Claudia Galli

Calcium-channel blockade with nifedipine and angiotensin converting-enzyme inhibition with captopril in the therapy of patients with severe primary hypertension.

Nifedipine (10 mg qid) and captopril (25 mg qid) were tested alone and in combination in 14 patients suffering from severe primary hypertension. Each study period was of 1 weeks duration. Circulatory response was evaluated through hourly pressure and pulse rate readings. The fall in pressure after oral nifedipine was maximal within 1 hr or less and was generally accompanied by palpitation and increase in pulse rate; with a six hourly dosing regimen the tendency of blood pressure to recover after each dose was interrupted by the next dose, so that values remained significantly reduced throughout the 24 hr, although pressure fluctuations were evident. Promptness of the antihypertensive action of captopril was similar, but the magnitude and the duration of the fall in pressure were less pronounced. When the converting-enzyme inhibitor was combined with the calcium-channel blocker, pressure fluctuations were not abolished, but the antihypertensive response was definitely enhanced, so that normal blood pressure was maintained for several hours during the day. Additional positive effects of captopril were mitigation of the heart rate reaction and prevention of the ankle pitting or edema elicited by nifedipine. A balance in arteriolar and venular dilatation promoted by captopril is the suggested mechanism for these effects. With the two-drug combination the function of the left ventricle was not reduced and possibly improved; blood urea nitrogen and serum electrolyte and creatinine concentration were not affected. Plasma renin activity increased with captopril and reverted toward baseline with the addition of nifedipine, suggesting an interference of the calcium-channel blocker with the release of renin.

A New Formula For Echo-Doppler Estimation of Right Ventricular Systolic Pressure

The Doppler formulas currently used for right ventricular systolic pressure (RVSP) evaluation include right ventricular-right atrial (RV-RA) gradient and RA pressure. The former is expressed by the velocity of the trans-tricuspid regurgitant flow; the latter is generally assumed and is different from one formula to another. In 110 patients with cardiac disease with normal or elevated pulmonary pressure, we tested a new echo-Doppler formula for the evaluation of RVSP based on the estimation of RA pressure by means of the inferior vena cava collapsibility index (IVCCI) and compared this method with two traditional formulas (methods A and B) and with cardiac catheterization values. Patients were classified into three groups on the basis of IVCCI (group 1 > 45%, group 2 between 35% and 45%, and group 3 < 35%). RVSP was evaluated by method A (RV-RA gradient + 10), method B (RV-RA gradient x 1.1 + 14), and our new method, method C, which assigns 6, 9, and 16 mmHg to RA pressure in the presence of normal (> 45%), moderately reduced (between 35% and 45%), or markedly reduced (< 35%) IVCCI, respectively. IVCCI correctly identified RA pressure in the three groups (group 1, 6.8 mmHg; group 2, 10.8 mm Hg; and group 3, 13.1 mmHg); a high correlation existed between Doppler-derived and invasively determined RV-RA gradient (r = 0.99). Method C improved noninvasive estimation of RVSP in groups 1 and 3 compared with the other methods; in group 2, Doppler estimation of RVSP by methods A and C were comparable, whereas method B significantly overestimated the actual values.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility of a new generation three-dimensional echocardiography for right ventricular volumetric and functional measurements.

Right ventricular (RV) dimensions and function are of diagnostic and prognostic importance in cardiac disease. Because of the peculiar morphology of the right ventricle, 2-dimensional echocardiography has several limitations in RV evaluation. Recently, new 3-dimensional transthoracic echocardiographic software adapted for RV morphology was introduced. The aims of this study were to evaluate the feasibility of 3-dimensional RV analysis in a large population and to compare and correlate 3-dimensional RV data with classic 2-dimensional and Doppler parameters, including tricuspid annular plane systolic excursion and peak systolic velocity on Doppler tissue imaging, RV fractional shortening area, RV stroke volume (by the Doppler method), and pulmonary arterial systolic pressure. Two hundred subjects were studied: 48 normal controls and 152 patients with valvular heart disease (104 patients), idiopathic dilated cardiomyopathy (20 patients), or pulmonary hypertension (28 patients). The mean times for 3-dimensional acquisition and 3-dimensional reconstruction were 3 +/- 1 and 4 +/- 2 minutes, respectively. Imaging quality was good in most cases (85%). The mean RV diastolic and systolic volumes were 103 +/- 38 and 46 +/- 28 ml, respectively. The RV ejection fraction (RVEF) was correlated negatively with pulmonary arterial systolic pressure and positively with tricuspid annular plane systolic excursion, peak systolic velocity, and fractional shortening area. The pathologic group was characterized by larger RV volumes and lower RVEFs. Three-dimensional echocardiography clearly showed that in the pathologic group, patients with pulmonary hypertension had the largest RV volumes and the lowest RVEFs and that those with idiopathic dilated cardiomyopathy were characterized by RVEFs lower than those of patients with valvular disease. In conclusion, this new quantitative 3-dimensional method to assess RV volumes and function is feasible, relatively simple, and not time consuming. Data obtained with 3-dimensional analysis are well correlated with those obtained by 2-dimensional and Doppler methods and can differentiate normal and pathologic subjects.

Pre-operative transthoracic real-time three-dimensional echocardiography in patients undergoing mitral valve repair: accuracy in cases with simple vs. complex prolapse lesions

AIMS The aim of this study, undertaken in patients who underwent mitral valve (MV) repair surgery, was to evaluate the accuracy of pre-operative three-dimensional (3D) transthoracic echocardiography (TTE) in the evaluation of MV pathology in cases with simple or complex lesions. METHODS AND RESULTS Two hundred consecutive patients with severe mitral regurgitation due to degenerative MV prolapse underwent a complete 3DTTE the day before surgery. Three-dimensional TTE data were compared with MV surgical inspection. Three-dimensional echocardiography was feasible in a relatively short time (5 ± 3 min) with good (67%) and optimal (21%) imaging quality in the majority of cases. Three-dimensional TTE allowed an accurate identification (95% accuracy) of all MV lesions. Seventy-three (36.5%) patients had simple lesions at 3DTTE and 71 of them (97.2%) underwent a simple surgical procedure; 127 (63.5%) had complex lesions at 3DTTE and, in these cases, surgeons performed either simple procedures (48%) or complex procedures (47.2%) or valve replacement in 4.7% (after a first attempt for repair). CONCLUSION Three-dimensional TTE is feasible, not time-consuming, and accurate in identifying cases with simple vs. complex MV lesions.

Enhanced hypoxic pulmonary vasoconstriction in hypertension.

In this study, we tested the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension. The hypothesis took origin from the following two considerations: alveolar hypoxia constricts the pulmonary vessels by enhancing the Ca2+ penetration across sarcolemma of the smooth muscle cells and systemic high blood pressure is associated with an elevation of tone and reactivity of the lung vessels, which seems to depend on an excessive cytosol free Ca2+ concentration due to alterations in sodium handling and in the Na+-Ca2+ exchange system. These considerations suggest the possibility that the disorders in the biochemistry of smooth muscle contraction in hypertension facilitate the rise of cytosol Ca2+ concentration during alveolar hypoxia, thus resulting in a potentiation of the vasoconstrictor properties of this stimulus. In 43 hypertensive and 17 normotensive men, pulmonary arteriolar resistance has been evaluated during air respiration and after 15 minutes of breathing 17%, 15%, and 12% oxygen in nitrogen. Curves relating changes in pulmonary arteriolar resistance to oxygen breathing contents had similar configuration in the two populations but in hypertension were steeper and significantly shifted to the left, reflecting a lower threshold and an enhanced reactivity. This pattern was not related to differences in severity of the hypoxic stimulus, plasma catecholamine concentration, or hypocapnia and respiratory alkalosis induced by hypoxia and probably was not mediated through alpha-receptor activation. Calcium channel blockade with nifedipine was able to almost abolish both the normotensive and the hypertensive pulmonary vasoconstriction reaction. These findings support the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension.

Pulmonary vascular overreactivity in systemic hypertension. A pathophysiological link between the greater and the lesser circulation.

This study was undertaken to test whether the emphasized systemic vasomotion during sympathetic activation in hypertension is shared by the pulmonary circulation. To this end, 10 normotensive and 29 primary hypertensive subjects were investigated during adrenergic stimulation by mental arithmetic and cold pressor test. Both stimuli induced a systemic pressor reaction in both groups, which was mediated through an increase in cardiac output and a mild reduction in vascular resistance during arithmetic and through a predominant rise in systemic vascular resistance during cold. Each of these changes was emphasized in the hypertensive population as compared with the normotensive one. Pressure in the pulmonary artery remained unchanged during cold and was slightly raised (systolic) during arithmetic in normotensive subjects. On the contrary, in hypertensive subjects systolic and diastolic pulmonary pressures were consistently augmented by both stimuli, and pulmonary arteriolar resistance (dyn sec cm-5) rose from 92 in the baseline to 125 (p less than 0.01) during arithmetic and to 124 (p less than 0.01) during the cold test. This reaction is interpreted as reflecting a neurally mediated vasoconstriction and not as the consequence of mechanical or chemical changes, since no difference was observed in pulmonary wedge pressure, pleural pressure, arterial blood gas levels, and pH between controls and hypertensive subjects in the steady state and during either stressful stimulation. Baseline pulmonary arteriolar resistance was also found to correlate positively with systemic vascular resistance in the hypertensive group. When pressure changes occurred, the time course was similar in the two circuits; resistance increased to a proportionally similar degree in the two districts during the cold stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vascular supersensitivity to catecholamines in systemic high blood pressure

Pulmonary pressure and arteriolar resistance are elevated in uncomplicated primary systemic hypertension. This study was carried out in 16 men with this form of hypertension and in 9 healthy men to compare 1) their pulmonary vascular reactivity to endogenous catecholamines released during mental arithmetic and cold pressor tests, and 2) the dose-response relation to exogenous epinephrine and norepinephrine. Arithmetic and cold pressor tests were associated, respectively, with a predominant increase in plasma epinephrine and norepinephrine concentration; changes were significantly greater in hypertensive men. During the two tests, pulmonary arteriolar resistance in the normotensive group was reduced by 13% and augmented by 7% of baseline, respectively, whereas it was raised by 31 and 70%, respectively, in the hypertensive group. In normal subjects, the dose (microgram)-response (delta dynes) relation to epinephrine was 1 = -4, 2 = -9, 3 = -9 and 4 = -10; to norepinephrine it was 2 = +3, 4 = +6, 6 = +7 and 8 = +7. In hypertensive patients, the respective relations were 1 = +18, 2 = +44, 3 = +59 and 4 = +77; and 2 = +39, 4 = +54, 6 = +76 and 8 = +98. Group differences were highly significant. In each of these circumstances, the driving pressure across the lungs was significantly augmented in the hypertensive but not the normotensive group. Both epinephrine and norepinephrine have a vasoconstrictor influence on the lesser circulation as a consequence of vascular overreactivity. The opposite changes in resistance between normotensive and hypertensive subjects produced by epinephrine suggest that a constrictor vascular supersensitivity becomes active in the pulmonary circuit with the development of systemic high blood pressure.

Usefulness of transoesophageal echocardiography before cardioversion in patients with atrial fibrillation and different anticoagulant regimens

Objectives: To evaluate the prevalence of atrial thrombi in patients with atrial fibrillation undergoing different anticoagulation regimens before cardioversion; to evaluate the usefulness of transoesophageal echocardiography (TOE) guided cardioversion to prevent thromboembolic complications; and to correlate the presence of atrial thrombi with clinical and echocardiographic data. Methods: 757 consecutive patients admitted as candidates for cardioversion of atrial fibrillation were enrolled in the study. They were divided into four groups: effective conventional oral anticoagulation, short term anticoagulation, ineffective oral anticoagulation or subtherapeutic anticoagulation, and effective oral anticoagulation with a duration of < 3 weeks for various clinical reasons. All patients underwent TOE before cardioversion; in the presence of atrial thrombi or extreme left atrial echo contrast, cardioversion was postponed. The incidence of thromboembolic events was evaluated after cardioversion. Results: Atrial thrombi were detected in 48 of the 757 (6.3%) patients. No significant differences in the percentage of atrial thrombosis were found in the four study groups. Patients with atrial thrombosis were older and had a higher percentage of mitral prosthetic valves, lower left ventricular ejection fraction, more severe atrial spontaneous echo contrast, and lower Doppler left atrial appendage velocities. 648 patients were scheduled for cardioversion. Cardioversion was successful in 89% of patients without any major thromboembolic event. Conclusions: The prevalence of atrial thrombosis before cardioversion despite different treatments with anticoagulants is about 7% and a TOE guided approach may prevent the risk of embolic events.

Influences of aortic pressure gradient and ventricular septal thickness with systolic coronary flow in aortic valve stenosis

This study evaluates flow patterns of the left anterior descending and circumflex coronary arteries by multiplane transesophageal echocardiography in 25 patients with aortic valve stenosis, and assesses the relation between coronary flow characteristics and anatomic and hemodynamic parameters.

Modulation of the atrioventricular node conduction to achieve rate control in patients with atrial fibrillation: long-term results.

Modulation of the AV node reduces the ventricular rate during AF, without affecting AV conduction during sinus rhythm. Acute and long‐term results of AV node modulation in 75 patients with AF and severe related symptoms of heart failure are presented in this study. The procedure involved, in all cases, the selective ablation of the posterior inputs to the AV node; in a subgroup of 15 patients with poor modification of AV conduction properties, a sequential approach involving subsequent anterior input ablation was performed. The procedure caused acutely a prolongation of the Wenckebach cycle length (38 patients in sinus rhythm) from 334 ± 88 to 470 ± 80 ms (P < 0.01), and a reduction of the average ventricular rate (37 patients in AF) from 154 ± 31 to 88 ± 40 beats/min (P < 0.01); permanent complete AV block was induced in 9 of 75 patients (12%). Considering the “sequential” approach, an increase of the Wenckebach cycle length from 362 ± 50 to 530 ± 45 ms (P < 0.01) and a reduction of the average heart rate in patients with AF from 158 ± 16 to 81 ± 20 beats/min (P < 0.01) was obtained in this subgroup of patients, in whom the AH interval prolonged from 93 ± 12 to 175 ± 27 ms, and no complete AV block was observed. At a mean follow‐up of 23 ± 9 months (range 2–48), the mean number of hospital admissions per patient per year decreased from 4.2 to 0.2. Five of 49 patients with paroxysmal AF and 3 of 26 patients with chronic AF had high rate recurrences (1 > 120 beats/min) that caused severe palpitations; these patients were considered as late clinical failures (8/75; 11%). All patients reported a substantial subjective improvement and an increased exercise tolerance, as documented by a semiquantitative questionnaire. There were no episodes of late AV block or sudden cardiac deaths. In conclusion, modulation of the AV node—either by slow pathway ablation, or by a “sequential” posterior and anterior approach in refractory patients—allows a long‐term control of the ventricular rate and prevents the recurrence of severe clinical symptoms in more than 75% of patients with drug refractory AF.