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STEMI patients admitted urgently to the hospital but experience early complete resolution of both ischemic symptoms and ST-elevations on the electrocardiogram are diagnosed as transient STEMI (TSTEMI). Current evidence indicates that primary intervention is plausible but in certain circumstances intervention can be delayed. We sought to examine whether there is a time limit to such a delay that may affect long-term outcome. Study population included prospectively admitted TSTEMI patients whose demographics, pertinent medical history, and clinical and angiographic features were recorded. Study patients were divided by the median time interval from admission to intervention and their characteristics and long-term survival were compared. Study population comprised 260 consecutive patients (age: 57±10 years, men: 84%) diagnosed as TSTEMI who were included from January 2000 to June 2019, which represent 6% of all STEMI patients. Coronary angiography was performed in 254 patients. The median time interval from admission to angiography was 17 hours (IQR: 7.2 to 38.7 hours). Early (<17 hours from admission) and late (>17 hours from admission) study groups were comparable. One patient died during admission and 41 throughout the long follow-up period of 8.5 ± 5.2 years (median: 8.2 years, IQR: 3.4 to 13.1). Mortality of early-treated TSTEMI patients (11.2%) was significantly lower than of the late-treated patients (21.6%, p <0.04). The Kaplan-Meier curve demonstrated a clear tendency toward improved survival in early-treated TSTEMI patients (p <0.09). In conclusion, the present data suggest that TSTEMI patients should be treated, if not by primary coronary intervention, then at least within 17 hours from admission to achieve better long-term outcome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Patients with acute myocardial infarctions (AMIs) present as persistent ST-elevation myocardial infarction (STEMI) or as non-ST-segment elevation myocardial infarction (NSTEMI). In some patients with STEMI, ST elevations are transient and resolve before coronary intervention (transient ST-elevation myocardial infarction [TSTEMI]). We analyzed our registry comprising all consecutive patients with AMI admitted during 2009 to 2014, and compared the characteristics, management, and outcome of patients with TSTEMI with those of patients with STEMI and NSTEMI. Of 1,847 patients with AMI included in the registry, 1,073 patients sustained a STEMI (58%), 649 had a NSTEMI (35%), and 126 presented with TSTEMI (6.9%). Patients with TSTEMI were younger than patients with NSTEMI and STEMI (56.5 vs 62.8, p <0.001, and 59.5 years, p <0.02, respectively), smoked more (77.8 vs 54.0, p <0.001, and 62.1%, p <0.0005), and fewer were hypertensive (52.4 vs 74.2% and 58.8%, both p <0.001) and diabetic (26.2% vs 47.7%, p <0.0001, and 36.9%, p <0.02). The extent of coronary artery disease in patients with TSTEMI was similar to that of patients with STEMI except for less involvement of the left anterior descending artery (p <0.001), but less extensive than in NSTEMI patients. TSTEMI involved less myocardial damage by troponin-T level (p <0.005) with better cardiac function (LVEF 61% vs 55% and 49%, both p <0.0001). Mortality was lower among TSTEMI both in-hospital (0 vs 2.3% [p = NS] and 4.2% [p <0.01]) and long-term (4.8% vs 14.7% and 14.2%, both p <0.003) at a median of 36 months. In conclusion, TSTEMI is an acute coronary syndrome distinct from NSTEMI and STEMI, characterized by fewer risk factors, a similar extent of coronary artery disease to STEMI, but is associated with less myocardial damage and portends a better outcome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Collaterals to occluded coronary arteries have been observed early after the onset of acute myocardial infarction (AMI). The pressure distal to the occluded segment of the culprit coronary artery (P(d)) is generated by collateral flow from the feeding coronary artery supplied by the systemic circulation. The aim of the study was to assess the relation between systemic blood pressure (BP) and P(d). Systemic BP and P(d) were measured simultaneously during intervention of totally occluded coronary arteries in 152 patients admitted for AMI. Patients were divided into groups by time from symptom onset to P(d) measurement. There was a significant positive correlation between P(d) and the systolic, diastolic, and mean BPs measured during the first 3 hours from symptom onset (n = 60; p <0.05, p <0.006, and p <0.005, respectively), from 3 to 12 hours (n = 56; p <0.02 for all), and >12 hours after symptom onset (n = 36; p <0.003 for all). The collateral flow, represented by calculated collateral flow index (mean 0.37 ± 0.14, median 0.36), was correlated with mean BP (p = 0.05) but not with diastolic or systolic BP (p = NS) in the overall study population. A direct relation was established during AMI between systemic BP and P(d) at all time intervals from symptom onset. Collateral flow index correlated with mean BP and was strongly associated with P(d) at all time intervals. In conclusion, the relation between P(d) and systemic BP suggests caution when administering therapy that may lower systemic BP during AMI before restoring flow in the occluded culprit artery, as it may compromise collateral pressure and exacerbate myocardial ischemia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Patients sustaining an ST-segment elevation myocardial infarction (STEMI) frequently develop pulmonary congestion or pulmonary edema (PED). We previously showed that lung impedance (LI) threshold decrease of 12% to 14% from baseline during admission for STEMI marks the onset of the transition zone from interstitial to alveolar edema and predicts evolution to PED with 98% probability. The aim of this study was to prove that pre-emptive LI-guided treatment may prevent PED and improve clinical outcomes. Five hundred sixty patients with STEMI and no signs of heart failure underwent LI monitoring for 84 ± 36 hours. Maximal LI decrease throughout monitoring did not exceed 12% in 347 patients who did not develop PED (group 1). In 213 patients LI reached the threshold level and, although still asymptomatic (Killip class I), these patients were then randomized to conventional (group 2, n = 142) or LI-guided (group 3, n = 71) pre-emptive therapy. In group 3, treatment was initiated at randomization (LI = -13.8 ± 0.6%). In contrast, conventionally treated patients (group 2) were treated only at onset of dyspnea occurring 4.1 ± 3.1 hours after randomization (LI = -25.8 ± 4.3%, p <0.001). All patients in group 2 but only 8 patients in group 3 (11%) developed Killip class II to IV PED (p <0.001). Unadjusted hospital mortality, length of stay, 1-year readmission rate, 6-year mortality, and new-onset heart failure occurred less in group 3 (p <0.001). Multivariate analysis adjusted for age, left ventricular ejection fraction, risk factors, peak creatine kinase, and admission creatinine and hemoglobin levels showed improved clinical outcome in group 3 (p <0.001). In conclusion, LI-guided pre-emptive therapy in patients with STEMI decreases the incidence of in-hospital PED and results in better short- and long-term outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Patients with recurrent acute myocardial infarction (AMI), who represent ≤35% of hospitalized patients with AMI, are at an increased risk of complications and death. Our study purpose was to compare the treatment and outcome of patients hospitalized with recurrent acute ST-segment elevation myocardial infarction (STEMI) from 1998 to 2006 with those of patients with a first STEMI. We performed 5 biennial nationwide 2-month surveys during 1998 to 2006, collecting data prospectively from all patients hospitalized for AMI or acute coronary syndrome in all 25 coronary care units in Israel. The present cohort included 4,543 patients with STEMI, 3,679 (76%) with first and 864 (24%) with recurrent STEMI. The patients with recurrent STEMI were older (66 ± 13 vs 62 ± 13 years), had greater rates of diabetes, hypertension, and previous angina, had a worse Killip class on admission, and experienced more in-hospital complications. The all-cause hospital crude mortality rate was 8.1% in patients with recurrent STEMI versus 5.5% in those with a first STEMI (adjusted odds ratio 1.71 95% confidence interval 1.19 to 2.44), and the 1-year mortality rate was 18.9% versus 10.9%, respectively (hazard ratio 1.85, 95% confidence interval 1.41 to 2.43). From 1998 to 2006, an insignificant trend toward a 1-year mortality reduction among patients with recurrent STEMI was seen and those with a first STEMI had a significant mortality decrease. In conclusion, patients admitted for recurrent STEMI have worse in-hospital and 1-year outcomes that did not improve during the study period. An improved therapeutic approach is needed for these high-risk patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The adjustment of medications and dosages to the needs of individual patients with heart failure is mostly intuitive, but even when their effect on global myocardial function is measured by classic indexes, their effect on segmental function is overlooked. This study was conducted to assess the feasibility of using echocardiographic myocardial strain imaging to evaluate the effect of medication on global and segmental function in 21 ambulatory patients with heart failure (mean age 65+/-11 years) who had echocardiographic studies performed before and 2 hours after ingesting their regular morning medications. The ejection fraction, global and regional strain, and time to regional peak strain were compared between the 2 examinations. Medication induced no significant changes in mean ejection fraction (28.6+/-7.8% to 27.5+/-9.9%) and mean global strain (-9.5+/-3.6% to -9.8+/-3.2%). Changes in segmental strain depended on baseline function: normal segments (peak strain more negative than -12%) deteriorated (-15.5+/-2.7% to -13.7+/-4.6%, p<0.0001), but dysfunctional segments (peak strain less negative than -8%) improved (-5.3+/-2.0% to -7.4+/-4.3%, p<0.0001). Medication also improved segmental synchronization: average time to peak strain of segments in which peak strain was attained before aortic valve closure increased (325+/-69 to 375+/-100 ms, p<0.0001), but that of segments with postsystolic shortening at baseline decreased (451+/-93 to 435+/-93 ms, p<0.006). Thus, the time interval between time to peak strain of segments with systolic and post-systolic shortening at baseline was halved after medication. In conclusion, medications for heart failure induced an increase in the echocardiographically determined peak strain of myocardial segments with impaired function at baseline but decreased the peak strain of normally contracting segments. Medications also improved the synchronization of myocardial contraction. Neither the global ejection fraction nor global strain reflected these changes. Thus, medication tended to improve the homogeneity of left ventricular contraction.

One hundred thirty-nine patients who underwent transesophageal echocardiographic studies were grouped by their maximal left atrial (LA) volumes, and their stroke volumes, emptying fractions, and fractional shortening were calculated. In large atria, an inverse relation was found between further increases in LA volume and LA function, determined by emptying fractions and fractional shortening.

Mortality and morbidity after acute myocardial infarction (AMI) is higher in diabetic than in nondiabetic patients. Angiotensin-converting enzyme (ACE) inhibitors have been shown to exert a beneficial effect after AMI. We sought to evaluate the association between treatment with ACE inhibitors and 1-year outcome after AMI in diabetic and nondiabetic patients in a national survey. The study population was drawn from a national survey conducted in all coronary care units operating in Israel during a 5-month period in 1996, and included 2,179 patients with AMI: 533 diabetics (24%), 322 of whom received ACE inhibitors (60%) and 211 who did not; and 1,646 nondiabetics, 805 of whom received ACE inhibitors and 841 who did not. In both groups of patients, those treated with ACE inhibitors were older, included more women, more had a history of AMI, anterior wall AMI, or hypertension, and more had worse Killip class on admission. Diabetic patients treated with ACE inhibitors experienced lower 1-year mortality rates than diabetics not treated with ACE inhibitors (16.2% vs 18.8%, respectively; covariate adjusted hazard ratio 0.47, 95% confidence interval 0.30 to 0.74). In nondiabetic patients, however, ACE inhibitor treatment was not associated with a better outcome (10.2% vs 7.3%, respectively; covariate adjusted hazard ratio 0.80; 95% confidence interval 0.56 to 1.15). Thus, treatment with ACE inhibitors after AMI appears to be particularly beneficial in diabetic patients. The beneficial effect observed supports the widespread use of ACE inhibitors in diabetic patients after AMI.

Purpose: Little is known about the advantages and disadvantages of participation in a clinical trial for patients with coronary heart disease. We hypothesized that participation itself in a long-term clinical trial with regular clinical evaluation and adjustment of treatments might lead to survival gain among patients with coronary artery disease who agreed or refused to participate in the Bezafibrate Infarction Prevention study., Subjects and Methods: The study was performed in 18 university hospitals. There were 3502 patients who fulfilled the inclusion criteria. Among them, 3122 patients signed informed consent and were included in the study ("participants"), whereas 380 declined to participate ("nonparticipants"). For all participants, routine visits to the clinics were scheduled bimonthly for study medication distribution and compliance assessment, and every 4 months for clinical evaluation and management. Nonparticipants continued with community-based treatment and were followed only for mortality., Results: The two groups were similar with regard to age, sex, and the prevalence of most cardiovascular diseases, risk factors, and medications, except that participants were more likely to have presented with an anginal syndrome (1788 [57%] vs. 190 [50%]) and to have symptomatic heart failure (754 [25%] vs. 66 [18%]). During follow-up (mean [+/- SD], 7.7 +/- 0.8 years), 475 patients died. All-cause mortality was similar in participants (n = 423 [13.6%]) and nonparticipants (n = 52 [13.7%]). In a multivariate analysis, participation in the clinical trial was not associated with all-cause mortality (hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.70 to 1.30) or cardiac mortality (HR = 1.12; 95% CI: 0.72 to 1.74)., Conclusion: Participation in a long-term clinical trial in a country with readily accessible community-based medicine may not lead to survival gain in patients with coronary artery disease.

Purpose: Plasma fibrinogen has emerged as an important predictor of cardiovascular disease, but few data are available on its association with stroke. We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke., Subjects and Methods: Patients from the Bezafibrate Infarction Prevention Study, a placebo-controlled, randomized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard (400 mg daily), were studied. Plasma fibrinogen levels were measured at baseline and yearly thereafter. Stroke, a prospectively monitored endpoint, was systematically assessed regarding stroke type, subtype, and functional outcome., Results: Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event (140 strokes, 36 transient ischemic attacks; mean follow-up, 6.2 years) than in patients who did not (375 vs. 349 mg/dL, P <0.0001). Fibrinogen levels did not differ significantly by the type, subtype, or severity of the cerebrovascular event. Risk of ischemic stroke increased from 3.3% in the lowest tertile (baseline fibrinogen <314 mg/dL) to 7.% in the middle tertile (fibrinogen 314 to 373 mg/dL) to 10% in the upper tertile (fibrinogen >373 mg/dL, P <0.001). Adjusting for age, blood pressure, and other covariates, fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile (hazard ratio = 2.6; 95% confidence interval: 1.5 to 4.3). We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events., Conclusion: Plasma fibrinogen is a strong predictor of, rather than a direct causative factor for, subsequent stroke among patients at increased risk owing to manifest coronary heart disease.

Few data are available regarding the prevalence and prognostic significance of the triple coexistence of undiagnosed systemic hypertension, diabetes mellitus, and coronary heart disease. This study aimed to evaluate the prevalence and prognostic significance of unrecognized hypertension in cardiac diabetic patients previously defined as "normotensives" over a 5-year follow-up period. The study sample comprised 11,515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who were screened but not included in the Bezafibrate Infarction Prevention study. Among them, 9,033 were nondiabetics and 2,482, diabetics. The diabetics were divided into 3 groups: (1) 1,272 normotensives, (2) 152 patients without history of hypertension but with elevated blood pressure ("unrecognized hypertensives"), and (3) 1,058 hypertensives with established diagnosis. The prevalence of both diagnosed and unrecognized hypertension in diabetics pooled together increased from 49% to 69% when World Health Organization and new Joint National Committee-VI criteria were compared. Crude all-cause mortality was lower in nondiabetics than in diabetics (11.2% vs 22.0%; p <0.001). Among diabetics the lowest all-cause mortality was documented for normotensives (19.3%), whereas the highest mortality was observed in unrecognized hypertensives (26.3%, p = 0.003). Both unrecognized and established hypertensives demonstrated a significant stroke-related mortality excess: about four- and threefold increases in cerebrovascular accident-related death, respectively, were observed (p = 0.002). On multivariate analysis, both unrecognized and diagnosed hypertension were consistent predictors of increased all-cause mortality, with a hazard ratio of 1.28 (95% confidence interval 0.90 to 1.82) and 1.24 (95% confidence interval 1.03 to 1.49), respectively. Our findings demonstrate widespread undiagnosed hypertension in diabetic coronary patients; their 5-year mortality was significantly increased compared with normotensives, and tended to be even higher than in diabetics previously identified as hypertensives.

Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality.

The aim of the study was to investigate the effect of beta-blocker treatment on a large cohort of patients with coronary artery disease in functional classes II and III according to the New York Heart Association (NYHA) classification. Among 11,575 patients with coronary artery disease screened for participation, but not included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were in NYHA classes II and III. In the latter group of patients we compared the prognosis of 1,109 (34%) treated with beta blockers with 2,116 counterparts not receiving beta-blocker therapy. After a mean follow-up of 4 years, all-cause and cardiac mortality rates were significantly lower among beta-blocker users, 9% and 5%, respectively, than among beta-blocker nonusers, 17% and 11%, respectively (p <0.01 for both). After multivariate adjustment, treatment with beta blockers was associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95% confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR = 0.61, 95% CI 0.45 to 0.83) than was no treatment with a beta blocker. Lower total mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to 0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a previous myocardial infarction. We conclude that beta-blocker therapy in coronary patients in NYHA classes II or III is safe and associated with a lower risk for all-cause and cardiac mortality.

We assessed the relation between symptoms and cardiac arrhythmias in 110 consecutive pregnant patients without evidence of heart disease referred for evaluation of palpitations, dizziness, and syncope (study group) and in 52 consecutive patients referred for evaluation of an asymptomatic functional precordial murmur (control group). Both groups had a high incidence of arrhythmias on Holter monitoring with atrial premature complexes (APCs) of 56% in the study group and 58% in the control group, > 100 APCs in 7% and 4% of the patients, respectively, and isolated ventricular premature complexes (VPCs) in 59% and 50%, respectively. The number of isolated VPCs was higher and > 50 VPCs/hour were seen in more patients in the study group (3,235 +/- 6,397 vs 678 +/- 3,358 beats/24 hours p < 0.05 and 22% vs 2% p = 0.03). Similarly, the incidence of multifocal VPCs was higher in the study patients (12% vs 2%, p < 0.05). There was no correlation between the incidence of both VPCs or APCs and symptoms, and only 10% of symptomatic episodes were accompanied by the presence of arrhythmias. Repeated Holter monitoring 6 weeks postpartum in 9 women with multiple premature contractions during pregnancy (9,073 +/- 9,210/24 hours) showed a substantial reduction to 1,345 +/- 1,997/24 hours (p < 0.05). Thus, this study confirms an increased incidence of arrhythmias during normal pregnancy. These arrhythmias consist mostly of APCs and VPCs. The number of simple and multifocal VPCs is higher in patients presenting with symptoms of palpitations, dizziness, or syncope; however, there is no correlation between the incidence of arrhythmias and symptoms, and only 10% of symptomatic episodes were accompanied by the presence of arrhythmias.

The benefit of beta-blocker therapy in patients after myocardial infarction is well established. The use of beta blockers in the high-risk subgroup of patients with combined diabetes mellitus (DM) and coronary artery disease (CAD) remains controversial. From a database of 14,417 patients with chronic CAD who had been screened for participation in the Bezafibrate Infarction Prevention (BIP) study, 2,723 (19%) had non-insulin-dependent DM. Baseline characteristics and 3-year mortality were analyzed in patients with DM receiving (n = 911; 33%) and not receiving (n = 1,812; 67%) beta blockers. Total mortality during a 3-year follow-up was 7.8% in those receiving beta blockers compared with 14.0% in those who were not (a 44% reduction). A reduction in cardiac mortality of 42% between the 2 groups was also noted. Three-year survival curves showed significant differences in mortality with increasing divergence (p = 0.0001). After multiple adjustment, multivariate analysis identified beta-blocker therapy as a significant independent contributor to improved survival (relative risk = 0.58; 90% confidence interval 0.46 to 0.74). Within the diabetic population, the main benefit associated with beta-blocker therapy was observed in older patients, in those with a history of myocardial infarction, those with limited functional capacity, and those at lower risk. Thus, therapy with beta blockers appears to be associated with improved long-term survival in the high-risk subpopulation of patients with DM and CAD.

Objective: To review reports on the use of angiotensin-converting enzyme inhibitors (ACE-I) during pregnancy in order to determine the incidence, nature, and potential mechanisms of fetal complications in an attempt to establish recommendations related to the use of these drugs during gestation., Data Sources: Relevant English-language articles identified through a Medline search and bibliographies found in recent articles., Study Selection: Large number of reports both on animals and on humans have consistently shown a high degree of morbidity and even mortality in fetuses or newborns exposed to ACE-I during pregnancy. The reported complications include oligohydramnios, intrauterine growth retardation, premature labor, fetal and neonatal renal failure, bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, and neonatal death. A high incidence of fetal complications was related to the use of ACE-I at all trimesters of pregnancy., Conclusion: The gestational use of ACE-I may be associated with a high degree of fetal and newborn morbidity and even mortality. The use of these drugs should be avoided at all trimesters of pregnancy.

Prolonged exposure to organic nitrates has been shown to lead to the rapid development of tolerance to the peripheral and coronary vasodilatory effects of these drugs. As a result of this phenomenon, the hemodynamic and anti-ischemic effects of nitrates may be rapidly attenuated in patients with ischemic heart disease, congestive heart failure, or both. This nitrate tolerance appears to be both dose- and time-dependent. Likely mechanisms proposed for its development are multifactorial and include depletion of sulfhydryl groups, a nitrate-mediated increase in blood volume, and neurohormonal stimulation with activation of vasoconstrictive mechanisms.

To evaluate the therapeutic potential of organic nitrates in patients with chronic congestive heart (CHF) failure already treated with angiotensin-converting enzyme (ACE) inhibitors, the temporal hemodynamic effects of oral isosorbide dinitrate, 40 to 120 mg administered every 6 hours to 11 nitrate responders who had been treated with captopril 89 +/- 32 mg/day, were studied. The administration of isosorbide dinitrate resulted in a significant decline in mean right atrial pressure, from 13 +/- 6 mm Hg at baseline (mean value of measurements performed every 2 hours for 24 hours with captopril therapy) to 9 +/- 4 mm Hg at 1 hour with persistent effect for most of the study period. Mean pulmonary artery pressure decreased from 38 +/- 7 mm Hg at baseline to 29 +/- 9 mm Hg at 1 hour, with effect persisting for 24 hours. Mean pulmonary artery wedge pressure also decreased from 24 +/- 6 to 15 +/- 7 mm Hg at 1 hour and remained significantly reduced for 20 hours. Systemic blood pressure demonstrated a transient decrease lasting 2 hours after initiation of therapy which was asymptomatic in all patients. The results of this study demonstrate a preserved vasodilatory effect of organic nitrates in patients already treated with ACE inhibitors. Nitrates mediated improvement in right and left ventricular filling pressures, and reduction of pulmonary hypertension demonstrates a rationale for the use of these therapeutic methods in combination and suggest the need for long-term evaluation of the effect of nitrate therapy in patients with chronic CHF already treated with ACE inhibitors.

Organic nitrates are commonly used in the treatment of chronic congestive heart failure (CHF). These drugs have been shown to improve exercise capacity and reduce symptoms and in combination with hydralazine to prolong life in patients with mild-to-moderate symptoms of CHF. Recent investigations, however, have indicated that nitrate-mediated benefit to patients with CHF may be limited by resistance to their hemodynamic effects seen in many patients and by early development of tolerance. The incidence, potential mechanisms, and possible methods for prevention of nitrate resistance and tolerance in patients with chronic CHF are reviewed.