Investigating the genetic characteristics of CAD: Is there a role for myocardial perfusion imaging techniques?

Several environmental and genetic factors have been found to influence the development and progression of coronary artery disease (CAD). Although the effects of the environmental hazards on CAD pathophysiology are well documented, the genetic architecture of the disease remains quite unclear. A number of single-nucleotide polymorphisms have been identified based on the results of the genome-wide association studies. However, there is a lack of strong evidence regarding molecular causality. The minority of the reported predisposing variants can be related to the conventional risk factors of CAD, while most of the polymorphisms occur in non-protein-coding regions of the DNA. However, independently of the specific underlying mechanisms, genetic information could lead to the identification of a population at higher genetic risk for the long-term development of CAD. Myocardial single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional imaging techniques that can evaluate directly myocardial perfusion, and detect vascular and/or endothelial dysfunction. Therefore, these techniques could have a role in the investigation of the underlying mechanisms associated with the identified predisposing variants, advancing our understanding regarding molecular causality. In the population at higher genetic risk, myocardial SPECT or PET could provide important evidence through the early depiction of sub-clinical dysfunctions, well before any atherosclerosis marker could be identified. Notably, SPECT and PET techniques have been already used for the investigation of the functional consequences of several CAD-related polymorphisms, as well as the response to certain treatments (statins). Furthermore, therefore, in the clinical setting, the combination of genetic evidence with the findings of myocardial SPECT, or PET, functional imaging techniques could lead to more efficient screening methods and may improve decision making with regard to the diagnostic investigation and patients' management.

A simple score for early risk stratification in acute heart failure.

INTRODUCTION: The use of many acute heart failure (AHF) risk scores is cumbersome. We therefore developed a simple AHF risk score (AHFRS) for early risk stratification. METHODS: The study consisted of a prospective derivation cohort (PDC; N=104; age, 77[21] years; LVEF (%), 35[29]) and a retrospective validation cohort (RVC; N=141; age, 76[15] years; LVEF (%), 35[25]). Clinical, echocardiography and laboratory assessment was performed at admission. The study end-point was death from any cause or HF-rehospitalization at 1year. RESULTS: In the PDC 46 (44.2%) patients experienced the end-point. Independent prognostic factors of outcome were hypertension (HTN) history, myocardial infarction (MI) history, and admission red cell distribution width (RDW). Multivariate logistic regression indicated 8-, 4-, and 3-times higher odds ratio for development of study end-point in patients without a HTN history, with MI history, and RDW≥15% (median) respectively. Thus in AHFRS, 2 points were assigned for absence of HTN history, 1 point for presence of MI history, and 1 point for RDW values ≥15% (0 best possible, whereas 4 worst possible score). The AHFRS identified patients who developed the end-point in the PDC with an area under the ROC curve (AUC) of 0.80 [95% C.I.: (0.71, 0.87)] denoting a high discriminative ability. These findings were confirmed in the RVC, in which the endpoint occurred in 52 (36.9%) patients and the AUC for the AHFRS was 0.82 [95% C.I.: (0.73, 0.89)]. CONCLUSIONS: AHFRS is easily obtained at admission and accurately risk stratifies AHF patients.

Evaluating the role of Mediterranean diet and eating behaviors on the likelihood of having a non-fatal acute coronary syndrome, under the context of stress perception: a case-control study.

BACKGROUND/OBJECTIVES: Mediterranean diet and perceived stress have long been associated with the likelihood of having an acute coronary syndrome (ACS). The aim of this study was to evaluate whether the Mediterranean diet and other eating behaviors mediate and/or moderate the unfavorable impact of perceived stress on the likelihood of having a non-fatal ACS. SUBJECTS/METHODS: This is a case-control study with individuals matched by age and sex. A total of 250 consecutive patients (60±11 years, 78% men) with a first ACS and 250 population-based, control subjects (60±8.6 years, 77.6% men) were enrolled. Perceived stress levels were evaluated with the Perceived Stress Scale (PSS-14; range 0-14), and adherence to the Mediterranean diet was assessed by the MedDietScore (range 0-55). Stress eating, eating heavy meals and eating alone were also evaluated. RESULTS: For each unit increase in the PSS-14, the likelihood of having an ACS increased by 14% (95% confidence interval (CI)=1.10, 1.18). Stratified analysis by Mediterranean diet adherence level revealed a similar association of PSS-14 with ACS likelihood between the low-to-moderate and moderate-to-high adherence groups (that is, odds ratio (OR)=1.15, 95% CI=1.09, 1.21 and OR=1.13, 95% CI=1.07, 1.80, respectively). Stress eating and eating alone were positively associated with the likelihood of having an ACS (OR=1.31, 95% CI=0.97, 1.77 and OR=1.36, 95% CI=1.08, 1.69, respectively). Eating heavy meals was not associated with ACS (OR=1.08, 95% CI=0.82, 1.41); no mediating or moderating effect of these behaviors on perceived stress ACS was observed. CONCLUSIONS: The highly significant impact of perceived stress on ACS likelihood was not mediated or moderated by the level of adherence to the Mediterranean diet or other eating behaviors, underlying the strong effect of this psychological disorder on ACS.

The influence of beta-blockade on the hemodynamic effects of levosimendan in elderly (>or= 70 years) patients with acutely decompensated systolic heart failure.

The purpose of this study was to evaluate the influence of chronic beta-blockade on the hemodynamic parameters in elderly (>or= 70 years) patients with acutely decompensated systolic heart failure treated with levosimendan. Eighteen patients with acutely decompensated systolic heart failure (8 on chronic beta-blockade) were included in this study. Inclusion criteria were symptoms and signs of acute heart failure in the presence of: a) left ventricular ejection fraction < 0.35; b) cardiac index < 2.5 l/min/m2, c) pulmonary capillary wedge pressure > 15 mmHg; and d) systolic blood pressure between 90 and 110 mmHg. After completion of baseline hemodynamic measurements, a levosimendan intravenous infusion was started (initial loading dose given as an infusion of 24 microg/kg over 10 minutes, followed by a continuous infusion of 0.1 microg/kg/min for 24 hours). At the end of levosimendan infusion hemodynamic measurements were repeated. Demographic characteristics as well as baseline systolic and diastolic blood pressure were not significantly different between patients not receiving beta-blockers (Group A) and those under beta-blockade (Group B), whereas heart rate was significantly lower in the latter. Treatment with levosimendan was associated with an increase in the cardiac index and a decrease in wedge pressure in both groups (Group A: 43.8% and 33%; p < 0.001 vs. baseline; Group B: 17.72% and 17.5%, p < 0.001 vs. baseline, respectively). Peripheral and pulmonary resistance significantly decreased in both groups (31% vs. 15%, p < 0.001 and 44.5% vs. 25%, p < 0.001, respectively). Thus, the beneficial hemodynamic effects of levosimendan are maintained in elderly patients with acute decompensated systolic heart failure treated with beta-blockers.

Hemodynamic effects of dobutamine in patients with an exacerbation of chronic systolic heart failure treated with low doses of carvedilol.

Although most patients in Europe with systolic heart failure (SHF) are treated with I(2)-blocking agents at doses significantly lower than the recommended dose, there is limited information available regarding the hemodynamic effects of dobutamine in this patient population. Therefore, a study was carried out in patients (n=31) admitted to the University Hospital, Larissa, Greece with an acute exacerbation of chronic SHF (25 men and 6 women, mean age 58 years, range 32 â 80 years, left ventricular (LV) ejection fraction

Acute hemodynamic effects of moderate doses of nebivolol versus metoprolol in patients with systolic heart failure.

OBJECTIVES: To determine the acute hemodynamic effect of moderate doses of nebivolol (vasodilating beta1-selective blocker) vs. metoprolol tartrate (non-vasodilating beta1-selective blocker) in systolic heart failure (SHF). MATERIAL AND METHODS: 20 stable patients with SHF (left ventricular (LV) ejection fraction < or = 35%) underwent right heart catheterization. Once a reproducible baseline was obtained, patients were randomized to 5 mg nebivolol PO (n = 10) or metoprolol tartrate 50 mg PO (n = 10). Hemodynamic studies were repeated hourly for the first 4 hours and at 6 hours. RESULTS: Both agents caused bradycardia. Nebivolol caused additionally a decrease in systemic vascular resistance (SVR) and no significant change in pulmonary capillary wedge pressure (PCWP), and cardiac output (CO). In contrast, metoprolol caused a deterioration of LV systolic function characterized by a decrease in cardiac output, and an increase in SVR and PCWP. CONCLUSIONS: Treatment initiation with moderate doses of nebivolol is not associated with the adverse hemodynamic effects of metoprolol in patients with SHF. These findings suggest that a long up-titration period may not be necessary with nebivolol.

Submitral left ventricular aneurysm compressing the left main coronary artery.

This report describes a 43-yr-old black women who was referred for evaluation of severe mitral regurgitation. Conventional echocardiography revealed a large submitral left ventricular aneurysm. A selective coronary angiography demonstrated compression of the left main coronary artery by submitral aneurysm. Successful surgical repair was performed.

Once-daily fixed dose combinations of verapamil and trandolapril in black patients with mild to moderate hypertension: a new choice for first line treatment.

Using ambulatory blood pressure (BP) monitoring, a potent ACE-inhibitor/calcium channel blocker combination was tested in 21 Black patients (age 52 +/- 10 years; 10 males, 11 females) with mild to moderate hypertension (mean 12-hour daytime diastolic BP > or = 90 mmHg and < or = 114 mmHg). After a 14-day wash-out and a 14-day placebo run-in period, therapy was initiated with verapamil 180 mg plus trandolapril 2 mg. At monthly visits, if mean daytime diastolic BP remained > or = 90 mmHg, the dose combination was uptitrated stepwise to verapamil 240 mg plus trandolapril 4 mg, verapamil 360 mg plus trandolapril 4 mg, and finally hydrochlorothiazide 12.5 mg were added. Mean 24-hour BP dropped from 150 +/- 14/96 +/- 7 mmHg at baseline to 131 +/- 13/82 +/- 8 mmHg after 4 months treatment (p < 0.001). In 16 (76%) patients mean 24-hour diastolic BP was < 90 mmHg at the end of the trial and 15 (71%) patients achieved a reduction of > 10 mmHg. Five out of 5 patients finishing on dose I were controlled, 5/6 patients on dose II, 5/8 patients on dose III, and 1/2 patients who received additional hydrochlorothiazide. The 24-hour BP load fell from 72 +/- 8% at baseline to 35 +/- 25% in 4 months (p < 0.001). Mean diastolic BP drop for the 2 peak hours during daytime was 20 mmHg and for the last 2 hours of monitoring was 13 mmHg, resulting in a trough to peak ratio of 65%. There were no significant adverse events or biochemical abnormalities. It is concluded that the combination doses tested showed a sustained and marked antihypertensive effect throughout the 24-hour dosing interval, and the starting dose (verapamil 180 mg plus trandolapril 2 mg) seems appropriate in this group of patients.

Comparison of captopril-thiazide and enalapril-thiazide combinations in the management of mild to moderate black hypertensive patients: how important is diuretic dose and duration of action of the ACE-inhibitor?

A double-blind, randomized, parallel-group study was performed to compare the efficacy and tolerability of captopril-thiazide and enalapril-thiazide combinations. After a 3-week placebo run-in period, 47 Black patients with mild to moderate essential hypertension (mean 24-hour diastolic blood pressure (BP) > 90 mmHg and < 115 mmHg) were randomized to receive 1 of 2 combination tablets: captopril 50 mg plus hydrochlorothiazide 25 mg (CAP, n = 24) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (COR, n = 23) once daily. After 12 weeks of active treatment the mean 24-hour ambulatory BP was reduced from 152 +/- 11/99 +/- 6 to 133 +/- 13/86 +/- 7 mmHg (p < 0.005) in the CAP group and 157 +/- 15/100 +/- 6 to 141 +/- 18/90 +/- 12 in the COR group (p < 0.005). Target BP (24-hour diastolic BP < 90 mmHg) was achieved in 75% (18/24) of patients on CAP and 48% (11/23) on COR (p = n.s.). 24-hour BP load fell significantly with both CAP (from 69% to 34%, p < 0.001) and COR (from 67% to 37%, p < 0.001). Left ventricular mass index decreased by 7% with CAP and 11% with COR. Cardiac index and fractional shortening remained essentially unchanged in both groups. Both treatments were well tolerated and overall incidence of side effects was very low. It is concluded that both CAP and COR are effective, safe first-line antihypertensive choices in Black patients with mild to moderate hypertension with the former showing a trend towards greater efficacy than the latter.

Long-term changes in left ventricular performance following mitral valve replacement for pure rheumatic mitral regurgitation.

Our data indicate that MVR, with or without chordal preservation, for pure severe MR in symptomatic younger rheumatic patients with a good preoperative ejection fraction results in normalization of LV size and performance by 1 year. Normalization of LV performance was only achieved at 1 year after surgery, and it is therefore essential to extend the assessment of LV function to at least 1 year postoperatively.

Pheochromocytoma associated with clinical and echocardiographic features simulating hypertrophic obstructive cardiomyopathy.

Left ventricular hypertrophy simulating hypertrophic obstructive cardiomyopathy is a rare complication of pheochromocytoma. In this report, two cases of pheochromocytoma with this complication are described. Successful tumor removal in both cases led to relief of symptoms, normalization of BP, regression of abnormal clinical features, normalization of the ECGs, but only partial regression of the echocardiographic features despite prolonged follow-up of 24 and 32 months, respectively.

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension.

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.

Low dose hydrochlorothiazide (12.5 to 25 mg daily) as monotherapy in black patients with mild to moderate hypertension. Assessment by ambulatory blood pressure monitoring.

The efficacy of low dose (12.5 to 25 mg daily) hydrochlorothiazide (HCTZ) was evaluated by ambulatory blood pressure monitoring (ABPM) in 19 mild to moderate hypertensive (mean daytime 12-h diastolic BP > or = 90 mm Hg and < 115 mm Hg) South African black patients. After a 3-week placebo run-in period, HCTZ was administered for 8 weeks as monotherapy. The mean daytime ABPM was reduced from 159 +/- 13/105 +/- 6 to 145 +/- 11/97 +/- 10 mm Hg (P < .005). Only 6/19 (32%) patients achieved BP control. The 24-h BP load fell from 69% at baseline, to 53% with 12.5 mg HCTZ and to 47% with 25 mg HCTZ daily. There were no side effects but the increase of HCTZ to 25 mg daily was followed by adverse changes (P < .05) in serum potassium levels. It is concluded that low dose of HCTZ monotherapy has only a moderate effect on the BP control and 24-h BP load while the higher 25 mg dose is associated with significant decrease in serum potassium level.

Emergency percutaneous balloon mitral valvotomy in a patient with septic shock.

We report an 18-year-old patient with severe mitral stenosis complicated by right lower lobe pneumonia, sepsis, and shock. Intractable low cardiac output led to an emergency percutaneous balloon mitral valvotomy in a patient, resulting in immediately improved hemodynamic parameters. We are unaware of another report of percutaneous balloon mitral valvotomy performed in a patient with sepsis and shock. This case supports previous isolated reports of the benefit from emergency percutaneous balloon mitral valvotomy in critical situations where thoracotomy is not possible due to coexisting medical problems.

Effect of isradipine in black patients with very severe hypertension. 24-hour ambulatory blood pressure monitoring and echocardiographic evaluation.

Fifty consecutive black patients with very severe hypertension (sitting diastolic blood pressure > or = 120 mm Hg and systolic > or = 210 mm Hg by the conventional cuff method) were treated in an open-label study (without a placebo or active drug control group) for 3 months with a long-acting preparation of isradipine (Dynacirc SRO), during which time serial changes in 24-h ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-h ABPM was reduced from 184 +/- 13/119 +/- 6 to 148 +/- 18/96 +/- 11 mm Hg at 3 months (P < .0001). The reduction in BP was sustained for 24 h after dosing. Simultaneous BP measurements using a conventional cuff method and Dinamap were significantly different from the ABPM pre- and posttherapy, suggesting a marked "white coat" pressor effect. LV mass index regressed from 143 +/- 36 to 122 +/- 32 g/m2 at 3 months (P < .02). Heart rate and mean body weight were unchanged. Left ventricular performance was not adversely affected. Cardiac index and fractional shortening changed insignificantly, from 2.6 +/- 0.6 to 2.7 +/- 0.5 L/min/m2, and from 28 +/- 6 to 31 +/- 7%, respectively. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. We conclude that in this group of patients long-acting isradipine 1) showed a marked and sustained antihypertensive action demonstrated by 24-h ABPM; and 2) was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of prosthetic valve-related complications with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using St. Jude Medical prostheses.

The safety of a very low level of anticoagulation combined with dipyridamole in a rheumatic population (mean age 31 +/- 13 years) with the St. Jude Medical (SJM) prosthesis has not yet been tested. Furthermore, no data are available on the safety of relatively infrequent monitoring of anticoagulation levels and of the necessity for different therapeutic targets according to valve position, number of risk factors, and other baseline risk factors for thromboembolism. In this study, the performance of the SJM prosthesis was tested using a target international normalized ratio (INR) of 2.0 to 2.5 combined with dipyridamole 300 mg/day applied uniformly to all patients. Clinical, biochemical, and echocardiographic data were acquired prospectively in 200 consecutive patients at 3-month intervals. Follow-up (mean 27 +/- 13 months) was complete in 95% of patients. Thirteen patients died (2.9%/patient year). Severe left ventricular dysfunction was the cause of death in 10 of 13 patients. Probability of survival (Kaplan-Meier) was 0.92 at 36 months and of event-free survival 0.84 at 36 months. The median INR was 2.0 +/- 0.9. Valve obstruction did not occur, and there were 3 thromboembolic events (0.6%/patient year). Incidence of bleeding was 1.6%/patient year (n = 7) and was major (hemorrhagic stroke) in 1 (0.2%/patient year). Thus, the SJM prosthesis performs very well despite the use of very low level warfarin anticoagulation combined with dipyridamole. A 3-month assessment of the anticoagulation level is safe. Left ventricular dysfunction rather than valve-related complications is the leading cause of mortality in this population.

Evaluation of the long-term results of mitral valve repair in 254 young patients with rheumatic mitral regurgitation.

BACKGROUND: Surgical valve repair for mitral regurgitation has significant advantages over valve replacement, but the durability of the technique varies according to the cause of mitral valve disease. In this study, we examined the long-term performance of this procedure in a young rheumatic population and also attempted to identify factors predicting a poor outcome. METHODS AND RESULTS: Between January 1981 and 1989, 308 patients underwent primary mitral valve repair for rheumatic mitral regurgitation at our institution. Forty-nine patients who failed to report after surgery and another 5 with discordant data were excluded from the analysis. Mitral regurgitation was pure in 182 patients (72%) and associated with mild commissural fusion in 72 patients (28%). Patient ages ranged from 6 to 52 years (mean, 18 +/- 9 years). A total of 243 patients (96%) were in New York Heart Association class III or IV before surgery, and 66 (26%) had atrial fibrillation. Mean follow-up period was 60 +/- 35 months (range, 1 to 132 months). Rheumatic activity was present clinically in 30% and macroscopically during surgery in 32%. Surgical techniques included insertion of a Carpentier ring (99%), chordal shortening (88%), leaflet resection (14%), chordal transposition (7%), and commissurotomy (28%). Operative mortality was 2.6%, late mortality was 15%, and the reoperation rate was 27%. At 5 years, 96.8% of the patients were free from thromboembolism, 97.7% were free from endocarditis, 74.9% were free from reoperation, 66% were free from valve failure, and 66.2% were free from major events. Multivariate analysis identified active rheumatic carditis as a significant predictor of reoperation, valve failure, and future events, while sinus rhythm and shorter bypass time at initial surgery were the only predictors of long-term survival. Patients with pure mitral regurgitation, sinus rhythm, and no active carditis at initial operation had the best overall 5-year results. Among the 148 survivors without reoperation, 142 (96%) were in New York Heart Association class I and II, and 107 (72%) were in sinus rhythm. Doppler echocardiographic studies showed absence of mitral regurgitation in 34 patients (23%), severe regurgitation in 23 (16%), and severe mitral stenosis in 6 (4%). CONCLUSIONS: Mitral valve repair in this young rheumatic population is associated with a high long-term morbidity. Presence of active rheumatic carditis has a significantly adverse effect on the success of mitral valve repair.

Nifedipine versus captopril in the management of moderate hypertension in black patients.

The efficacy of nifedipine (20 to 40 mg twice daily) and captopril (25 to 50 mg twice daily) was assessed during a 12-week single-blind randomized trial in 41 moderately hypertensive black patients (mean 24-h diastolic blood pressure [BP] > or = 90 mm Hg and < 115 mm Hg). Nifedipine and captopril were administered as monotherapy in increasing dosage while a diuretic was added after 8 weeks in patients who failed to reach the target BP (24-h mean diastolic BP < 90 mm Hg) on monotherapy. After 8 weeks of monotherapy, the mean 24-h ambulatory BP was reduced from 156 +/- 12/101 +/- 5 to 128 +/- 11/84 +/- 7 mm Hg (P < .0001) in the nifedipine group while it remained essentially unchanged (156 +/- 15/101 +/- 7 to 158 +/- 17/102 +/- 9) in the captopril group. Left ventricular (LV) mass index was also reduced significantly (P < .05) in the nifedipine group, while cardiac index and fractional shortening changed marginally. The addition of diuretic in the captopril group (16/21 patients) resulted in a significant fall in BP to 123 +/- 11/81 +/- 7. Only 2/20 patients in the nifedipine group required the addition of diuretic. The overall incidence of side effects was similar with both treatments but the addition of diuretic in the captopril group was followed by adverse changes in serum sodium (P < .01), urea (P < .05), and creatinine (P < .01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)