Haemodynamic effects and potential clinical implications of inhaled nitric oxide during right heart catheterization in heart transplant candidates.

AIMS: Right heart catheterization (RHC) is indicated in all candidates for heart transplantation (HT). An acute vasodilator challenge is recommended for those with pulmonary hypertension (PH) to assess its reversibility. The effects of inhaled nitric oxide (iNO) on pulmonary and systemic haemodynamics have been reported only in small series. Our purpose was to describe the response to iNO in a larger population and its potential clinical implications. METHODS AND RESULTS: From 210 RHC procedures performed between 2010 and 2019, vasodilator challenge with iNO was used in 108 patients, of which 66 had advanced heart failure undergoing assessment for HT (55±11 years old; 74.2% male gender; 43.9% ischaemic cardiomyopathy; left ventricular ejection fraction 28.4 ± 11,4%; and peak VO2 12.1 ± 3.0 mL/kg/min). iNO was administered through a tight-fitting facial mask regardless of baseline pulmonary pressures. Clinical endpoints (all-cause mortality and acute right heart failure) were assessed according to baseline haemodynamic findings over the available follow-up period. There were no side effects from iNO administration. Typical response consisted of a reduction in pulmonary vascular resistance, consequent to an increase in left ventricular filling pressures, no significant change in mean pulmonary artery pressure (resulting in a lower mean transpulmonary gradient) and a mild increase in cardiac ouput. Pulmonary arterial compliance increased significantly, whereas systemic vascular resistance was only mildly affected. In five cases (7.6%), pulmonary vascular resistance increased paradoxically. All-cause mortality and post-HT right heart failure events were overall low and similar in patients without PH or reversible PH. CONCLUSIONS: Vasodilator challenge with iNO is safe in advanced heart failure patients undergoing RHC prior to HT listing. It produces a reasonably predictable haemodynamic response, which occurs predominantly at the pulmonary circulation level. Clinical implications of iNO-induced reversibility may be relevant, but further systematic validation is warranted in larger cohorts.

Dabigatran reversal with idarucizumab in a patient undergoing heart transplantation: first European report.

BACKGROUND: Dabigatran is a direct thrombin inhibitor with a favorable effectiveness and safety profile when compared to vitamin K antagonists, both in randomized trials and real world registries of atrial fibrillation patients. Yet, physicians' fear of high bleeding risk scenarios in daily clinical practice still precludes a more widespread use of oral anticoagulation. We hereby report a successful case of dabigatran reversal with the novel monoclonal antibody fragment idarucizumab in a patient undergoing heart transplantation. CASE PRESENTATION: A 45-year old male patient on dabigatran for atrial fibrillation thromboprophylaxis was enlisted for heart transplantation due to end-stage ischemic heart failure. Upon donor availability and suitability and following the last intake of the drug 12 h previously, activated partial thromboplastin time was measured and found to be elevated. After general anesthesia and before extracorporeal circulation, idarucizumab was administered as two boluses of 2.5 g. Orthotopic heart transplantation ensued under full heparinization and cardiopulmonary bypass. Total chest tube output was 1125 mL after 3 days and 4 units of fresh frozen plasma and one platelet pool were administered in the operating room without further need for blood products. The post-operative period was uneventful. CONCLUSIONS: Idarucizumab was associated with an effective hemostasis in the setting of heart transplantation. Dabigatran may be considered as an alternative to vitamin K antagonists in heart transplant candidates with an indication for oral anticoagulation.

A rare case of persistent troponin elevation in a patient with chronic heart failure.

We present the case of a woman diagnosed with hypertrophic cardiomyopathy who suffered a myocardial infarction when she was 28 years old, without coronary artery disease on coronary angiography. Two years later, she presented signs of heart failure and left ventricular systolic dysfunction with persistent troponin I elevation, followed by progressive worsening of ventricular dysfunction.

[Diagnosis, prevention and treatment of cardiac allograft vasculopathy]. / Diagnóstico, prevenção e tratamento da doença vascular do aloenxerto.

The major limitation of long-term survival after cardiac transplantation is allograft vasculopathy, which consists of concentric and diffuse intimal hyperplasia. The disease still has a significant incidence, estimated at 30% five years after cardiac transplantation. It is a clinically silent disease and so diagnosis is a challenge. Coronary angiography supplemented by intravascular ultrasound is the most sensitive diagnostic method. However, new non-invasive diagnostic techniques are likely to be clinically relevant in the future. The earliest possible diagnosis is essential to prevent progression of the disease and to improve its prognosis. A new nomenclature for allograft vasculopathy has been published in July 2010, developed by the International Society for Heart and Lung Transplantation (ISHLT), establishing a standardized definition. Simultaneously, the ISHLT published new guidelines standardizing the diagnosis and management of cardiac transplant patients. This paper reviews contemporary concepts in the pathophysiology, diagnosis, prevention and treatment of allograft vasculopathy, highlighting areas that are the subject of ongoing research.

[Complications of endomyocardial biopsy after heart transplantation: a lesser evil]. / Complicações da biópsia endomiocárdica após transplante cardíaco. Um mal menor.

Endomyocardial biopsy is still the principal method for diagnosing cardiac allograft rejection. However, this procedure can be associated, albeit rarely, with potentially serious complications. We describe the case of a patient with extensive anterior myocardial infarction without revascularization, who developed cardiogenic shock and required heart transplantation. Post-transplantation, a coronary artery fistula to the right ventricle associated with an aneurysm and two restrictive ventricular septal defects were detected.

The value of routine intracoronary ultrasound to assess coronary artery disease in cardiac allograft recipients.

UNLABELLED: Cardiac allograft vasculopathy is the main cause of morbidity and mortality after cardiac transplantation. Intravascular ultrasound (IVUS) is a sensitive imaging technique that provides detailed quantification of coronary atherosclerosis burden and could be a complement to routine angiography. AIM: To determine the value of IVUS for detecting silent atherosclerotic disease in cardiac allograft recipients. METHODS: The study cohort consisted of 40 consecutive patients (mean age 55 +/- 11 years, 25% female) who underwent left anterior descending coronary artery IVUS (Volcano Therapeutics, Inc.) examination after transplantation. None of the patients had suspected or documented ischemia. Cardiac transplantation was due to ischemic cardiomyopathy in 30% (12 patients). Coronary artery disease (CAD) was defined as the presence of > or = 30% stenosis of vessel diameter (QCA analysis - Siemens CASS) on angiography and atherosclerotic lesions causing > or = 30% stenosis of vessel area by IVUS. The angiographic definition of significant CAD lesions was > or = 50% stenosis of vessel diameter, and by IVUS a minimum cross-sectional area of < or = 4 mm2. RESULTS: CAD was identified in 20% (8 patients) by angiography and in 55% (22 patients) by IVUS (p = 0.003). Significant CAD was detected in 15% (6 patients) by angiography and in 7.5% (3 patients) by IVUS (p = 0.3). CONCLUSION: The use of IVUS on routine screening coronary angiography detects a higher prevalence of early atherosclerotic disease than normal angiography, which should lead to implementation of preventive strategies to control disease progression. IVUS was no more sensitive than angiography in detecting severe coronary stenosis. IVUS should be used as a standard imaging technique together with routine coronary angiography to assess atherosclerosis burden in cardiac allograft recipients.

Serum creatinine values underestimate surgical risk.

INTRODUCTION: Renal insufficiency is associated with increased mortality and morbidity from cardiac surgery. Serum creatinine (SCr) values are routinely used for the assessment of renal dysfunction. However, this parameter can overestimate renal function, especially in low-weight and elderly patients, who can have normal creatinine values despite impaired renal function. OBJECTIVE: 1) To evaluate the prevalence and prognostic impact of different degrees of preoperative renal dysfunction (RD); 2) to assess the prevalence of normal SCr values among patients in different stages of RD. METHODS: This was a retrospective study of 1314 consecutive adult patients (836 male, mean age 66 +/- 11 years) undergoing cardiac surgery. Patients were assigned to one of the five stages of RD of the National Kidney Foundation classification according to their glomerular filtration rate (GFR), estimated by the Cockcroft-Gault equation and indexed to body surface area. The impact of each stage of RD on in-hospital mortality was assessed after adjusting for all the other EuroSCORE components in multivariate analysis. RESULTS: The median logistic EuroSCORE was 3.8 (interquartile range: 1.9-7.0). In-hospital mortality was 3.4% (n = 35). The prevalence of stages 3, 4 and 5 RD was 30.2% (n = 397), 3.4% (n = 45) and 4.3% (n = 56) respectively. Increasing in-hospital mortality was observed across ascending stages of RD. After adjustment for other EuroSCORE risk factors. stage 3 or higher RD was an independent predictor of in hospital mortality--OR 2.0 (95% CI: 1.1-3.9, p = 0.03). Among patients with stage 3 or higher RD, 61% (n = 304) had SCr values < 1.50 mg/dl and 83% (n = 414) had SCr < 2.26 mg/dl (the EuroSCORE cutoff value). CONCLUSIONS: Renal impairment is common among patients undergoing cardiac surgery and the presence of even mild forms of RD is associated with increased mortality. SCr values within the normal range frequently correspond to moderate or even severe RD, indicating that GFR should be calculated systematically to avoid underestimation of surgical risk.

Nitric oxide in the management of pulmonary hypertension in the context of cardiac surgery in the adult.

Pulmonary hypertension is a significant problem to take into account in the post-operative management of cardiac patients, especially valvular patients. Inhaled nitric oxide allows more effective control of pulmonary pressure and other hemodynamic parameters, with better post-operative results. We present a clinical case of a patient with mitral stenosis and severe pulmonary hypertension, with post-operative hemodynamic instability, in which we used inhaled nitric oxide for better control of pulmonary pressures and to help ventilator weaning.

Recovery kinetics of oxygen uptake after cardiopulmonary exercise test and prognosis in patients with left ventricular dysfunction.

INTRODUCTION: The prognostic value of peak oxygen uptake (peak VO2) in patients with left ventricular systolic dysfunction is currently recognized and accepted. Some studies have shown that other cardiopulmonary exercise test (CPET) parameters have additional value. OBJECTIVES: To evaluate whether our population of patients with left ventricular dysfunction had similar results to those found by other investigators who showed that a slow normalization of oxygen uptake (VO2) during the recovery period of a CPET has prognostic value, and whether the recovery phase parameters have additional prognostic value to peak VO2 in these patients. METHODS: We studied 292 consecutive adult patients (81.5% male; mean age 52.4 +/- 10.6 years) with an ejection fraction below 40% (mean 23.6 +/- 8.8%) given their first symptom-limited CPET between 03/1993 and 08/2000. The etiology was ischemic heart disease in 154, idiopathic cardiomyopathy in 130 and other in 8 patients. NYHA class was I in 7%, II in 50.6% and III in 42.4% of the patients. Two years was defined as the maximum follow-up time; it was 551.5 +/- 242.2 days on average, and 62 events (death or cardiac transplantation) occurred. The following parameters were analyzed: peak VO2 (l/min and ml/kg/min), percent predicted peak VO2 (pred VO2) (l/min and ml/kg/min), VO2 every 15 seconds (sec) of the first 3 minutes of recovery (the difference between peak VO2/kg and VO2/kg every 15 sec in the recovery period (dif VO2), expressed in ml/kg/min, and also the time (sec) to reach 50% of peak VO2 (T1/2). It was considered that a combined end-point was reached if patients died or underwent cardiac transplantation. RESULTS: ROC curves of these parameters showed the following as cut-off values (area under the curve > 0.7) for the occurrence of events: peak VO2 < 60% of pred VO2, dif VO2 at 60 sec (< 3 ml/kg/min), 90 sec (< 5), 120 sec (< 8), 150 sec (< 8.6) and 180 sec (< 10.5) of the recovery and T1/2 > 115 sec. Survival analysis was performed considering pred VO2 < 60%, dif VO2 at 150 sec (the largest area under the curve) and T1/2 > 115 sec. In the survival analysis, when the decrease in VO2 at 150 sec was less than 8.6 ml/kg/min the number of patients with events increased from 9.2% to 43.5% (p < 0.001; log-rank), and when T1/2 was less than 115 sec the number of events increased from 12.3 to 34.2% (p < 0.001; log-rank). When the criteria of T1/2 and dif VO2 at 150 sec were considered together with pred VO2 < 60%, mortality increased from 31 to 54% and from 33 to 51%, respectively (p < 0.001, for both parameters; chi-square). CONCLUSIONS: A slow VO2 kinetics in the recovery period of the CPET by itself identified groups of patients with poor prognosis. The association of these parameters with peak VO2 enhanced the identification of groups at greater risk for events. A global evaluation of the CPET should be performed, considering other parameters besides peak VO2, particularly those related to VO2 kinetics in recovery (T1/2 and dif VO2 at 150 sec) as identified in this study.

Heart transplantation in Portugal: current status and future perspectives.

No other form of therapy, whether medical or surgical, has an impact comparable to heart transplantation on the quality of life and survival of selected patients with severe heart failure. In the EU and in the USA about 10 patients per million of population are transplanted each year. In Portugal, a country with a population of 10 million, 100 patients should be transplanted each year, but only 12 patients were in fact transplanted in 1999. We rank 17th, in terms of the rate of heart transplantation per million of population, among the 23 European countries with registries of this activity. This is due to structural and organizational deficiencies of three main types: the lack of professional teams dedicated to severe heart failure treatment and heart transplantation; the lack of infrastructure, particularly heart failure wards and heart failure outpatient clinics; and the inappropriate distribution of the tasks associated with heart transplantation and patient follow-up. We present an estimate of the number of potential heart transplant candidates in Portugal, based on the EPICA study and a prediction of the resources needed for a successful heart transplantation program serving a population of 2 million. This was based on what is known of the natural history, morbidity and mortality of severe heart failure, on our own experience in this field, and finally on the experience of a large international heart transplantation center. The recommendations of the British Transplantation Society and those of the Department of Cardiothoracic Surgery of Stanford University were also taken into account.