Diastolic heart failure

Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF>50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E>A), delayed relaxation (E<A), and restrictive (E≫A) filling patterns. Invasive assessment of diastolic function allows determination of the time constant of relaxation from the exponential pressure decay during isovolumic relaxation, and the evaluation of the passive elastic properties from the slope of the diastolic pressure-volume (=constant of chamber stiffness) and stress-strain relationship (=constant of myocardial stiffness). The prognosis of diastolic heart failure is usually better than for systolic dysfunction. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and AT2-blockers as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approac

Collateral and collateral-adjacent hyperemic vascular resistance changes and the ipsilateral coronary flow reserve: Documentation of a mechanism causing coronary steal in patients with coronary artery disease

Objectives: The goal of this clinical study was to assess the influence of hyperemic ipsilateral, collateral and contralateral vascular resistance changes on the coronary flow velocity reserve (CFVR) of the collateral-receiving (i.e. ipsilateral) artery, and to test the validity of a model describing the development of collateral steal. Methods: In 20 patients with one- to two-vessel coronary artery disease (CAD) undergoing angioplasty of one stenotic lesion, adenosine induced intracoronary (i.c.) CFVR during vessel patency was measured using a Doppler guidewire. During stenosis occlusion, simultaneous i.c. distal ipsilateral flow velocity and pressure (Poccl, using a pressure guidewire) as well as contralateral flow velocity measurements via a third i.c. wire were performed before and during intravenous adenosine. From those measurements and simultaneous mean aortic pressure (Pao), a collateral flow index (CFI), and the ipsilateral, collateral, and contralateral vascular resistance index (Ripsi, Rcoll, Rcontra) were calculated. The study population was subdivided into groups with CFI<0.15 and with CFI≥0.15. Results: The percentage-diameter coronary artery stenosis (%-S) to be dilated was similar in the two groups: 78±10% versus 82±12% (NS). CFVR was not associated with %-S. In the group with CFI≥0.15 but not with CFI<0.15, CFVR was directly and inversely associated with Rcoll and Rcontra, respectively. Conclusions: A hemodynamic interaction between adjacent vascular territories can be documented in patients with CAD and well developed collaterals among those regions. The CFVR of a collateralized region may, thus, be more dependent on hyperemic vascular resistance changes of the collateral and collateral-supplying area than on the ipsilateral stenosis severity, and may even fall below

Unveiling gender differences in demand ischemia: a study in a rat model of genetic hypertension

Objective: Female gender is associated with reduced tolerance against acute ischemic events and a higher degree of left ventricular hypertrophy under chronic pressure overload. We tested whether female and male rats with left ventricular hypertrophy present the same susceptibility to demand ischemia. Methods: Hearts from hypertrophied female and male salt-resistant and salt-sensitive Dahl rats (n=8 per group) underwent 30min of demand ischemia induced by rapid pacing (7Hz) and an 85% reduction of basal coronary blood flow, followed by 30min of reperfusion on an isovolumic red cell perfused Langendorff model. Results: In female hearts, high-salt diet induced a pronounced hypertrophy of the septum (2.38±0.09 vs 2.17±0.08mm; p≪0.01), whereas male hearts showed the greatest increase in the anterior/posterior wall of the left ventricle (LV) (3.19±0.22 vs 2.01±0.16mm; p≪0.05) compared with salt-resistant controls. At baseline, LV-developed pressure/g LV was significantly higher in female than male hearts (200±13 and 196±14 vs 161±10 and 152±15mmHgg−1; p≪0.01), independent of hypertrophy, indicating greater contractility in females. During ischemia, LV-developed pressure decreased in all groups; at the end of reperfusion, hypertrophied female and male hearts showed higher developed pressures independent of gender (148±3 and 130±8 vs 100±7 and 85±6mmHg; p≪0.01). In contrast, diastolic pressure was more pronounced in female than in male hypertrophied hearts during ischemia and reperfusion (24±3 vs 12±2mmHg; p≪0.01). Conlusions: In the pressure overload model of the Dahl salt-sensitive rat, female gender is associated with a more pronounced concentric hypertrophy, whereas male hearts develop a more eccentric type of remodeling. Although present at baseline, after ischemia/reperfusion systolic function is gender-independent but more determined by hypertrophy. In contrast, diastolic function is gender-dependent and aggravated by hypertrophy, leading to pronounced diastolic dysfunction. We can conclude that in the malignant setting of demand ischemia/reperfusion gender differences in hypertrophied hearts are unmasked: female hypertrophied hearts are more susceptible to ischemia/reperfusion than males. To determine whether in female hypertensive patients with acute coronary syndromes, diastolic dysfunction could contribute to the worse clinical course, further experimental and clinical studies are neede

Angiotensin II receptor blockade attenuates the deleterious effects of exercise training on post-MI ventricular remodelling in rats

Objectives: The effects of exercise training on LV remodelling following large anterior myocardial infarction (MI) remains controversial. Blockade of the renin-angiotensin system has been shown to prevent ventricular dilation and deleterious remodeling. We therefore tested, in a rat model of chronic MI, whether any potentially deleterious effects of exercise on post-MI remodelling could be ameliorated by angiotensin II receptor blockade. Methods: Male Wistar rats underwent coronary ligation or sham operation. Treatment with losartan (10 mg/kg/day) began 1 week post-MI and moderate treadmill exercise (25 m/min, 60 min/day, 5 days/week) was initiated 2 weeks post-MI. Systolic and diastolic pressure-volume relationships were measured in isolated, red-cell perfused, isovolumically beating hearts 8 weeks post-MI. Morphometric measurements were performed in trichrome stained cross sections of the heart. Five groups of animals were compared: sham (n=13), control MI (MI; n=11), MI plus losartan (MI-Los; n=13), MI plus exercise (MI-Ex; n=10) and MI plus exercise and losartan (MI-Ex-Los; n=12). Results: Infarct size (% of left ventricle, LV) was similar among the infarcted groups [MI=43±4%, MI-Los=49±2%, MI-Ex=45±1%, MI-Ex-Los=48±2% (NS)]. Exercise, losartan and exercise+losartan treatments all attenuated LV dilation post-MI to a similar degree. Exercise training increased LV developed pressure in both untreated and losartan treated hearts (P<0.05 vs. other MI groups). In addition, exercise resulted in additional scar thinning in untreated hearts, while no additional scar thinning was seen in post-infarct hearts receiving both losartan and exercise. Conclusions: Following large anterior MI, losartan attenuated LV dilation and scar thinning. In untreated animals, exercise decreased dilation, but also contributed to scar thinning. Therefore, exercise concurrent with blockade of the renin-angiotensin system may provide optimal therapeutic benefit following large anterior M

Is there collateral flow in normal coronary arteries?

Rarefaction plot of sampling effort. The plot shows the number of species expected to be found for the number of individuals sampled for Sweden (blue), Italy (green) and the Netherlands (orange). (PNG 6 kb

Stent thrombosis following bare-metal stent implantation: success of emergency percutaneous coronary intervention and predictors of adverse outcome

Aims To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis. Methods and results Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%) patients. Procedural and clinical outcomes of emergency PCI for treatment of stent thrombosis were investigated. Emergency PCI was successful in 86 (91%), complicated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%) patients. Myocardial infarction occurred in 77 (81%) patients with a peak creatine kinase level of 1466±1570 U/L. Left ventricular ejection fraction declined from 0.54±0.19 prior to 0.48±0.16 (P<0.05) at the time of stent thrombosis after emergency PCI. A 6 month major adverse clinical events comprised death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after emergency PCI. Multivariable logistic regression analysis identified the achievement of TIMI 3 flow (OR=0.1, CI 95% 0.01-0.54, P<0.001) and diameter stenosis <50% (OR=0.06, CI 95% 0.01-0.32, P<0.001) during emergency PCI to be independently associated with a reduced risk of cardiac death. Recurrent stent thrombosis was independently predicted by the omission of abciximab (OR=4.3, CI 95% 1.1-17.5). Conclusion Emergency PCI for treatment of stent thrombosis effectively restores vessel patency and flow. Patients presenting with stent thrombosis are at risk for recurrent myocardial infarction and recurrent stent thrombosi

Impact of incomplete stent apposition on long-term clinical outcome after drug-eluting stent implantation

Aims Late acquired incomplete stent apposition (ISA) is more common after drug-eluting stent (DES) than bare metal stent (BMS) implantation and has been associated with vascular hypersensitivity and stent thrombosis (ST). We investigated the impact of incidentally discovered ISA as assessed by intravascular ultrasound (IVUS) 8 months after DES implantation on the long-term clinical outcome. Methods and results A total of 194 patients with 221 lesions were prospectively followed through 5 years. At 8 months, IVUS showed evidence of ISA among 37 patients with 39 lesions (18%) (mean ISAmax 4.7 ± 5.0 mm2), whereas no ISA was observed among 157 patients with 182 lesions. Incomplete stent apposition was more prevalent among segments treated with sirolimus-eluting (n = 103) than paclitaxel-eluting stents (n = 118) (27 vs. 9%, P = 0.001). Between IVUS investigation at the 8-month and 5-year follow-up, major adverse cardiac events occurred more frequently in patients with (18.9%, n = 7) than without ISA (7.0%, n = 11) (HR = 2.71, 95% CI: 1.05-6.96, P = 0.031). While there were no differences with respect to death, the rate of myocardial infarction was higher among patients with (13.5%, n = 5) than without ISA (1.9%, n = 3) (HR = 7.53, 95% CI: 1.79-31.6, P = 0.001). Very late ST was more common among patients with than without ISA [Academic Research Consortium-definite ST:13.5% (n = 5) vs. 0.6% (n = 1) HR = 23.2, 95% CI: 2.65-203, P < 0.001]. Conclusion In the present study, the presence of ISA as assessed by IVUS 8 months after DES implantation was associated with a higher rate of myocardial infarction and very late stent thrombosis during long-term follow-up. The prognostic impact of ISA on long-term clinical outcomes requires further investigatio

Two-year clinical outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents in diabetic patients

Aims Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents. Methods and results In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years. Conclusion Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patient