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1.
J Cardiovasc Dev Dis ; 11(4)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38667748

RESUMO

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

2.
Basic Res Cardiol ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520533

RESUMO

Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vitro and pembrolizumab's (Pem's) cardiotoxicity in vivo, seeking for translational prevention means. Cytotoxicity was investigated in primary cardiomyocytes and splenocytes, incubated with ipilimumab, Pem and avelumab. Pem's cross-reactivity was assessed by circular dichroism (CD) on biotechnologically produced human and murine PD-1 and in silico. C57BL6/J male mice received IgG4 or Pem for 2 and 5 weeks. Echocardiography, histology, and molecular analyses were performed. Coronary blood flow velocity mapping and cardiac magnetic resonance imaging were conducted at 2 weeks. Human EA.hy926 endothelial cells were incubated with Pem-conditioned media from human mononuclear cells, in presence and absence of statins and viability and molecular signaling were assessed. Atorvastatin (20 mg/kg, daily) was administered in vivo, as prophylaxis. Only Pem exerted immune-related cytotoxicity in vitro. Pem's cross-reactivity with the murine PD-1 was confirmed by CD and docking. In vivo, Pem initiated coronary endothelial and diastolic dysfunction at 2 weeks and systolic dysfunction at 5 weeks. At 2 weeks, Pem induced ICAM-1 and iNOS expression and intracardiac leukocyte infiltration. At 5 weeks, Pem exacerbated endothelial activation and triggered cardiac inflammation. Pem led to immune-related cytotoxicity in EA.hy926 cells, which was prevented by atorvastatin. Atorvastatin mitigated functional deficits, by inhibiting endothelial dysfunction in vivo. We established for the first time an in vivo model of Pem-induced cardiotoxicity. Coronary endothelial dysfunction precedes Pem-induced cardiotoxicity, whereas atorvastatin emerges as a novel prophylactic therapy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38452886

RESUMO

BACKGROUND: In light of the updated lowered threshold for diagnosing pulmonary hypertension (PH), the reversibility of precapillary PH with left ventricular assist device (LVAD) and the associated post-heart transplantation (HT) outcomes remain unclear. METHODS: Using data from the United Network for Organ Sharing database, we aimed to investigate predictors of persistent precapillary PH in HT recipients bridged with LVAD and examine the interrelated post-HT survival using the updated pulmonary vascular resistance (PVR) cutoff of >2 Wood units for precapillary PH. RESULTS: Among 2169 HT recipients bridged with LVAD, 1299 had PVR >2 at baseline; 551 (42.4%) of whom normalized their PVR ≤2 and 748 (57.6%) remained with elevated PVR >2 after LVAD implantation. Female sex (adjusted odds ratio [aOR]; 2.22, 95% confidence interval [CI], 1.61-3.07; P < .001) and inotrope treatment at listing (aOR, 1.31; 95% CI, 1.03-1.66; P = .028) were associated with persistently elevated PVR after LVAD. Conversely, longer duration of LVAD support (aOR, 0.74; 95% CI, 0.65-0.84; P < .001) and use of HeartMate II (aOR, 0.74; CI, 0.59-0.93; P = .011) were found to be protective against persistently elevated PVR after LVAD. Persistently elevated PVR >2 after LVAD was associated with increased risk of death compared with those who normalized their PVR (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.01-1.57; P = .037). However, the normalized PVR post-LVAD group had comparable survival with those with PVR ≤2 at baseline (aHR, 0.76; 95% CI, 0.57-1.02; P = .07). CONCLUSIONS: Many recipients of HT bridged with LVAD remain with PVR >2 after LVAD implantation, which is associated with increased risk of death after HT compared with patients with normalized PVR after LVAD.

4.
J Clin Med ; 13(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256691

RESUMO

Heart transplantation (HTx) remains the last therapeutic resort for patients with advanced heart failure. The present work is a clinically focused review discussing current issues in heart transplantation. Several factors have been associated with the outcome of HTx, such as ABO and HLA compatibility, graft size, ischemic time, age, infections, and the cause of death, as well as imaging and laboratory tests. In 2018, UNOS changed the organ allocation policy for HTx. The aim of this change was to prioritize patients with a more severe clinical condition resulting in a reduction in mortality of people on the waiting list. Advanced heart failure and resistant angina are among the main indications of HTx, whereas active infection, peripheral vascular disease, malignancies, and increased body mass index (BMI) are important contraindications. The main complications of HTx include graft rejection, graft angiopathy, primary graft failure, infection, neoplasms, and retransplantation. Recent advances in the field of HTx include the first two porcine-to-human xenotransplantations, the inclusion of hepatitis C donors, donation after circulatory death, novel monitoring for acute cellular rejection and antibody-mediated rejection, and advances in donor heart preservation and transportation. Lastly, novel immunosuppression therapies such as daratumumab, belatacept, IL 6 directed therapy, and IgG endopeptidase have shown promising results.

5.
J Cardiol ; 83(5): 338-347, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37562542

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated the efficacy and safety of P2Y12 inhibitor monotherapy following short-term dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). However, no studies have compared P2Y12 inhibitor and aspirin monotherapy following short-term DAPT. We aimed to compare available strategies for DAPT duration and post-DAPT antiplatelet monotherapy following PCI. METHODS: Seven DAPT strategies [ticagrelor or clopidogrel following 1-month DAPT, ticagrelor following 3-month DAPT, aspirin following 3-6 months of DAPT (reference strategy), aspirin or P2Y12 inhibitor following 6-18-months of DAPT, and DAPT for ≥18 months] were compared using a network meta-analysis. The primary efficacy outcome was defined as a composite of all-cause death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding. RESULTS: Our analysis identified 25 eligible RCTs, including 89,371 patients who underwent PCI. Overall, none of the strategies negatively affected the primary efficacy outcomes. For primary bleeding outcomes, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes (HR 0.73; 95 % CI 0.57-0.95). Clopidogrel following 1-month DAPT was also associated with a reduced risk of primary bleeding outcomes (HR 0.54; 95 % CI 0.34-0.85), however, the strategy was associated with an increased risk of myocardial infarction or stent thrombosis. Similar trends were observed among patients with acute coronary syndrome and high bleeding risk. CONCLUSIONS: Compared with aspirin monotherapy following short-term DAPT, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes without increasing any ischemic outcomes.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Clopidogrel/efeitos adversos , Ticagrelor/efeitos adversos , Metanálise em Rede , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Aspirina/efeitos adversos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/induzido quimicamente , Hemorragia/induzido quimicamente , Quimioterapia Combinada , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento
6.
Eur Heart J Cardiovasc Imaging ; 25(5): 698-707, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38142437

RESUMO

AIMS: Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance. METHODS AND RESULTS: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year. Patients were stratified according to haematologic response as complete or not complete responders. A significant reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2771-1486 pg/mL; P < 0.001) and posterior wall thickness (13-12 mm; P = 0.002) and an increase in global work index (GWI) (1115-1356 mmHg%; P = 0.018) was observed at 1 year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2-12.0 mm; P = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; P for interaction = 0.045), increased global constructive work (1245-1436 mmHg%; P = 0.008), and GWI (926-1250 mmHg%, P = 0.002) compared with non-CR. Furthermore, deltaGLS (ρspearman = 0.35; P < 0.001) and deltaGWI (ρspearman = -0.32; P = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank P = 0.048 and log-rank P = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS [hazard ratio (HR) = 1.404, P = 0.046 per 1% increase] and deltaGWI (HR = 0.996, P = 0.042 per 1mmHg% increase) were independent predictors of survival. CONCLUSION: Complete haematologic response to treatment is associated with improved left ventricular myocardial work indices, and their change is associated with improved survival in AL-CA.


Assuntos
Ecocardiografia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Prognóstico , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/mortalidade , Peptídeo Natriurético Encefálico/sangue , Amiloidose/diagnóstico por imagem , Amiloidose/mortalidade , Resultado do Tratamento , Fragmentos de Peptídeos/sangue , Análise de Sobrevida , Estudos de Coortes , Medição de Risco , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Índice de Gravidade de Doença , Taxa de Sobrevida
7.
J Pers Med ; 13(12)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38138924

RESUMO

OBJECTIVE: Thoracic aortic aneurysm dissection (TAAD) represents a cardiac surgery emergency characterized by the disrupted integrity of the aortic wall and is associated with poor prognosis. In this context, the identification of biomarkers implicated in the pathobiology of TAAD is crucial. Our aim in the present original in silico study is to assess the differential gene expression profile of the tight junction proteins (TJPs) in patients with TAAD and to propose novel biomarkers for the diagnosis and prognosis of this disease. METHODS: We implemented bioinformatics methodology in order to construct the gene network of the TJPs family, identify the differentially expressed genes (DEGs) in pathologic aortic tissue excised from patients with TAAD as compared to healthy aortic tissue, and assess the related biological functions and the associated miRNA families. RESULTS: Data regarding the transcriptomic profile of selected genes were retrieved and incorporated from three microarray datasets, including 23 TAAD and 20 healthy control samples. A total of 32 TJPs were assessed. The zona occludens 2 (ZO-2) protein encoded by the gene TJP2 was significantly under-expressed in patients with TAAD compared to the control group (p = 0.009). ZO-2 was associated with fair discrimination and calibration traits in predicting the TAAD presentation. CpG islands of ZO-2 were demonstrated. No important difference was found regarding ZO-2 expression between aneurysmal non-dissected and healthy control aortic tissue. Finally, we performed gene set enrichment analysis (GSEA) and uncovered the major biological functions and miRNA families (hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-2118-5p, hsa-miR-4691-3p, and hsa-miR-1229-3p) relevant to ZO-2. CONCLUSIONS: These outcomes demonstrated the important role of ZO-2 in the pathobiology of TAAD.

8.
Hellenic J Cardiol ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37805173

RESUMO

BACKGROUND: Clinical characteristics and outcomes of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) vary by region, necessitating the acquisition of country-specific evidence for proper management. METHODS: This is an observational study including sequential patients presenting in the Amyloidosis Reference Center of Greece, from 01/2014 to 12/2022. ATTR-CM was diagnosed by positive scintigraphy and exclusion of light-chain amyloidosis or positive biopsy typing. Genetic testing was performed in all cases. RESULTS: One-hundred and nine ATTR-CM patients were included (median age, 81 years) of which 15 carried TTR mutations (27% Val30Met). Most patients (82%) presented with heart failure and 59% with atrial fibrillation, while 10% had aortic stenosis. Importantly, 78 (71.6%) had clinically significant extracardiac manifestations (45% musculoskeletal disorder, 40% peripheral neuropathy and 33% gastrointestinal symptoms). Sixty-five (60%) received disease-specific treatment with tafamidis. Estimated median survival was 48 months; advanced NYHA class, National Amyloidosis Center stage, eGFR<45 ml/kg/1.73m2, NT-pro-BNP>5000 pg/mL were associated with worse survival, while tafamidis treatment was associated with improved survival in patients with IVS≥ 12 mm. DISCUSSION: These are the first data describing the characteristics, management, and outcomes of patients with ATTR-CM in Greece, which could influence local guidelines. SHORT TITLE: Transthyretin cardiomyopathy in Greece.

9.
J Am Heart Assoc ; 12(21): e030072, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37889175

RESUMO

Background Data on clinical outcomes after transcatheter aortic valve replacement (TAVR) in specific cancer types or the presence of metastatic disease remain sparse. This study aimed to investigate the impact of active cancer on short-term mortality, complications, and readmission rates after TAVR across different cancer types. Methods and Results The authors assessed the Nationwide Readmissions Database for TAVR cases from 2012 to 2019. Patients were stratified by specific cancer types. Primary outcome was in-hospital mortality. Secondary outcomes included bleeding requiring blood transfusion and readmissions at 30, 90, and 180 days after TAVR. Overall, 122 573 patients undergoing TAVR were included in the analysis, of whom 8013 (6.5%) had active cancer. After adjusting for potential confounders, the presence of active cancer was not associated with increased in-hospital mortality (adjusted odds ratio [aOR], 1.06 [95% CI, 0.89-1.27]; P=0.523). However, active cancer was associated with an increased risk of readmission at 30, 90, and 180 days after TAVR and increased risk of bleeding requiring transfusion at 30 days. Active colon and any type of metastatic cancer were individually associated with readmissions at 30, 90, and 180 days after TAVR. At 30 days after TAVR, colon (aOR, 2.51 [95% CI, 1.68-3.76]; P<0.001), prostate (aOR, 1.40 [95% CI, 1.05-1.86]; P=0.021), and any type of metastatic cancer (aOR, 1.65 [95% CI, 1.23-2.22]; P=0.001) were individually associated with an increased risk of bleeding requiring transfusion. Conclusions Patients with active cancer had similar in-hospital mortality after TAVR but higher risk of readmission and bleeding requiring transfusion, the latter depending on certain types of cancer.


Assuntos
Estenose da Valva Aórtica , Neoplasias , Substituição da Valva Aórtica Transcateter , Masculino , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/cirurgia , Fatores de Risco , Resultado do Tratamento , Hemorragia/etiologia , Valva Aórtica/cirurgia
10.
J Cardiovasc Dev Dis ; 10(8)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37623350

RESUMO

Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in CA, including supraventricular arrhythmias, conduction system disturbances, or ventricular arrhythmias, play a major role in CA morbidity and mortality, and thus require supplementary management. Among them, AF is the most frequent arrhythmia during CA hospitalizations and is associated with significantly higher mortality, while ventricular arrhythmias are also common and are usually associated with poor prognosis. Early diagnosis of potential arrythmias could be performed through ECG, Holter monitoring, and/or electrophysiology study. Clinical management of these patients is quite significant, and it usually includes initiation of amiodarone and/or digoxin in patients with AF, potential electrical cardioversion, or ablation in specific patients with indication, as well as initiation of anticoagulants in all patients, independent of AF and CHADS-VASc score, for potential intracardiac thrombus. Moreover, identification of patients with conduction disorders that could benefit from prophylactic pacemaker implantation and/or CRT as well as identification of patients with life-threatening ventricular arrythmias that could benefit from ICD could both increase the survival rates of these patients and improve their quality of life.

11.
J Clin Med ; 12(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37510991

RESUMO

We conducted a thorough literature review on the emerging role of failure to rescue (FTR) as a quality metric for cardiovascular surgery and critical care. For this purpose, we identified all original research studies assessing the implementation of FTR in cardiovascular surgery and critical care from 1992 to 2023. All included studies were evaluated for their quality. Although all studies defined FTR as mortality after a surgical complication, a high heterogeneity has been reported among studies regarding the included complications. There are certain factors that affect the FTR, divided into hospital- and patient-related factors. The identification of these factors allowed us to build a stepwise roadmap to reduce the FTR rate. Recently, FTR has further evolved as a metric to assess morbidity instead of mortality, while being also evaluated in the context of interventional cardiology. All these advances are further discussed in the current review, thus providing all the necessary information to surgeons, anesthesiologists, and physicians willing to implement FTR as a metric of quality in their establishment.

12.
Tex Heart Inst J ; 50(3)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37302149

RESUMO

BACKGROUND: For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated. METHODS: Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed. RESULTS: This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant difference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P = .049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P = .97) and was superior to ticagrelor (P = .29) and clopidogrel (P = .24). CONCLUSION: Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study highlights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/uso terapêutico , Hemorragia/induzido quimicamente , Metanálise em Rede , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Resultado do Tratamento
13.
J Cardiovasc Dev Dis ; 10(6)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37367421

RESUMO

The appropriate diagnosis and subtyping of cardiac amyloidosis (CA) is frequently missed or delayed due to its vague presentation, clinical overlapping, and diagnostic pitfalls. Recent developments in both invasive and non-invasive diagnostic techniques have significantly changed the diagnostic approach of CA. With the present review, we aim to summarize the current diagnostic approach of CA and to underline the indications of tissue biopsy, either surrogate site or myocardial. The most important factor for timely diagnosis is increased clinical suspicion, especially in certain clinical scenarios. Appropriate imaging with echocardiography or cardiac magnetic resonance (CMR) can provide significant evidence for the diagnosis of CA. Importantly, all patients should undergo monoclonal proteins assessment, with these results significantly determining the steps to follow. A negative monoclonal protein assessment will lead to a non-invasive algorithm which, in combination with positive cardiac scintigraphy, can establish the diagnosis of ATTR-CA. The latter is the only clinical scenario in which the diagnosis can be established without the need of biopsy. However, if the imaging results are negative but the clinical suspicion remains high, a myocardial biopsy should be performed. In the case of the presence of monoclonal protein, an invasive algorithm follows, first by surrogate site sampling and then by myocardial biopsy if the results are inconclusive or prompt diagnosis is needed. The role of endomyocardial biopsy, even though limited by current advances in other techniques, is highly valuable in selected patients and is the only method to reliably establish a diagnosis in challenging cases.

14.
J Cardiovasc Dev Dis ; 10(6)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37367424

RESUMO

Cancer is among the major causes of death globally, accounting for nearly 10 million deaths in 2020 [...].

15.
JACC CardioOncol ; 5(1): 1-21, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36875897

RESUMO

Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström's macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.

16.
Hematol Oncol ; 41(4): 725-732, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36974438

RESUMO

Patients with cardiac light chain amyloidosis and Mayo stage 3b disease define a high-risk population with very poor prognosis. Here, we report treatment outcomes of 80 consecutive patients with newly diagnosed AL and Mayo 3b who received novel regimens. Early mortality (<1 month) rate was 12.5%. On intention-to-treat, overall hematologic response rate was 40%, with complete response (CR)/very good partial response (VGPR) in 25% and partial response (PR) in 15%. At 1- and 3- month landmark analysis CR or VGPR/PR rates were 25%/23.5% and 34%/25.5%, respectively. Among patients that were treated with daratumumab-based therapies, 52.6% and 85.7% achieved at least VGPR within one 1 and 3 months, respectively. Three-month cardiac response rate was 11.3% and 6-month was 18.8%. At least hemVGPR at 3 months was associated with cardiac response at 6 months (p = 0.034). Median overall survival (OS) was 6.3 months. At 1-month landmark at least hemPR was associated with better median OS (24.1 vs. 4.9 months, p = 0.017) and at 3-month landmark, at least hemVGPR was associated with a median OS of 40.7 versus 17 months for hemPR and 7.4 months for those without hematologic response (p = 0.028). Cardiac response at 3 months was associated with longer median OS (59.7 vs. 10.9 months, p = 0.044). Factors associated with poorer survival were κ-light chain amyloidosis (median OS 2.9 vs. 7.4 months, p = 0.028), peripheral nerve involvement (3.4 vs. 10.45 months, p = 0.024), systolic blood pressure <90 mmHg (2 vs. 8 months, p = 0.002), baseline LVEF <55% (median OS 3.4 vs. 32 months, p = 0.29) and New York Heart Association (NYHA) class (2.7 months for NYHA 3B-4 vs. 8 months for NYHA 2-3A, p = 0.02). Twenty-one patients (26.3%) received salvage therapy and ORR was 57.1%. Median OS for patients who received second line therapy was 24 months. In conclusion, patients with Mayo 3b disease benefit from early hematologic response but cardiac response rates remain low.


Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose/complicações , Amiloidose/diagnóstico , Resultado do Tratamento , Prognóstico , Cadeias kappa de Imunoglobulina , Estudos Retrospectivos
17.
Curr Probl Cardiol ; 48(7): 101700, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36931332

RESUMO

Coronary artery aneurysms (CAAs) are rare anatomical disorders of the coronary arteries. Atherosclerosis and Kawasaki disease are the principal causes of CCAs, while other causes including genetic factors, inflammatory arterial diseases, connective tissue disorders, endothelial damage after cocaine use, iatrogenic complications after interventions and infections, are also common among patients with CAAs. Although there is a variety of noninvasive methods including echocardiography, computed tomography, and magnetic resonance imaging, coronary angiography remains the gold standard diagnostic method. There is still no consensus about the most appropriate therapeutic strategy. Medical therapy including antiplatelets, anticoagulants, statins and ACEs are preferred either in patients with atherosclerosis, inflammatory status and stable CAAs, while percutaneous or surgery interventions are usually applied in patients with acute coronary syndrome due to a CAA culprit, obstructive coronary artery disease or large saccular aneurysms at a high risk of rupturing.


Assuntos
Aterosclerose , Aneurisma Coronário , Doença da Artéria Coronariana , Humanos , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Angiografia Coronária/efeitos adversos
19.
J Investig Med ; 71(4): 380-383, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36645060

RESUMO

Cardiac graft failure may require repeat heart transplantation (HTx). Outcomes of patients that undergo repeat HTx have not been well described. We compared patients that received repeat HTx with patients that received initial HTx by inquiring the United Network for Organ Sharing (UNOS) database between 2015 and 2021. The primary endpoint was all-cause mortality, while the role of baseline characteristics was also investigated. Patients were stratified according to whether they received initial HTx (n = 19,727, 97%) or repeat HTx (n = 578, 3%). Among the study population, 10,860 (53.5%) patients received a HTx using the old UNOS allocation system, whereas 9445 (46.5%) patients received a HTx after the implementation of the new UNOS donor allocation system in October 2018. In this sub-group of HTx recipients in the new allocation system era, the adjusted 1-year survival of repeat HTx patients remained lower than that of initial HTx patients (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.15, 3.18; p = 0.013). When we compared the 1-year survival of repeat HTx patients before and after the implementation of the new allocation system, the adjusted 1-year survival was similar between groups (HR: 1.14; 95% CI: 0.71, 1.84; p = 0.591). The unadjusted risk of 30-day mortality was not significantly different in the new vs old allocation system. Mortality associated with repeat HTx remained higher than initial HTx but the new donor allocation system implementation did not affect outcomes.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Humanos , Transplante de Coração/efeitos adversos , Reoperação , Doadores de Tecidos , Resultado do Tratamento , Estudos Retrospectivos
20.
Curr Probl Cardiol ; 48(4): 101573, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36586704

RESUMO

Early diagnosis is crucial for the improvement of outcomes of patients with cardiac amyloidosis (CA). Emerging non-late gadolinium enhancement (LGE) based cardiac magnetic resonance (CMR) parameters may facilitate early identification of CA. We sought to investigate the diagnostic and prognostic value of T1, T2 mapping and extracellular volume (ECV) in CA. This single-center prospective analysis included 88 patients with CA, 33 patients with aortic stenosis (AS) and left ventricular hypertrophy (LVH), and 15 healthy controls who completed 3T cardiac MRI at the time of their diagnosis and were assessed with T1, T2 (modified Look-Locker inversion recovery), and ECV mapping of the heart and spleen. Echocardiographic, and biochemical parameters and clinical characteristics and outcomes were collected and analyzed. Of the patients with CA, 71 had light-chain (AL) and 17 had transthyretin (ATTR) amyloidosis. Native T1, native T2 and ECV were significantly higher in patients with CA compared to both patients with LVH-AS (P<0.001) and healthy controls (P<0.001). Good diagnostic accuracy was also demonstrated by measuring the area under the curve (AUC) of the receiver operating characteristic (ROC) curves for native T1 in the region of interest (ROI) (AUC=0.90), native T2 ROI (AUC=0.88), and ECV (AUC=0.90). Furthermore, native T1 ROI, native T2 ROI and ECV, correlated with both NT-proBNP levels and Mayo stage of patients (with AL). Spleen ECV was significantly increased in patients with AL versus ATTR amyloidosis (38.5 vs 30.5; P=0.004) and demonstrated good diagnostic accuracy in differentiating between the two types (AUC=0.79). Native T2 ROI was prognostic of mortality in AL CAwith a HR of 1.97 per 5 ms increase (P=0.001) and remained prognostic after adjustment for age, and Mayo stage. Non-LGE based CMR techniques correlated with established markers of disease and demonstrated good diagnostic accuracy, while native T2 ROI was also prognostic of mortality, thus reinforcing their use in the diagnosis and prognosis of CA.


Assuntos
Amiloidose , Estenose da Valva Aórtica , Humanos , Meios de Contraste , Gadolínio , Prognóstico , Imagem Cinética por Ressonância Magnética , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Miocárdio
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