Fractional exhaled nitric oxide in adult congenital heart disease.

BACKGROUND: Fractional exhaled nitric oxide levels are related to various clinical diseases. This study investigated the associations between the clinical characteristics and the level of fractional exhaled nitric oxide in patients with adult congenital heart disease. METHODS AND RESULTS: Fractional exhaled nitric oxide values were measured in 30 adult patients with stable congenital heart disease who had undergone right heart catheterization and 17 healthy individuals (controls). There was no significant difference in fractional exhaled nitric oxide values between patients with congenital heart disease and healthy controls. Depending on whether their fractional exhaled nitric oxide values were above or below the median value, patients with congenital heart disease were divided into two groups (low vs. high fractional exhaled nitric oxide groups). The relationship between fractional exhaled nitric oxide values and clinical characteristics was investigated. There was a higher percentage of patients with cyanosis in the low fractional exhaled nitric oxide group (50%) than in the high fractional exhaled nitric oxide group (7.1%). There was no significant difference in right heart catheterization data between the low and high fractional exhaled nitric oxide groups. The fractional exhaled nitric oxide value was correlated to the number of neutrophils in patients with cyanosis (r = 0.84 (N = 8), p = 0.005). CONCLUSIONS: In this cohort of patients with adult congenital heart disease, lower levels of fractional exhaled nitric oxide corresponded to the presence of cyanosis.

Balloon Valvuloplasty to Treat Adult Symptomatic Pulmonary Valve Stenosis with Sequential Follow-Up Using Cardiac Magnetic Resonance Imaging in Combination with Echocardiography.

Pulmonary valve stenosis (PVS) accounts for approximately 10% of all congenital heart defects. Echocardiography and right heart catheterization are the gold standards for diagnosis of PVS and for assessing disease severity and responsiveness to treatment.Recently, cardiac magnetic resonance imaging (cMRI) has been established as an important tool to comprehensively evaluate cardiac structure and function; however, research into the usefulness of cMRI for PVS management is limited. Here, we describe a case of a 59-year-old female with isolated, severe PVS who was successfully treated with balloon pulmonary valvuloplasty (BPV) followed by sequential cMRI at 1 and 12 months. Exertional dyspnea and elevated plasma BNP concentration were observed 1 month after BPV; however, echocardiographic findings did not indicate recurrent stenosis or increased pulmonary valve regurgitation but an increase in mitral E/e'. cMRI demonstrated improved systolic forward flow and RV function with enlargement of LV volume, and the rapid increase in LV preload might be associated with the transient deterioration in symptoms and BNP level, which both gradually improved within 3 months after BPV. cMRI further depicted that a reduced RV mass index and increased RV cardiac output were achieved gradually during the follow-up period.In conclusion, cMRI in combination with echocardiography was sufficiently informative to follow-up this PVS patient both before and after BPV. cMRI is easily reproducible in adult patients; therefore, cMRI should be recommended for long-term follow-up in adult PVS patients.

The Clinical Efficacy of Endothelin Receptor Antagonists in Patients with Pulmonary Arterial Hypertension.

Therapeutic strategies for pulmonary arterial hypertension (PAH) have made remarkable progress over the last two decades. Currently, 3 types of drugs can be used to treat PAH; prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists (ERA). In Japan, the first generation ERA bosentan was reimbursed in 2005, following which the 2nd generation ERAs ambrisentan and macitentan were reimbursed in 2009 and 2015, respectively. The efficacy of each ERA on hemodynamics in PAH patients remains to be elucidated. The aims of this study were to evaluate the hemodynamic effects of ERAs and compare these effects among each generation of ERAs.We retrospectively examined the clinical parameters of 42 PAH patients who were prescribed an ERA (15 bosentan, 12 ambrisentan, and 15 macitentan) and who underwent a hemodynamic examination before and after ERA introduction at our institution from January 2007 to July 2019.In a total of 42 patients, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were significantly decreased and cardiac index was significantly increased after ERA introduction (P < 0.001) and the World Health Organization-Functional class (WHO-Fc) was significantly improved after ERA introduction (P = 0.005). Next, in a comparison between 1st and 2nd generation ERAs, 2nd generation ERAs were found to have brought about greater improvements in hemodynamic parameters (mPAP and PVR. P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan.

Regular Treatment Strategy with a Large Amount of Carvedilol for Heart Failure Improves Biventricular Systolic Failure in a Patient with Repaired Tetralogy of Fallot.

It is widely known that ß-blockers exert beneficial effects on non-ischemic and ischemic systolic heart failure (sHF) in nonstructural hearts. However, whether ß-blockers exert similar effects on sHF associated with congenital heart disease (CHD), particularly in an anatomical right ventricle, remains under debate.Here we report the case of an adult man with repaired tetralogy of Fallot suffering from biventricular heart failure. Treatment with carvedilol directly improved the systolic function of the right and left ventricles. This case report strongly suggests there is potential for carvedilol to exert a beneficial effect on heart failure in CHD. The appropriate titration of carvedilol and patient follow-up for long-term effects are important when treating adult patients with CHD with ß-blockers.

Combined Surgical and Medical Therapy for Candida Prosthetic Endocarditis in a Patient with Repaired Tetralogy of Fallot.

Candida prosthetic endocarditis (CPE) is an uncommon and fatal complication in adults with congenital heart disease. The current guidelines for the management of fungal endocarditis recommend a combination of surgical and medical therapy. However, it still remains uncertain when surgical management in CPE patients should be performed. Therefore, the prognosis of CPE patients is very poor. Here we report a case of CPE in a 31-year-old woman who had undergone surgical repair for tetralogy of Fallot during childhood and pulmonary valve replacement at the age of 21 years. She underwent re-pulmonary valve replacement after being sufficiently sterilized with a 5-week course of antifungal medical therapy, leading to clinical improvement. In CPE patients, it is necessary to perform surgical therapy while suppressing the activity of fungi as much as possible.

Novel Scoring System to Predict Ineligibility for Bridge to Implantable Left Ventricular Assist Device as Destination Therapy Before Extracorporeal Ventricular Assist Device Implantation - For the Coming Era of Destination Therapy in Japan.

BACKGROUND: Although destination therapy (DT) is now expected to be a promising strategy for those who are not suitable for heart transplantation in Japan, there has not been any investigation into ineligibility for bridging to implantable left ventricular assist device (I-LVAD) as DT among patients with extracorporeal LVAD. METHODS AND RESULTS: We retrospectively studied 85 patients who had received an extracorporeal LVAD. To assess ineligibility for a bridge to I-LVAD for DT, we defined DT ineligibility (DTI) as BiVAD requirement, death within 6 months, and persistent end-organ dysfunction (medium or high J-VAD risk score) at 6 months after extracorporeal LVAD implantation. DTI was recorded for 32 patients. Uni/multivariate analysis showed that smaller left ventricular diastolic dimension (<64 mm; [odds ratio (OR) 4.522]), continuous hemodiafiltration (OR 4.862), past history of cardiac surgery (OR 6.522), and low serum albumin level (<3.1 g/dl; OR 10.064) were significant predictors of DTI. By scoring 2, 2, 3, 4 points, respectively, considering each OR, we constructed a novel scoring system for DTI (DTI score), which stratified patients into 3 risk strata: low (0-3 points), medium (4-6 points), and high (7-11 points), from the view point of DTI risk (low 8%, medium 46%, high 93%, respectively). CONCLUSIONS: DTI score is a promising tool for predicting ineligibility for I-LVAD as DT before extracorporeal VAD implantation.

A case of interferon-α-induced pulmonary arterial hypertension after living donor liver transplantation.

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by elevated pulmonary vascular resistance, which results in right-heart failure. We present a case of interferon (IFN)-α-induced PAH developed after living donor liver transplantation. Although IFN is categorized as a "possible" risk factor for PAH in the current international classification, it is still under recognized. Moreover, the prognosis of IFN-induced PAH is poor in the limited number of published cases. In our case, we achieved good outcome by the withdrawal of IFN and administration of combination therapy using tadalafil, beraprost, and treprostinil. Since IFN is an important treatment option in current medical therapy, its contribution to the pathogenesis of PAH should be taken into consideration. In conclusion, our case suggests the importance of PAH screening in patients treated with IFN.

Novel scoring system using cardiopulmonary exercise testing predicts prognosis in heart failure patients receiving guideline-directed medical therapy.

BACKGROUND: Among variables obtained from cardiopulmonary exercise testing (CPXT), peak oxygen consumption (PV̇O2) and the minute ventilation vs. carbon dioxide output (V̇E vs. V̇CO2) slope were established as predictors of death of patients with heart failure (HF) at the cutoff points of 14 ml·min(-1)·kg(-1)and 34, respectively. However, a recent update of guideline-directed medical treatment (GDMT) might alter the implication of these variables. METHODS AND RESULTS: We enrolled 77 HF patients receiving GDMT who had undergone symptom-limited CPXT between 2006 and 2014. Among them, 29 patients were re-hospitalized for HF and there were 13 cardiac deaths during the 4-year study period. Cox regression analyses demonstrated that the V̇E vs. V̇CO2slope, peak heart rate, peak systolic blood pressure, and PV̇O2were significant predictors of both re-admission and cardiac death at each cutoff point calculated by receiver-operating characteristic analyses. A new scoring system was constructed using the following criteria: 1 point was assigned to a variable meeting the cutoff point for re-admission; 2 points were assigned to that for cardiac death. The total scores calculated as the summation of each point (range, 0-8 points) had significantly highest area under the curves compared with each CPXT variable (P<0.05), and significantly stratified both event-free rate into 3 groups (P<0.05). CONCLUSIONS: A novel scoring system using 4 CPXT variables simultaneously predicted re-admission and cardiac death even in patients with HF receiving GDMT.

Aortic insufficiency in patients with sustained left ventricular systolic dysfunction after axial flow assist device implantation.

BACKGROUND: Predicting the occurrence of aortic insufficiency (AI) during left ventricular assist device (LVAD) support has remained unsolved. METHODS AND RESULTS: We enrolled 52 patients who had received continuous flow LVAD (14 axial and 38 centrifugal pumps) and who been followed for ≥6 months between Jun 2006 and Dec 2013. Native aortic valve (AV) opening was observed in 18 patients (35%) with improved LV systolic function, and none of them had AI. On multivariate logistic regression analysis preoperative shorter heart failure duration was the only independent predictor of postoperative native AV opening (P=0.042; odds ratio [OR], 0.999). Of the remaining 34 patients (65%) with closed AV, 11 had AI with enlargement of the aortic root and narrow pulse pressure. Among those with closed AV, axial pump use (n=13) was the only significant predictor of the development of AI (P=0.042; OR, 4.950). Patients with AI had lower exercise capacity and a higher readmission rate than those without AI during 2-year LVAD support (55% vs. 8%; P<0.001). CONCLUSIONS: Native AV opening during LVAD support is profoundly associated with reversal of LV systolic function, especially in patients with preoperative shorter heart failure duration. Among those in whom the native AV remains closed, low pulsatility of axial flow pump may facilitate aortic root remodeling and post-LVAD AI development that results in worse clinical outcome.

Novel scoring system using postoperative cardiopulmonary exercise testing predicts future explantation of left ventricular assist device.

BACKGROUND: Although cardiopulmonary exercise (CPX) testing is an established tool for predicting survival in patients with heart failure (HF), its prognostic impact on explantation of left ventricular assist device (LVAD) was unknown. METHODS AND RESULTS: We enrolled 33 patients who had undergone implantation of extracorporeal pulsatile flow LVAD and symptom-limited CPX testing at 3 months after operation, and who were followed between 2005 and 2014. Patients who received conversion to continuous flow LVAD were excluded. On Cox regression analysis, E1 (maximum load ≥51W; HR, 27.55), E2 (minute ventilation/carbon dioxide output [V̇E/V̇CO2] slope ≤34; HR, 16.86), and E3 (peak oxygen consumption [PV̇O2] ≥12.8 ml·kg(-1)·min(-1); HR, 18.35) significantly predicted explantation expectancy during 2 years after LVAD implantation (P<0.05 for all). Explantation score, the sum of positive E1-3, significantly stratified 2-year cumulative explantation rate into low (0 points), intermediate (1-2 points), and high (3 points) expectancy groups (0%, 29%, and 86%, respectively, P<0.001). When the scoring system was used for 45 patients with continuous flow LVAD, the 2 patients who had explantation were assigned to the high expectancy group. CONCLUSIONS: Explantation score, calculated simply from 3 postoperative symptom-limited CPX testing parameters, is a novel tool to predict explantation expectancy of LVAD and to select good candidates for the weaning test.

Quality of Life and Influential Factors in Patients Implanted With a Left Ventricular Assist Device.

BACKGROUND: Improving quality of life (QOL) has become an important goal in left ventricular assist device (LVAD) therapy. We aimed (1) to assess the effect of an implantable LVAD on patients' QOL, (2) to compare LVAD patients' QOL to that of patients in different stages of heart failure (HF), and (3) to identify factors associated with patients' QOL. METHODS AND RESULTS: The QOL of 33 Japanese implantable LVAD patients was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Short-form 8 (SF-8), before and at 3 and 6 months afterwards. After LVAD implantation, QOL significantly improved [MLHFQ, SF-8 physical component score (PCS), SF-8 mental component score (MCS), all P<0.05]. Implanted LVAD patients had a better QOL than extracorporeal LVAD patients (n=33, 32.1±21.9 vs. n=17, 47.6±18.2), and Stage D HF patients (n=32, 51.1±17.3), but the score was comparable to that of patients who had undergone a heart transplant (n=13). In multiple regression analyses, postoperative lower albumin concentration and right ventricular failure were independently associated with poorer PCS. Female sex and postoperative anxiety were 2 of the independent factors for poorer MCS (all P<0.05). CONCLUSIONS: Having an implantable LVAD improves patients' QOL, which is better than that of patients with an extracorporeal LVAD. Both clinical and psychological factors are influence QOL after LVAD implantation.

Lower rotation speed stimulates sympathetic activation during continuous-flow left ventricular assist device treatment.

Although the suppression of sympathetic activity is an essential mission for the current heart failure treatment strategy, little is known about the relationship between the rotation speed setting and autonomic nervous activity during continuous-flow left ventricular assist device (LVAD) treatment. We evaluated 23 adult patients with sinus rhythm (36 ± 13 years) who had received continuous-flow LVAD and been followed at our institute between March 2013 and August 2014. Heart rate variability measurement was executed along with hemodynamic study at 3 rotation speeds (low, middle, and high) at 5 weeks after LVAD implantation. Lower rotation speed was associated with higher ratio of low-frequency over high-frequency spectral level (LF/HF), representing enhanced sympathetic activation (p < 0.05 by repeated analyses of variance). Among hemodynamic parameters, cardiac index was exclusively associated with LFNU = LF/(LF + HF), representing relative sympathetic activity over parasympathetic one (p < 0.05). After 6 months LVAD support at middle rotation speed, 19 patients with higher LFNU eventually had higher plasma levels of B-type natriuretic peptide and achieved less LV reverse remodeling. A logistic regression analysis demonstrated that lower LFNU was significantly associated with improvement of LV reverse remodeling (p = 0.021, odds ratio 0.903) with a cut-off level of 55 % calculated by the ROC analysis (AUC 0.869). In conclusion, autonomic activity can vary in various rotation speeds. Patients with higher LFNU may better be controlled at higher rotation speed with the view point to suppress sympathetic activity and achieve LV reverse remodeling.

Readmission due to driveline infection can be predicted by new score by using serum albumin and body mass index during long-term left ventricular assist device support.

Survival in patients with continuous flow left ventricular assist device (CF LVAD) had been increased owing to improved perioperative management procedures. The second target for successful long-term LVAD treatment was to reduce readmission especially due to device-specific infection, which was one of the major unsolved complications. Among 57 enrolled patients who had received CF LVAD and been followed for 530 days on median at our institute between 2008 and 2014, 21 patients experienced readmission due to driveline infection (DLI) at 190 days after the surgery on median. Considering the result of Uni/Multivariate Cox regression analyses demonstrating lower serum albumin concentration (S-ALB) (hazard ratio 0.144) and body mass index (BMI) (hazard ratio 0.843) both obtained at discharge were independent predictors of readmission due to DLI, we constructed a New Score "7 × [S-ALB (g/dL)] + [BMI]", which significantly stratified readmission-free rate into 3 groups [low (>50 Pt), intermediate (44-50 Pt), and high risk group (<44 Pt)] during 2-year study period (p = 0.008). Survival remained unchanged irrespective of DLI, whereas those with DLI needed longer in-hospital treatment (p < 0.05). In conclusion, readmission due to DLI could be predicted by using two simple nutrition parameters at discharge. Early nutrition assessment and intervention may reduce readmission and improve patients' quality of life during long-term LVAD support.

An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension.

Tachyarrhythmias such as atrial fibrillation (AF) or atrial flutter (AFL) sometimes invoke life-threatening collapse of hemodynamics in patients with severe heart failure. Recently, landiolol, an ultra-short acting ß1-selective antagonist, has been reported to be safe and useful for the treatment of supraventricular tachyarrhythmias with reduced left ventricular function. Here we report a case of advanced heart failure with severe hypotension who was treated successfully by landiolol for rapid AF. The patient was a 20-year old male with dilated cardiomyopathy. He presented with low output syndrome in spite of optimal medical therapy and was referred to our department to consider ventricular assist device implantation and heart transplantation. Soon after admission, he developed rapid atrial fibrillation at 180 beats per minute (bpm) followed by severe hypotension and liver enzyme elevation. Low dose landiolol at 2 µg/kg/minute was started because digoxin was not effective. After landiolol administration, his heart rate decreased to 110 bpm, and finally returned to sinus rhythm without hemodynamic deterioration. Intra-aortic balloon pumping was inserted soon after sinus recovery and he was discharged successfully with an implantable left ventricular assist device.

Is the internal jugular vein or femoral vein a better approach site for endomyocardial biopsy in heart transplant recipients?

Scheduled serial endomyocardial biopsies are executed by an internal jugular vein (IJV) or femoral vein (FV) approach to survey acute rejection after heart transplantation (HTx). However, a better approach site is needed. A total of 379 sessions consisting of 329 IJV approaches and 50 FV approaches in 48 HTx recipients executed at 75 ± 127 days (41182 days) after HTx between September 2007 and April 2014 at University of Tokyo Hospital were retrospectively analyzed. The IJV approach had shorter operation and radiation exposure times, and a lower dose of radiation exposure and lower usage of contrast agents than the FV approach (all P < 0.001). There were no fatal complications requiring surgical management or resulting in death during all sessions. The IJV approach had less complications than the FV approach (2.7% versus 10.0%, P = 0.011). Among the complications, atrial tachyarrhythmia occurred only with the IJV approach (0.9%), whereas transient ventricular tachyarrhythmia and bundle branch block were more frequently observed in the FV approach (8.0% versus 0.9%, P = 0.042). In conclusion, endomyocardial biopsy from the IJV approach was safer and less invasive than that of the FV approach if we only consider the incidence of atrial tachyarrhythmia.

Late rejection occurred in recipients who experienced acute cellular rejection within the first year after heart transplantation.

Serial endomyocardial biopsies (EMBs) are scheduled even several years after heart transplantation (HTx) to monitor for late rejection (LR). However, repeated EMBs are associated with an increased risk for fatal complications and decrease the quality of life of the recipient. We retrospectively analyzed clinical data from 42 adult recipients who had received HTx and were followed > 1 year at the University of Tokyo Hospital. Five recipients experienced LR at 1130 ± 157 days after HTx, and all 5 had experienced acute cellular rejection (ACR) with ISHLT grade ≥ 2R within the first year, which was treated with methylprednisolone pulse therapy (sensitivity, 1.000; specificity, 0.7027). Logistic regression analyses demonstrated that positive panel reactive antibody (PRA) was the only significant predictor for LR among all parameters at 1 year after HTx (P = 0.020, odds ratio 24.00). Among the 5 recipients with LR, LR occurred earlier in the two PRA positive recipients than in those with a negative PRA (981 ± 12 versus 1230 ± 110 days, P = 0.042). Among the perioperative parameters, gender mismatch [n = 13 (31%)] was the only significant predictor for ACR within the first year in logistic regression analyses (P = 0.042, odds ratio 4.200). In conclusion, the current schedule of serial EMBs should perhaps be reconsidered for recipients without any history of ACR within the first year due to their lower risk of LR.

Parasympathetic reinnervation accompanied by improved post-exercise heart rate recovery and quality of life in heart transplant recipients.

Although sympathetic reinnervation is accompanied by the improvement of exercise tolerability during the first years after heart transplantation (HTx), little is known about parasympathetic reinnervation and its clinical impact. We enrolled 21 recipients (40 ± 16 years, 71% male) who had received successive cardiopulmonary exercise testing at 6 months, and 1 and 2 years after HTx. Exercise parameters such as peak oxygen consumption or achieved maximum load remained unchanged, whereas recovery parameters including heart rate (HR) recovery during 2 minutes and the delay of peak HR, which are influenced by parasympathetic activity, improved significantly during post-HTx 2 years (P < 0.05 for both). HR variability was analysed at post-HTx 6 months in 18 recipients, and high frequency power, representing parasympathetic activity, was significantly associated with the 2 recovery parameters (P < 0.05 for all). We also assessed quality of life using the Minnesota Living with Heart Failure (HF) Questionnaire at post-HTx 6 months and 2 years in the same 18 recipients, and those with improved recovery parameters enjoyed a better HF-specific quality of life (P < 0.05 for both). In conclusion, parasympathetic reinnervation emerges along with improved post-exercise recovery ability of HR and quality of life during post-HTx 2 years.

Targeted therapy is required for management of pulmonary arterial hypertension after defect closure in adult patients with atrial septal defect and associated pulmonary arterial hypertension.

BACKGROUND: Therapeutic strategies for pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) remain a matter of debate. METHODS AND RESULTS: We identified 5 outpatients who had been diagnosed with ASD-PAH and undergone ASD closure in combination with targeted therapy with certified PAH drugs. We assessed changes in hemodynamic parameters and exercise capacity. The combination of ASD closure and targeted therapy significantly increased systemic blood flow (Qs) from the baseline (from 3.3 ± 0.6 L/minute to 4.2 ± 1.0 L/minute, P < 0.05) with a significant improvement in the World Health Organization Functional Class (WHO-FC; from 2.8 ± 0.4 to 1.6 ± 0.5, P < 0.05). The hemodynamic data before and after ASD closure without targeted therapy showed further elevation of pulmonary vascular resistance shortly after ASD closure (678 dyne · s/cm(5) to 926 dyne · s/cm(5)) in 1 case, as well as after a long time since ASD closure (491.0 ± 53.7 dyne · s/cm(5) to 1045.0 ± 217.8 dyne · s/cm(5)) in 2 cases. This worsening was reversed after the targeted therapy, accompanied by an increase in Qs and an improvement in WHO-FC in all cases. CONCLUSIONS: Targeted therapy should be added to ASD closure in adult patients with ASD-PAH.

Opening of native aortic valve accomplished after left ventricular assist device implantation in patients with insufficient preoperative Beta-blocker treatment.

Although we recently demonstrated that opening of a native aortic valve (AV) after left ventricular assist device (LVAD) implantation is a sufficient condition to prevent development of aortic insufficiency (AI), its preoperative predictors remain unknown. Data were obtained from 58 patients who had been treated with continuous flow LVAD for ≥ 6 months at our institute between 2006 and 2014. Opening of native AV was accomplished in 21 patients (36%) at postoperative 6 months. Uni/Multivariate logistic regression analyses demonstrated that a preoperative lower cumulative dose of ß-blocker was the only independent predictor for postoperative opening of native AV (P = 0.020, OR 0.905) at the cutoff level of 4.5g (equivalent dose of carvedilol), calculated by an ROC analysis. Prevalence of native AV opening was increased gradually along with improvement of LV ejection fraction only in patients with preoperative insufficient ß-blocker treatment during postoperative 6 months (P < 0.05 for both). Patients with opening of native AV had higher exercise capacity and a lower re-admission rate than those with closed native AV during 2-year LVAD support (5% versus 44%, P < 0.05). Opening of native AV during LVAD support is profoundly associated with LV reverse remodeling especially in patients with insufficient preoperative ß-blocker exposure probably due to their better responsiveness to combination therapy with ß-blocker and LVAD. Patients who accomplished native AV opening can enjoy better exercise performance and avoid re-admission due to cardiovascular events.

Platelet-derived growth factor receptor-tyrosine kinase inhibitor, imatinib, is effective for treating pulmonary hypertension induced by pulmonary tumor thrombotic microangiopathy.

Pulmonary hypertension (PH) induced by pulmonary tumor thrombotic microangiopathy (PTTM) can be fatal because its rapid progression confounds diagnosis, and it is difficult to control with therapy. Here we describe a woman with symptomatic PTTM-PH accompanying gastric cancer that was suspected from perfusion scintigraphy. PTTM-PH was diagnosed by gastroesophageal endoscopy and lung biopsy after partial control of PH using the platelet-derived growth factor (PDGF) receptor (PDGFR) tyrosine kinase inhibitor, imatinib. Treatment with sildenafil and ambrisentan further decreased PH, and she underwent total gastrectomy followed by adjuvant TS-1 chemotherapy. PH did not recur before her death from metastasis. Postmortem histopathology showed recanalized pulmonary arteries where the embolized cancer masses disappeared. PDGF-A, -B, and PDGFR-α, ß expression was detected in cancer cells and proliferating pulmonary vascular endothelial cells. Thus, PTTM-PH was successfully controlled using a combination of imatinib, drugs to treat pulmonary arterial hypertension, and cancer management.