; 95% CI 0.3 – 1.9), but overall complication frequency was higher in the >14-day group (11% ≤14-days, 41% >14 days, p < 0.01).Conclusion:I5.5-based tMCS beyond 14 days was not associated with increased mortality or decreased probability of eventual durable VAD/transplant. We did not observe an increased incidence rate of complications for I5.5 usage beyond 14 days but did note an increased absolute probability of complications with prolonged support. Future randomized-control studies which better control for potential confounds are warranted to better identify appropriate indications for I5.5 tMCS utilization beyond 14 days.
Presentato alla Camera il policy brief di Europa Donna Italia
Circulation, Volume 150, Issue 12, Page e268-e268, September 17, 2024.
Stroke, Ahead of Print. BACKGROUND:This study aimed to quantify the global stroke burden attributable to low physical activity and high body mass index in adults aged ≥55 years using data from the Global Burden of Disease 2019 study.METHODS:We extracted data on stroke mortality, disability-adjusted life years, and risk factor exposure from the Global Burden of Disease 2019 study for people aged ≥55 years. We calculated the population-attributable fraction and absolute number of stroke cases and disability-adjusted life years attributable to low physical activity and high body mass index by location, age group, sex, and year.RESULTS:Globally, body mass index and physical inactivity-attributable stroke burden have declined modestly since 1990, but with diverging escalatory regional trajectories. Population growth and aging drive this rising burden.CONCLUSIONS:Multidimensional, context-specific strategies focused on modifiable lifestyle risks are imperative to address the modest declines and escalatory regional trajectories in body mass index and physical inactivity-attributable stroke burden.
Al via Congresso,test su popolazione insieme alla GdF a L’Aquila
New England Journal of Medicine, Volume 390, Issue 11, Page 1030-1043, March 2024.
Circulation, Ahead of Print. BACKGROUND:Heart failure (HF), which is the terminal stage of many cardiovascular diseases, is associated with low survival rates and a severe financial burden. The mechanisms, especially the molecular mechanism combined with new theories, underlying the pathogenesis of HF remain elusive. We demonstrate that phosphorylation-regulated dynamic liquid–liquid phase separation of HIP-55 (hematopoietic progenitor kinase 1–interacting protein of 55 kDa) protects against HF.METHODS:Fluorescence recovery after photobleaching assay, differential interference contrast analysis, pull-down assay, immunofluorescence, and immunohistochemical analysis were used to investigate the liquid–liquid phase separation capacity of HIP-55 and its dynamic regulation in vivo and in vitro. Mice with genetic deletion of HIP-55 and mice with cardiac-specific overexpression of HIP-55 were used to examine the role of HIP-55 on β-adrenergic receptor hyperactivation-induced HF. Mutation analysis and mice with specific phospho-resistant site mutagenesis were used to identify the role of phosphorylation-regulated dynamic liquid–liquid phase separation of HIP-55 in HF.RESULTS:Genetic deletion of HIP-55 aggravated HF, whereas cardiac-specific overexpression of HIP-55 significantly alleviated HF in vivo. HIP-55 possesses a strong capacity for phase separation. Phase separation of HIP-55 is dynamically regulated by AKT-mediated phosphorylation at S269 and T291 sites, failure of which leads to impairment of HIP-55 dynamic phase separation by formation of abnormal aggregation. Prolonged sympathetic hyperactivation stress induced decreased phosphorylation of HIP-55 S269 and T291, dysregulated phase separation, and subsequent aggregate formation of HIP55. Moreover, we demonstrated the important role of dynamic phase separation of HIP-55 in inhibiting hyperactivation of the β-adrenergic receptor–mediated P38/MAPK (mitogen-activated protein kinase) signaling pathway. A phosphorylation-deficient HIP-55 mutation, which undergoes massive phase separation and forms insoluble aggregates, loses the protective activity against HF.CONCLUSIONS:Our work reveals that the phosphorylation-regulated dynamic phase separation of HIP-55 protects against sympathetic/adrenergic system–mediated heart failure.
Stroke, Volume 55, Issue Suppl_1, Page AWP107-AWP107, February 1, 2024. Objectives:The purpose of this study was to assess the trends in mortality rate after ischemic stroke and cocaine drug abuse in different demographics in the United States, compared to non-cocaine users.Introduction:Cocaine misuse has been linked to a higher risk of stroke. This has been observed in the US over the last decade and requires further investigation.Methods:Death certificates from Centers for Disease Control and Prevention Wide-Ranging On Line Data for Epidemiologic Research database were examined from 1999 to 2020 for multiple causes of death MCD-ICD 10 Codes (F14.0-14.9 and T40.5). Age-adjusted mortality rates (AAMRs) per 1000,000 persons and annual percent change (APC) were calculated and stratified by ten-year age group, sex, race/ethnicity, and urbanization.Results:From 1999 to 2020, adults aged 15-55 had 307,615 stroke-related deaths and cocaine-related death were 180,155 and combined stroke plus cocaine-related deaths were 6392.. The AAMR inclined from 1.7 in 1999 to 2.6 in 2007 (APC: 5.4; 95% CI: 3.6 to 8.2), after which it declined to 1.5 in 2010 (APC: -21.32; 95% CI: -25.8 to 12.6), then steadily inclined to 1.6 in 2020 (APC: 2.50, CI: 0.57 to 6.4). Men had consistently higher AAMR than women from 1999 (AAMR men: 1.9 vs women: 1.6) to 2020 (AAMR men: 2.3 vs. women: 0.9). Non-Hispanic (NH) Black or African American adults had the highest overall AAMR (7.8), followed by Hispanic or Latino (2.8), followed by NH White (1.8). AAMR also varied substantially by Urbanization.Conclusions:Deaths from cocaine-related stroke rose from 2007-2010, then declined until 2020. African American adults and men in large cities had high mortality rates. Preventing stroke related to drug abuse is crucial..
Stroke, Volume 55, Issue Suppl_1, Page AWMP52-AWMP52, February 1, 2024. Background:The estimated range for the prevalence of Opioid Use Disorder (OUD) among adolescents and adults in the United States in 2019 was between 6.7 million and 7.6 million individuals. The overall mortality rate is increasing over the last 20 years.Objective:This study aimed to assess the trends in stroke-related mortality in chronic opioid users in different demographics in the United States.Methods:We analyzed Center for Disease Control and Prevention Wide-Ranging On-Line Data for the Epidemiologic Research database examined from 1999 to 2020 for multiple causes of death MCD-ICD 10 Codes. Stroke-related mortality rates, with and without opioid use, were stratified by age, sex, and race/ethnicity and expressed as age-adjusted mortality rates (AAMRs) per 100,000 persons. Annual percent change (APC) from 1999-2020 was calculated and graphically plotted.Results:Between 1999 and 2020, The were 307,615 stroke-related deaths and 358,322 opioid-related deaths occurred among adults (15-55), and 1615 deaths were related to stroke and opioid use. The age-adjusted mortality rate (AAMR) steadily increased from 0.1 in 1999 to 0.8 in 2020, with an annual percent change (APC):9.6 % (CI: 8.0-12.14). Men and women had unreliable differences from 1999 till 2011. Men had consistently higher AAMR than women from 2011 (AAMR men: 0.4 vs. women: 0.2; p:
Stroke, Volume 55, Issue Suppl_1, Page A55-A55, February 1, 2024. Introduction:Risk of maternal stroke is higher in patients with preeclampsia (PEC), with the highest risk seen in those with chronic hypertension with superimposed preeclampsia (siPEC). Most strokes occur postpartum. Changes in cerebral autoregulation (CA) could contribute to elevated postpartum stroke risk. We describe CA curves in postpartum patients with no hypertension, PEC and siPEC.Methods:We prospectively recruited postpartum patients with and without PEC and measured 10-minute continuous mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) with finger plethysmography and transcranial Doppler within 1 week of delivery. We generated polynomial S-curves to derive limits of CA, CA plateaus (defined as slope < 0.15), and mean and minimum slopes between CA limits. We calculated Pearson correlation coefficients (Mx) between normalized MAP and CBVF; Mx > 0.3 indicates high MAP-CBFV correlation, suggesting impaired CA.Results:CA curves were produced from 71 patients (28% normotensive, 42% PEC, 30% siPEC). Group means for MAP were higher in those with PEC and siPEC (normotensive 72 mmHg, PEC 88, siPEC 87 [p=0.001]). CA was preserved in all groups, with Mx nadirs below 0.3 (Figure). The normotensive group demonstrated a wide, flat plateau in the S-curve (minimum slope 0.02). In the PEC group, we observed a narrower and slightly steeper autoregulatory plateau (minimum slope 0.05). The siPEC group displayed the narrowest and steepest plateau (minimum slope 0.15).Conclusion:In conclusion, in our sample of postpartum patients with normotension, PEC and siPEC, we observed a gradient in CA plateau range and slope. Compared with the normotensive group, the PEC and siPEC groups had progressively narrower and steeper CA plateaus, suggesting a more limited CA range and diminished CA efficacy. Future studies should investigate whether sustained MAP outside CA limits contributes to adverse maternal outcomes, particularly in those with siPEC.