Abstract P270: Covid19 Hypertension In Primary Care

One of the symptoms of Sars-cov-2 is hypertension with diastolic dysfunction. Out of 432 patients, 112 had hypertension and 102 of them had diastolic hypertension that helped identify early infection despite having a negative PCR test. Diastolic hypertension led to pulmonary edema. The use of spironolactone, an aldosterone antagonist selective diuretic, at a dose of 25-50mg po q d reduced the effects of hypertension and pulmonary edema in 94/112 of the treated patients. This treatment was added to the regimen the patient was on for previously diagnosed hypertension or initiated due to Sars-cov-2 infection causing hypertension. The key to this medication is in the renin aldosterone system. Uncontrolled aldosterone promotes myocardial fibrosis and is most likely why many people have long haul covid19 cardiac complications. Aldosterone also causes perivascular fibrosis, blocks the myocardial uptake of norepinephrine, and increases plasminogen activator inhibitor levels. In conjunction with angiotensin II, aldosterone causes vascular damage that sends coagulation signals to platelets, endothelial dysfunction, and decreased vascular compliance. Therefore, aldosterone management plays a major role in the development of both hypertension and heart failure in Sars-cov-2 and a key target for therapeutic interventions.

Organoprotective Effects of Spironolactone on Top of Ramipril Therapy in a Mouse Model for Alport Syndrome

Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an “aldosterone escape”. Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy. COL4A3-/- mice were treated with ramipril (ACEi), starting at 4.5 weeks of age, and spironolactone was added at 7 weeks of age. Lifespan until renal failure, as well as kidney function parameters, were investigated. Dual therapy decreased proteinuria levels compared to ACEi monotherapy. Matrix accumulation, as well as tubulointerstitial and glomerular scar-tissue formation, were significantly reduced compared to untreated mice and ACEi-monotherapy at 75 and 100 days. Lifespan in dual treated mice was extended compared to untreated mice. However, lifespan was not superior to ACEi monotherapy–despite improved urea-nitrogen levels in the dual therapy group. In conclusion, adding the aldosterone-antagonist spironolactone to ACEi therapy further improved kidney function and reduced proteinuria and fibrosis. However, survival was not improved further, possibly due to premature death from side effects of dual therapy such as hyperkalemia. Thus, dual therapy could offer an effective therapy option for Alport syndrome patients with progressive proteinuria. However, the risks of adverse events require close monitoring.

Association of Body-Weight Fluctuation With Outcomes in Heart Failure With Preserved Ejection Fraction

Aims: To investigate the relationship between body-weight fluctuation and risks of clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).Methods and Results:We measured intra-individual variations in body weight from baseline and follow-up visits in 1,691 participants with HFpEF from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. The primary endpoint was any cardiovascular events (a composite of death from cardiovascular disease, non-fatal myocardial infarction, aborted cardiac arrest, or hospitalization for HF). The body-weight fluctuation was measured according to average successive variability and high variability was defined as greater than or equal to the median. After adjustment for risk factors, mean body weight and weight change, each increase of 1 standard deviation in body-weight variability was significantly associated with increased risks of any cardiovascular events (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.15–1.33, P < 0.001). Patients with high variability had a 47% increased risk of any cardiovascular events and 27% increased risk of all-cause death compared with those with low variability. Such association was similar among patients with New York Heart Association functional class I/II vs. III/IV, obesity vs. non-obesity, and weight loss, gain vs. stability (the P-values for interaction were all insignificant).Conclusion: Among patients with HFpEF, body-weight fluctuation was associated with increased risks of cardiovascular events independent of traditional cardiovascular risk factors, and regardless of HF severity, baseline weight or weight change direction.Clinical Trial Registration: Aldosterone antagonist therapy for adults with heart failure and preserved systolic function (TOPCAT), https://clinicaltrials.gov, identifier [NCT00094302].

Peripartum Cardiomyopathy (PPCM): How to Diagnose and Deal with?

Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion, where patients present with heart failure (HF) secondary to left ventricular (LV) systolic dysfunction without any other cause of HF identified in the last month of pregnancy or within first five months after delivery, abortion, or miscarriage. PPCM is a life-threatening condition which frequently under diagnosed and inadequately treated, whereas the morbidity and mortality rate ranges between 7% and 50%. Early diagnosis is important to decrease morbidity and mortality. Therefore, it is necessary to report the case related to this condition. A 34-year-old woman was referred to RSSA with worsening shortness of breath (SOB). She has given birth about 2.5 months prior to admission. History taking and supporting findings form this case were supported to diagnosis of PPCM. She was treated with diuretic, aldosterone antagonist, ACE-I, beta blocker, anticoagulant, and bromocriptine. The symptoms were improved in the following days. She was discharged with better condition and educated to comply with medication.

Tolvaptan therapy of Chinese cirrhotic patients with ascites after insufficient diuretic routine medication responses: a phase III clinical trial

Background To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. Methods In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. Results The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). Conclusions Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. Trial registration NCT01349348. Retrospectively registered May 2011.

Abstract 14370: Rapidly Improving Adherence to Guideline-Directed Medical Therapies in Metropolitan Heart Failure Systems of Care

Background: The 2017 AHA/ACC/HFSA Focused Update of the 2013 ACC/AHA Guidelines for the Management of Heart Failure provided additional support for the clinical use of ACEI, ARBs or ARNIs in conjunction with Evidence-Based Beta Blockers and Aldosterone Antagonists in HFrEF, otherwise known as Guideline-Directed Medical Therapy (GDMT). Although these updates clarified the benefits of GDMT to patient outcomes, low rates of adherence at the provider level for both hospitalized and ambulatory patients continue to be seen. Methods: With the objective of rapidly improving GDMT utilization, as well as improving patient outcomes, the American Heart Association initiated a multidisciplinary collaborative in three metropolitan markets - Chicago, Milwaukee, and St. Louis. Utilizing Get With The Guidelines®-Heart Failure (GWTG-HF), 40 hospitals tracked patients discharged with a primary diagnosis of heart failure and entered data from their inpatient and 30-days post-acute record. An initiative benchmark group was created to track progress and revisions were made to the post-acute care form. Hospitals were provided targeted consultation using hospital-specific data compared to regional and initiative benchmarks. The initiative provided exclusive professional education, including webinars, collaboration meetings, and best-practice recommendations. Results: Between January 1, 2019 and December 31, 2019, 10,532 patients with a primary diagnosis of heart failure, were entered into GWTG-HF from the 40 initiative hospitals, in which 3807 had an EF of <40%. A comparison from Q1 to Q4, 2019 of the mean adherence for GDMT was performed at discharge and yielded the following results: ACEI/ARB or ARNi from 89.3% to 91.6%, Evidenced-Based Beta Blockers from 90.3% to 94.2% and Aldosterone Antagonist from 53.6% to 64.7%; At 30-Days the mean adherence for Q1 and Q4 were calculated as follows: ACEI/ARB or ARNi from 60.4% to 72.9% and Aldosterone Antagonist from 28.2% to 55.3%. Evidence-Based Beta Blocker was only captured for Q3 and Q4, 2019 and the mean adherence improved from 70.3% to 73.8%. Conclusions: The multi-city quality initiative early results show a positive correlation in improving adherence to GDMT in both the hospital and ambulatory setting.