Hypotensive Blood Pressure Response Research Articles

Impact of SGLT2i Use on Functional Capacity in Heart Failure

<h3>Purpose</h3> Recently published trials have shown benefit for patients with heart failure with reduced or preserved ejection fraction with the addition of sodium glucose co-transporter 2 inhibitors (SGLT2i) to optimal medical therapy (OMT). Outcomes are limited to readmission and mortality but fail to elucidate a benefit in functional capacity. Data regarding the impact of SGLT2i on hemodynamic optimization has not demonstrated benefit in heart failure patients. The impact of SGLT2i on peak oxygen consumption measured by cardiopulmonary stress testing (CPET) has only been evaluated in animal models. Our aim was to evaluate the physiological impact of SGLT2i in the advanced heart failure population. <h3>Methods</h3> We performed a retrospective study between August 1, 2020 and August 15, 2021 to evaluate all patients with heart failure (preserved or reduced ejection fraction) undergoing CPET. Pre and post CPET were required after initiation of SGLT2i or after OMT. The SGLT2i group was compared to matched controls on OMT. <h3>Results</h3> A total of 13,213 patients were on SGLT2i during our study period. Of those, 2,063 (16%) had a diagnosis of heart failure with a total of 96 patients with CPET. 46 of these (48%) patients were in the SGLT2i group and 50 (52%) were matched controls on OMT. Median LVEF was 33% (IQR 25-40) in the SGLT2i group and 38% (IQR 25 -50) in the OMT group, p=0.10. Median duration between baseline and follow-up CPET in SGLT2i group was 352 days and 437 days in the OMT group, p=0.06. Pre and post comparison between OMT and SGLT2i was not different for exercise time (p=0.09), VE/VCO2 (p=0.11), RER (p=0.45), METS (p=0.25) or NYHA class (p=0.28). Less ARNI use (29 vs. 39, p=0.05), higher A1C (6.5 vs 5.7, p=0.01), similar GFR (65 vs 63, p=0.25) and less hypotensive blood pressure response at peak exercise (p<0.01) was noted in the SGLT2i group. Estimated GFR was not impacted by SGLT2i use (p=0.21) There was no significant difference in VO2 max at baseline (p=0.18) or follow-up (p=0.19) between the two groups. Change in VO2 max after SGLT2i was not significant (p=0.31). <h3>Conclusion</h3> The pluripotent mechanism of SGLT2i effect in heart failure is not clearly understood. Current outcomes have limited focus on readmission and mortality. Our data suggest that SGLT2i use does not improve functional capacity in heart failure. Optimization with SGLT2i is potentially due to a predominant effect on neurohormonal modulation and diuretic effect in addition to OMT.

Hypotensive Response on Cardiopulmonary Stress Test is Associated with Increased One Year Mortality After Continuous Flow Left Ventricular Assist Device Implantation

Purpose Cardiopulmonary stress testing (CPX) is widely used to evaluate patients with end stage heart failure who may benefit from advanced therapies, such as durable left ventricular assist devices (LVAD). A hypotensive systolic blood pressure response on CPX may identify a subpopulation with the highest risk physiology. We sought to evaluate long term outcomes among LVAD recipients with a pre-implantation hypotensive response. Methods This was a retrospective single center study using consecutive patients implanted with a continuous flow LVAD between 1/2011 and 1/2019 at our Institution. Patients with CPX performed within 12 months before implantation were included. Hypotensive response was defined as a peak exercise systolic blood pressure lower than the resting systolic blood pressure. The primary outcome was 1-year mortality. Multivariable cox regression analysis was performed to evaluate the relationship between hypotensive exercise blood pressure response and mortality. Multivariate linear regression analysis was used to determine pre-implant variables and mortality. Results 313 patients were enrolled in the study and 123 were identified to meet our inclusion criteria. The mean age was 60.1 years, 58% had ischemic cardiomyopathy and 85% were classified as INTERMACS 3-5. 54 patients had a hypotensive response on CPX (44%). A total of 14 patients died at 1 year, 10 from the hypotensive cohort (p=0.043), hazard ratio 3.54 with 95% CI (1.1, 11.3, p=0.033). Post-implantation ICU and overall hospital length of stay were similar to the group with normal blood pressure response. There was also no significant difference in post-operative complications and the risk of re-hospitalization at 1 month, 6 months and 1 year. Conclusion Hypotensive blood pressure response on the CPX performed pre-LVAD implantation is independently associated with increased 1-year mortality. Additional studies are needed to further characterize this high-risk patient population and to identify strategies to improve survival rates.

Myocardial Repolarization Dispersion and Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy

Growing evidence suggests that late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) is an additive marker of disease severity, and possibly of arrhythmic risk, in hypertrophic cardiomyopathy (HCM). We investigated the possible relationship between LGE and markers of myocardial repolarization dispersion in HCM. Eighty-five HCM outpatients underwent CMR and short-period electrocardiogram analysis to calculate the temporal myocardial repolarization dispersion through the QT variance normalized for QT mean (QTVN) and the QT variability index (QTVI). The QT dispersion in the spatial domain was also obtained. Patients with LGE (62%) had higher left atrial volume, maximum wall thickness, and left ventricular mass (P<0.0001), as well as a greater prevalence of non-sustained ventricular tachycardia (P<0.0001) and hypotensive blood pressure response (P=0.044). Both QTVN and QTVI were higher in the group with LGE (P<0.0001). At multivariate analysis, using QTVI as the dependent variable, %LGE (P<0.0001), age (P<0.0001), left ventricular outflow obstruction (P=0.038), and sudden cardiac death risk factor burden (P=0.020) reached statistical significance. Otherwise, only %LGE (P=0.005) and left ventricular mass index (P=0.015) remained associated with QTVN. Temporal myocardial repolarization dispersion correlates with LGE extent. Whether these variables could be useful in HCM clinical management warrants confirmation by larger prospective studies.

Exercise blood pressure response and perioperative complications after major vascular surgery

Earlier studies have shown that hypertensive or hypotensive blood pressure (BP) response during a preoperative treadmill exercise test in patients with peripheral arterial disease is associated with a two-fold increased risk of cardiovascular events and mortality. However, it is unknown if these patients also experience an increased perioperative complication risk at major vascular surgery. In total 665 consecutive patients with peripheral arterial disease underwent elective major vascular surgery (carotid endarterectomy, abdominal aorta repair, or lower extremity revascularization). Perioperative complications (infection, myocardial infarction, angina pectoris, cardiac arrhythmia, heart failure, cerebrovascular accident or spinal cord ischemia, dialyses, amputation, thrombectomy, reoperation or death) were defined as occurring within 30 days after surgery and were collected using medical records. Hypertensive BP response was defined as a difference between exercise systolic BP and resting systolic BP of more than 55 mmHg. Hypotensive BP response was defined as a drop in exercise systolic BP below resting systolic BP. Patients with a hypertensive BP response during a preoperative exercise test (n = 66) showed a higher risk of early perioperative thrombectomy [hazard ratio (HR) 2.80 95% CI (1.24-6.33)] compared with patients with a normal BP response (n = 582). Patients with a hypotensive BP response (n = 18) showed an increased risk of perioperative myocardial infarction [HR 3.69 95% CI (1.08-12.64)] and cardiac complications [HR 2.90 95% CI (1.02-8.19)] compared with patients with a normal BP response. Patients with an abnormal BP response have more cardiovascular complications at elective major vascular surgery.

50 Diagnostic role of exercise tolerance testing in familial premature sudden cardiac death

<h3>Background</h3> Investigation of blood relatives for evidence of an inherited cardiac condition is advocated following an unexplained sudden cardiac death (SCD). <h3>Aim</h3> We determined the diagnostic yield of exercise tolerance testing (ETT) in investigation of inherited cardiac conditions following familial premature SCD. <h3>Methods</h3> Between 2006 and 2010, we evaluated 308 blood relatives of 148 SCD victims, who completed at least 3 min of the Bruce protocol. ETTs were analysed for: QT prolongation; Brugada type 1 pattern; ST depression: blood pressure (BP) response; multiple ventricular ectopics or arrhythmia. Individual pathological phenotypes were determined by a combination of 12-lead ECG, echocardiogram, 24-h holter monitor, with additional MRI, CT coronary angiography and genetic mutation analysis, as appropriate. <h3>Results</h3> Thirty (9.8%) patients had an abnormality during ETT, details of which are summarised in Abstract 50 figure 1. All ETTs with abnormal QT prolongation and dynamic Brugada pattern were associated with diagnoses of long QT syndrome and Brugada syndrome respectively. An example of dynamic Brugada phenotype is given in Abstract 50 figure 2. Ventricular ectopy was seen in 15 patients, of whom 5 demonstrated phenotypic cardiomyopathy or channelopathy on further investigations. No patients with significant ST depression had evidence of coronary abnormalities on imaging. No hypotensive BP response was seen, but exertional hypertension was associated with systemic hypertension. <h3>Conclusion</h3> The ETT is a useful diagnostic adjunct when evaluating relatives of victims of premature SCD. Reliable diagnostic indicators include inappropriate QT prolongation and dynamic Brugada pattern. Ventricular ectopy is non-specific, but is associated with both cardiomyopathic and channelopathic processes in a significant minority. ST segment depression, however, is unhelpful and should be viewed in the context of the patient9s cardiovascular risk profile.

Prognostic value of hypotensive blood pressure response during single-stage exercise test on long-term outcome in patients with known or suspected peripheral arterial disease

A decline in systolic blood pressure during exercise is thought to be a sign of severe coronary artery disease. However, no studies have yet examined this effect in patients with known or suspected peripheral arterial disease. Therefore, we investigated the prognostic value of hypotensive blood pressure response after single-stage exercise test on long-term mortality, major adverse cerebrovascular and cardiac events (MACCE) and the effects of statin, beta-blocker and aspirin use in patients with known or suspected peripheral arterial disease. A total of 2022 patients were enrolled in an observational study with a mean follow-up of 5 years. Hypotensive blood pressure response, 4.6% of the total population, was defined as a drop in exercise systolic blood pressure below resting systolic blood pressure. Our study showed that hypotensive blood pressure response was associated with an increased risk of all-cause mortality [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.10-2.73] and MACCE (HR: 1.85, 95% CI: 1.14-3.00), independent of other clinical variables. Additionally, after adjustments for clinical risk factors and propensity score, baseline statin use was associated with a reduced risk of all-cause mortality (HR: 0.60, 95% CI: 0.44-0.80). Besides, statin and aspirin use were both also associated with a reduced risk of MACCE (HR: 0.65, 95% CI: 0.47-0.89 and HR: 0.69, 95% CI: 0.53-0.88, respectively). Hypotensive blood pressure response after single-stage treadmill exercise tests in patients with known or suspected peripheral arterial disease was associated with a higher risk for all-cause long-term mortality and MACCE, which might be reduced by statin and aspirin use.

Oral citrulline administration enhances NO‐dependent vasodilation

L-citrulline (L-Cit) is the precursor of L-arginine (L-Arg), substrate for NOS in NO production. L-Cit is converted into L-arg via arginosuccinate synthase and lyase. Our purpose was to determine the efficacy of L-Cit versus L-Arg supplementation in the production of NO, both in bovine aortic endothelial cells (BAEC) and in intact rabbits. Preincubation of BAEC with supplemental L-arginine (5 x 10 −4 M) for 2 hrs increased NO production in response to ionomycin (10−6 M) by 38% compared to control conditions (5 x 10−5 M, L-Arg), while incubation with L-Cit (5 x 10−4 M) did not augment the rise in NO. Because the duration (T1/2)of the hypotensive blood pressure response (DBPR) to acetylcholine (ACh) in intact animals is dependent on amount of NO released, we examined the effect of i.v. administration of L-Cit or L-Arg - both at 30 mg/kg, initially, followed by 10 mg/kg/min for 60 min - on the DBPR to Ach (0.1 to 5μg/kg, i.v.) in anesthetized rabbits. Administration of L-Arg markedly lengthened DBPR to Ach by 210 to 350%, but treatment with L-Cit was far less effective (only 20 to 70%). However, after 3 days of oral administration of L-Cit (~0.2 gm/kg/day), the duration of the responses to Ach was increased by 40 to 220%. In contrast, the same oral dose of L-Arg resulted in either no enhancement or a 36% reduction in DBPR to highest dose of ACh. Treatment with the NOS inhibitor L-NAME (5 mg/kg, i.v.) shortened DBPR and prevented any effects of L-Arg or L-Cit. Our data indicate that acute supplemental L-Arg augments NO responses to Ach, but longer periods of administration can reduce responses, possiblly through induction of arginase. Conversely, supplemental L-Cit, while less effective acutely in augmenting NO production to Ach, when given over three days appears to effectively raise L-arg levels and availability, and NO production. Lack of metabolism of L-Cit by arginase may be involved.

Hypertrophische Kardiomyopathie

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease phenotypically expressed in the general population at about 0.2%. Annual mortality rate is about 1% in unselected patients, 3-6% in patients with severe symptoms, and 17% following resuscitation from ventricular tachycardia (VT)/ventricular fibrillation (VF). 50-80% of deaths are sudden. Beneath effective treatment in severe symptoms of heart failure (most common in midlife and beyond) the prevention of sudden death (most common in young patients) continues to be a major challenge. The highest risk has been associated with any of the following markers: 1. prior cardiac arrest or spontaneous sustained VTs, 2. a family history of premature HCM-related death, 3. extreme left ventricular hypertrophy (> or = 30 mm), 4. syncope, 5. multiple bursts of nonsustained VTs, 6. hypotensive blood pressure response to exercise, and 7. marked septal scarring (hyperenhancement in magnetic resonance imaging). Treatment options in patients with drug-refractory symptoms or increased risk of sudden death are surgical myectomy, transcoronary ablation of septal hypertrophy (TASH), dual-chamber pacing, ablation of atrial fibrillation (or the AV node), and the implantable cardioverter defibrillator (ICD). 1. Surgical myectomy effectively improves symptoms, hemodynamics and probably prognosis. Long-term results are well known, but patients' preference and the number of experienced surgical centers are fading. Randomized studies are missing. 2. TASH induces quite similar improvements in symptoms and hemodynamics. It is remarkably evaluated for a postprocedural follow-up of up to 10 years, and it is the preferred mode of treatment in patients. However, information on long-term prognosis, rhythmogenic effects and randomized studies are missing. For the prevention of sudden death, TASH has to be combined with an ICD. 3. Dual-chamber pacing was evaluated in randomized crossover studies, but symptomatic and hemodynamic improvements and patients' preference are substantially lower than for TASH. 4. The ICD has the potential to alter prognosis in secondary (class I indication) and primary prevention. HCM patients should undergo a risk stratification assessment. Prophylactic implants base on a clinical profile with two or more risk markers (sometimes one risk marker). 5. Ablation of atrial fibrillation or the AV node is indicated to improve symptoms in patients with fast ventricular rates despite medical treatment. For the prevention of sudden death, it has to be combined with an ICD.

Prognostic value of systemic blood pressure response during exercise in a community-based patient population with hypertrophic cardiomyopathy

OBJECTIVESThe present study was designed to prospectively evaluate the prognostic relevance of abnormal blood pressure response to exercise (ABPR), defined as hypotension or failed blood pressure increase (<20 mm Hg) with exercise, in a community-based hypertrophic cardiomyopathy (HCM) population representative of the overall disease spectrum.BACKGROUNDAbnormal blood pressure response to exercise has been proposed as a marker for hemodynamic instability and increased risk for disease-related mortality in highly selected patient populations with HCM.METHODSThe study population comprised 126 patients (aged 42 ± 14 years) who underwent maximal symptom-limited cycloergometer exercise testing as part of the standard evaluation at our institution, and who were followed systematically for 4.7 ± 3.7 years after testing.RESULTSOf the 126 study patients, 98 (78%) had a normal blood pressure response during exercise, whereas the other 28 (22%) had ABPR, including nine with hypotension and 19 with failed blood pressure rise. During the follow-up period, nine patients (7%) died of HCM-related causes (three suddenly and six heart failure–related), of whom four had ABPR. In those patients aged ≤50 years, survival analysis after exercise testing showed a significantly increased risk for cardiovascular mortality associated with ABPR compared with a normal exercise response (p = 0.04), with an odds ratio of 4.5 (95% confidence interval: 1.1, 20.1). However, ABPR showed low positive predictive accuracy for cardiovascular mortality (i.e., 14%), whereas negative predictive accuracy was high (i.e., 95%).CONCLUSIONSA hypotensive blood pressure response during exercise occurred in over 20% of a community-based patient cohort with HCM, and was associated with adverse long-term prognosis in patients <50 years old. However, the positive predictive accuracy of this blood pressure response is too low to justify modifications of clinical management or to allow identification of the high-risk patient based solely on an abnormal test result. By virtue of its high negative predictive accuracy for HCM-related mortality, the blood pressure response to exercise appears to be most valuable (in conjunction with the absence of other well recognized risk factors) as a screening test for the identification of low-risk subsets of patients.

Usefulness of exercise testing shortly after acute myocardial infarction for predicting 10-year mortality

Previous studies on the prognostic value of exercise test variables after acute myocardial infarction (AMI) are limited methodologically and have yielded inconsistent results. This study determined whether 6 exercise test variables (systolic blood pressure, ST-segment depression or elevation, exercise capacity, arrhythmias, and angina pectoris) after controlling for age and sex, enhance 6 clinical variables (digoxin, previous AMI, history of systemic hypertension and angina, Killip class, and stress) as predictors of cardiovascular death and act as independent predictors as well. The present study followed 258 patients for 10.6 years, each of whom had AMI between 1977 and 1980 and an exercise test before hospital discharge. By 1988, 71 of the 258 patients had died, 56 of cardiovascular causes. This study is unique because exposure and outcome variables are clearly defined and follow-up was complete and longer than in previous studies. Multivariate survival analysis using an exponential model was tested to evaluate the conditional effects of the exercise test and clinical variables and to control for confounders. The model combined the exercise test and clinical variables. Results are reported with hazard ratios (HR) and 95% confidence intervals (CI). For important clinical risk predictors, the HRs with CIs are: digoxin use, HR 4.0 (CI 1.8, 8.5); history of prior AMI, HR 2.4 (CI 1.2, 4.7); history of systemic hypertension, HR 2.5 (CI 1.3, 4.5); angina, HR 2.4 (CI 1.3, 4.5); and stress, HR 4.2 (CI 2.2, 7.9). Three exercise test variables—hypotensive blood pressure response, HR 5.1 (CI 1.9,13.6); ST-segment depression, HR 1.8 (CI 0.98, 3.6); and ST-segment elevation, HR 2.4 (CI 0.98, 5.9)—were strong independent predictors of cardiovascular death after controlling for age, sex, and clinical variables. This is the only exercise test study with a complete 10.6-year followup in the U.S., a clearly defined outcome, and showing that 3 exercise test variables—hypotensive blood pressure response, and ST-segment depression and elevation—are strong independent predictors of cardiovascular death after controlling for clinical variables. These results support the use of exercise testing after AMI for predicting long-term prognosis.

Clinical Significance of Early vs Late Hypotensive Blood Pressure Response to Treadmill Exercise

It is generally believed that exercise-induced hypotension is the result of severe left-main or triple-vessel disease. Since this is not invariably so, and since most studies were performed in male populations, this study was done to determine the frequency of, and the significance of, exercise-induced hypotension in a more general population. The treadmill exercise tests of 4850 consecutive patients performed at a university medical center over a period of 7.5 years were reviewed. To identify patients for further analysis, a hypotensive blood pressure response was initially defined (1) as a progressive fall in systolic blood pressure, (2) as a failure of the systolic blood pressure to rise more than 5 mm Hg during exercise, or (3) as an initial rise followed by a fall below the resting standing systolic blood pressure. The incidence of exercise-induced hypotension so defined was less than 2%. Exercise-induced hypotension occurred in two patterns. An early hypotension response was defined as a fall in systolic blood pressure of more than 10 mm Hg, associated with symptoms or ST-segment depression, during the first 5 minutes of exercise or as a progressive fall in systolic blood pressure of at least 20 mm Hg. The majority of patients (nine of 10) with an early hypotensive response had severe coronary artery disease. The late hypotension pattern was characterized by an initial rise, followed by a fall in the systolic blood pressure with continued exercise. Only half of the patients with this pattern had significant coronary artery disease, and half of the patients had other causes for exercise-induced hypotension. A late hypotensive response was six times more frequent than an early hypotensive response. This study identified two patterns of exercise-induced hypotension. Early, almost always due to severe coronary artery disease, and late, six times more common than early in which only half were due to coronary artery disease. Causes of a late hypotensive response to exercise that were not due to severe coronary artery disease included valvular heart disease, orthostatic hypotension, cardiomyopathy, idiopathic causes, and drugs. Drugs that contributed to a late exercise-induced hypotension response were diuretics, vasodilators, and negative inotropic agents.

Clinical significance of early vs late hypotensive blood pressure response to treadmill exercise

Clinical significance of early vs late hypotensive blood pressure response to treadmill exercise

Prognostic value of exercise-induced ventricular ectopic activity for mortality after acute myocardial infarction

To evaluate the importance of ventricular ectopic activity on the predischarge treadmill exercise test for predicting mortality in patients after acute myocardial infarction (AMI), 163 patients with uncomplicated AMI were studied using symptom limited low-level treadmill exercise testing and 24-hour ambulatory electrocardiographic monitoring before hospital discharge. All patients were followed for at least 2 years or until recurrent AMI, coronary artery bypass grafting or death. Seventeen patients (10%) died during the follow-up period, 15 patients (9%) had recurrent AMI and 45 patients (28%) underwent bypass surgery. Ventricular ectopic activity was the only single treadmill abnormality that predicted subsequent cardiac death; angina pectoris, electrocardiographic ST-segment depression and a hypotensive blood pressure response did not. The mortality rate in the 20 patients with exercise induced ventricular ectopic activity was 25%, compared with 8% in those without (p < 0.004). Furthermore, in this patient population, exercise-induced ventricular ectopic activity was a much better predictor of cardiac death than that detected by ambulatory monitoring. Thus, ventricular ectopic activity on the predischarge treadmill exercise test is an important risk factor for death after AMI.