Infective Endocarditis and Phlebotomies May Have Killed Mozart

Thirty-five year-old Amadeus Mozart died in Vienna after an acute illness that lasted only 15 days but no consensus has been reached on the cause of his death. From many letters written by his farther it is almost certain that he experienced at least three episodes of acute rheumatic fever attack in his childhood, and a relapse of rheumatic fever was suggested to have killed Mozart, although death from acute rheumatic fever is very rare in adults. His last illness was characterized by high fever, massive edema, vomiting and skin rash. His last illness can be explained by infectious endocarditis and heart failure. During his last hours, he was given phlebotomy, possibly for the third time in two weeks, and soon after he became unconscious and died. As such, phlebotomy performed on a man dehydrated by high fever and vomiting may have caused systemic shock. In summary, Mozart probably died from chronic rheumatic heart disease complicated by infective endocarditis and heart failure, and repeated phlebotomy-induced hypovolemic shock.

Safety and Validity of Ergonovine Echocardiography before Coronary Angiography for Diagnosis of Coronary Vasospasm

BACKGROUND: Detection of left ventricular regional wall motion abnormality(RWMA) by 2 dimensional echocardiography during ergonovine provocation(Erg Echo) can be used for noninvasive diagnosis of coronary vasospasm(CVS). The aim of this study was to test the safety and diagnostic validity of Erg Echo as a screening test in patients with chest pain syndromes before coronary angiography was undertaken. METHODS: From Mar 1993 to Jun 1994, Erg Echo was performed in 80 consecutive patients (56 males) with chest pain syndromes suggestive of variant angina, after the confirmation of negative treadmill or normal stress myocardial perfusion scan using thallium 201. A bolus of ergonovine maleate was injectedd at 5min intervals up to total cumulative dosage of 0.35mg with echocardiographic montioring of the left ventricular wall motion. Twelve leads ECG was also recorded every 3min after each ergonovine injection. The positive criteria of the test was transient ST segment clevation or depression greater than 0.1mV in 12-leads ECG or development of RWMA. Coronary angiography was undertaken 2(+/-4) days after Erg Echo, and spasm provocation test with acetylcholine, or ergonovine was done in case of normal angiogram or luminal narrowing of less than 70%. The appearance of total or subtotal occlusion of a major coroary artery associated with ST segment elevation or depression on the ECG or chest pain, or both, was considered to be a manifestation of spasm. RESULTS: According to the invasive angiographic criteria, 56 patients revealed CVS ; CVS was ruled oup in 19 patients showing near normal angiogram with negative spasm provocation test and in 5 patients with restion high degree fixed stenosis(luminal narrowing of 97+/-4%). Erg Echo could diagnose CVS before the angiography with the sensitivity of 91%(51/56,95% confidence interval [CI] ; 84-98%) and the specificity of 88%(21/24,95% CI ; 75-100%). Of 53 patients showing RWMA in Erg Echo, 42%(22/53) revealed no significant changes in the simultaneously recorded ECG and characteristic ST elevation was recorded in only 38%(20/53). There was no case of myocardial infarction or fatal arrhythmia during Erg Echo. CONCLUSION: Erg Echo befor the coronary angiography is safe and can e utilized as a reliable diagnostic screening test of CVS in patients with negative tradmill or normal stess myocardial perfusion scan, This finding suggests that invasive coronary angiography can be avioded in selected patients for the diagnosis of vasospastic angina.

Efficacy of Pravastatin Monotherapy in Patients with Hypercholesterolemia

BACKGROUND: The HMG-CoA reductase inhibitor is the most powerful cholesterol lowering drug and lovastatin, simvastatin and pravastatin are used clinically. We studied the efficacy and side effects of pravastatin monotherapy in patients with hypercholesterolemia(type IIa or IIb). METHODS: Patients who showed 12-hours fasting serum total cholesterol level more than 240mg% were enrolled to diet therapy. After 4weeks of diet therapy, serum lipid profiles were checked and the drug therapy was considered according to NCEP guidelines. The pravastatin 5mg po bid was administrated and the patients had regular follow-up every 2weeks for 8week. RESULTS: The total study population was 20 patients and the mean age of them was 55 years old (55+/-18, M : F=6 : 14). There were a few side effects in 5% of study patients and no patient discontinued pravastatin due to side effects.The side effect was G-I trouble and there were not other side effects. Serum CK was elevated in only one patient but the elevation was mild(less than 3 times) and transient. The LFT, serum uric acid, BUN and creatinine level did not show any significant changes during therapy. Among lipid profiles, total cholesterol, LDL-cholesterol and apolipoprotein B level showed significant reduction after therapy and the maximum reduction was achieved after 2week of therapy. The mean reduction was 20%, 33% and 23% respectively. HDL-cholesterol and apolipoprotein A1 11% and 17% respectively. The triglyceride level did not show any changes during therapy but in one type IIb patient, the triglyceride level decreased significantly. CONCLUSIONS: The pravastatin is effective and safe in patients with hypercholesterolemia.

Directional Coronary Atherectomy (Simpson AtheroCath) : Reasons for Device Selection, Angiographic and Histologic Findings, and Its Mechanisms

BACKGROUND: Despite improved operator technique and advanced equipment designs, acute closure and restenosis remain as serious limitations to both the short and long-term success of balloon angioplasty. Atherectomy is a new transluminal interventional technique for the treatment of coronary artery obstructive disease. We evaluate preliminary experience of directonal coronary atherectomy (DCA) for complex coronary artery lesions. METHODS: We tried DCA in the 16 lesions of 15 nonrandomized sequential patients(mean age 66 years, M/F : 12/3) with coronary artery lesions that were ostial lesion in 4, ulcerated and/or eccentric in 13, restenosis after PTCA in 2 and after stent implantation in 2. The target vessel was right coronary artery in 7 and left anterior descending artery in 9. RESULTS: Primary success was achieved in 14 of 16 lesions (88%) by atherectomy and in 5(36%) by additional use of balloon angioplasty. Atherectomy retrieved tissue in 15 out of 15 attempts(100%). One patients suffered acute closure due to large dissection during the DCA which was solved successfully after stent implantation. CONCLUSIONS: Atherectomy can predictably treat selected patients with eccentric, ostial bulky coronary lesions with overall safety comparable to that of conventional balloon angioplasty, although the procedure as currently performed does not appear to prevent restenosis.

Clinical Feasibility of Bedside Intravenous Ergonovine Test on the Diagnosis of Variant Angina

Establishment of a noninvasive diagnostic method to document coronary vasospasm would be useful in the management of the patients with variant angina, especially in the screening of the patients, evaluation of the therapeutic efficacy of the prescribed drugs and determination of the activity of the disease. The present study was performed to clarify the clinical feasibility and diagnostic validity of bedside intravenous ergonovine test and to determine the variables affecting the diagnostic sensitivity of the test. The study group consisted of 59 patients with chest pain in whom diagnostic coronary angiography with intracoronary acetylcholine challenge test for the induction of coronary vasospasm was performed ; 30 patients were proven to have variant angina and 29 patients to have atypical chest pain. Bedside ergonovine test was done one day after the diagnostic coronary angiography and reversible ST segment displacement(elevation or depression) and/or T wave changes in ECG with ergonovine injection was used as the only positive criteria of the test. A bolus of ergonovine maleate(0.025 or 0.050mg) was injected intravenously at 5 minute intervals up to total cumulative dosage of 0.25 mg, and blood pressure and a 12-lead ECG were recorded every 3 minutes after each injection. Intravenous nitroglycerin of 0.25mg was administered for the termination of the test when hypertension(systolic BP>200mmHg), hypotension(systolic BP<90mmHg) or significant arrhythmia was observed. Twenty seven out of 30 patients with variant angina developed chest pain or discomport during the test and among them 22 showed simultaneous reversible ECG changes. In 29 patients with atypical chest pain 11 patients(38%) complained of chest pain or discomport without reversible ECG change during the test, and the overall sensitivity and specificity of the beside ergonovine test were 73% and 100% respectively. The mean cumulative dose of ergonovine which evoked the positive reponse was 117microgram. The patterns of reversible ECG changes of the positive response were variable : 50%(11/22) showed significant ST segment elevation, while ST segment depression(18%) and T wave changes without ST segment displacement(32%) were observed with ergonovine injection. Degree of disease activity of the variant angina, number of spasm-induced vessels and presence of concomitant fixed lesion are important variables affecting the sensitivity of the test. The changes of blood pressure and heart rate were minimal during the test and there was neither significant arrhythmia nor test-related mortality. Thus we concluded that bedside intravenous ergonovine test is a safe, sensitive and highly specific test for coronary vasospasm in selected group of patients with chest pain syndrome. Further study with other methods besides ECG to document myocardial ischemia seems to be necessary for improvement of the sensitivity of bedside ergonovine test.

Immediate and Late Results of Percutaneous Mitral Balloon Valvuloplasty Using Inoue and Double Balloon Techniques(Prospective Randomized Trial): Comparison of Mechanism of Dilation and 1 Year Follow-up

BACKGROUND: Large series of patients with symptomatic mitral stenosis have undergone percutaneous mitral balloon valvuloplasty(PMV) with use of the Inoue or double balloon technique. But to date the result of the two procedure have not been compared with a single series prospectively. METHODS: In order to assess the immediate hemodynamic results and the longterm efficacy of two different PMV technique, a prospective, randomized trial of PMV was performed using the Inoue balloon(Toray, I group) in 59 patients and the double balloons(a pair of Mansfield balloon. D group) in 61 patients with moderate to severe mitral stenosis. Before valvuloplasty, the patients series were comparable with regard to average age. gender, most clinical and echocardiographic variables. All the patients(120 patients, M/F 38/82, mean age 41+/-11 year) were preselected with good echoscore> or =9. RESULTS: The success rate was 83% in the I group and 89% in the D group when the success defined as mitral valve area(MVA)> or =1.5cm2 with 25% gain in MVA and mitral regurgitation> or =2+ at the end of procedure. The magnitude of increase of mitral valve area and decrease of mitral gradient, left atrial pressure and pulmonary arterial pressure were not significantly different in the Inoue and double balloon series(1.0+/-0.4 and 1.1+/-0.4cm2 for mitral vale area, 10.2+/-6.6 and 11.7+/-6.4mmHg for mitral gradient, 10.5+/-6,4 and 12.9 +/-7,3mmHg for left atrial pressure, and 8.7+/-7.3 and 10.1+/-9.4 mmHg for pulmonary artrial pressure respectively). Immediatly after dilation, the long diameter changes of the mitral orifice was more prominent in the D group(from 1.0+/-0.2 to 2.6+/-0.4cm p1.5) was 3.4% in group I and 4.9% in group D. Severe mitral regurgitation> or =3+ occurred in 2 patients in each I(3.4%) and D(3.3%) group respectively. At follow-up, the mitral valve area was significantly decreased(1.6 in group I vs 1.8cm2 in group D, P<0.001 vs immediate after MVA) at 6 months and well maintained at 1 year follow-up in both groups. Until 6 months after valvuloplasty, the long diameter of orifice was greater in group D, however the difference was not apparent at 1 year follow-up. CONCLUSION: The Inoue and double balloon techniques obtained equivalent results of the success rate and the frequently of complications. However, the Inoue balloon technique reduced significantly fluoroscope time and total procedure duration. Double balloon technique afforded a longer longitudinal splitting of the commissure immediatly and 6 months after valvuloplasty. However the differences was not apparent at 1 year follow-up. Increased MVA was well maintained at 1 year in both groups. The severity of the newly developed mitral regurgitation immediately after valvuloplasty reduced significantly in 53% of the Inoue and 43% in the double balloon group at 6 months follow-up. In the view point of similiar immediate and late results of the two methods, the stepwise dilation with Doppler echocardiographic monitoring during the Inoue procedure appeared to be cumbersome.

Acetylcholine-Induced Endothelium-Dependent Responses in the Internal Mammary Artery and Grafted Saphenous Vein in Humans(in Vivo)

BACKGROUND: Coronary artery bypass grafts obtained from internal mammary artery(IMA) have a greater patency rate than do saphenous vein grafts(SVG). The release or production of endothelium-derived relaxing factor(EDRF), which regulates blood flow and inhibits platelets function, may contribute to the higher patency rate of IMA. In order to evaluate the difference between endothelium dependent relaxation in IMA and in grafted saphenous veins, we observed acetylcholine responses of IMAs and SVGs in humans. METHOD: Incremental dose if acetylcholine(Ach:A1-20, A2-50, A3-100microg) or single dose if acetylcholine(A3) were infused into the non-grafted IMA in 16 patients with different clinical presentation of coronary artery disease(3 with stable angina, 2 with acute myocardial infarction 4 with variant angina and atypical chest pain syndrome in 7). After the dose-response to Ach was completed nitroglycerine 200microg was injected into the IMA. Graded dose of Ach (A1, A2, A3) was also infused in 13 grafted saphenous veins(SVG). RESULTS: The overall vascular effects of Ach into the IMA were dilatory responses regardless of different clinical presentation. Two or 3 minutes after Ach injection, the diameter of IMA increased by 9.2%(A1) and 16. 7%(A3) respectively(p<0.01). Maximal dilatory response after A3 was comparable to that after nitroglycerin injection. Angiographically normal segements of SVGs also increased its diameter 2 minutes after Ach injection (7.2% with A1, 6.9% with A2 and 8.5% with A3). Thus the degree of relaxation of IMA was more prominent than that of SVGs. Angiographically dicreased segments of SVGs had no response after Ach injection. The overall responses of native coronary artery to Ach was dose dependant constriction. CONCLUSION: Injection of Ach to IMA and angiographically normal segments of SVGs caused vascular dilatation probably due to EDRF response. However the degree of relaxation was more prominent in IMA than in SVG. Angiographically diseased segments of SVGs had no response to Ach injection, suggesting that diseased SVG does not produce EDRF. However the finding of a consistent Ach-induced EDRF relaxation in the SVGs despite of constrictive response in the majority of native coronary arteries might suggest that the regenerated endothelial cell in the SVGs were probably of saphenous vein origin rather than derived from the coronary arterial endothelium.

Coronary Artery Stenting(Palmaz-Schatz) ; Immediate Results

Since after first report of percutaneous transluminal coronary angioplasty in 1977, improved operator technique and advanced equipment designs have resulted in an increase in primary success rate from 67% to 92% in recent days. Despite these improvement, acute closure and restenosis remain as serious limitations to both the short and long-term success of PTCA. Coronary artery stents have been proposed as a method of treating acute closure and preventing restenosis. We implanted 21 balloon expandable Palmaz-Schatz Stent in selected 21 Patients(mean age 62+/-8 years, M/F : 16/5) with atherosclerotic coronary artery disease. The indications were elective stenting in 17, acute dissection postangioplasty in 2 and restenosis following angioplasty in 2. The clinical diagnosis of the subjects was unstable angina in 12 pts(57%), stable angina in 1, and post infarction angina in 8 including 6 acute myocardial infarction. The target vessel was right coronary artery In 12(57%), left anterior descending artery in 6(29%) and left circumflex in 3(14%). The size of implanted stent was 3mm in 15, 3.5mm in 5 and 4.0mm in 1. The morphology of attempted lesion was AHA/ACC classification type A in 1, type B in 17(B1 ; 1, B2 ; 16) and type C in 3. Angiographic findings were 1-vessel disease in 16 patients, 2-vessel disease in 4 and 3-vessel disease in 1. Coronary artery stenting wast technically successful in 21 all patients(100%) and complications included subacute total occlusion 1 week after stenting in 1, which was recanalized successfully by repeat PTCA without myocardial infarction, prolonged sinus arrest after stenting due to microembolism in 1 and puncture site bleeding requiring transfusion in 1. CONCLUSION: Coronary artery stenting was a safe and effective procedure to obtain adequate coronary blood flow in selected patients but long-term efficacy of primary elective coronary stenting should be evaluated prospectively.

Coronary Artery Stenting(Palmaz-Schatz) ; Immediate Results

Since after first report of percutaneous transluminal coronary angioplasty in 1977, improved operator technique and advanced equipment designs have resulted in an increase in primary success rate from 67% to 92% in recent days. Despite these improvement, acute closure and restenosis remain as serious limitations to both the short and long-term success of PTCA. Coronary artery stents have been proposed as a method of treating acute closure and preventing restenosis. We implanted 21 balloon expandable Palmaz-Schatz Stent in selected 21 Patients(mean age 62+/-8 years, M/F : 16/5) with atherosclerotic coronary artery disease. The indications were elective stenting in 17, acute dissection postangioplasty in 2 and restenosis following angioplasty in 2. The clinical diagnosis of the subjects was unstable angina in 12 pts(57%), stable angina in 1, and post infarction angina in 8 including 6 acute myocardial infarction. The target vessel was right coronary artery In 12(57%), left anterior descending artery in 6(29%) and left circumflex in 3(14%). The size of implanted stent was 3mm in 15, 3.5mm in 5 and 4.0mm in 1. The morphology of attempted lesion was AHA/ACC classification type A in 1, type B in 17(B1 ; 1, B2 ; 16) and type C in 3. Angiographic findings were 1-vessel disease in 16 patients, 2-vessel disease in 4 and 3-vessel disease in 1. Coronary artery stenting wast technically successful in 21 all patients(100%) and complications included subacute total occlusion 1 week after stenting in 1, which was recanalized successfully by repeat PTCA without myocardial infarction, prolonged sinus arrest after stenting due to microembolism in 1 and puncture site bleeding requiring transfusion in 1. CONCLUSION: Coronary artery stenting was a safe and effective procedure to obtain adequate coronary blood flow in selected patients but long-term efficacy of primary elective coronary stenting should be evaluated prospectively.

A Comparative Study of Acetylcholine and Ergonovine Provocative Test in Patients with Chest Pain Syndrome with Normal or Near Normal Coronary Arteriograms

Intracoronary acetylcholine and intravenous ergonovine tests have been used to induce coronary artery spasm. To evaluate the usefulness of these provocative tests, acetylcholine and ergonovine tests were performed in 86 patients with normal or near normal coronary angiograms(clinically variant angina in 30, effort angina in 6, unstable angina in 5, myocardial infarction in 6, atypical chest pain in 39 patients). Acetylcholine was injected into each coronary artery in incremental doses (0.02, 0.05 and 0.1 mg into left coronary artery, 0.02 and 0.05 mg into right coronary artery) and ergonovin was given intravenously in graded doses of 0.05, 0.1 and 0.2 mg after completion of acetylcholine test. The results were as follow : 1) Among 86 patients, both acetylcholine and ergonovine tests were positive in 29 patients, both tests were negative in 50 patients, and acetylcholine test was positive but ergonovine test was negative in 7 patients ; The responses of acetylcholine and ergonovine tests were concordant in 92% of patients. The sensitvity and specificity of the acetylcholine test with reference to ergonovine test were 100% and 88% respectively. 2) In 7 patients(8%) acetylcholine test was positive but ergonovine test was negative, and this group may represent a spectrum of coronary spasm syndrome. CONCLUSION: Acetylcholine test is a safe and useful provocative test for coronary artery spasm, especially in the multivessel spasm.

A Comparative Study of Acetylcholine and Ergonovine Provocative Test in Patients with Chest Pain Syndrome with Normal or Near Normal Coronary Arteriograms

Intracoronary acetylcholine and intravenous ergonovine tests have been used to induce coronary artery spasm. To evaluate the usefulness of these provocative tests, acetylcholine and ergonovine tests were performed in 86 patients with normal or near normal coronary angiograms(clinically variant angina in 30, effort angina in 6, unstable angina in 5, myocardial infarction in 6, atypical chest pain in 39 patients). Acetylcholine was injected into each coronary artery in incremental doses (0.02, 0.05 and 0.1 mg into left coronary artery, 0.02 and 0.05 mg into right coronary artery) and ergonovin was given intravenously in graded doses of 0.05, 0.1 and 0.2 mg after completion of acetylcholine test. The results were as follow : 1) Among 86 patients, both acetylcholine and ergonovine tests were positive in 29 patients, both tests were negative in 50 patients, and acetylcholine test was positive but ergonovine test was negative in 7 patients ; The responses of acetylcholine and ergonovine tests were concordant in 92% of patients. The sensitvity and specificity of the acetylcholine test with reference to ergonovine test were 100% and 88% respectively. 2) In 7 patients(8%) acetylcholine test was positive but ergonovine test was negative, and this group may represent a spectrum of coronary spasm syndrome. CONCLUSION: Acetylcholine test is a safe and useful provocative test for coronary artery spasm, especially in the multivessel spasm.

Exercise Capacity and Maximum Oxygen Consumption before and after Percutaneous Mitral Balloon Valvuloplasty

To evaluate exercise capacity, treadmill test and exercise pulmonary function test with cycle ergometer were preformed in 52 patients(pts) (M/F : 18/34, mean age : 43+/-11 yrs) with mitral stenosis before and 5~10 days after percutaneous mitral balloon valvuloplasty(PMV). Twenty four pts had atrial fibrillation. The results are as follow : 1) The mitral valve area increased from 0.9+/-0.2 to 1.8+/-0.3cm2(P<0.001). 2) The duration of exercise time on treadmill test(modified Bruce protocol) increased from 7.7+/-3.3min to 11.1+/-2.6min(P<0.001), but peak heart rate(HR) and maximum double product(MDP) did not change significantly. After exclusion of the patients with atrial fibrillation, peak HR and MDP increased from 157+/-24beats/min and 22350+/-8220mmHg beat to 165+/-19beats/min and 26290+/-5770mmHg beat respectively(P<0.05). 3) Diffusion capacity and diffusing capacity/alveolar volume at rest decreased from 95+/-25% and 112+/-24% to 87+/-22% and 100+/-18% respectively(p<0.001). 4) FVC, FEV1, FEV1/FVC, FEF25~75% and maximum voluntary ventilation increased from 77+/-12%, 79+/-16%, 104+/-10%, 69+/-25%, and 68+/-14%, to 80+/-11%, 84+/-14%. 106+/-9%, 78+/-25%, and 74+/-12%, respectively(P<0.05). But total lung capacity, residual volume and functional residual capacity did not change significantly. 5) Maximum oxygen consumption, anaerobic threshold, oxygen pulse and maximum work load during exercise increased form 53+/-14%, 34+/-8%, 6.2+/-2.1ml/min and 48+/-18 watts to 61+/-13%, 39+/-7%, 7.3+/-2.0ml/min and 58+/-20 watts respectively(P<0.0005). We conclude that oxygen transport and exercise capacity improve within 10days after PMV and the improvement results from not only hemodynamic improvement but also improvement of static pulmonary function.

Comparison of Results of Percutaneous Mitral Balloon Valvotomy Using Single(Inoue) and Double Balloon Techniques(Randomized Trial) ; Mechanism of Dilation, Immediate Results and Follow Up

To assess the efficacy of 2 different mitral balloon valvotomy (PMV) techniques, PMV was performed using Inoue balloon (I) in 35 pts and double balloon (D) in 33 pts with mitral stenosis (male 27, female 41, mean age 42+/-12 years). The success rate of PMV was 89%(31/35 pts) in I group and 97%(33/33 pts) in D group. Mitral valve area after dilation increased equally effectively in both groups (I and D) from 0.9+/-0.2 and 0.8+/-0.2 to 1.9+/-0.2 and 1.9+/-0.3cm2 respectively (p1.2) was 20% in D, 13% in I group respectively and mean amount of left to right shunt (Qp/Qs) was 1.7+/-0.3 in D and 1.5+/-0.1 in I group. Total procedure and fluoroscopic time were 84+/-24 and 25+/-11 min. in D and 56+/-20 and 16+/-6 min. In I, which had statistically significant differences (p<0.002). Thus we concluded PMV using Inoue or double balloons was equally effective in selected patients. Total procedure and fluoroscopic time of Inoue balloon technique were significantly shorter than those of double balloons. Double balloon technique had more tendency of longitudinal splitting of the commissures.