Takotsubo Cardiomyopathy : an Acute and Reversible Cardiomyopathy Mimicking Acute Myocardial Infarction

Takotsubo cardiomyopathy is an acute; reversible form of left ventricular dysfunction precipitated by emotional or physical stress. The condition is important to recognise as it mimics acute myocardial infarction and acute coronary syndrome. Most patients are female and postmenopausal. Presenting symptoms include severe chest pain; acute dyspnoea; hypotension or even cardiogenic shock. The ECG changes are suggestive of an acute coronary syndrome with T-wave inversion with / without ST elevation; most often in the precordial leads. The syndrome is characterised by a sudden onset of transient extensive akinesia of the left ventricle; often involving all three major coronary artery territories; in the absence of significant coronary artery stenosis. The wall motion typically involves the apex of the left ventricle with hyperkinesis of the base of the heart. Variant forms have recently been described where the wall motion abnormality involves the mid-ventricular wall with hyperkinesis of the base and apex; or the base of the heart with hyperkinesis of the apex. Characteristically; there is only a limited release of cardiac enzymes disproportionate to the extent of regional wall motion abnormality. Transient right ventricular dysfunction may occur and is associated with more complications; longer hospitalisation and worse left ventricular systolic dysfunction. Serial echocardiography is useful to document improvement in cardiac function. The pathogenesis is unclear. Transient mid-cavity obstruction has been invoked with subsequent myocardial stunning in the akinetic segments. Treatment is supportive. The most effective long-term management remains to be defined. Although the prognosis is good with recovery of ventricular function at about three weeks; some patients have died. The syndrome may recur

Use of ambulatory blood pressure monitoring to compare antihypertensive efficacy and safety of two angiotensin II receptor antagonists, losartan and valsartan. Losartan Trial Investigators.

The efficacy and safety of losartan and valsartan were evaluated in a multicenter, double-blind, randomized trial in patients with mild to moderate essential hypertension. Blood pressure responses to once-daily treatment with either losartan 50 mg (n = 93) or valsartan 80 mg (n = 94) for 6 weeks were assessed through measurements taken in the clinic and by 24-hour ambulatory blood pressure monitoring (ABPM). Both drugs significantly reduced clinic sitting systolic (SiSBP) and diastolic blood pressure (SiDBP) at 2, 4, and 6 weeks. Maximum reductions from baseline in SiSBP and SiDBP on 24-hour ABPM were also significant with the two treatments. The reduction in blood pressure was more consistent across patients in the losartan group, as indicated by a numerically smaller variability in change from baseline on all ABPM measures, which achieved significance at peak (P = .017) and during the day (P = .002). In addition, the numerically larger smoothness index with losartan suggested a more homogeneous antihypertensive effect throughout the 24-hour dosing interval. The antihypertensive response rate was 54% with losartan and 46% with valsartan. Three days after discontinuation of therapy, SiDBP remained below baseline in 73% of losartan and 63% of valsartan patients. Both agents were generally well tolerated. Losartan, but not valsartan, significantly decreased serum uric acid an average 0.4 mg/dL at week 6. In conclusion, once-daily losartan 50 mg and valsartan 80 mg had similar antihypertensive effects in patients with mild to moderate essential hypertension. Losartan produced a more consistent blood pressure-lowering response and significantly lowered uric acid, suggesting potentially meaningful differences between these two A II receptor antagonists.

The Quattro valve and active infective endocarditis of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: Even today, infective endocarditis remains a therapeutic challenge. Active endocarditis at the time of valve implantation is an important risk factor for the development of prosthetic valve infection. This study reports results following implantation of the Quattro valve, a stentless chordally supported quadrileaflet mitral valve made from bovine pericardium. METHODS: The Quattro valve was implanted in seven patients (four females, three males; mean age 34 years) requiring isolated mitral valve replacement for active bacterial endocarditis. All had congestive heart failure; two were in cardiogenic shock. The diagnosis of active endocarditis was based on clinical and echocardiographic findings, together with macroscopic evidence of acute infection at surgery, blood culture or histopathological evidence of valve infection. Postoperatively, all patients received at least four weeks of parenteral antibiotic therapy. RESULTS: Congestive heart failure (and large pedunculated vegetations and mobile septic left atrial thrombi in two patients) prompted early surgical intervention. Patients underwent surgery at a mean of 7 days (range: 1-16 days) after admission. Endocarditis was caused by Gram-positive cocci in all patients except one. At a mean follow up of 15 months (range: 6-24 months) all patients were alive and symptomatically improved. To date, all remain free of prosthetic valve endocarditis, reoperation and thromboembolism. CONCLUSION: The Quattro valve can be implanted safely in patients with acute bacterial endocarditis. The results also reflect the benefit of early surgical intervention in patients with infective endocarditis complicated by congestive heart failure, with or without large vegetations.

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.

The stentless quadrileaflet bovine pericardial mitral valve: early clinical results.

BACKGROUND AND AIMS OF THE STUDY: Although bioprosthetic valves currently in use have low thrombogenicity, durability remains very unsatisfactory. Valve failure occurs early from calcification, and later from tissue wear. Stentless design lessens the latter, and anticalcification treatments the former. Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium, treated to minimize calcification, has become available for clinical study. The aim of this study was to report the early results relating to valve performance, and patient outcome. METHODS: Since December 1996, the QMV has been implanted in 23 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not suited for repair. All patients were symptomatic (three in NYHA functional class II, 16 in class III, four in class IV). Preoperatively, all underwent full clinical and echocardiographic assessment, and intraoperative transesophageal evaluation immediately after valve implantation. Blood tests for hemolysis were performed preoperatively and at 3 months after surgery. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), 22 patients were alive and symptomatically improved (NYHA class I or II). One patient died of sternal sepsis soon after surgery. There have been no reoperations, nor cases of infective endocarditis or thromboembolism. Subclinical hemolysis was shown pre- and postoperatively in 35% and 32% of cases, respectively. Intraoperative transesophageal echocardiography post valve implantation demonstrated mitral regurgitation which was trivial in 15 patients (78%) and mild in five (22%). CONCLUSIONS: The QMV can be implanted safely, and the early clinical results relating to patient outcome and valve performance are encouraging.

The stentless quadrileaflet bovine pericardial mitral valve: echocardiographic assessment.

BACKGROUND AND AIMS OF THE STUDY: Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium treated to minimize calcification, has become available for clinical trial. The aim of this study was to report both the echocardiographic appearance and hemodynamic performance of this valve by means of echocardiography. METHODS: The QMV was implanted in 22 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not deemed suitable for repair. Echocardiography was performed pre-operatively, and at one and three months postoperatively. Transthoracic echocardiography (TTE) was used to monitor mean instantaneous pressure gradient as calculated from the long modified Bernoulli equation, cardiac index (CI), pressure half-time and effective orifice area (EOA) using the Hatle and continuity equations. Regurgitation patterns were sought by color Doppler transesophageal echocardiography in all valves intraoperatively following valve implantation, and by TTE in the outpatient clinic at follow up. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), all patients were well and symptomatically improved. At three months postoperatively, the mean pressure gradient ranged from 1.7 to 2.2 mmHg. The EOA was larger using the Hatle as compared with the continuity equation (2.4 +/- 0.7 cm2 versus 1.8 +/- 0.5 cm2, respectively; p < 0.005). Mitral regurgitation was trivial in 77% and mild in 14% of patients at 3 months after surgery; moderate mitral stenosis was noted in one patient. The CI improved significantly postoperatively (p < 0.005), and left ventricular function was maintained. CONCLUSIONS: The hemodynamic performance of this novel prosthesis is favorable. Although follow up is too short to assess durability, it is hoped that the unique design and improved valve preservation technique of this device will enhance long-term durability.

The quadrileaflet mitral valve: follow-up in rheumatic heart disease.

This prospective study evaluated the clinical performance of a novel stentless quadrileaflet bovine pericardial mitral valve implanted at one center since December 1996. After giving informed consent, patients were included in the study if they required isolated mitral valve replacement. All underwent comprehensive clinical evaluation, as well as transthoracic M-mode, two-dimensional and Doppler (pulsed, continuous, and color) echocardiography preoperatively and postoperatively at 1 month, 3 months, and annually thereafter. Mitral valve area was derived by planimetry, the pressure half-time method, and the continuity equation. The degree of mitral regurgitation was semi-quantitated using color Doppler. In all 38 patients with rheumatic valvular heart disease (mean age 35+/-13 years) were monitored for 13.8+/-7.5 months (range, 1 to 29 months). All but three patients are alive and symptomatically improved (functional New York Heart Association class I or II). One valve was explanted because of early prosthetic valve endocarditis. There were no episodes of thromboembolism or anticoagulation-related hemorrhage. Left ventricular function was maintained with increased cardiac output and low transmitral pressure gradients. The mitral valve area was larger when measured by pressure half-time and planimetry than by the continuity equation (P<.05). In an independent clinical evaluation of a subset of 30 patients, mitral stenosis was considered absent in 33%, mild in 30%, mild to moderate in 26%, and moderate in 10% of cases. No or less than or equal to mild mitral regurgitation was noted in the majority of patients postoperatively, both clinically and echocardiographically. We are encouraged by the clinical performance of the quadrileaflet mitral valve and with patient outcome. Long-term follow-up data are needed to assess durability.

Effectiveness of enalapril in combination with low-dose hydrochlorothiazide versus enalapril alone for mild to moderate systemic hypertension in black patients.

The importance of concomitant low-dose hydrochlorothiazide was assessed in black hypertensive patients treated with enalapril. Left ventricular (LV) mass and function, metabolic parameters, 24-hour ambulatory blood pressure (BP), exercise duration, and systolic BP response were evaluated before and after drug therapy. Enalapril 20 mg (group 1) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (single tablet; group 2) was given to 38 patients for 9 weeks in a double-blind, placebo-controlled, randomized study. LV mass measured 61 +/- 17 versus 102 +/- 23 g/m2, and 24-hour ambulatory BP measured 120 +/- 8/75 +/- 6 versus 155 +/- 12/100 +/- 6 mm Hg in matched control subjects (n = 40) versus hypertensive patients, respectively. No clinically important changes occurred in total cholesterol, serum uric acid or potassium in either group. Enalapril slightly reduced 24-hour ambulatory BP from 154 +/- 15/100 +/- 7 mm Hg to 148 +/- 19/96 +/- 11 mm Hg after treatment (p < 0.05 for systolic BP); systolic BP load (70% to 59%, p < 0.05), and diastolic BP load (67% to 60%, p = NS) decreased. Baseline BP decreased from 157 +/- 9/101 +/- 6 to 132 +/- 13/86 +/- 8 mm Hg (p < 0.0001); systolic BP load (64% to 29%, p < 0.0001), and diastolic BP load (64% to 33%, p < 0.0001) decreased in group 2. Exercise systolic BP was attenuated (p = 0.007, group 2; p = NS, group 1) and duration increased (p = NS) only in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy.

OBJECTIVES: This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. BACKGROUND: Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement. METHODS: Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13). RESULTS: Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance. CONCLUSIONS: Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.

Frequency and severity of intravascular hemolysis after left-sided cardiac valve replacement with Medtronic Hall and St. Jude Medical prostheses, and influence of prosthetic type, position, size and number.

Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, but in most cases is of mild degree and subclinical. The severity of hemolysis is reported to be related to the type, position and size of prostheses used, as well as the presence of valve malfunction. Hemolysis was evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic Hall (MH) prostheses, with normal mechanical function. The presence and severity of hemolysis was assessed on the basis of serum lactic dehydrogenase, serum haptoglobin, blood hemoglobin and reticulocyte levels as well as the presence of schistocytes. Overall, patients with SJM prostheses had greater frequency (51.2 vs 18.7%, p < 0.005) and severity (p < 0.005) of hemolysis than patients with MH prostheses, irrespective of position and size. No patient had decompensated anemia. The frequency of hemolysis was similar in both groups with double-valve replacement, whereas severity was greater with SJM than MH prostheses (p < 0.001). The number and position of the prostheses were correlated with severity of hemolysis: Double-valve replacement and mitral position were correlated with greater hemolysis than single-valve replacement (p < 0.01) and aortic position (p < 0.01). Valve size, cardiac rhythm and time from operation did not correlate either with frequency or severity of hemolysis. It is concluded that in normally functioning SJM and MH prostheses: (1) hemolysis is frequent but never severe; (2) SJM demonstrates greater frequency and severity when compared with MH valve; and (3) number, position, but not size, significantly affect the severity of hemolysis.

Pulmonary hypertension is a contraindication to beta-blockade in patients with severe mitral stenosis.

Intravenous atenolol was given to 31 patients just before balloon mitral valvotomy to assess the hemodynamic efficacy and safety of beta-blockade in mitral stenosis complicated by pulmonary hypertension. Hemodynamic response in patients with pulmonary resistance > 600 dynes.sec.cm-5 (group 2, n = 17) was compared with those (group 1, n = 14) with a resistance below this value. In addition to a higher pulmonary arterial resistance (by design), patients in group 2 had a higher systemic resistance, lower cardiac index, and smaller mitral valve area compared with those in group 1. After atenolol infusion, transmitral gradient and left atrial pressure improved similarly. In spite of the decline in left atrial pressure, pulmonary vascular resistance increased in both groups, more in group 2 (847 +/- 398 dynes.sec.cm-5 to 135 +/- 648 dynes.sec.cm-5) than in group 1 (291 +/- 149 dynes.sec.cm-5 to 363 +/- 200; p < 0.001 for drug effect and p = 0.027 for group effect by two-way analysis of variance). Cardiac index declined similarly from 2.77 +/- 0.51 L/min/m2 to 2.37 +/- 0.37 L/min/m2 in group 1 and from 2.33 +/- 0.58 L/min/m2 to 1.92 +/- 0.54 L/min/m2 in group 2. Systemic pressure tended to decline only in group 2 (mean aortic pressure, 89 +/- 12 mm Hg to 89 +/- 12 mm Hg in group 1 and 90 +/- 9 mm Hg to 83 +/- 12 mm Hg in group 2; p = 0.06 for group effect).(ABSTRACT TRUNCATED AT 250 WORDS)

Excessive vasoconstriction in rheumatic mitral stenosis with modestly reduced ejection fraction.

OBJECTIVES: The primary hypothesis examined was that underfilling due to inflow obstruction accounts for modestly depressed ejection performance in mitral stenosis. Having found little evidence to support this hypothesis, we sought to determine other factors that might differentiate patients with different levels of ejection performance. METHODS: Ventricular load and performance were compared in two groups of patients before and immediately after successful balloon valvuloplasty that was not complicated by mitral regurgitation: those in whom prevalvuloplasty ejection fraction was > or = 0.55 (group I, n = 10) and those in whom it was < 0.55 (group II, n = 11). RESULTS: Before valvuloplasty, mitral valve area was less in group II (0.65 cm2) than in group I (0.84 cm2, p = 0.02), but end-diastolic pressure (12 vs. 12 mm Hg in group I), end-diastolic wall stress (46 vs. 44 kdynes/cm2 in group I) and end-diastolic volume (152 vs. 150 ml in group I) were not less in group II, nor were these variables significantly reduced compared with those of a normal control group. In group II, end-systolic volume was larger (77 vs. 55 ml in group I, p = 0.001) and cardiac output was less (3.1 vs. 3.6 liters/min in group I, p = 0.03), possibly owing to higher systemic vascular resistance (2,438 vs. 1,921 dynes.s.cm-5 in group I, p = 0.05) and end-systolic wall stress (273 vs. 226 kdynes/cm2 in group I, p = 0.06), although mean arterial pressure in the two groups was similar (91 vs. 84 mm Hg in group I, p = 0.22). Group II patients also had higher values for pulmonary vascular resistance (712 vs. 269 dynes.s.cm-5 in group I, p = 0.03) and mean pulmonary artery pressure (47 vs. 29 mm Hg in group I, p = 0.02) despite similar values for mean left atrial pressure (20 vs. 18 mm Hg in group I, p = 0.35). After valvuloplasty, mitral valve area increased by 2.5- and 3-fold, respectively, in group I (to 2.1 cm2) and group II (to 2.0 cm2). Modest increases in left ventricular end-diastolic pressure, end-diastolic stress and end-diastolic volume (+9%) after valvuloplasty were statistically significant only for group II. End-systolic wall stress did not decline in either group II (281 kdynes/cm2) or group I (230 kdynes/cm2), and ejection fraction failed to increase significantly (0.49 to 0.51 for group II and 0.62 to 0.61 for group I) after valvuloplasty. Contractile performance estimated with a preload-corrected ejection fraction-afterload relation was within or near normal limits in all 19 patients in whom it was assessed. CONCLUSIONS: Excessive vasoconstriction may account for the higher afterload, lower ejection performance and lower cardiac output observed in a subset of patients with mitral stenosis because contractile dysfunction could not be detected and left ventricular filling--which was not subnormal despite severe inflow obstruction--improved only modestly after valvuloplasty.

Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension.

Thirty-nine black patients with mild to moderate hypertension were treated for 1 year with various long-acting preparations of nifedipine, during which time serial changes in 24-hour ambulatory blood pressure (BP), exercise performance, left ventricular (LV) mass index and LV systolic function were evaluated. Mean 24-hour ambulatory BP decreased from 156 +/- 15/99 +/- 8 to 125 +/- 10/79 +/- 6 mm Hg at 1 year (p less than 0.0001). LV mass index decreased from 130 +/- 40 to 114 +/- 39 g/m2 at 6 weeks (p less than 0.005) and to 95 +/- 32 at 1 year (p less than 0.0001). There was a significant reduction in septal and posterior wall thickness from 11.0 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.0001) and from 10.9 +/- 2.0 to 9.3 +/- 2.0 mm (p less than 0.005), respectively. Cardiac index and fractional shortening changed insignificantly from 2.9 +/- 0.7 to 2.9 +/- 0.6 liters/min/m2, and from 35 +/- 5 to 36 +/- 6%, respectively. At 1 year, using a modified Bruce protocol, exercise time increased from 691 +/- 138 to 845 +/- 183 seconds (p less than 0.05); peak exercise and 1 minute post-effort systolic BP decreased from 240 +/- 26 to 200 +/- 21 mm Hg and from 221 +/- 27 to 169 +/- 32 mm Hg (p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial phase left atrial opacification in acute massive pulmonary embolism.

Classic angiographic features in acute massive pulmonary embolism include main or lobar arterial branch cut-off, and/or arterial filling defects with matching impaired venous drainage. Six haemodynamically compromised patients with acute massive pulmonary embolism (mean pulmonary artery pressure 55 +/- 12 mmHg), confirmed by pulmonary arteriography, are described. Early opacification of the left atrium during the arterial phase of the pulmonary angiogram was seen in all patients. Follow-up pulmonary arteriography after successful thrombolytic therapy was performed 4 days later in 2 cases. A marked haemodynamic improvement was accompanied by resolution of the previous abnormal angiographic signs, including early opacification of the left atrium. The latter might be a response to intensive reactive vasodilatation of the remaining perfused lung fields resulting in a more rapid pulmonary transit time and the opening of arteriovenous channels with further systemic desaturation. This angiographic sign is a marker of severe, but reversible, vasoconstriction in acute massive pulmonary embolism.