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1.
Am J Respir Crit Care Med ; 209(11): 1376-1391, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38261723

ABSTRACT

Rationale: The ubiquitous polyamine spermidine is essential for cell survival and proliferation. One important function of spermidine is to serve as a substrate for hypusination, a posttranslational modification process that occurs exclusively on eukaryotic translation factor 5A (eIF5A) and ensures efficient translation of various gene products. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive obliteration of the small pulmonary arteries (PAs) caused by excessive proliferation of PA smooth muscle cells (PASMCs) and suppressed apoptosis. Objectives: To characterize the role of hypusine signaling in PAH. Methods: Molecular, genetic, and pharmacological approaches were used both in vitro and in vivo to investigate the role of hypusine signaling in pulmonary vascular remodeling. Measurements and Main Results: Hypusine forming enzymes-deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH)-and hypusinated eukaryotic translation factor 5A are overexpressed in distal PAs and isolated PASMCs from PAH patients and animal models. In vitro, inhibition of DHPS using N1-guanyl-1,7-diaminoheptane or shRNA resulted in a decrease in PAH-PASMC resistance to apoptosis and proliferation. In vivo, inactivation of one allele of Dhps targeted to smooth muscle cells alleviates PAH in mice, and its pharmacological inhibition significantly decreases pulmonary vascular remodeling and improves hemodynamics and cardiac function in two rat models of established PAH. With mass spectrometry, hypusine signaling is shown to promote the expression of a broad array of proteins involved in oxidative phosphorylation, thus supporting the bioenergetic requirements of cell survival and proliferation. Conclusions: These findings support inhibiting hypusine signaling as a potential treatment for PAH.


Subject(s)
Pulmonary Arterial Hypertension , Signal Transduction , Vascular Remodeling , Animals , Vascular Remodeling/drug effects , Vascular Remodeling/physiology , Rats , Humans , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/metabolism , Male , Disease Models, Animal , Pulmonary Artery/physiopathology , Pulmonary Artery/drug effects , Mice , Peptide Initiation Factors/metabolism , Peptide Initiation Factors/genetics , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Eukaryotic Translation Initiation Factor 5A , Cell Proliferation/drug effects , Oxidoreductases Acting on CH-NH Group Donors/genetics , Oxidoreductases Acting on CH-NH Group Donors/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/physiopathology , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/metabolism , Lysine/analogs & derivatives
2.
Am J Physiol Heart Circ Physiol ; 327(1): H131-H137, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38700470

ABSTRACT

Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, P < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m2 (P < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m2, P < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), P = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg-1 (P = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index.NEW & NOTEWORTHY This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.


Subject(s)
Heart Transplantation , Hemodynamics , Isoproterenol , Pulmonary Artery , Ventricular Dysfunction, Right , Ventricular Function, Right , Humans , Isoproterenol/pharmacology , Heart Transplantation/adverse effects , Middle Aged , Male , Pulmonary Artery/physiopathology , Pulmonary Artery/drug effects , Female , Ventricular Function, Right/drug effects , Retrospective Studies , Adult , Hemodynamics/drug effects , Aged , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/etiology , Heart Failure/physiopathology , Heart Failure/drug therapy , Dobutamine/pharmacology , Treatment Outcome , Heart Rate/drug effects , Recovery of Function , Cardiotonic Agents/pharmacology
3.
Heart Fail Rev ; 29(2): 559-569, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38329583

ABSTRACT

The use of left ventricular assist devices (LVAD) has significantly increased in the last years, trying to offer a therapeutic alternative to heart transplantation, in light also to the significant heart donor shortage compared to the growing advanced heart failure population. Despite technological improvements in the devices, LVAD-related mortality is still fairly high, with right heart failure being one of the predominant predictors. Therefore, many efforts have been made toward a thorough right ventricular (RV) evaluation prior to LVAD implant, considering clinical, laboratory, echocardiographic, and invasive hemodynamic parameters. However, there is high heterogeneity regarding both which predictor is the strongest as well as the relative cut-off values, and a consensus has not been reached yet, increasing the risk of facing patients in which the distinction between good or poor RV function cannot be surely reached. In parallel, due to technological development and availability of mechanical circulatory support of the RV, LVADs are being considered even in patients with suboptimal RV function. The aim of our review is to analyze the current evidence regarding the role of RV function prior to LVAD and its evaluation, pointing out the extreme variability in parameters that are currently assessed and future prospective regarding new diagnostic tools. Finally, we attempt to gather the available information on the therapeutic strategies to use in the peri-operative phase, in order to reduce the incidence of RV failure, especially in patients in which the preoperative evaluation highlighted some conflicting results with regard to ventricular function.


Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Ventricular Dysfunction, Right , Humans , Heart-Assist Devices/adverse effects , Heart Failure/surgery , Heart Failure/etiology , Heart Transplantation/adverse effects , Echocardiography , Retrospective Studies
4.
Catheter Cardiovasc Interv ; 103(6): 909-916, 2024 May.
Article in English | MEDLINE | ID: mdl-38584525

ABSTRACT

BACKGROUND: Utilization of right ventricular mechanical circulatory support (RV-MCS) devices has been limited by a lack of recognition of RV failure as well as a lack of availability and experience with RV-MCS. AIMS: We report a single-center experience with the use of percutaneous RV-MCS and report predictors of adverse outcomes. METHODS: This was a single-center retrospective cohort study. Data from consecutive patients who received RV-MCS for any indication between June 2015 and January 2022 were included. Data on baseline comorbidities, hemodynamics, and laboratory values were collected. The primary outcome was in-hospital mortality analyzed as a logistic outcome in a multivariable model. These variables were further ranked by their predictive value. RESULTS: Among 58 consecutive patients enrolled, the median age was 66 years, 31% were female and 53% were white. The majority of the patients (48%) were hospitalized for acute on chronic heart failure. The majority of the patients were SCAI SHOCK Stage D (67%) and 34 (64%) patients had MCS placed within 24 h of the onset of shock. Before placement of RV-MCS, median central venous pressure (CVP) and RV stroke work index were 20 mmHg and 8.9 g m/m2, respectively. Median serum lactate was 3.5 (1.6, 6.2) mmol/L. Impella RP was implanted in 50% and ProtekDuo in the remaining 50%. Left ventricular MCS was concomitantly used in 66% of patients. Twenty-eight patients (48.3%) died. In these patients, median serum lactate was significantly higher (4.1 [2.3, 13.0] vs. 2.2 [1.4, 4.0] mmol/L, p = 0.007) and a trend toward higher median CVP (24 [18, 31] vs. 19 [14, 24] mmHg, p = 0.052). In the multivariable logistic model, both serum lactate and CVP before RV-MCS placement were independent predictors of in-hospital mortality. Serum lactate had the highest predictive value. CONCLUSION: In our real-world cohort, 52% of patients treated with RV-MCS survived their index hospitalization. Serum lactate at presentation and CVP were the strongest predictors of in-hospital mortality.


Subject(s)
Heart Failure , Heart-Assist Devices , Hospital Mortality , Recovery of Function , Ventricular Dysfunction, Right , Ventricular Function, Right , Humans , Female , Male , Retrospective Studies , Aged , Heart Failure/physiopathology , Heart Failure/mortality , Heart Failure/therapy , Heart Failure/diagnosis , Treatment Outcome , Middle Aged , Risk Factors , Time Factors , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/mortality , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/therapy , Ventricular Dysfunction, Right/diagnostic imaging , Risk Assessment , Prosthesis Implantation/instrumentation , Prosthesis Implantation/adverse effects , Prosthesis Implantation/mortality , Biomarkers/blood
5.
Artif Organs ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38887186

ABSTRACT

BACKGROUND: An inflammatory milieu after left ventricular assist device (LVAD) implantation is associated with multi-organ dysfunction and pre-operative heightened inflammatory state is associated with right ventricular failure after LVAD implantation. METHODS: We performed a retrospective analysis of 30 LVAD patients in our institution within the last 2 years for the development of fever and compared them to 30 non-LVAD open-heart surgery patients. RESULTS: Our results suggest that patients undergoing LVAD implantation are more likely to develop fever in the immediate post-operative period compared to other open-heart surgeries. This is independent of pharmacological treatment, age, or ethnical background. Females and obese patients were more likely to develop fever. CONCLUSION: Patients with right ventricular dysfunction, as demonstrated by elevated central venous pressure (CVP), had the strongest correlation with fever development. These results pose the question if there is a systemic inflammatory response-like phenomenon driven by increased right ventricular dysfunction.

6.
BMC Anesthesiol ; 24(1): 128, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575875

ABSTRACT

BACKGROUND: Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. METHODS: We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. RESULTS: Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302-0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007-1.903, p = 0.045) were independently associated with 30-day mortality. CONCLUSIONS: Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.


Subject(s)
Sepsis , Ventricular Dysfunction, Right , Humans , Central Venous Pressure , Heart Ventricles/diagnostic imaging , Retrospective Studies , Echocardiography , Hypertrophy, Right Ventricular , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Function, Right , Stroke Volume
7.
Curr Cardiol Rep ; 26(8): 815-820, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38913233

ABSTRACT

PURPOSE OF REVIEW: The endotracheal intubation of patients with pulmonary arterial hypertension (PAH) in respiratory distress is a highly morbid procedure that can precipitate hemodynamic collapse. Here we review our strategy for confronting this difficult clinical situation. RECENT FINDINGS: There are no clinical trials that explore best practices in the management of patients with PAH and respiratory failure. Here we provide a practical approach to respiratory support, inopressor and pulmonary vasodilator selection, hemodynamic considerations, point-of-care ultrasound monitoring, and endotracheal intubation in patients with PAH in respiratory failure.


Subject(s)
Intubation, Intratracheal , Respiratory Insufficiency , Humans , Respiratory Insufficiency/therapy , Respiratory Insufficiency/etiology , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Arterial Hypertension/therapy , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/therapy , Hemodynamics , Vasodilator Agents/therapeutic use
8.
Curr Cardiol Rep ; 26(2): 23-34, 2024 02.
Article in English | MEDLINE | ID: mdl-38108956

ABSTRACT

PURPOSE OF REVIEW: To describe medical therapies and mechanical circulatory support devices used in the treatment of acute right ventricular failure. RECENT FINDINGS: Experts have proposed several algorithms providing a stepwise approach to medical optimization of acute right ventricular failure including tailored volume administration, ideal vasopressor selection to support coronary perfusion, inotropes to restore contractility, and pulmonary vasodilators to improve afterload. Studies have investigated various percutaneous and surgically implanted right ventricular assist devices in several clinical settings. The initial management of acute right ventricular failure is often guided by invasive hemodynamic data tracking parameters of circulatory function with the use of pharmacologic therapies. Percutaneous microaxial and centrifugal extracorporeal pumps bypass the failing RV and support circulatory function in severe cases of right ventricular failure.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Humans , Heart Ventricles , Heart Failure/surgery , Hemodynamics , Perfusion , Treatment Outcome
9.
J Electrocardiol ; 82: 73-79, 2024.
Article in English | MEDLINE | ID: mdl-38043477

ABSTRACT

BACKGROUND: Right bundle branch block (RBBB) can be benign or associated with right ventricular (RV) functional and structural abnormalities. Our aim was to evaluate QRS-T voltage-time-integral (VTI) compared to QRS duration and lead V1 R' as markers for RV abnormalities. METHODS: We included adults with an ECG demonstrating RBBB and echocardiogram obtained within 3 months of each other, between 2010 and 2020. VTIQRS and VTIQRST were obtained for 12 standard ECG leads, reconstructed vectorcardiographic X, Y, Z leads and root-mean-squared (3D) ECG. Age, sex and BSA-adjusted linear regressions were used to assess associations of QRS duration, amplitudes, VTIs and lead V1 R' duration/VTI with echocardiographic tricuspid annular plane systolic excursion (TAPSE), RV tissue Doppler imaging S', basal and mid diameter, and systolic pressure (RVSP). RESULTS: Among 782 patients (33% women, age 71 ± 14 years) with RBBB, R' duration in lead V1 was modestly associated with RV S', RV diameters and RVSP (all p ≤ 0.03). QRS duration was more strongly associated with RV diameters (both p < 0.0001). AmplitudeQRS-Z was modestly correlated with all 5 RV echocardiographic variables (all p ≤ 0.02). VTIR'-V1 was more strongly associated with TAPSE, RV S' and RVSP (all p ≤ 0.0003). VTIQRS-Z and VTIQRST-Z were among the strongest correlates of the 5 RV variables (all p < 0.0001). VTIQRST-Z.√BSA cutoff of ≥62 µVsm had sensitivity 62.7% and specificity 65.7% for predicting ≥3 of 5 abnormal RV variables (AUC 0.66; men 0.71, women 0.60). CONCLUSION: In patients with RBBB, VTIQRST-Z is a stronger predictor of RV dysfunction and adverse remodeling than QRS duration and lead V1 R'.


Subject(s)
Bundle-Branch Block , Electrocardiography , Male , Adult , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Bundle-Branch Block/diagnostic imaging , Electrocardiography/methods , Echocardiography , Heart Ventricles/diagnostic imaging , Ventricular Function, Right
10.
Perfusion ; 39(3): 514-524, 2024 Apr.
Article in English | MEDLINE | ID: mdl-36602044

ABSTRACT

OBJECTIVES: In patients at risk of developing right ventricular failure after cardiac surgery, right ventricular support with a ventricular assist device may be a promising strategy to reduce mortality. We present our experience with intraoperative right ventricular assist device implantation as a prevention strategy of right ventricular failure after cardiac surgery. METHODS: Between 2016 and 2022, we implanted four right ventricular assist devices prophylactically in a series of patients with surgical indication for valvular heart disease and high risk of postoperative right ventricular failure. Indications for the right ventricular assist device were suprasystemic pulmonary hypertension or severe right ventricular dysfunction. RESULTS: Externalization of the device cannulas through intercostal spaces was performed in three patients, allowing early mobilization and withdrawal without resternotomy. Removal of the device ocurred on the eighth postoperative day. ICU and hospital length of stay was 12 (±1.6) and 23 days (±4.2) respectively. Hospital mortality was null. No patient died during follow-up, mean follow-up was 32.5 months [1-72]. Patients improved their NYHA functional class up to grade II during follow-up. CONCLUSIONS: Acute right ventricular failure after cardiac surgery remains a significant cause of morbidity and mortality. Prophylactic strategies to prevent postoperative right ventricular dysfunction may decrease the incidence of refractory postoperative right ventricular failure. We propose a novel approach to prevent right failure after cardiac surgery with prophylactic intraoperative ventricular assist device implantation.


Subject(s)
Cardiac Surgical Procedures , Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Humans , Heart-Assist Devices/adverse effects , Prosthesis Implantation/adverse effects , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/prevention & control , Treatment Outcome , Retrospective Studies , Heart Failure/prevention & control , Heart Failure/surgery , Heart Failure/etiology , Cardiac Surgical Procedures/adverse effects
11.
Perfusion ; : 2676591241284862, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39275994

ABSTRACT

INTRODUCTION: The Protek Duo (PtD) dual lumen, single cannula was developed as a percutaneous system for temporary mechanical support, inserted through the internal jugular vein (IJ) for both atrial inflow and pulmonary artery outflow. Outcomes of PtD compared to alternative Peripheral Right Ventricular Assist Device (pRVAD) methods are limited. METHODS: A retrospective analysis was conducted of pRVAD recipients from January 2017 - February 2022 (n = 111). These were classified into PtD (n = 52) patients and Non-Protek [(N-PtD) (n = 59)] recipients undergoing cannulation of the IJ and femoral vein. Results were further stratified by indication for pRVAD support: cardiogenic etiologies of heart failure and progressive ARDS. RESULTS: No survival benefit was detected between PtD and N-PtD groups at 1-week (OR: 1.32, 95% CI: 0.49-3.56, p = 0.58) or 6-month (OR: 9.83, 95% CI: 0.37-1.84, p = 0.64) follow-up. There were no statistically significant differences in whether patients' mobility progressed to out-of-bed activity (p = 0.26) or ambulation (p = 0.38). No differences were noted in time to out-of-bed (p = 0.26) or time to ambulation (p = 0.36). On subgroup analysis of patients by indication for pRVAD cannulation, these results persisted; no difference was noted in mid-term mortality (Cardiogenic: p = 0.39; ARDS: p = 0.91), progression to out-of-bed (p = 0.59; p = 1.00), or ambulation (p = 0.51; p-0.68). Among secondary outcomes, PtD patients had an increased dialysis requirement (p = 0.02). There were no differences in ability to wean from RVAD (p = 0.06), tracheostomy (p = 0.88), major bleeding events (p = 0.57), stroke (p = 0.58), or hospital length of stay (p = 0.39). CONCLUSIONS: Outcomes with PtD are comparable to those of traditional pRVAD cannulation strategies. Of note, no mobility benefit was observed to the use of PtD across several metrics.

12.
J Transl Med ; 21(1): 888, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38062516

ABSTRACT

BACKGROUND: Right ventricle failure (RVF) is a progressive heart disease that has yet to be fully understood at the molecular level. Elevated M-type pyruvate kinase 2 (PKM2) tetramerization alleviates heart failure, but detailed molecular mechanisms remain unclear. OBJECTIVE: We observed changes in PKM2 tetramerization levels during the progression of right heart failure and in vitro cardiomyocyte hypertrophy and explored the causal relationship between altered PKM2 tetramerization and the imbalance of redox homeostasis in cardiomyocytes, as well as its underlying mechanisms. Ultimately, our goal was to propose rational intervention strategies for the treatment of RVF. METHOD: We established RVF in Sprague Dawley (SD) rats by intraperitoneal injection of monocrotaline (MCT). The pulmonary artery pressure and right heart function of rats were assessed using transthoracic echocardiography combined with right heart catheterization. TEPP-46 was used both in vivo and in vitro to promote PKM2 tetramerization. RESULTS: We observed that oxidative stress and mitochondrial disorganization were associated with increased apoptosis in the right ventricular tissue of RVF rats. Quantitative proteomics revealed that PKM2 was upregulated during RVF and negatively correlated with the cardiac function. Facilitating PKM2 tetramerization promoted mitochondrial network formation and alleviated oxidative stress and apoptosis during cardiomyocyte hypertrophy. Moreover, enhancing PKM2 tetramer formation improved cardiac mitochondrial morphology, mitigated oxidative stress and alleviated heart failure. CONCLUSION: Disruption of PKM2 tetramerization contributed to RVF by inducing mitochondrial fragmentation, accumulating ROS, and finally promoted the progression of cardiomyocyte apoptosis. Facilitating PKM2 tetramerization holds potential as a promising therapeutic approach for RVF.


Subject(s)
Heart Failure , Pyruvate Kinase , Animals , Rats , Heart Ventricles , Hypertrophy/complications , Mitochondrial Dynamics , Oxidative Stress , Rats, Sprague-Dawley
13.
J Card Fail ; 29(4): 479-502, 2023 04.
Article in English | MEDLINE | ID: mdl-36828256

ABSTRACT

The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.


Subject(s)
Heart Failure , Heart-Assist Devices , Humans , Heart-Assist Devices/adverse effects , Lung , Cohort Studies , Arrhythmias, Cardiac
14.
Artif Organs ; 47(7): 1094-1103, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37012224

ABSTRACT

BACKGROUND: Right ventricular failure is associated with increased morbidity and mortality. The ProtekDuo (Livanova, Uk) is a dual-lumen cannula that allows for percutaneous right ventricular support and may be connected to a centrifugal blood pump such as the TandemHeart or LifeSparc (Livanova, UK). This systematic review aims to evaluate the safety and efficacy of ProtekDuo right ventricular support and evaluate potential clinical variables that can influence outcomes. METHODS: PubMed, MEDLINE, SCOPUS, EMBASE, and the Cochrane Library were systematically searched. Studies meeting inclusion criteria, where ProtekDuo was used as the right ventricular assist device with reported numerical death counts for mortality as outcome measures. The primary endpoints were in-hospital 30-day and 1-year mortality rates. Secondary endpoints included ICU length of stay, conversion rates to surgical RVADs, ProtekDuo wean rates, duration of use of ProtekDuo, and adverse event rates. RESULTS: Of 49 studies reviewed, 7 met inclusion criteria with study periods between October 2014 and November 2019. ProtekDuo was utilized due to RV failure post-LVAD insertion in 64.8% (68/105) of patients. In-hospital mortality, 30-day mortality, and 1-year mortality ranged between 9%-46%, 15%-40%, and 19%-40%, respectively. Weaning from ProtekDuo and conversion to surgical RVAD ranged between 24%-91% and 11%-35%, respectively. The ICU stay average ranged from 15.8 to 36 days and ProtekDuo mean support duration ranged from 10.5 to 58 days. CONCLUSION: The ProtekDuo cannula is increasingly utilized as a right ventricular support device. Despite the sparse retrospective data available with variable patient characteristics and study design, percutaneous RV mechanical support via ProtekDuo cannula is a safe and feasible option.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Humans , Heart-Assist Devices/adverse effects , Retrospective Studies , Treatment Outcome , Heart Failure/surgery , Prosthesis Implantation , Ventricular Dysfunction, Right/surgery
15.
Artif Organs ; 47(12): 1831-1847, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37746896

ABSTRACT

BACKGROUND: Left ventricular assist device (LVAD) is associated with a high incidence of right ventricular (RV) failure, which is hypothesized to be caused by the occurring inter-ventricular interactions when the LV is unloaded. Factors contributing to these interactions are unknown. METHODS: We used computer modeling to investigate the impact of the HeartMate 3 LVAD on RV functions. The model was first calibrated against pressure-volume (PV) loops associated with a heart failure (HF) patient and validated against measurements of inter-ventricular interactions in animal experiments. The model was then applied to investigate the effects of LVAD on (1) RV chamber contractility indexed by V 60 derived from its end-systolic PV relationship, and (2) RV diastolic function indexed by V 20 derived from its end-diastolic PV relationship. We also investigated how septal wall thickness and regional contractility affect the impact of LVAD on RV function. RESULTS: The impact of LVAD on RV chamber contractility is small at a pump speed lower than 4k rpm. At a higher pump speed between 4k and 9k rpm, however, RV chamber contractility is reduced (by ~3% at 6k rpm and ~10% at 9k rpm). The reduction of RV chamber contractility is greater with a thinner septal wall or with a lower myocardial contractility at the LV free wall, septum, or RV free wall. CONCLUSION: RV chamber contractility is reduced at a pump speed higher than 4k rpm, and this reduction is greater with a thinner septal wall or lower regional myocardial contractility. Findings here may have clinical implications in identifying LVAD patients who may suffer from RV failure.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Animals , Humans , Heart-Assist Devices/adverse effects , Ventricular Function, Right , Diastole , Heart Ventricles , Heart Failure/surgery , Heart Failure/complications , Ventricular Dysfunction, Right/etiology , Ventricular Function, Left
16.
J Cardiothorac Vasc Anesth ; 37(11): 2318-2326, 2023 11.
Article in English | MEDLINE | ID: mdl-37625918

ABSTRACT

The right ventricle (RV) is intricately linked in the clinical presentation of critical illness; however, the basis of this is not well-understood and has not been studied as extensively as the left ventricle. There has been an increased awareness of the need to understand how the RV is affected in different critical illness states. In addition, the increased use of point-of-care echocardiography in the critical care setting has allowed for earlier identification and monitoring of the RV in a patient who is critically ill. The first part of this review describes and characterizes the RV in different perioperative states. This second part of the review discusses and analyzes the complex pathophysiologic relationships between the RV and different critical care states. There is a lack of a universal RV injury definition because it represents a range of abnormal RV biomechanics and phenotypes. The term "RV injury" (RVI) has been used to describe a spectrum of presentations, which includes diastolic dysfunction (early injury), when the RV retains the ability to compensate, to RV failure (late or advanced injury). Understanding the mechanisms leading to functional 'uncoupling' between the RV and the pulmonary circulation may enable perioperative physicians, intensivists, and researchers to identify clinical phenotypes of RVI. This, consequently, may provide the opportunity to test RV-centric hypotheses and potentially individualize therapies.


Subject(s)
Heart Failure , Ventricular Dysfunction, Right , Humans , Heart Ventricles , Critical Illness , Pulmonary Circulation/physiology , Echocardiography , Critical Care , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , Ventricular Function, Right/physiology
17.
J Cardiothorac Vasc Anesth ; 37(8): 1418-1423, 2023 08.
Article in English | MEDLINE | ID: mdl-37173169

ABSTRACT

OBJECTIVES: To evaluate the association of pulmonary artery diameter and pulmonary artery- to-aorta diameter ratio (PA/Ao) with right ventricular failure and mortality within 1 year after left ventricular assist device implantation. DESIGN: This was a retrospective observational study between March 2013 and July 2019. SETTING: The study was conducted at a single, quaternary-care academic center. PARTICIPANTS: Adults (≥18 years old) receiving a durable left ventricular assist device (LVAD). Inclusion if (1) a chest computed tomography scan was performed within 30 days before the LVAD and (2) a right and left heart catheterization was completed within 30 days before the LVAD. INTERVENTIONS: A left ventricular assist device was used for intervention. MEASUREMENTS AND MAIN RESULTS: A total of 176 patients were included in this study. Median PA diameter and PA/Ao ratio were significantly greater in the severe right ventricular failure (RVF) group (p = 0.001, p < 0.001, respectively). Receiver operating characteristic analysis revealed PA/Ao and RVF as predictors for mortality (area under the curve = 0.725 and 0.933, respectively). Logistic regression analysis-predicted probability gave a PA/Ao ratio cutoff point of 1.04 (p < 0.001). Survival probability was significantly worse in patients with a PA/Ao ratio ≥1.04 (p = 0.005). CONCLUSIONS: The PA/Ao ratio is an easily measurable noninvasive indicator that can predict RVF and 1-year mortality after LVAD implantation.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Adult , Humans , Adolescent , Pulmonary Artery/diagnostic imaging , Risk Factors , Heart Failure/diagnostic imaging , Heart Failure/surgery , Retrospective Studies , Aorta
18.
Curr Heart Fail Rep ; 20(3): 218-229, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37155123

ABSTRACT

PURPOSE OF REVIEW: Acute right ventricular failure (RVF) is a frequent condition associated with high morbidity and mortality. This review aims to provide a current overview of the pathophysiology, presentation, and comprehensive management of acute RVF. RECENT FINDINGS: Acute RVF is a common disease with a pathophysiology that is not completely understood. There is renewed interest in the right ventricle (RV). Some advances have been principally made in chronic right ventricular failure (e.g., pulmonary hypertension). Due to a lack of precise definition and diagnostic tools, acute RVF is poorly studied. Few advances have been made in this field. Acute RVF is a complex, frequent, and life-threatening condition with several etiologies. Transthoracic echocardiography (TTE) is the key diagnostic tool in search of the etiology. Management includes transfer to an expert center and admission to the intensive care unit (ICU) in most severe cases, etiological treatment, and general measures for RVF.


Subject(s)
Heart Failure , Hypertension, Pulmonary , Ventricular Dysfunction, Right , Humans , Heart Failure/diagnosis , Heart Failure/etiology , Heart Failure/therapy , Echocardiography , Ventricular Dysfunction, Right/diagnosis , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/therapy
19.
Perfusion ; 38(1_suppl): 59-67, 2023 05.
Article in English | MEDLINE | ID: mdl-36597024

ABSTRACT

INTRODUCTION: Acute right ventricular failure (aRVF) is associated with high mortality and morbidity. Mechanical circulatory support (MCS) may be considered as an advanced treatment option. The ProtekDuo is a cannula that can be used to provide acute right ventricular support as part of a temporary percutaneous (tp) right ventricular assist device (RVAD) system. The primary objective of this systematic review is to describe patient survival and complications when the ProtekDuo cannula was used as part of an tpRVAD system. METHODS: MEDLINE, Embase, and Scopus were searched from database inception to August 26, 2022. Reference sections of studies were reviewed to screen for database omissions. RESULTS: Seven studies with 127 patients were eligible for inclusion. The studies included patients with aRVF from a variety of causes. Mean duration of support was between 10 and 58 days in five studies. Patient survival to discharge was between 60% and 85.2% in two studies. Four authors reported 30-day survival between 60% and 85.2%. Devicerelated and non-device related complications were low. CONCLUSIONS: Patients treated with RVAD using the ProtekDuo cannula have comparable survival rates and complications to other tpRVAD systems. Several advantages exist compared to other RVAD systems.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Humans , Cannula , Retrospective Studies , Treatment Outcome , Heart Failure/etiology , Heart-Assist Devices/adverse effects , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/therapy
20.
Heart Lung Circ ; 32(2): 156-165, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36503731

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients. METHODS: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation). RESULTS: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs). CONCLUSION: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Calcium Channel Blockers/therapeutic use , Pulmonary Arterial Hypertension/therapy , Pulmonary Arterial Hypertension/drug therapy , Familial Primary Pulmonary Hypertension , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/drug therapy , Cardiac Catheterization
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