Onset of systemic arterial hypertension after initiation of elexacaftor/tezacaftor/ivacaftor in adults with cystic fibrosis: A case series.

Elexacaftor/tezacaftor/ivacaftor (ETI) is associated with major improvements in respiratory outcomes of individuals with cystic fibrosis (CF) and at least one Phe508del mutation. Although ETI was well tolerated in registration studies, the attention on adverse events not previously described is very high in the post-marketing phase. In this case series we report the onset of systemic arterial hypertension in 4 individuals with CF within the first weeks of starting therapy. All patients needed cardiac evaluation and started chronic anti-hypertensive therapy. Until more data is available, this report could foster the attention of CF physicians towards careful monitoring of cardiovascular parameters in patients starting ETI.

Patients with Hypertensive Nephropathy and Chronic Kidney Disease Might Not Benefit from Strict Blood Pressure Control.

BACKGROUND/AIMS: In patients with chronic kidney disease (CKD) strict blood pressure (BP) control is reno-protective. However, renal benefits from BP control might depend also on the etiology of CKD. We investigated if maintenance of BP at target is equally effective in subjects with hypertensive nephropathy (HN+) and in those with other nephropathies (HN-). METHODS: We evaluated 148 patients with CKD (stages 3-5) in two visits at least 12 months apart. BP was measured both as office BP and 24h ambulatory blood pressure (ABP). Glomerular filtration rate (eGFR) was estimated with CKD-EPI formula. The slope of eGFR variation (ΔeGFR) was calculated as: (eGFR1-eGFR0)/months of follow up. RESULTS: Cohort characteristics were: HN-(n=82) and HN+ (n=66), age (71±9 vs 74±9 years; p=0.09); prevalence of diabetes (57 vs 43%; p=0.19); average follow up (19±7 vs 21±9 months; p=0.3). HN- and HN+ did not differ regarding both baseline eGFR (34±18 vs 35±14 ml/min; p=0.97) and ΔeGFR (0.00±0.53 vs -0.06±0.35 ml/min/month, p=0.52). The proportion of patients with BP at target at both visits was similar in HN- and HN+ (office BP: HN- 18% and HN+ 27%; p=0.21; ABP: HN- 42% and HN+ 43; p=0.96). In patients with office BP at target at both visits HN- showed a significant improvement of ΔeGFR respect to HN+ (HN-: 0.240 ± 0.395 and HN+: -0.140±0.313 ml/min/ month; p=0.026). In patients with office BP not at target HN- and HN+ did not show any difference in ΔeGFR (HN- 0.00±0.47; HN+ -0.030±0.420 ml/min/month; p=0.66). ABP was not associated with differences in ΔeGFR either if it was at target (HN- 0.104±0.383 and HN+ 0.00±0.476 ml/min/month; p=0.42) or not (HN- -0.057±0.503 and HN+ -0.092±0.325 ml/ min/month; p=0.87). CONCLUSION: In patients with CKD and HN+ maintenance of BP targets recommended by current guidelines is less reno-protective than it is in HN-.

Cor triatriatum dexter associated with atrial septal defect: Management in a complex clinical case.

The coexistence of an atrial septal defect and a prominent eustachian valve is a rare congenital anomaly, rarely reported in literature. Differentiation between a giant eustachian valve and cor triatriatum dexter can be difficult. A case of a large atrial septal defect associated with cor triatriatum dexter diagnosed by echocardiography in an asymptomatic woman is reported. A watchful waiting strategy was adopted.

Pharmacological Interactions on Blood Pressure Control in Arterial Hypertension, An Issue not to be Overlooked.

Our vision of long-term treatment strategies for the prevention of target organ damage and eventually cardiovascular morbidity and mortality in essential arterial hypertension needs to be continually monitored and updated for at least three issues: 1--the achievement of target pressure required to obtain the expected benefit needs continuous monitoring, a dose adjustment of the drug and, often, the use of combination therapies; 2--the chronic use of certain drugs, even in combination, is associated with the possible onset of side effects; 3--increasing of population life expectancy is inevitably associated with in an increase in drugs use with the unavoidable occurrence of adverse drug reactions, some of which can interfere with blood pressure control. These issues, still poorly studied, pose considerable problems in applying proper strategies for prevention. In this review, we will evaluate the goals of antihypertensive therapy, and its weak spots, such as the frequent side effects, that lead to poor therapy compliance. Moreover, we will review the interactions between antihypertensive and drugs used for other common disease, and their importance in not achieving the expected blood pressure reduction.

Non-invasive monitoring of cardiac hemodynamic parameters in doxorubicin-treated patients: comparison with echocardiography.

Cardiotoxicity represents the major factor that limits the use of anthracyclines in long-term cancer chemotherapy, therefore, the early detection of cardiac dysfunction is very important. Currently, the left ventricular ejection fraction is routinely used to screen cardiotoxicity. The most common methods in use are represented by 2-dimensional (2D) echocardiography and radionuclide angiography. The aim of the present investigation was to compare the findings obtained in patients subjected to doxorubicin (DXR) chemotherapy, by 2D echocardiography with hemodynamic parameters, resulting from a new non-invasive method based on an inert gas rebreathing technique. The study was conducted in 35 adult female patients (mean age 48 years, range 30-67) submitted to chemotherapy for metastatic breast cancer with DXR and paclitaxel. DXR was administered at a dose of 60 mg/m2 and paclitaxel at a dose of 200 mg/m2 every 3 weeks for a maximum of 8 cycles. Heart function evaluation was performed before initiating chemotherapy, after 3 cycles, 1 month after the completion of chemotherapy and when clinically requested. The mean cumulative dose of DXR, in patients who had received at least 4 or more cycles, was 320 mg/m2 of body surface area with a range of 240 to 480 mg/m2. The data obtained with 2D echocardiography (left ventricular end diastolic and systolic dimensions and ejection fraction) were compared with hemodynamic parameters obtained by the inert gas rebreathing technique (cardiac output, stroke volume, cardiac index and stroke index). Hemodynamic monitoring showed a progressive decrease of all parameters during DXR treatment, which became statistically significant at the end of the treatment. A significant reduction of ejection fraction due to an increase in the end systolic dimension of the left ventricle, without significant modification of the end diastolic dimensions, was observed. A good correlation was found between data obtained with the echocardiographic method and those obtained by the inert gas rebreathing technique. Two patients showed symptoms of congestive heart failure, the deterioration of cardiac function was simultaneously detected by both methods. These data confirm that cardiac function deterioration is detectable at a cumulative dose lower than 550 mg/m2 and that the inert gas rebreathing method for the determination of hemodynamic parameters could represent an alternative tool, in addition to conventional echocardiographic examination, in the evaluation of anthracycline-induced cardiotoxicity.

Respiratory changes in transvalvular flow velocities versus two-dimensional echocardiographic findings in the diagnosis of cardiac tamponade.

BACKGROUND: The purpose of this study was to compare the sensitivity, specificity and positive predictive value of the respiratory changes in the transvalvular flow velocities to those of right atrial collapse and right ventricular collapse in the diagnosis of cardiac tamponade. METHODS: Standard two-dimensional and Doppler echocardiography were performed with respiratory monitoring in 56 consecutive patients with mild to severe pericardial effusion. Sixteen patients met the clinical criteria for cardiac tamponade and underwent pericardiocentesis or surgical drainage. Forty patients were found to have no tamponade and were followed up for at least 2 weeks and none of them showed clinical worsening. RESULTS: The sensitivity, specificity and predictive value were, respectively, 77, 80 and 62% for an inspiratory decrease > 22% in the peak velocity of the early mitral flow; 75, 89 and 73% for an inspiratory reduction > 20% in the peak velocity of the aortic flow; 50, 69 and 36% for an inspiratory increase > 30% in the peak velocity of the early tricuspid flow; 87, 85 and 64% for an inspiratory increase > 25% in the peak velocity of the pulmonary flow. Right atrial collapse and right ventricular collapse had a sensitivity of 100 and 75%, a specificity of 33 and 85%, and a predictive value of 37 and 66%, respectively. CONCLUSIONS: In the diagnosis of cardiac tamponade: 1) right atrial collapse is the most sensitive sign but lacks any specificity; 2) except for the tricuspid valve, the respiratory variations in the transvalvular flow velocities have a reliability and a predictive value comparable with those of right ventricular collapse; 3) the predictive value is not very high, indicating that at both techniques false positive results are not negligible.