Cardiovascular Organ Damage and Blood Pressure Levels Predict Adverse Events in Multiple Myeloma Patients Undergoing Carfilzomib Therapy.

Carfilzomib is a second-generation proteasome inhibitor approved for the treatment of multiple myeloma (MM). It seems to determine cardiovascular toxicity, primarily arterial hypertension. No predictive factors for cardiovascular adverse events (CVAEs) are known in patients affected by multiple myeloma treated with carfilzomib. We evaluated the role of cardiovascular organ damage parameters to predict CVAEs in MM patients taking carfilzomib. Seventy patients affected by MM were prospectively enrolled. A comprehensive cardiovascular evaluation was performed before carfilzomib therapy; they underwent a transthoracic echocardiogram and the assessment of carotid-femoral pulse wave velocity. All the patients were followed up (FU) to determine the incidence of CVAEs. The mean age was 60.3 ± 8.2, and 51% were male. The median FU was 9.3 (4.3; 20.4) months. A proportion of 33% experienced CVAEs, 91% of them had uncontrolled hypertension, 4.5% acute coronary syndrome, and 4.5% cardiac arrhythmias. Subjects with CVAEs after carfilzomib treatment had significantly higher blood pressure values, left ventricular mass (98 ± 23 vs. 85 ± 17 g/m2, p = 0.01), and pulse wave velocity (8.5 ± 1.7 vs. 7.5 ± 1.6 m/s, p = 0.02) at baseline evaluation compared to the others. Furthermore, baseline uncontrolled blood pressure, left ventricular hypertrophy, and pulse wave velocity ≥ 9 m/s were able to identify patients at higher risk of developing CVAEs during FU. These preliminary findings indicate that blood pressure control, left ventricular mass, and pulse wave velocity may predict CVAEs in MM patients treated with carfilzomib.

Arterial Hypertension and Multiple Myeloma: Physiopathology and Cardiovascular Risk and 'Practical' Indications in Patients Receiving Carfilzomib.

The introduction of carfilzomib in the treatment of relapsing and refractory multiple myeloma has allowed a significant increase in survival. The most frequent adverse effect of Carfilzomib treatment is arterial hypertension, even though the exact physiopathological mechanism are still unclear. MM patients, on the other hand, often present significant cardiovascular risk factors and comorbidities. Uncontrolled hypertension is frequently the cause of cardiovascular complications. It has been estimated that up to 50% of subjects in the general population are unaware of their hypertensive condition and only half of those who are aware of this risk factor present good control of blood pressure. Although the management of arterial hypertension is clearly important in reducing the risk of cardiovascular events, and is well described by the current guidelines, no clear indications are provided on how to approach and treat specifically MM patients undergoing treatment with proteasome inhibitors. The aim of our work is to summarize a practical approach to the stratification of cardiovascular risk of hypertensive in patients who are candidates for or actively treated with carfilzomib for refractory multiple myeloma (MMR). MM patients eligible for carfilzomib treatment should preliminary undergo a careful cardiovascular risk stratification. Perspective studies will help to better identify the specific risk factors that should be considered and treated in these patients.

Extent of, and variables associated with, blood pressure variability among older subjects.

BACKGROUND: Blood pressure variability (BPV) may have prognostic implications for cardiovascular risk and cognitive decline; however, BPV has yet to be studied in old and very old people. AIMS: Aim of the present study was to evaluate the extent of BPV and to identify variables associated with BPV among older subjects. METHODS: A retrospective study of patients aged ≥ 65 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) was carried out. Three different BPV indexes were calculated for systolic and diastolic blood pressure (SBP and DBP): standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Demographic variables and use of antihypertensive medications were considered. RESULTS: The study included 738 patients. Mean age was 74.8 ± 6.8 years. Mean SBP and DBP SD were 20.5 ± 4.4 and 14.6 ± 3.4 mmHg. Mean SBP and DBP CV were 16 ± 3 and 20 ± 5%. Mean SBP and DBP ARV were 15.7 ± 3.9 and 11.8 ± 3.6 mmHg. At multivariate analysis older age, female sex and uncontrolled mean blood pressure were associated with both systolic and diastolic BPV indexes. The use of calcium channel blockers and alpha-adrenergic antagonists was associated with lower systolic and diastolic BPV indexes, respectively. CONCLUSIONS: Among elderly subjects undergoing 24-h ABPM, we observed remarkably high indexes of BPV, which were associated with older age, female sex, and uncontrolled blood pressure values.

Accuracy of transthoracic echocardiography in the assessment of proximal aortic diameter in hypertensive patients: comparison with cardiac magnetic resonance.

BACKGROUND: Accurate and reproducible measurements of proximal thoracic aorta diameters are essential in the diagnosis and follow-up of patients with aortic dilatation, a condition particularly common in hypertensive patients. AIM: to evaluate the accuracy of transthoracic echocardiography (TTE) in comparison with cardiac magnetic resonance (CMR) for the assessment of proximal thoracic aorta diameters in a cohort of hypertensive patients. METHODS: A total of 75 essential hypertensive outpatients previously evaluated by TTE and than by CMR were included in the study. We specifically compared the two techniques at the level of sinuses of Valsalva (SoV) and ascending aorta (Asc) diameter. For the TTE images, the inner edge-to-inner edge and leading edge-to-leading edge conventions were compared. RESULTS: TTE and CMR diameters were significantly related (SoV: r 0.931, P < 0.001; Asc: r 0.949, P < 0.001) when the leading edge-to-leading edge convention was used. Mean difference between CMR and TTE diameters was 2.49 ±â€Š2.01 mm at the level of SoV and 1.13 ±â€Š1.77 mm at the level of Asc. Correlation was good also for the TEE diameters measured by inner edge-to-inner edge convention (SoV: r 0.936, P < 0.001; Asc: r 0.947, P < 0.001). Comparing the two approaches in the evaluation of Asc, inner edge-to-inner edge showed a trend to a better correlation with CMR measurements than leading edge-to-leading edge, with a good interobserver and intraobserver agreement. CONCLUSION: The results of the current study suggest that TTE could be a reliable tool to assess proximal aorta diameters in hypertensive patients.

Cardiovascular complications in patients with autonomic failure.

Patients with autonomic failure are characterized by orthostatic hypotension, supine hypertension, high blood pressure variability, blunted heart rate variability, and often have a "non-dipping" or "reverse dipping" pattern on 24-h ambulatory blood pressure monitoring. These alterations may lead to cardiovascular and cerebrovascular changes, similar to the target organ damage found in hypertension. Often patients with autonomic failure are on treatment with anti-hypotensive drugs, which may worsen supine hypertension. The aim of this review is to summarize the evidence for cardiac, vascular, renal, and cerebrovascular damage in patients with autonomic failure.

Arrhythmic syncope in neurogenic orthostatic hypotension: two case reports.

Patients with autonomic failure experience orthostatic hypotension (OH) often leading to syncope. Arrhythmias may cause severe syncope, characterized by an increased risk of mortality. We report two cases of patients with primary autonomic neuropathy suffering from both severe OH and arrhythmic syncope.

Non invasive evaluation of cardiac hemodynamics in end stage renal disease (ESRD).

OBJECTIVE: Volume overload is typical of haemodialysis patients; correct volume status evaluation is crucial in achieving blood pressure homeostasis, hypertension management and good treatment planning. This study evaluates the effect of acute volume depletion on ultrasonographic parameters and suggests two of them as able to predict patients volume overload. PATIENTS AND INTERVENTION: 27 patients with end stage renal disease treated with haemodialysis underwent a complete echocardiographic exam before, after 90 min and at the end of the dialysis. MAIN OUTCOME AND RESULTS: Blood pressure levels significantly drop during the first 90 min of dialysis (139 ± 20 vs 126 ± 18; p < 0.0001), reaching a steady state with significantly lower values compared to baseline (130 ± 28; p = 0.02). LV and left atrial volume significantly decreased (baseline vs end dialysis 98 ± 32 vs 82 ± 31 p = 0.003 and 28 ± 10 vs. 21 ± 9 cc/m(2) p < 0.001). A significant reduction of systolic function (EF 61.6 % ± 9 vs 58.7 % ± 9 p = 0.04), of diastolic flow velocities (E/A 1.13 ± 0.37 vs. 0.87 ± 0.38 p < 0.001) and mitral annulus TDI tissue velocity (i.e. E' lat 10.6 ± 3 vs. 9.4 ± 3 cm/s; p 0.0001) were observed. Stroke work (SW) and LV end-diastolic diameter (LVEDd) indexed to height 2.7(LVEDdi) were able to predict volume overload: cut off values of respectively 13.5 mm/m(2.7) for LVEDdi and 173 cJ for SW were able to predict with a specificity of 100 % the presence of a volemic overload of at least 4 %. CONCLUSIONS: Blood pressure, cardiac morphology and function are significantly modified by acute volume depletion and such variations are strictly interrelated. SW and LVEDd/height(2.7) may identify ESRD patients carrying an higher volume load.