Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial.

BACKGROUND: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. METHODS: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. RESULTS: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). CONCLUSIONS: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. TRIAL REGISTRATION: clinicaltrials.gov NCT02908308 , Registered September 20, 2016.

Association between early airway intervention in the pre-hospital setting and outcomes in out of hospital cardiac arrest patients: A post-hoc analysis of the Target Temperature Management-2 (TTM2) trial.

INTRODUCTION: Airway management is a critical component of out-of-hospital cardiac arrest (OHCA) resuscitation. The primary aim of this study was to describe pre-hospital airway management in adult patients post-OHCA. Secondary aims were to investigate whether tracheal intubation (TI) versus use of supraglottic airway device (SGA) was associated with patients' outcomes, including ventilator-free days within 26 days of randomization, 6 months neurological outcome and mortality. METHODS: Secondary analysis of the Target Temperature Management-2 (TTM2) trial conducted in 13 countries, including adult patients with OHCA and return of spontaneous circulation, with data available on pre-hospital airway management. A multivariate logistic regression model with backward stepwise selection was employed to assess whether TI versus SGA was associated with outcomes. RESULTS: Of the 1900 TTM2 trial patients, 1702 patients (89.5%) were included, with a mean age of 64 years (Standard Deviation, SD = 13.53); 79.1% were males. Pre-hospital airway management was SGA in 484 (28.4%), and TI in 1218 (71.6%) patients. At hospital admission, 87.8% of patients with SGA and 98.5% with TI were mechanically ventilated (p < 0.001). In the multivariate analysis, TI in comparison with SGA was not independently associated with an increase in ventilator-free days within 26 days of randomization, improved neurological outcomes, or decreased mortality. The hazard ratio for mortality with TI vs. SGA was 1.06, 95%Confidence Interval (CI) 0.88-1.28, p = 0.54. CONCLUSIONS: In the multicentre randomized TTM2-trial including patients with OHCA, most patients received prehospital endotracheal intubation to manage their airway. The choice of pre-hospital airway device was not independently associated with patient clinical outcomes. TRIAL REGISTRATION NUMBER: NCT02908308.

Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.

Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial.

INTRODUCTION: Mechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients. METHODS AND ANALYSIS: This is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)-target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients' prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay. ETHICS AND DISSEMINATION: The TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02908308.

Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial.

PURPOSE: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. METHODS: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. RESULTS: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH20, plateau pressure was 20 cmH20 (IQR = 17-23), driving pressure was 12 cmH20 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36-45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003-1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001-1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. CONCLUSIONS: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.

Comparison of duplex ultrasonography and magnetic resonance imaging in the detection of significant renal artery stenosis.

OBJECTIVE: The aim of our study was to evaluate duplex ultrasonography (DUS) and magnetic resonance angiography (MRA) in detection of haemodynamically significant renal artery stenosis (RAS). METHODS: The study included patients with high clinical suspicion of renovascular hypertension (RVH). The imaging of renal arteries was performed by DUS, MRA and digital subtraction angiography (DSA). Significant RAS was defined as maximum systolic velocity > or =180 cm/sec (DUS) or as 60% reduction of the endoluminal arterial diameter (MRA, DSA). The results of DUS and MRA were assessed in respect to the results of DSA. RESULTS: Arterial supply of 186 kidneys in 94 patients was evaluated. DSA revealed significant RAS in 61 kidneys evaluated. DUS was not able to examine arterial supply in 18 kidneys of 13 patients. In the detection of significant RAS, DUS was characterized by sensitivity and specificity of 85% and 84%. MRA achieved satisfactory imaging quality in all but one kidney evaluated. The sensitivity and specificity of MRA in the detection of significant RAS was 93% and 93%, respectively. CONCLUSION: In patients with high clinical probability of RVH, MRA proved to be more reliable and superior in both sensitivity and specificity to DUS in the detection of significant RAS.

Doxazosin: safety and efficacy in the treatment of resistant arterial hypertension.

Five classes of antihypertensive drugs have proven efficacy in the prevention of cardiovascular morbidity and mortality. Among the remaining antihypertensives, the action of alpha-1-blockers is supported by most clinical evidence; however, in combination therapy, the published data concern their use as third-line drugs at the most. The data from patients with drug-resistant hypertension remain limited. The aim of our study was to evaluate the efficacy and safety of doxazosin in this clinical setting. Data from 97 patients with resistant hypertension treated by doxazosin were analysed retrospectively. Doxazosin was usually added as the fifth antihypertensive drug in individuals who were either unresponsive to or intolerant of the combination of other antihypertensives. The dose of doxazosin ranged from 2 to 16 mg/day. The mean duration of follow-up was 21+/-17 months. Adverse events related to doxazosin treatment were rare and led to discontinuation of the therapy in only five patients (5.2%). Data from 34 patients were subjected to analysis of efficacy. In this subgroup, doxazosin therapy led to the reduction of blood pressure from 159+/-20/92+/-14 to 126+/-16/73+/-10 mmHg. We found that doxazosin is a well-tolerated and effective drug for patients with resistant arterial hypertension who require a combination of multiple antihypertensive drugs.

Giant renal cyst mimicking ascites on abdominal ultrasonography.

An article describes diagnostic difficulties in patient with giant renal cyst, erroneously diagnosed as ascites on ultrasonographic examination. Patient was initially suspected to have disseminated intraabdominal malignancy. Abdominal paracentesis of supposed ascites was performed. The diagnosis of giant renal cyst was finally made by CT and patient was treated surgically. The limitations of ultrasonographic examination are pointed out are and a brief review of similar cases is given.

The Assessment of Serum Drug Levels to Diagnose Non-Adherence in Stable Chronic Heart Failure Patients.

BACKGROUND: The aim of our study was to evaluate the prevalence of drug non-adherence in stable chronic heart failure (CHF) patients using serum drug levels (SDL) assessment. METHODS: CHF patients were prospectively enrolled during scheduled outpatient visit. Except standard procedures an unanticipated blood sampling for the SDL assessment was obtained. Analysis was focused on the prescribed heart failure and antihypertensive medication and was performed by liquid chromatography coupled with mass spectrometry. The patient was labelled as non-adherent if at least one of drugs assessed was not found in the serum. In the first half of patients multiple SDL have been evaluated during the follow-up. RESULTS: Eighty one patients were enrolled. The non-adherence was proven in twenty of them (25%). In the subgroup of thirty eight patients with multiple SDL evaluation the non-adherence raised significantly with increasing number of visits assessed together (21% for single visit, 29% for two of three visits assessed together and 34% for all three visits evaluated together, all p < 0.001). CONCLUSION: The non-adherence was proven in significant part of stable CHF patients using SDL assessment. This method seems to be reliable and effective and should be a part of clinical assessment in selected patients with CHF.

Comparison of magnetic resonance imaging and cardiac catheterization in patients with suspected severe aortic stenosis.

OBJECTIVE: Magnetic resonance imaging (MRI) is a novel technique used in the assessment of aortic stenosis. The aim of the study was to compare MRI and cardiac catheterization (CAT) that is still considered to be a "golden standard" in this indication. METHODS: Thirty-four patients referred to CAT for the evaluation of aortic stenosis were enrolled into the study. CAT was performed according to the standardized protocol. Cardiac output was measured by thermodilution and mean aortic gradient was determined using simultaneous blood pressure measurement in aorta and left ventricle. MRI was performed within the period of 3 weeks after CAT. True FISP sequence with retrospective ECG gating was used for the imaging of the aortic valve orifice. Planimetry of the aortic valve area (AVA) was performed at the time of maximal opening of the valve during systole. RESULTS: MRI enabled the measurement of AVA in all patients enrolled. Mean AVA defined by CAT and MRI were 0,97 (+/- 0,41) cm2 and 1,38 (+/- 0,55) cm2, respectively. The correlation between the evaluated methods was statistically significant (p=0,003), but not very strong (r=0,43). The comparison of both methods in the identification of the severe aortic stenosis was characterized by kappa value of 0,331. CONCLUSION: Our study shows low agreement between cardiac catheterization and magnetic resonance imaging in the assessment of aortic stenosis. However, MRI might have a role in the diagnostic algorithm in patients with suspected severe aortic stenosis and moderate mean aortic gradient or concomitant valvular insufficiency.

Acute hypoxia due to right to left blood shunting in a patient with atrial septal defect.

Acute right to left blood shunt is an unusual cause of acute hypoxia. We describe a case of a patient with an atrial septal defect who developed acute hypoxia due to cardiac tamponade. Acute haemopericardium developed as a complication of temporary transvenous cardiac pacing. Bubble contrast echocardiography confirmed right to left blood shunting at the atrial level. Acute hypoxaemia and the right to left blood shunt resolved when the pericardium was drained. The case underscores the importance of evaluating the presence of an intracardial shunt in patients with otherwise inexplicable hypoxia.

Out-of-hospital cardiac arrest from air embolism during sexual intercourse: case report and review of the literature.

We report the successful resuscitation of a 38-year-old woman in cardiac arrest following heterosexual intercourse 7 days after spontaneous abortion and an instrumental uterine evacuation. The collapse was thought to be due to venous air embolism (VAE). Her survival neurologically intact was attributed to appropriate first aid, pre-hospital and subsequent hospital intensive care. Neither a case of an out-of-hospital air embolism where the patient made a good recovery, nor a case of miscarriage followed by collapse from air embolism has been reported in the literature. Air embolism is a very infrequent cause of out-of-hospital cardiac arrest with a high mortality rate. Predominant causal reasons are severe penetrating neck or thoracic injuries and sexual activities in pregnancy, when air can pass into the damaged veins in the wall of the uterus and lead to total obstruction in the heart. Diagnostics and management techniques for venous air embolism are discussed. Air embolism should be included in the differential diagnosis for all young women in cardiac arrest, particularly when occurring during sexual activity. Instructions in risks of sexual intercourse during pregnancy and the puerperium should become part of pregnant women's education.

Clinical use of magnetic resonance imaging for the diagnosis of acute myocardial infarction in the survivors of cardiac arrest.

The ventricular arrhythmias with underlying coronary artery disease are a leading cause of sudden cardiac death (SCD). While the SCD survivors with proven AMI are considered to be at low risk of SCD recurrence, those without the evidence of AMI represent a high risk group that benefits from implantable cardioverter defibrillator. Therefore, the evaluation of SCD survivors for the presence of acute myocardial infarction (AMI) as a triggering factor of cardiac arrest is essential. In SCD survivors, the use of the standard diagnostic criteria of AMI may be difficult, as both serum cardiac biomarkers and electrocardiogram can be influenced by previous cardiac arrest. A novel technique that may be used for the diagnosis of AMI is magnetic resonance imaging (MRI). We report its use in four patients after cardiopulmonary resuscitation where the diagnosis of AMI could not be definitely established or excluded by means of other diagnostic procedures.

Aldosterone-Producing Adenomas: Histopathology-Genotype Correlation and Identification of a Novel CACNA1D Mutation.

Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 are thought to cause the excessive autonomous aldosterone secretion of aldosterone-producing adenomas (APAs). The histopathology of KCNJ5 mutant APAs, the most common and largest, has been thoroughly investigated and shown to have a zona fasciculata-like composition. This study aims to characterize the histopathologic spectrum of the other genotypes and document the proliferation rate of the different sized APAs. Adrenals from 39 primary aldosteronism patients were immunohistochemically stained for CYP11B2 to confirm diagnosis of an APA. Twenty-eight adenomas had sufficient material for further analysis and were target sequenced at hot spots in the 5 causal genes. Ten adenomas had a KCNJ5 mutation (35.7%), 7 adenomas had an ATP1A1 mutation (25%), and 4 adenomas had a CACNA1D mutation (14.3%). One novel mutation in exon 28 of CACNA1D (V1153G) was identified. The mutation caused a hyperpolarizing shift of the voltage-dependent activation and inactivation and slowed the channel's inactivation kinetics. Immunohistochemical stainings of CYP17A1 as a zona fasciculata cell marker and Ki67 as a proliferation marker were used. KCNJ5 mutant adenomas showed a strong expression of CYP17A1, whereas ATP1A1/CACNA1D mutant adenomas had a predominantly negative expression (P value =1.20×10-4). ATP1A1/CACNA1D mutant adenomas had twice the nuclei with intense staining of Ki67 than KCNJ5 mutant adenomas (0.7% [0.5%-1.9%] versus 0.4% [0.3%-0.7%]; P value =0.04). Further, 3 adenomas with either an ATP1A1 mutation or a CACNA1D mutation had >30% nuclei with moderate Ki67 staining. In summary, similar to KCNJ5 mutant APAs, ATP1A1 and CACNA1D mutant adenomas have a seemingly specific histopathologic phenotype.

Serum drug levels to diagnose non-adherence in acute decompensated heart failure.

BACKGROUND: The aim of this study was to analyze medication non-adherence by measuring serum drug levels (SDL) in patients presenting with acute decompensated heart failure (ADHF). METHODS: Included in the study were chronic heart failure patients presenting with signs of acute decompensation. Blood sampling for the measurement of SDL was performed shortly after presentation. SDL were measured using liquid chromatography coupled with mass spectrometry. The estimation of SDL was calculated from the recommended chronic cardiac medications with the exception of drugs administered as part of the acute treatment prior to blood sampling. The patients were labeled as non-adherent when any one of the evaluated medications was not found in the serum. RESULTS: Fifty patients with ADHF were prospectively enrolled. All of the evaluated drugs were detected in the sera of 28 (56%) patients. Non-adherence was diagnosed in the remaining 22 (44%) patients. None of the evaluated medications was detected in the sera of 5 (10%) patients. CONCLUSION: The estimation of SDL indicates that non-adherence to the recommended chronic therapy is a common problem among patients presenting with ADHF. This method should be an essential aspect of routine clinical evaluation in these patients.

Transplantation of bone marrow derived progenitor cells in acute myocardial infarction. The first results.

The intracoronary administration of autologous bone marrow cells (BMCs) has been shown to improve the left ventricle function in the course of acute myocardial infarction. Therefore we have started a clinical trial using transplantation of BMCs in the acute phase of myocardial infarction. The aim of our study is to assess the feasibility and safety of this procedure, and effect on the left ventricle function of these patients. We describe the first experience in two patients with acute myocardial infarction reperfused using direct stenting. The aspiration of bone marrow from the sternum provided sufficient amount of the cells for transplantation. No serious ischemia and no changes in coronary artery patency were detected after intracoronary infusion. The left ventricle ejection fraction was increasing throughout the time of three-month follow-up. No other complications (ventricular arrhythmias, reinfarction, thrombus formation) were detected.

Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.

At least 5% of individuals with hypertension have adrenal aldosterone-producing adenomas (APAs). Gain-of-function mutations in KCNJ5 and apparent loss-of-function mutations in ATP1A1 and ATP2A3 were reported to occur in APAs. We find that KCNJ5 mutations are common in APAs resembling cortisol-secreting cells of the adrenal zona fasciculata but are absent in a subset of APAs resembling the aldosterone-secreting cells of the adrenal zona glomerulosa. We performed exome sequencing of ten zona glomerulosa-like APAs and identified nine with somatic mutations in either ATP1A1, encoding the Na(+)/K(+) ATPase α1 subunit, or CACNA1D, encoding Cav1.3. The ATP1A1 mutations all caused inward leak currents under physiological conditions, and the CACNA1D mutations induced a shift of voltage-dependent gating to more negative voltages, suppressed inactivation or increased currents. Many APAs with these mutations were <1 cm in diameter and had been overlooked on conventional adrenal imaging. Recognition of the distinct genotype and phenotype for this subset of APAs could facilitate diagnosis.

Confirmatory testing in primary aldosteronism: extensive medication switching is not needed in all patients.

OBJECTIVE: Confirmatory testing of suspected primary aldosteronism (PA) requires an extensive medication switch that can be difficult for patients with severe complicated hypertension and/or refractory hypokalemia. For this reason, we investigated the effect of chronic antihypertensive medication on confirmatory testing results. To allow the results to be interpreted, the reproducibility of confirmatory testing was also evaluated. DESIGN AND METHODS: The study enrolled 114 individuals with suspected PA who underwent two confirmatory tests. The patients were divided into two groups. In Group A, both tests were performed on the guidelines-recommended therapy, i.e. not interfering with the renin-angiotensin-aldosterone system. In Group B, the first test was performed on chronic therapy with the exclusion of thiazides, loop diuretics, and aldosterone antagonists; and the second test was performed on guidelines-recommended therapy. Saline infusion, preceded by oral sodium loading, was used to suppress aldosterone secretion. RESULTS: Agreement in the interpretation of the two confirmatory tests was observed in 84 and 66% of patients in Groups A and B respectively. For all 20 individuals in Group A who ever had end-test serum aldosterone levels ≥240 pmol/l, aldosterone was concordantly nonsuppressible during the other test. Similarly, for all 16 individuals in Group B who had end-test serum aldosterone levels ≥240 pmol/l on modified chronic therapy, aldosterone remained nonsuppressible with guidelines-recommended therapy. CONCLUSION: Confirmatory testing performed while the patient is on chronic therapy without diuretics and aldosterone antagonists can confirm the diagnosis of PA, provided serum aldosterone remains markedly elevated at the end of saline infusion.