WEBVTT 00:00:00.299 --> 00:00:03.989 Now meet Angela. Her heart failure diagnosis has been confirmed. 00:00:04.224 --> 00:00:07.765 Angela has confirmed heart failure with preserved ejection fraction. 00:00:08.107 --> 00:00:10.837 A diuretic helped her edema, but she still stops on 00:00:10.880 --> 00:00:12.051 the walk to her mailbox. 00:00:12.283 --> 00:00:15.184 She asks whether heart-failure medicines can help when she does 00:00:15.227 --> 00:00:18.275 not have diabetes. Established diagnosis. 00:00:18.549 --> 00:00:22.347 heart failure with preserved ejection fraction confirmed after clinical and 00:00:22.389 --> 00:00:26.571 objective assessment; left ventricular ejection fraction 58 percent. 00:00:26.997 --> 00:00:31.247 Current context. body mass index 35 kilograms per square meter; 00:00:31.375 --> 00:00:35.300 A one C 5.8 percent; no diabetes. 00:00:35.599 --> 00:00:39.207 Safety starting point. E G F R 48 milliliters per 00:00:39.250 --> 00:00:42.876 minute per one point seven three square meters; potassium 4.6 00:00:42.962 --> 00:00:45.991 milliequivalents per liter; review current volume status. 00:00:46.204 --> 00:00:49.731 Patient goal. Walk to the mailbox with fewer stops; preserve 00:00:49.774 --> 00:00:53.273 strength and independence. Match each treatment to the problem it 00:00:53.315 --> 00:00:56.721 is meant to solve. Begin with current congestion, blood pressure, 00:00:56.892 --> 00:01:01.581 kidney function, rhythm, comorbidities, medication access and Angela’s goal. 00:01:01.834 --> 00:01:04.479 A drug that relieves fluid overload and a therapy that 00:01:04.522 --> 00:01:07.636 reduces future heart failure events may both have a role, 00:01:07.850 --> 00:01:09.428 but their purposes should be clear. 00:01:09.770 --> 00:01:12.415 Do not use improved edema as evidence that the overall 00:01:12.628 --> 00:01:16.655 risk has disappeared. Contemporary heart failure with preserved ejection fraction 00:01:16.826 --> 00:01:21.818 care integrates heart failure-directed treatment with management of obesity, diabetes 00:01:21.860 --> 00:01:27.247 when present, hypertension, kidney disease, atrial fibrillation and coronary disease. 00:01:27.599 --> 00:01:32.079 The 2026 American College of Cardiology update incorporates newer evidence 00:01:32.335 --> 00:01:36.516 for S G L T 2 inhibitors, nonsteroidal mineralocorticoid receptor 00:01:36.601 --> 00:01:40.408 antagonists and incretin-based therapies within that broader approach. 00:01:40.758 --> 00:01:42.934 This is not a direction to give every agent to 00:01:42.977 --> 00:01:44.747 every patient in a fixed sequence. 00:01:44.982 --> 00:01:47.755 Ask what Angela is already taking, what she has previously 00:01:47.926 --> 00:01:51.239 stopped and why. A medication list may contain an agent 00:01:51.282 --> 00:01:54.072 she never obtained or a dose she no longer uses. 00:01:54.429 --> 00:01:57.714 Explain the expected benefit in terms that match the evidence: 00:01:58.056 --> 00:02:03.240 symptoms, worsening heart failure events, hospitalization or another measured endpoint. 00:02:03.645 --> 00:02:07.364 Avoid promising an individual outcome from an average trial result. 00:02:07.712 --> 00:02:10.997 S G L T 2 inhibition is not restricted to 00:02:11.040 --> 00:02:17.213 patients with diabetes. In EMPEROR-Preserved, 5,988 participants with symptomatic heart 00:02:17.298 --> 00:02:21.821 failure and left ventricular ejection fraction above 40 percent received 00:02:21.949 --> 00:02:26.451 empagliflozin or placebo. The primary composite of cardiovascular death or 00:02:26.494 --> 00:02:31.925 heart failure hospitalization occurred in 13.8 percent versus 17.1 percent; 00:02:32.279 --> 00:02:37.242 the hazard ratio was 0.79 (95 percent confidence interval 0.69 00:02:37.448 --> 00:02:41.654 to 0.90). The effect was largely driven by fewer heart 00:02:41.739 --> 00:02:45.656 failure hospitalizations and was observed with and without diabetes. 00:02:45.946 --> 00:02:51.450 DELIVER tested dapagliflozin in 6,263 participants with left ventricular ejection 00:02:51.663 --> 00:02:56.468 fraction above 40 percent. Worsening heart failure or cardiovascular death 00:02:56.639 --> 00:03:01.314 occurred in 16.4 percent versus 19.5 percent, with a hazard 00:03:01.356 --> 00:03:07.884 ratio of 0.82 (95 percent confidence interval 0.73 to 0.92). 00:03:08.183 --> 00:03:11.369 The trials support heart failure treatment beyond glucose lowering. 00:03:11.654 --> 00:03:13.847 They do not show that one S G L T 00:03:13.847 --> 00:03:15.836 2 inhibitor is superior to the other. 00:03:16.134 --> 00:03:19.206 Angela’s absence of diabetes is therefore not a reason by 00:03:19.249 --> 00:03:21.894 itself to exclude an appropriate S G L T 2 00:03:21.937 --> 00:03:26.827 inhibitor. Review the selected product’s heart failure indication, renal-use instructions, 00:03:27.169 --> 00:03:29.874 volume status, contraindications and access. 00:03:30.318 --> 00:03:34.499 Discuss genital infection symptoms, volume depletion and the possibility of 00:03:34.542 --> 00:03:37.778 ketoacidosis even without marked hyperglycemia. 00:03:38.071 --> 00:03:43.148 Provide individualized instructions for illness, fasting and procedures; empagliflozin’s label 00:03:43.233 --> 00:03:46.348 specifies withholding for at least three days before surgery or 00:03:46.391 --> 00:03:49.324 procedures associated with prolonged fasting, when possible. 00:03:49.697 --> 00:03:52.343 Do not turn a monitoring conversation into a list the 00:03:52.385 --> 00:03:55.884 patient cannot use. Ask Angela which instruction she would follow 00:03:56.055 --> 00:03:57.719 if she were unable to eat or drink. 00:03:57.975 --> 00:04:00.073 Clarify whom she calls and when. 00:04:00.380 --> 00:04:03.367 Coordinate any diuretic adjustment with her volume assessment and the 00:04:03.409 --> 00:04:06.737 prescribing team rather than giving a universal instruction to reduce 00:04:06.823 --> 00:04:08.859 or stop it. Here is the decision. 00:04:09.189 --> 00:04:12.602 Angela asks why a medicine commonly discussed for diabetes is 00:04:12.645 --> 00:04:15.803 being considered. Which answer is most accurate? 00:04:16.058 --> 00:04:17.723 Pause here if you would like a moment to think 00:04:17.765 --> 00:04:20.309 it through. The best next step in this case is: 00:04:20.522 --> 00:04:23.210 It is being considered for heart failure benefit; the evidence 00:04:23.424 --> 00:04:27.136 includes people without diabetes. The indication and evidence should be 00:04:27.178 --> 00:04:28.788 explained in heart failure terms. 00:04:29.118 --> 00:04:32.025 What the newer obesity trials actually establish. 00:04:32.573 --> 00:04:37.351 STEP H F peff studied semaglutide 2.4 milligrams in 529 00:04:37.437 --> 00:04:41.191 participants with obesity and heart failure with preserved ejection fraction 00:04:41.447 --> 00:04:46.264 without diabetes. At 52 weeks, the between-group improvement in Kansas 00:04:46.306 --> 00:04:51.512 City Cardiomyopathy Questionnaire clinical summary score was 7.8 points, and 00:04:51.554 --> 00:04:53.976 weight reduction was greater with semaglutide. 00:04:54.264 --> 00:04:57.848 The main lesson is improvement in symptoms, physical limitations and 00:04:57.891 --> 00:04:59.491 weight in the studied population. 00:04:59.811 --> 00:05:01.534 It was not a mortality trial. 00:05:01.808 --> 00:05:06.885 SUMMIT studied tirzepatide in 731 participants with obesity and left 00:05:07.013 --> 00:05:09.820 ventricular ejection fraction of at least 50 percent. 00:05:10.195 --> 00:05:14.078 Cardiovascular death or worsening heart failure occurred in 9.9 percent 00:05:14.419 --> 00:05:20.583 versus 15.3 percent (hazard ratio 0.62, 95 percent confidence interval 00:05:20.711 --> 00:05:25.106 0.41 to 0.95). Fewer worsening heart failure events drove the 00:05:25.149 --> 00:05:28.534 result; cardiovascular death alone was not shown to be reduced. 00:05:28.847 --> 00:05:31.492 These trials ask different questions and cannot be used as 00:05:31.535 --> 00:05:35.461 a head-to-head ranking. Their effect sizes use different endpoints, populations 00:05:35.759 --> 00:05:39.590 and follow-up. Weight loss, symptom improvement and clinical event reduction 00:05:39.889 --> 00:05:42.576 should not be collapsed into a single claim that all 00:05:42.662 --> 00:05:44.390 incretin therapies do the same thing. 00:05:44.624 --> 00:05:47.007 Current US product indications also matter. 00:05:47.341 --> 00:05:51.820 The reviewed Wegovy and Zepbound labels contain obesity-related indications; the 00:05:51.863 --> 00:05:55.660 reviewed Zepbound label also includes obstructive sleep apnea in adults 00:05:55.746 --> 00:05:58.755 with obesity. Neither should be described here as carrying a 00:05:58.797 --> 00:06:02.143 specific heart failure with preserved ejection fraction indication. 00:06:02.459 --> 00:06:04.934 A clinician may use a medicine for an approved obesity 00:06:05.104 --> 00:06:07.835 indication in a patient who also has heart failure with 00:06:07.920 --> 00:06:11.462 preserved ejection fraction, while discussing heart failure with preserved ejection 00:06:11.675 --> 00:06:15.580 fraction trial evidence accurately. Verify the current exact label at 00:06:15.622 --> 00:06:17.201 prescribing and at course release. 00:06:17.500 --> 00:06:20.422 What belongs in an individualized obesity conversation. 00:06:20.828 --> 00:06:23.686 Ask permission to discuss weight and the symptoms that matter 00:06:23.772 --> 00:06:26.674 to Angela. Her goal is not simply a lower number: 00:06:26.952 --> 00:06:29.256 she wants to reach the mailbox and manage her daily 00:06:29.384 --> 00:06:33.962 responsibilities. Discuss treatment options in the context of access, preferences, 00:06:34.112 --> 00:06:37.354 other conditions and the ability to sustain nutrition and function. 00:06:37.738 --> 00:06:41.653 Review the selected agent’s contraindications, precautions and interactions. 00:06:42.070 --> 00:06:45.952 For semaglutide and tirzepatide, the relevant labeling includes the medullary 00:06:46.080 --> 00:06:52.800 thyroid carcinoma/multiple endocrine neoplasia type 2 contraindication and important gastrointestinal, 00:06:52.907 --> 00:06:55.978 gallbladder, pancreatitis and other precautions. 00:06:56.469 --> 00:06:58.730 This case is not a dose-escalation protocol. 00:06:58.986 --> 00:07:03.012 Use the product-specific prescribing information and the patient’s clinical context. 00:07:03.326 --> 00:07:07.422 Ask whether nausea, food insecurity, dental problems or living alone 00:07:07.550 --> 00:07:11.689 interfere with intake. A registered dietitian can help individualize nutrition 00:07:11.902 --> 00:07:15.763 while protecting function. Do not assign a universal protein, fluid 00:07:15.848 --> 00:07:19.560 or sodium prescription from this vignette; heart failure symptoms, kidney 00:07:19.603 --> 00:07:22.562 disease and nutritional status can change what is appropriate. 00:07:22.833 --> 00:07:26.972 Adapt physical activity to stability, symptoms and ability, and revisit 00:07:27.142 --> 00:07:29.553 strength and daily function as weight changes. 00:07:30.129 --> 00:07:33.628 At follow-up, ask what was obtained, what was tolerated and 00:07:33.670 --> 00:07:37.527 what changed. Include symptoms and a functional goal alongside weight, 00:07:37.741 --> 00:07:39.703 blood pressure and laboratory findings. 00:07:40.002 --> 00:07:43.117 A change in weight could reflect fluid, nutritional intake or 00:07:43.202 --> 00:07:46.219 intentional loss; interpreting it requires context. 00:07:46.547 --> 00:07:50.899 Read mineralocorticoid receptor antagonist evidence without assuming a class effect. 00:07:51.198 --> 00:07:55.476 Mineralocorticoid receptor antagonists are not interchangeable evidence packages. 00:07:55.829 --> 00:08:01.461 Spironolactone and eplerenone are steroidal mineralocorticoid receptor antagonists; finerenone is 00:08:01.546 --> 00:08:06.613 nonsteroidal. Receptor selectivity and pharmacologic properties differ, but a mechanistic 00:08:06.826 --> 00:08:10.062 difference does not establish comparative clinical superiority. 00:08:10.355 --> 00:08:14.750 In TOPCAT, spironolactone did not significantly reduce the overall primary 00:08:14.835 --> 00:08:18.120 composite endpoint in the studied heart failure with preserved ejection 00:08:18.291 --> 00:08:22.926 fraction population. heart failure hospitalization was lower, and hyperkalemia was 00:08:23.011 --> 00:08:27.099 more frequent. Important regional differences complicate interpretation. 00:08:27.475 --> 00:08:30.888 Selected patients may still have reasons for a steroidal mineralocorticoid 00:08:30.973 --> 00:08:33.832 receptor antagonist, but the result should not be described as 00:08:33.875 --> 00:08:37.714 an unequivocally positive overall heart failure with preserved ejection fraction 00:08:37.885 --> 00:08:43.440 trial. In FINEARTS H F, 6,001 participants with left ventricular 00:08:43.568 --> 00:08:47.152 ejection fraction of at least 40 percent were randomized to 00:08:47.194 --> 00:08:50.820 finerenone or placebo. The composite rate of total worsening heart 00:08:50.863 --> 00:08:54.618 failure events and cardiovascular death was lower with finerenone (rate 00:08:54.703 --> 00:09:01.239 ratio 0.84, 95 percent confidence interval 0.74 to 0.95). 00:09:01.456 --> 00:09:04.208 Cardiovascular death alone was not significantly reduced. 00:09:04.357 --> 00:09:08.112 Hyperkalemia was more frequent. Its current heart failure indication and 00:09:08.154 --> 00:09:10.793 monitoring requirements are addressed in Teresa’s case. 00:09:11.128 --> 00:09:14.413 Do not compare TOPCAT and FINEARTS H F as though 00:09:14.456 --> 00:09:17.777 patients were randomized between spironolactone and finerenone. 00:09:18.068 --> 00:09:22.335 Do not stack two mineralocorticoid receptor antagonists without a specific 00:09:22.548 --> 00:09:25.535 specialist-directed reason and a careful safety review. 00:09:25.919 --> 00:09:29.546 The treatment decision should identify the indication, the evidence and 00:09:29.588 --> 00:09:32.834 the monitoring burden. Separate a pooled analysis from a heart 00:09:32.920 --> 00:09:35.346 failure with preserved ejection fraction trial. 00:09:35.510 --> 00:09:39.989 FINE-HEART pooled participant-level data from FIDELIO D K D, FIGARO 00:09:40.120 --> 00:09:42.250 D K D and FINEARTS H F. 00:09:42.491 --> 00:09:47.672 Its 18,991 participants span chronic kidney disease with type 2 00:09:47.716 --> 00:09:51.536 diabetes and heart failure with mildly reduced or preserved ejection 00:09:51.712 --> 00:09:54.896 fraction. It is not a new head-to-head trial and is 00:09:54.940 --> 00:09:58.559 not a heart failure with preserved ejection fraction-only population. 00:09:58.927 --> 00:10:03.933 Its primary cardiovascular-death result did not reach statistical significance (hazard 00:10:03.977 --> 00:10:10.195 ratio 0.89, 95 percent confidence interval 0.78 to 1.01). 00:10:10.366 --> 00:10:15.955 A 2026 sex analysis included 6,664 women, 35 percent of 00:10:15.998 --> 00:10:20.040 the pooled population. Women had a greater multimorbidity burden and 00:10:20.083 --> 00:10:23.368 were less likely to receive several commonly indicated CKM therapies 00:10:23.411 --> 00:10:27.891 at baseline. No evidence of treatment-effect heterogeneity by sex was 00:10:27.933 --> 00:10:30.012 found for the assessed finerenone outcomes. 00:10:30.341 --> 00:10:34.139 This supports attention to treatment access and equitable assessment; it 00:10:34.181 --> 00:10:37.310 does not establish a special female-only drug effect. 00:10:37.579 --> 00:10:40.651 For Angela, close the treatment discussion by listing the clinical 00:10:40.779 --> 00:10:44.833 problem, the option chosen or deferred, the reason, the safety 00:10:45.046 --> 00:10:46.347 plan and her own goal. 00:10:46.539 --> 00:10:49.441 A defensible decision may include a reason not to use 00:10:49.483 --> 00:10:54.021 a therapy. Educational success is appropriate selection and follow-through, not 00:10:54.063 --> 00:10:57.029 the number of prescriptions or adoption of a particular brand. 00:10:57.349 --> 00:11:00.454 Here is the decision. Angela reads that one trial improved 00:11:00.539 --> 00:11:03.440 symptoms and another reduced a composite event outcome. 00:11:03.654 --> 00:11:05.467 What should the clinician clarify? 00:11:05.830 --> 00:11:07.622 Pause here if you would like a moment to think 00:11:07.664 --> 00:11:10.399 it through. The best next step in this case is: 00:11:10.676 --> 00:11:14.388 Confirm each study’s population, endpoint and current product label before 00:11:14.644 --> 00:11:17.972 applying the result. This avoids converting different evidence into an 00:11:18.058 --> 00:11:22.347 unsupported drug ranking. The takeaway: Use heart failure evidence even 00:11:22.475 --> 00:11:27.467 without diabetes, distinguish symptom and event endpoints, and individualize obesity 00:11:27.595 --> 00:11:31.008 treatment. Compare each option with its own evidence and current 00:11:31.136 --> 00:11:34.610 label. Before we move on, let’s apply that reasoning in 00:11:34.652 --> 00:11:37.596 more detail. A treatment gap is a prompt to assess 00:11:37.682 --> 00:11:44.764 eligibility. A US registry study published in 2025 examined 759,915 00:11:44.849 --> 00:11:50.183 patients at 191 outpatient cardiovascular practices using records from July 00:11:50.311 --> 00:11:55.449 2019 through June 2023. In the combined heart failure with 00:11:55.492 --> 00:12:00.025 mildly reduced ejection fraction/heart failure with preserved ejection fraction group, 00:12:00.249 --> 00:12:04.772 recorded S G L T 2-inhibitor prescribing reached 12.8 percent 00:12:05.070 --> 00:12:08.313 in the final quarter. Female sex was associated with lower 00:12:08.441 --> 00:12:11.072 prescribing across the overall heart failure cohort. 00:12:11.357 --> 00:12:15.411 This is a historical observational finding, not a current 2026 00:12:15.539 --> 00:12:18.098 rate or proof that every untreated patient should receive a 00:12:18.141 --> 00:12:21.887 medicine. Use the gap to improve the decision process: confirm 00:12:21.973 --> 00:12:26.453 the syndrome, assess clinical and product-specific eligibility, explain the expected 00:12:26.623 --> 00:12:30.165 benefit and limits, review safety and cost, and document the 00:12:30.207 --> 00:12:33.943 agreed plan. A balanced education program measures the quality of 00:12:33.986 --> 00:12:37.015 those decisions. It does not set a target for prescriptions 00:12:37.100 --> 00:12:40.428 of a particular product or assume that education alone removes 00:12:40.556 --> 00:12:43.299 insurance, laboratory or referral barriers. 00:12:43.652 --> 00:12:47.705 For heart failure, empagliflozin and dapagliflozin are each given at 00:12:47.748 --> 00:12:51.076 10 milligrams daily when appropriate, but their renal-use instructions are 00:12:51.119 --> 00:12:55.107 not identical. Dapagliflozin initiation is not recommended below an E 00:12:55.193 --> 00:12:58.179 G F R of 25 milliliters per minute per one 00:12:58.264 --> 00:13:02.309 point seven three square meters; empagliflozin heart failure studies enrolled 00:13:02.351 --> 00:13:04.997 patients down to 20 and did not enroll those below 00:13:05.167 --> 00:13:08.581 20. Review the current complete label and clinical context rather 00:13:08.666 --> 00:13:10.491 than applying a single class cutoff. 00:13:10.780 --> 00:13:15.388 Assess volume status and correct depletion before initiation; the loop-diuretic 00:13:15.516 --> 00:13:20.307 plan may need adjustment. Review genital symptoms, serious urinary symptoms, 00:13:20.542 --> 00:13:24.821 poor intake and the possibility of ketoacidosis without marked hyperglycemia. 00:13:25.133 --> 00:13:27.778 Both labels direct withholding for at least three days before 00:13:27.949 --> 00:13:32.002 surgery or procedures associated with prolonged fasting, when possible. 00:13:32.344 --> 00:13:35.939 Restarting requires clinical stability and resumed oral intake. 00:13:36.206 --> 00:13:39.150 Give the patient an actionable instruction and a contact route 00:13:39.193 --> 00:13:41.817 rather than an unexplained list of adverse effects. 00:13:42.052 --> 00:13:44.718 Separate guidance, approval and the woman in front of you. 00:13:44.910 --> 00:13:47.140 Evidence evolves after a course is written. 00:13:47.450 --> 00:13:52.655 The 2026 European Society of Cardiology guideline adds contemporary European 00:13:52.740 --> 00:13:57.391 recommendations across ejection fraction categories and discusses obesity therapies in 00:13:57.434 --> 00:14:02.191 symptomatic heart failure. US indication, dosing and safety decisions still 00:14:02.276 --> 00:14:05.562 require the current US product label and applicable US guidance. 00:14:05.775 --> 00:14:09.884 A guideline recommendation and a regulatory indication answer different questions. 00:14:10.324 --> 00:14:14.292 In the STEP H F peff pooled sex analysis, health-status 00:14:14.420 --> 00:14:18.217 improvement with semaglutide was similar in women and men, despite 00:14:18.345 --> 00:14:19.956 greater weight reduction in women. 00:14:20.286 --> 00:14:23.785 A women-focused case therefore does not justify claiming a uniquely 00:14:23.913 --> 00:14:26.129 larger heart failure treatment effect in women. 00:14:26.425 --> 00:14:30.009 Explain the population studied and the outcome measured, and avoid 00:14:30.137 --> 00:14:33.117 turning a subgroup description into a superiority claim. 00:14:33.408 --> 00:14:37.035 Build an individualized plan that also addresses blood pressure, atrial 00:14:37.077 --> 00:14:42.539 fibrillation when present, kidney health, sleep-disordered breathing, physical function, nutrition 00:14:42.795 --> 00:14:48.109 and access. Diuretics treat congestion; disease-modifying treatment and comorbidity management 00:14:48.237 --> 00:14:51.651 have distinct purposes. Neither weight loss nor relief of edema 00:14:51.821 --> 00:14:54.083 is a reason to stop asking whether the complete heart 00:14:54.168 --> 00:14:55.561 failure plan is appropriate.