Clinical findings associated with incomplete hemodynamic left ventricular unloading in patients with a left ventricular assist device.

INTRODUCTION AND OBJECTIVES: The effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined. METHODS: We retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients. RESULTS: Twenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001). CONCLUSIONS: An optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD.

Clinical implications of late-onset right ventricular failure after implantation of a continuous-flow left ventricular assist device as bridge to transplantation.

OBJECTIVES: The development of late-onset right ventricular failure (LoRVF) that occurs months after a continuous-flow left ventricular assist device (LVAD) is implanted is a clinical problem that warrants investigation. Our goal was to study the incidence, clinical manifestations and prognosis of LoRVF in a population of patients who received an LVAD as bridge to transplantation. METHODS: Data were analysed from 97 consecutive patients who received an LVAD as bridge to transplantation and underwent a right heart catheterization at least 3 months after receiving an LVAD implantation. LoRVF was defined if both haemodynamic criteria of a central venous pressure >16 mmHg and a cardiac index <2.3 l/min/m2 were present. Clinical and echocardiographic variables, hospitalizations for heart failure and survival were compared between patients with and without LoRVF. RESULTS: LoRVF was diagnosed in 13% of patients after a median time of 11 months. Patients with LoRVF presented preoperative worse right ventricular (RV) dilatation and severe tricuspid regurgitation. LORVF was also associated with postoperative RV dilatation, moderate to severe tricuspid regurgitation and lower tricuspid annular plane systolic excursion. LoRVF resulted in increased brain natriuretic peptide levels and the need for diuretics, lower haemoglobin levels and a higher rate of atrial fibrillation and gastrointestinal bleeding. The rate of hospitalizations for heart failure in patients with LoRVF was 46%, and 15% required an urgent transplantation due to refractory RV failure. LoRVF decreased global survival and survival free from hospitalizations for heart failure (P < 0.0001). CONCLUSIONS: LoRVF after the implantation of an LVAD as bridge to transplantation is associated with higher morbidity and lower survival. The results suggest that the routine use of a right heart catheterization and transthoracic echocardiography may contribute to an early diagnosis before further severe complications due to refractory RV failure might occur. ID NUMBER OF THE IRB APPROVAL: AZ-2019-521 on 10 July 2019.

Risk factors of early right ventricular failure in patients undergoing LVAD implantation with intermediate Intermacs profile for advanced heart failure.

BACKGROUND: The clinical profile of left ventricular assist device (LVAD) candidates is rapidly changing, with increasing proportion of patients in more stable clinical conditions. However, early postoperative right ventricular failure (eRVF) is still one of the cornerstones associated with increased mortality and the preoperative recognition of associated risk factors remains challenging. The aim of this study was to identify predictive parameters for eRVF after LVAD implantation in patients with preoperative intermediate Intermacs (InM) risk profile 3-5. METHODS: Preoperative laboratory, echocardiography, and right heart catheterization data collected from 80 patients with InM profile 3-5 before LVAD implantation were retrospectively tested with respect to their ability to predict the risk for eRVF after the implantation of a continuous-flow LVAD. RESULTS: Preoperative higher bilirubin and blood urea nitrogen (BUN) levels, higher Model for End-stage Liver Disease score, lower estimated glomerular filtration rate, and higher central venous pressure to pulmonary capillary wedge pressure ratio (CVP/PCWP) were associated to higher risk of eRVF. Regarding the echocardiographic assessment, higher end diastolic linear dimensions of the RV, higher basal end diastolic RV linear dimension to LV ratio, severe tricuspid regurgitation, lower tricuspid annular plane systolic excursion, and lower RV fractional area contraction identified patients with higher risk for eRVF. In the multivariable analysis, a CVP/CPWP > 0.55 (odds ratio [OR]: 4, 95% confidence interval [CII]: 1.4-11.8;P = .01) and BUN > 44.5 mg/dL (OR: 6.6, 95% CI: 1.51-23; P = .011) independently predicted the risk of eRVF. CONCLUSION: Preoperative BUN > 44.5 mg/dL and CVP/PCWP > 0.55 are associated to an increased risk of eRVF following LVAD implantation in intermediate InM patients.

Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation.

BACKGROUND: Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting. METHODS: Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies. RESULTS: Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%). CONCLUSIONS: The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases.

Pulmonary arterial hypertension related to human immunodeficiency virus infection: A case series.

AIM: To present 18 new cases of human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH) with presenting features, treatment options and follow-up data. METHODS: This is a single-centre, retrospective, observational study that used prospectively collected data, conducted during a 14-year period on HIV-related PAH patients who were referred to a pulmonary hypertension unit. All patients infected with HIV were consecutively admitted for an initial evaluation of PAH during the study period and included in our study. Right heart catheterisation was used for the diagnosis of PAH. Specific PAH treatment was started according to the physician's judgment and the recommendations for idiopathic PAH. The data collected included demographic characteristics, parameters related to both HIV infection and PAH and disease follow-up. RESULTS: Eighteen patients were included. Intravenous drug use was the major risk factor for HIV infection. Risk factors for PAH, other than HIV infection, were present in 55.5% patients. The elapsed time between HIV infection and PAH diagnoses was 12.2 ± 6.9 years. At PAH diagnosis, 94.1% patients had a CD4 cell count > 200 cells/µL. Highly active antiretroviral therapy (present in 47.1% patients) was associated with an accelerated onset of PAH. Survival rates were 93.8%, 92.9% and 85.7% at one, two and three years, respectively. Concerning specific therapy, 33.3% of the patients were started on a prostacyclin analogue, and the rest were on oral drugs, mainly phosphodiesterase-5 inhibitors. During the follow-up period, specific therapy was de-escalated to oral drugs in all of the living patients. CONCLUSION: The survival rates of HIV-related PAH patients were higher, most likely due to new aggressive specific therapy. The majority of patients were on oral specific therapy and clinically stable. Moreover, sildenafil appears to be a safe therapy for less severe HIV-related PAH.

Giant pulmonary artery aneurysm in a patient with vasoreactive pulmonary hypertension: a case report.

BACKGROUND: Pulmonary artery aneurysms are a rare condition, frequently associated with pulmonary hypertension. However, the evolution and treatment of this pathology is still not clear. CASE PRESENTATION: The authors report a case of a 65-year old patient with pulmonary artery aneurysm associated with pulmonary arterial hypertension. Due to a positive vasoreactivity test, treatment with calcium channel blockers was started with near normalization of the right cardiac pressures. Nevertheless, after 20 months of treatment, the pulmonary artery aneurysm size remained unchanged with an associated severe pulmonary regurgitation and causing extrinsic compression of the main left coronary artery. Surgical correction was successfully performed. CONCLUSIONS: This is the first case report of a pulmonary artery aneurysm described to be associated with vasoreactive pulmonary hypertension in a living patient. Although medical therapy for pulmonary hypertension was started, surgical correction of the aneurysm was executed in order to prevent its future complications.

Implante de desfibrilador como prevención primaria de muerte súbita en pacientes en lista de espera de trasplante cardiaco: experiencia de un centro / Defibrillator implantation for the primary prevention of sudden death in patients awaiting cardiac transplantation: one center’s experience

Los pacientes incluidos en lista de espera de trasplante cardiaco frecuentemente presentan un perfil acorde a las recomendaciones actuales en cuanto al implante de desfibrilador automático implantable como prevención primaria de muerte súbita. El eventual trasplante a corto-medio plazo hace dudar de la efectividad de dicha terapia. Analizamos la incidencia de terapias administradas por el desfibrilador implantado como prevención primaria en pacientes en lista, así como la evolución histórica en la frecuencia de muerte súbita en nuestro centro. Se revisaron los 308 pacientes incluidos en lista desde 1998 hasta 2008. En 17 pacientes se indicó desfibrilador automático implantable como prevención primaria al momento de la inclusión. El 53% de éstos recibió terapias adecuadas, habiendo portado el dispositivo una media de 7,8 meses (±4,8). Sólo 1 paciente presentó terapias inadecuadas y ninguno sufrió complicaciones asociadas al dispositivo. La frecuencia de muerte súbita se ha reducido a lo largo de los últimos años(AU)

Patients who are on a waiting list for cardiac transplantation often have a clinical profile that satisfies current recommendations for the implantation of an implantable cardioverter–defibrillator for the primary prevention of sudden death. The prospect that transplantation may take place within the shortto- medium term puts the effectiveness of this therapy in doubt. We investigated the incidence of therapy delivered by implantable cardioverter–defibrillators implanted for primary prevention in patients awaiting cardiac transplantation. Recent changes in the incidence of sudden death at our center were also investigated. Data on 308 patients listed for heart transplantation between 1998 and 2008 were reviewed. An implantable cardioverter–defibrillator was indicated for primary prevention at initial evaluation in 17 patients. Of these, 53% received appropriate implantable cardioverter–defibrillator therapy while carrying an implantable cardioverter–defibrillator for amean period of 7.8months (+/-4.8). Only one patient received inappropriate therapy and none had any complications associated with device use. The frequency of sudden death has decreased over the course of recent years(AU)

Induction treatment with monoclonal antibodies for heart transplantation.

Individualization of induction therapy for heart transplantation (HT) is needed, given that only patients at significant risk for fatal rejection seem to present a favorable risk-benefit ratio. The question whether monoclonal interleukin 2 antagonists or antilymphocyte antibodies should be recommended remains unanswered. As most studies suggest that they have similar efficacy in preventing acute rejection, other variables related to safety or management costs should be taken into account. The cytokine release syndrome, associated with the use of OKT3, complicates management of HT patient. The experience in our center with 2 consecutive cohorts, treated with basiliximab (BAS) and OKT3, respectively, suggests that the use of BAS is associated, in addition to similar immunosuppressive efficacy and better safety profile than OKT3, with simpler patient management during the initial hospital stay, which could be associated with a reduction in posttransplant costs. Because few centers continue to use OKT3 as induction therapy in HT, more studies comparing cost-effectiveness of BAS vs polyclonal antilymphocyte antibodies (ATG) are needed.

Complicaciones de los aneurismas proximales de arteria pulmonar en pacientes con hipertensión pulmonar severa / Complications of proximal pulmonary artery aneurysm in patients with severe pulmonary arterial hypertension

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Comparison of baseline characteristics and survival between patients with idiopathic and connective tissue disease-related pulmonary arterial hypertension.

BACKGROUND: Both idiopathic pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension (PAH) related to connective tissue diseases (CPAH) are classified in the group of PAH disorders. However, CPAH has a particularly worse prognosis than IPAH. Few studies have compared the clinical, functional and hemodynamic profiles of IPAH and CPAH. METHODS: We performed a retrospective cohort study of patients with IPAH or CPAH. Demographic characteristics, functional status (FE), pulmonary function test and hemodynamic values at the time of diagnosis were compared between the two etiologies. Global cumulative survival rates free from transplantation (SFT) and survival according to date of diagnosis were analyzed. RESULTS: Despite similar PAH severity, patients with CPAH showed a more severe baseline impairment of 6-minute walking test (6MWT) (307 +/- 116 m vs 378 +/- 101 m) and diffusion capacity of the lung for carbon monoxide (DLCO) (57 +/- 25% vs 75 +/- 30% of predicted) than IPAH (p < 0.01). Survival rates at 1, 3 and 5 years of follow-up were 87%, 71% and 63% for IPAH, and 70%, 53% and 42% for CPAH, respectively (p < 0.05). IPAH showed better survival when treatment was started after Year 2000 (p = 0.01). However, CPAH showed a poorer prognosis than IPAH in the more recent era (p < 0.05). CPAH (hazard ratio [HR] = 2.03), DLCO <80% (HR = 1.98) and treatment before Year 2000 (HR = 2.27) were associated with an independent increased risk of death or transplantation. CONCLUSIONS: Despite similar functional and hemodynamic severity, patients with CPAH showed a more severe baseline impairment of 6MWT and DLCO and worse overall prognosis than IPAH. Both IPAH and CPAH survival improved in the current era. Nevertheless, CPAH still showed a poorer prognosis than IPAH.

[Treatment of HIV-associated pulmonary hypertension with treprostinil]. / Tratamiento de la hipertensión pulmonar asociada a la infección por VIH con treprostinil.

BACKGROUND AND OBJECTIVE: The treatment of pulmonary hypertension associated with infection by human immunodeficiency virus has not been well defined. Treprostinil is a prostacyclin analogue that has recently been shown to be useful for the treatment of pulmonary hypertension, whether primary, secondary to congenital heart disease, or associated with collagen disease, in a 12-week, double-blind study. We report the results of a one-year follow-up of three patients with pulmonary hypertension associated with human immunodeficiency virus infection who are being treated with treprostinil at our center. PATIENTS AND METHOD: After secondary causes of pulmonary hypertension were excluded by a routine work-up, patients started treatment with subcutaneous prostacyclin (treprostinil) with progressive up-titration of the dose. Functional status and effort capacity were assessed every three months and an echocardiographic study was performed every six months. RESULTS: All patients showed improvement in clinical status, as shown by the NYHA functional class and the results of the six-minute walking test (increase of at least 75 meters). All the patients remain alive after one year of follow-up. Echocardiographic systolic pulmonary pressure decreased in two patients. No serious adverse events were observed. CONCLUSIONS: Subcutaneous prostacyclin (treprostinil) seems to be an effective and safe therapeutic option for the treatment of pulmonary hypertension associated with human immunodeficiency virus infection.