Nabeel Makhoul

Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.

Nitrate tolerance in heart failure: Differential venous, pulmonary and systemic arterial effects

The hemodynamic profile of tolerance to intravenous nitroglycerin was studied in 9 patients with New York Heart Association Class III to IV congestive heart failure. After rapid dosage build-up to the maximal tolerated dose (decrease in pulmonary wedge pressure to 10 mm Hg or systolic blood pressure to 90 mm Hg), nitroglycerin (525 +/- 548 micrograms/min) was administered at a constant continuous intravenous infusion for a total of 24 hours. The extent of nitrate tolerance at 24 hours was calculated as the percentage loss of the benefit achieved at time of peak effect of nitroglycerin. Tolerance had a different time course and magnitude in the venous, arterial and pulmonary circulations. At 24 hours, right atrial pressure and pulmonary vascular resistance returned to control values in most patients, while 40 to 50% of the effect on systemic vascular resistance, cardiac index and pulmonary wedge pressure was maintained. These findings emphasize the importance of precise definitions in studies relating to nitrate tolerance.

Atrial natriuretic peptide in severe heart failure: Response to controlled changes in atrial pressures during intravenous nitroglycerin therapy

Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe congestive heart failure (New York Heart Association functional class IV), and the response of the peptide was studied during changes in cardiac filling pressures induced by a 24-hour infusion of nitroglycerin. In the control state plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the administration of nitroglycerin, natriuretic peptide levels decreased (p less than 0.005) with changes matching very closely the decreases in pulmonary arterial wedge and right atrial pressures, a 1% mean decrease in the peptide level for every 1.5 to 2% mean change in atrial filling pressures. In patients with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting increase in atrial pressures was accompanied by an appropriate secondary increase in the plasma ANP level. During the 24-hour study period there was a direct linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure). The findings were no different in a subgroup of five patients receiving simultaneous treatment with captopril, except that plasma renin activity was higher and the aldosterone level lower than in the control group by a factor of approximately 2.5. The close relationship and tracking of atrial pressure and natriuretic peptide curves suggested that the sensitivity of the atrial stretch response to changes in atrial filling pressures was maintained in severe congestive heart failure.

Embolic protection: Limitations of current technology and novel concepts

Distal embolic event is one of the major limitations of coronary and non‐coronary vascular interventions. Balloon and filter‐based Embolic Protection Devices (EPDs) are a new class of interventional devices, used to prevent consequential morbidity and mortality of the distal embolic events. Data from first generation EPD supply proof of concept and show approximately 40% reduction in mortality and morbidity, when EPDs are used during saphenous vein grafts (SVGs) interventions. Current limitations of all first generation EPD technology taper their penetration. With breakthroughs in embolic protection technology, it is estimated that, in the near future, EPDs will be used with stenting in all high‐risk lesions (SVGs, carotid arteries and acute coronary syndromes), become the standard of care and even be used in low risk cases.

Effect of Nisoldipine on Exercise Performance in Heart Failure following Myocardial Infarction

The effects of the second generation calcium channel blocking drug nisoldipine on subjective and objective measurements of exercise performance were studied in 19 patients with moderate to severe heart failure (9 New York Heart Association functional class 2, 9 class 3 and 1 class 4) due to fixed ventricular dysfunction following myocardial infarction. Nisoldipine (10 mg 3 times daily) or placebo were administered for 8 weeks in a double-blind parallel study, assessing exercise performance by symptom-limited treadmill exercise testing using a modified Naughton protocol. Nisoldipine was well-tolerated and produced a small increase in peak estimated workload performed (6.2 +/- 2.9 to 8.2 +/- 3.0 METs, p = 0.06). The rate of perceived exertion (Borg scale) increased from 17.5 +/- 2.2 to 18.8 +/- 1.2 (p less than 0.02). The higher workload was performed at a lower peak systolic blood pressure (p = 0.03), higher peak heart rate (p = 0.06) and identical double product (NS). There was no change in resting and peak heart rate and blood pressure or in exercise performance in patients receiving placebo. Resting left ventricular ejection fraction, measured by radionuclide ventriculography, was unchanged after 8 weeks both in the placebo (21 +/- 9 to 20 +/- 9%) and nisoldipine (34 +/- 17 to 36 +/- 19%) groups.

Behçet’ Disease (‘Silk Route Disease’) and Mitral Valve Prolapse

Dear Sir, I read with interest the article on cardiac involvement in Behçet’s disease by Morelli et al. [1]. The finding of a high incidence of mitral valve prolapse in 50% of their patients is not surprising. The association of mitral valve prolapse and Behçet’s disease was first reported from China [2]. Shen et al. [3] from Shanghai reported in 1985 also a 50% incidence of mitral valve prolapse in their patients with Behçet’s disease. Behçet’s disease occurs most frequently in Japan and the Mediterranean countries but also in the population linking these two areas to each other [4]. It occurs most frequently between latitudes 30° and 45° north, in Asian and Eurasian populations. This area coincides with the old Silk Route. Thus, Behçet’s disease is sometimes also called ‘Silk Route disease’ [2, 4]. OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO

Doppler Diastolic Transmitral Flow Patterns in Severe Heart Failure: Response to Controlled Changes in Filling Pressure Using Intravenous Isosorbide Dinitrate

Serial Doppler diastolic transmitral flow patterns were compared with simultaneous hemodynamic measurements in a homogeneous group of patients with severe (New York Heart Association class 4) heart failure who were receiving high dose (508 +/- 271 micrograms/min) intravenous isosorbide dinitrate. The Doppler tracing uniformly showed a severe restrictive pattern, with tall peak early diastolic filling (E) wave (84 +/- 12 cm/s), small late filling (A) wave (28 +/- 8 cm/s) and very high E/A ratio (3.2 +/- 0.8). Isosorbide dinitrate decreased wedge pressure and systemic vascular resistance by a third and increased cardiac index by more than 40%. Transmitral Doppler E/A ratio changed directly in relation to the changes in pulmonary capillary wedge (r = 0.85, p = 0.03) and right atrial pressure (r = 0.84, p = 0.03), indicating preload dependence of transmitral flow velocity, even in severe heart failure.

Mitral annulus caseous calcification imaged with 64-slice MDCT

A 70-year-old woman with a previous cerebrovascular accident underwent routine TTE to assess her cardiac morphology and function. She was found to have mild mitral valve regurgitation with severe m...

Accuracy of Exercise-Induced Left Axis QRS Deviation as a Specific Marker of Left Anterior Descending Coronary Artery Disease

In this prospective study, we examined the diagnostic accuracy of exercise-induced left QRS axis deviation as a marker of LAD coronary artery stenosis. The mean frontal QRS axis of 66 consecutive patients with chest pain and exercise-induced ST segment depression referred for diagnostic coronary angiography was analyzed and related to the angiographic findings. An exercise-induced leftward QRS axis deviation was found in 9/40 patients with and 0/26 patients without obstructive (≥70%) LAD disease (sensitivity 23%, specificity 100%, p = 0.025). In 7 of the 9 patients with left axis deviation, the lesion was proximal to and in 2 in the region of the first septal perforator. Inclusion of patients with 0° exercise-induced QRS axis deviation provided a more sensitive but less specific marker of LAD disease [sensitivity 53% (21/40), specificity 81% (21/26), p = 0.015]. The findings were similar in patients with single and with multivessel coronary artery disease. Grouping all patients in the present prospective and two previous retrospective studies (n = 165), the sensitivity was 29% and specificity 100% (p < 0.0001). Exercise-induced left QRS axis deviation was a highly specific marker of LAD coronary artery stenosis.

Bivalirudin and Heparin Effects on Coronary Flow, Microcirculation and Recovery of Left Ventricular Systolic Function after Primary Coronary Angioplasty

In ST elevation myocardial infarction (STEMI) treated by primary per-coetaneous coronary intervention (PPCI), bivalirudin caused less bleeding and was as effective as combined heparin and IIb IIIa antagonist. Aim : Compare the effects of bivalirudin and heparin on coronary flow, microcirculation and recovery of left ventricular systolic function in patients with STEMI undergoing PPCI. Methods: Forty five patients with anterior STEMI undergoing PPCI, 30 treated with heparin and 15 with bivalirudin were compared. All patients had complete trans-thoracic Doppler echocardiographic studies and sampling of blood velocities in the left anterior descending coronary artery (LAD) early after PPCI and 5 days later. Results : TIMI and myocardial blush grades were similar in both groups before after PPCI. Peak LAD diastolic velocities early after PPCI were higher in the bivalirudin group 42.2±14.4 compared to the heparin group 34.06±8.27 cm/sec, p<0.03. Peak velocities in the LAD did not change significantly on follow up in both groups. Early diastolic velocity integrals in the LAD in patients treated with bivalirudin, 12.3±4.2 were higher than in those treated with heparin, 8.91±3.21cm, p<0.02, and this difference between the groups was maintained on late evaluation. Left ventricular systolic function parameters were similar in both treatment groups early and late after PPCI, however only heparin was associated with increase in these parameters on discharge from the hospital. Conclusions : Bivalirudin treatment in patients with anterior STEMI treated by PPCI was associated with higher LAD velocities and integrals compared to heparin, however only heparin increased LV systolic function after PPCI.