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Biomedical subjects

Bernard J Gersh

Publications and source records attributed to Bernard J Gersh.

At least 19 recordsLinked to original sources
PubMed2007

Impact of diabetes on five-year outcomes of patients with multivessel coronary artery disease.

BACKGROUND: Diabetes mellitus is a major cause of coronary artery disease. Despite improvement in the management of patients with stable coronary artery disease, diabetes remains a major cause of increased morbidity and mortality. Although coronary artery bypass grafting surgery (CABG) and percutaneous coronary intervention are widely used, no conclusive evidence exists that either treatment modality is better than medical therapy alone for the treatment of stable single- or multivessel coronary disease in patients with diabetes. METHODS: We compared medical therapy, percutaneous coronary intervention, and CABG in 499 diabetic patients (38.5%) and 799 nondiabetic patients (61.5%) with single- or multivessel coronary disease. The composite primary endpoint was cardiac-related death, Q-wave myocardial infarction, or refractory angina requiring revascularization. RESULTS: We treated 1,298 patients with either CABG (n = 524), percutaneous coronary intervention (n = 378), or medical therapy (n = 396). More deaths occurred among patients with diabetes than among patients without diabetes, regardless of which option was used (p < 0.001). When treatment modalities were stratified according to the number of diseased vessels, CABG was shown to be more beneficial for patients with diabetes and multivessel disease than for patients with diabetes and single-vessel disease (p < 0.001). However, when stratified by treatment, patients with diabetes receiving medical therapy had a worse prognosis than patients with diabetes treated with CABG (p = 0.005). CONCLUSIONS: All three therapeutic regimens resulted in high rates of cardiac-related deaths among patients with diabetes compared with patients without diabetes. Moreover, we observed better outcomes among patients with diabetes and multivessel coronary artery disease undergoing CABG regarding the primary endpoint at 5-year follow-up.

Adult↗
PubMed2007

Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris.

OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. METHODS: Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.

Angina Pectoris↗
PubMed2006

Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) can be classified into at least four major anatomic subsets based upon the septal contour, and the location and extent of hypertrophy: reverse curvature-, sigmoidal-, apical-, and neutral contour-HCM. Here, we sought to identify genetic determinants for sigmoidal-HCM and hypothesized that Z-disc-HCM may be associated preferentially with a sigmoidal phenotype. Utilizing PCR, DHPLC, and direct DNA sequencing, we performed mutational analysis of five genes encoding cardiomyopathy-associated Z-disc proteins. The study cohort consisted of 239 unrelated patients with HCM previously determined to be negative for mutations in the eight genes associated with myofilament-HCM. Blinded to the Z-disc genotype status, the septal contour was graded qualitatively using standard transthoracic echocardiography. Thirteen of the 239 patients (5.4%) had one of 13 distinct HCM-associated Z-disc mutations involving residues highly conserved across species and absent in 600 reference alleles: LDB3 (6), ACTN2 (3), TCAP (1), CSRP3 (1), and VCL (2). For this subset with Z-disc-associated HCM, the septal contour was sigmoidal in 11 (85%) and apical in 2 (15%). While Z-disc-HCM is uncommon, it is equal in prevalence to thin filament-HCM. In contrast to myofilament-HCM, Z-disc-HCM is associated preferentially with sigmoidal morphology.

Actin Cytoskeleton↗
PubMed2006

Relation of arterial stiffness to left ventricular diastolic function and cardiovascular risk prediction in patients > or =65 years of age.

There is a paucity of data regarding the relation between the various noninvasive indexes of arterial stiffness and left ventricular diastolic function. In 188 subjects aged > or =65 years (mean 75 +/- 5; 71% men), the concordance and strength of the association between measures of arterial stiffness and left ventricular diastolic function were evaluated. Indexes of arterial stiffness (brachial and aortic pulse pressure [PP], carotid-femoral pulse-wave velocity [PWV], and augmentation pressure [AP]) were measured using applanation tonometry. Diastolic function was classified in terms of instantaneous diastolic function grade and quantitated as left atrial volume, a measure of chronic diastolic burden. Risk for new cardiovascular events was estimated using a validated clinical echocardiographic risk algorithm. Aortic and brachial PP, PWV, and AP were correlated positively with left atrial volume and diastolic function grade. After adjusting for age, gender, and clinical and echocardiographic covariates, 1-SD increases in aortic PP, brachial PP, PWV, and AP were associated with 6%, 6%, 4%, and 4% increases in indexed left atrial volume, respectively. Similarly, 1-SD increases in aortic PP, brachial PP, and AP were associated with 84%, 81%, and 83% increased risk for diastolic dysfunction, respectively (all p <0.04). PWV and aortic and brachial PP were superior to AP in discriminating subjects with the highest risk of having new cardiovascular events (5-year risk >50%; area under receiver-operating characteristic curve 0.67, 0.67, 0.70, and 0.56, respectively; p <0.05). In conclusion, increased arterial stiffness was associated with more severe left ventricular diastolic dysfunction, although the strength of the association varied according to the specific measure used. Aortic PP, brachial PP, and PWV appeared superior to AP in risk discrimination in this elderly cohort.

Aged↗
PubMed2006

Left atrial volume predicts the risk of atrial fibrillation after cardiac surgery: a prospective study.

OBJECTIVES: This study sought to identify preoperative predictors of postoperative atrial fibrillation (POAF) among patients undergoing cardiac surgery. BACKGROUND: Postoperative atrial fibrillation is frequent after cardiac surgery and is associated with increased morbidity, mortality, prolonged hospital stay, and increased costs. Left atrial volume (LAV), a marker of chronically elevated left ventricular filling pressure, is a predictor of atrial fibrillation (AF) in the nonsurgical setting. METHODS: A total of 205 patients (mean age 62 +/- 16 years; 35% women) undergoing cardiac surgery were prospectively enrolled. Clinical risk factors were obtained by detailed medical record review and patient interview. Preoperative transthoracic echocardiograms were performed for assessment of LAV, left ventricular ejection fraction, and diastolic function. Follow-up was complete. Detection of POAF was based on documentation of AF episodes by continuous telemetry throughout hospitalization. RESULTS: Postoperative atrial fibrillation occurred in 84 patients (41.4%) at a median of 1.8 days after cardiac surgery. The LAV was significantly larger in patients in whom AF developed (49 +/- 14 ml/m2 vs. 39 +/- 16 ml/m2, p = 0.0001). Patients with LAV >32 ml/m2 had an almost five-fold increased risk of POAF, independently of age and clinical risk factors (adjusted hazard ratio 4.84, 95% confidence interval 1.93 to 12.17, p = 0.001). Age and LAV were the only independent predictors of POAF. The area under the receiver-operator characteristics curve to predict POAF was 0.729 for LAV and 0.768 for the combination of LAV and age (both p < 0.0001). CONCLUSIONS: The LAV is a strong and independent predictor of POAF. Risk stratification using LAV and age enables clinicians to identify high-risk patients before cardiac surgery.

Adult↗
PubMed2006

Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence.

BACKGROUND: Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050. METHODS AND RESULTS: The adult residents of Olmsted County, Minnesota, who had ECG-confirmed first AF in the period 1980 to 2000 (n=4618) were identified. Trends in age-adjusted incidence were determined and used to construct model-based prevalence estimates. The age- and sex-adjusted incidence of AF per 1000 person-years was 3.04 (95% CI, 2.78 to 3.31) in 1980 and 3.68 (95% CI, 3.42 to 3.95) in 2000. According to Poisson regression with adjustment for age and sex, incidence of AF increased significantly (P=0.014), with a relative increase of 12.6% (95% CI, 2.1 to 23.1) over 21 years. The increase in age-adjusted AF incidence did not differ between men and women (P=0.84). According to the US population projections by the US Census Bureau, the number of persons with AF is projected to be 12.1 million by 2050, assuming no further increase in age-adjusted incidence of AF, but 15.9 million if the increase in incidence continues. CONCLUSIONS: The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000. Whether or not this rate of increase continues, the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.

Adult↗
PubMed2006

Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.

BACKGROUND: Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function. METHODS AND RESULTS: We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13). CONCLUSIONS: Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

Aged↗
PubMed2006

Rationale for the revascularization arm of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial.

Modern coronary revascularization therapies, coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI), continue to evolve and are widely applied. However, for patients with mild stable angina, or those who are asymptomatic with angiographically documented coronary artery disease (CAD), no survival benefit or reduction in the incidence of myocardial infarction has been demonstrated with CABG or PCI, except in the case of subgroups with angiographically determined high risk due to extensive multivessel disease with depressed LV function or left main CAD. At the same time, medical therapy continues to advance, with demonstrable benefit in both primary and secondary prevention of atherosclerotic coronary disease events. Patients with type 2 diabetes mellitus, at increased risk for adverse cardiac events, have been shown to benefit from these approaches as well. However, in asymptomatic or mildly symptomatic patients with documented ischemia and angiographically significant CAD, the incremental benefit-or hazard-associated with early revascularization superimposed on aggressive medical and risk factor modification therapies is unknown. We discuss the background and rationale for investigating the impact of early revascularization in patients with diabetes and CAD.

Angioplasty, Balloon, Coronary↗
PubMed2006

Aborted myocardial infarction: a new target for reperfusion therapy.

Reperfusion therapy for ST-elevation acute coronary syndromes aims at early and complete recanalization of the infarct-related artery in order to salvage myocardium and improve both early and late clinical outcomes. Myocardial necrosis is usually confirmed and quantified by myocardial enzyme release in plasma. However, over 10% of patients treated with reperfusion therapy fail to develop an enzyme rise, but do exhibit transient ECG changes, which are consistent with an aborted myocardial infarction. The earlier the reperfusion therapy is instituted, the higher the incidence of aborted infarction. Treatment within an hour after symptom onset may result in 25% of aborted infarction and is in combination with complete (70%) ST-segment resolution associated with better survival. This endpoint is easy to define and occurs promptly in time. The faster that effective treatment is initiated, the more likely aborted infarction will occur. Given that mortality, re-infarction, and stroke are declining in incidence, we suggest the introduction of aborted infarction as an endpoint in clinical trials of ST-elevation acute coronary syndromes.

Emergency Treatment↗
PubMed2006

A total of 1,007 percutaneous coronary interventions without onsite cardiac surgery: acute and long-term outcomes.

OBJECTIVES: We sought to compare clinical outcomes of elective percutaneous coronary intervention (PCI) and primary PCI for ST-segment elevation myocardial infarction (STEMI) at a community hospital without onsite cardiac surgery to those at a tertiary center with onsite cardiac surgery. BACKGROUND: Disagreement exists about whether hospitals with cardiac catheterization laboratories, but without onsite cardiac surgery, should develop PCI programs. Primary PCI for STEMI at hospitals without onsite cardiac surgery have achieved satisfactory outcomes; however, elective PCI outcomes are not well defined. METHODS: A total of 1,007 elective PCI and primary PCI procedures performed from March 1999 to August 2005 at the Immanuel St. Joseph's Hospital-Mayo Health System (ISJ) in Mankato, Minnesota, were matched one-to-one with those performed at St. Mary's Hospital (SMH) in Rochester, Minnesota. Strict protocols were followed for case selection and PCI program requirements. Clinical outcomes (in-hospital procedural success, death, any myocardial infarction, Q-wave myocardial infarction, and emergency coronary artery bypass surgery) and follow-up survival were compared between groups. RESULTS: Among 722 elective PCIs, procedural success was 97% at ISJ compared with 95% at SMH (p = 0.046). Among 285 primary PCIs for STEMI, procedural success was 93% at ISJ and 96% at SMH (p = 0.085). No patients at ISJ undergoing PCI required emergent transfer for cardiac surgery. Survival at two years' follow-up by treatment location was similar for patients with elective PCI and primary PCI. CONCLUSIONS: Similar clinical outcomes for elective PCI and primary PCI were achieved at a community hospital without onsite cardiac surgery compared with those at a tertiary center with onsite cardiac surgery using a prospective, rigorous protocol for case selection and PCI program requirements.

Aged↗
PubMed2006

Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter?

OBJECTIVES: We sought to compare left atrial (LA) volume to LA area and diameter for the prediction of adverse cardiovascular outcomes. BACKGROUND: The incremental value of LA volume compared with LA area or diameter as a cardiovascular risk marker has not been evaluated prospectively for patients with sinus rhythm or atrial fibrillation (AF). METHODS: Left atrial size was assessed with biplane LA volume, four-chamber LA area, and M-mode dimension for 423 patients (mean age 71 +/- 8 years, 56% men) who were prospectively followed for development of first AF, congestive heart failure, stroke, transient ischemic attack, myocardial infarction, coronary revascularization, and cardiovascular death. RESULTS: Of the 317 subjects in sinus rhythm at baseline, 62 had 90 new events during a mean follow-up of 3.5 +/- 2.3 years. All three LA size parameters were independently predictive of combined outcomes (all p < 0.0001). The overall performance for the prediction of cardiovascular events was greatest for LA volume (area under the receiver operator characteristic curve: indexed LA volume 0.71; LA area 0.64; LA diameter 0.59). A graded association between the degree of LA enlargement and risk of cardiovascular events was only evident for indexed LA volume. For subjects with AF, there was no association between LA size and cardiovascular events. CONCLUSIONS: Left atrial volume is a more robust marker of cardiovascular events than LA area or diameter in subjects with sinus rhythm. The predictive utility of LA size for cardiovascular events in AF was poor, irrespective of the method of LA size quantitation.

Age Factors↗
PubMed2006

Effects of quinapril on left atrial structural remodeling and arterial stiffness.

Left atrial (LA) enlargement, left ventricular (LV) diastolic dysfunction, and increased arterial stiffness are all associated with adverse cardiovascular outcomes. The rate, magnitude, and concordance of modifiability of these risk markers have not been well characterized. Twenty-one patients (mean age 69 +/- 8 years; 52% women) with isolated diastolic dysfunction and indexed LA volumes > or =32 ml/m(2) were randomly assigned to receive either quinapril at a target dose of 60 mg/day or matching placebo for 12 months. Echocardiographic maximum LA volume and LV diastolic function and arterial stiffness by the augmentation index were measured at baseline and 6 and 12 months. Analysis was based on intention to treat. Baseline characteristics were comparable between the treatment (n = 9) and placebo (n = 12) groups. The mean reduction in LA volume of 4.2 +/- 7.8 ml/m(2) in the quinapril group was significant (p = 0.01) compared with the increase in LA volume in the placebo group (5.5 +/- 8.1 ml/m(2)). This represents a relative improvement of 9.7 ml/m(2). Change in LV filling pressure in terms of E/e' and diastolic function grade did not reach significance. A reduction in the augmentation index was associated with a decrease in indexed LA volume (odds ratio 11, p = 0.046), independent of changes in systolic blood pressure. In conclusion, LA structural remodeling appeared reversible with quinapril, which occurred in parallel with an improvement in arterial stiffness but independent of blood pressure changes.

Aged↗
PubMed2006

Relapse and mortality following cardioversion of new-onset vs. recurrent atrial fibrillation and atrial flutter in the elderly.

AIMS: Trials of rate control vs. rhythm control for atrial fibrillation or flutter included few patients with new-onset arrhythmia. Our objective was to assess the relapse rate and the effect of the relapse of new-onset atrial arrhythmias on mortality after direct-current cardioversion (DCCV). METHODS AND RESULTS: A cohort of 351 patients with atrial fibrillation (new onset in 179) and 126 patients with atrial flutter (new onset in 78) was followed-up after DCCV. Cox proportional hazard models were used. Median age was 74.6 years. Mean follow-up for relapse was 7.7 months; for death, 29.4 months. Patients with new-onset atrial flutter [adjusted hazard ratio (HR) = 1] were more likely to maintain sinus rhythm than the patients with recurrent atrial flutter (adjusted HR = 2.5, P < 0.01), new-onset atrial fibrillation (adjusted HR = 2.4, P < 0.01), or recurrent atrial fibrillation (adjusted HR = 2.7, P < 0.01). Patients with new-onset atrial fibrillation were as likely to have relapses as patients with recurrent atrial fibrillation or flutter. Relapse of atrial arrhythmia after DCCV was associated with increased mortality (adjusted HR= 3.1, P < 0.01). CONCLUSION: DCCV is more successful in maintaining sinus rhythm in patients with new-onset atrial flutter than in patients with new-onset atrial fibrillation. Relapse of atrial arrhythmia after cardioversion is associated with increased mortality.

Aged↗
PubMed2006

Controversies in ventricular remodelling.

Ventricular remodelling describes structural changes in the left ventricle in response to chronic alterations in loading conditions, with three major patterns: concentric remodelling, when a pressure load leads to growth in cardiomyocyte thickness; eccentric hypertrophy, when a volume load produces myocyte lengthening; and myocardial infarction, an amalgam of patterns in which stretched and dilated infarcted tissue increases left-ventricular volume with a combined volume and pressure load on non-infarcted areas. Whether left-ventricular hypertrophy is adaptive or maladaptive is controversial, as suggested by patterns of signalling pathways, transgenic models, and clinical findings in aortic stenosis. The transition from apparently compensated hypertrophy to the failing heart indicates a changing balance between metalloproteinases and their inhibitors, effects of reactive oxygen species, and death-promoting and profibrotic neurohumoral responses. These processes are evasive therapeutic targets. Here, we discuss potential novel therapies for these disorders, including: sildenafil, an unexpected option for anti-transition therapy; surgery for increased sphericity caused by chronic volume overload of mitral regurgitation; an antifibrotic peptide to inhibit the fibrogenic effects of transforming growth factor beta; mechanical intervention in advanced heart failure; and stem-cell therapy.

Animals↗
PubMed2006

Controversies in stable coronary artery disease.

Coronary heart disease is still highly prevalent worldwide, and stable angina pectoris is one of its more common presentations. Three major controversies are risk factor management, drug therapy, and intervention. As well as the major risk factors stated by the Framingham study and European guidelines, other factors include abdominal obesity, metabolic syndrome, and psychological stress. How should these additional factors be rated? With respect to drug therapy, apart from aspirin, all patients with stable angina should be assessed for statin treatment. Although statins will reduce coronary events by about one third in patients with vascular disease, the absolute benefit depends on the absolute risk. Non-controversially, all patients should be considered for angiotensin-converting-enzyme inhibitors. The concept that beta blockers are protective from future coronary events can be disputed. Percutaneous coronary intervention can relieve symptoms without extending lifespan beyond medical therapy. However, strong mortality data favour coronary-artery bypass grafting in individuals with triple-vessel or even double-vessel disease. Thus, effort angina needs comprehensive assessment, lifestyle changes, and treatment tailored to the individual patient.

Adolescent↗
PubMed2006

Incidence and mortality risk of congestive heart failure in atrial fibrillation patients: a community-based study over two decades.

AIMS: We sought to determine whether the incidence of and survival following congestive heart failure (CHF) in patients with atrial fibrillation (AF) have changed over time. METHODS AND RESULTS: Olmsted County, Minnesota residents diagnosed with first AF during 1980-2000 were identified and followed in medical records to 2004. The trends of incidence and survival of CHF over time were assessed. Of the 3288 subjects (mean age 71+/-15 years) diagnosed with first AF and without CHF prior to or at AF diagnosis, 790 (24%) developed a first CHF during a mean follow-up of 6.1+/-5.2 years (unadjusted incidence, 44 per 1000 person years). Age- and sex-adjusted CHF incidence was unrelated to calendar year of AF diagnosis (P = 0.86). The age- and sex-adjusted mortality risk following CHF was higher than that in patients without CHF (hazard ratio 3.4, 95% confidence interval 3.1-3.8, P < 0.0001). There were no detectable changes over time with respect to the absolute (P = 0.94) or the relative (P = 0.68) mortality risk after CHF diagnosis. CONCLUSION: In this study spanning two decades, there appeared to have been no significant reduction in terms of the incidence and mortality risk of CHF following first AF diagnosis.

Aged↗